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What is agenda number 7?

lzxl0226

lzxl0226_p0

letter from John r.commons, Letter from John R.Commons

EXECUTIVE COMMITTEE MEETING AGENDA 1. Minutes 2. Equalizing stocks in withdrawn warehouses. 3. Non-rebating pleages from warehousemen. (a) Enforcement Committee clearing. (b) To eccompany notice of new warehouse accounts. 4. Car tracers. - 5. Warehouse receipts. (a) Result of survey. (b) Uniform practice. 6. Moog letter and telegram. (a) Discussion with Bartlett. (b) Propriety of circularizing letter. 7. Letter from John R.Commons. 8. Wire from Charles Godchaux. Source: https://www.industrydocuments.ucsf.edu/docs/lzx10226

What is the page number?

xjhl0226

xjhl0226_p25, xjhl0226_p26, xjhl0226_p27, xjhl0226_p28, xjhl0226_p29, xjhl0226_p30, xjhl0226_p31, xjhl0226_p32, xjhl0226_p33, xjhl0226_p34, xjhl0226_p35, xjhl0226_p36, xjhl0226_p37, xjhl0226_p38, xjhl0226_p39, xjhl0226_p40, xjhl0226_p41

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17. timely and related as closely as possible to current events. If in the form of an advertisement, it should serve a useful war-time purpose with the reader. The above themes are not intended to tell what members' advertis- ing is doing to assist various government campaigns, such as "buy bonds", "plant victory gardens", "save fats", "how to make foods go farther", etc. Such advertising is commendable but serves an entirely different purpose from what we have in mind. Advertising of this type tells consumers what they should do. In our campaign we wish to tell the consumer what we have done in terms of public interest. It is suggested that the first theme to be carried out would be how well the consumer at home has been served notwithstanding the tremendous supplies furnished to our armed forces and allies-wwwith particular emphasis on the industry's accomplishments in increasing supplies and by making exist- ing supplies go farther. Some members are already running advertising copy of this nature. The amount of material along this line could be stepped up immediately on a voluntary basis without waiting for the co-ordinated schedules to be worked out. Information on the decline in the average percentage of profits during the war-period should be introduced in connection with the above. Such presentations will not only help the individual companies and the entire grocery manufacturing industry, but also will help to drive home the fact that private enterprise and private management are constructive- ly serving the national interest. At a later date, as a more long-range theme, the campaign may be directed toward getting consumers better acquainted with the great amount of useful information being printed on labels and emphasizing the value of trade-marks to the public. This would constitute one positive answer to the 18. The above themes would be adapted, or new ones selectedj for special material to be directed to farners, stockholders and other groups, in order to approach the subject from the viewpoint of their particular interest. Source: https://wvww.industrydocuments.ucsf.edu/docs/xjhl0226 19. ADVERTISING It is recommended that, for the present, all advertising be done by the participating companies over their respective names in space or time purchased and set aside in their regular schedules for this particular forn of promoticn. Each participating company will be urged to contribute voluntarily whatever amount of its total space and radio time it can provide for the themes suggested periodically by G.M.A. The headquarters office would supply thenes, fact sheets, source material and suggested subjects for specific time periods. The copy would be prepared and placed by the members and their respective advertising agencies. Each appeal should be considered as an individual presentation by an individual company which is speaking to a large number of people with whom it has established an acquaintance and a business relationship. Great care should be exercised not to indulge in boastful institu- tional advertising about achievements which, however commendable, mean little or nothing to the reader's self interest. The important thing is to concentrate on activities which are of timely interest and will answer the consumer's question, "what does it nean to me?" Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 20. Media used and release dates would be co-ordinated according to a master schedule. Participating companies would be urged to abide by the master schedule. It is anticipated that in all probability the major advertisers, who are members of G.M.A., will chiefly participate in the plan of co- ordinated schedules. However, other members will be urged to follow the themes according to their own schedules. It is proposed that, after the plans have been approved by the G.M.A., they be submitted to the heads of all member companies with an invitation to participate. Then a special meeting would be called to which the Advertising Managers of the participating companies and their agencies would be in- vited. At this meeting the detailed program would be fully presented and the active cooperation of the companies would be solicited. The Committee recommends that steps be taken at once to get the active support of allied interests such as newspapers, magazines, radio and other consumer goods industries with an interest in brands. This work should be well organized and vigorously followed through. A committee of newspaper publishers should be formed to enlist the active support of the newspaper field. Comparable committees should be organized in the magazine, radio, advertising and allied fields. G.M.A. should keep in close touch with these committees, and should use all other means at our disposal to maintain the interest and vigorous support of all who can be of help to us in making this program a success. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 21. SPECIFIC THREATS While the major purpose of this plan is to build good will for the industry in a broad gauged, public spirited way, it must nevertheless be recognized that from time to time the well being of the industry is threatened by unsound and destructive measures which must be handled promptly and effectively. Grade labeling coupled with flat pricing con- stitutes such a threat to the entire grocery industry. "Grade labeling, in my sincerest estimation, presents the greatest threat to American industry and our way of life that ever existed, because it is without ques- tion the spearhead in a drive to eliminate brands, trade- marks and eventually free enterprise." Lou Maxon, in a statement at the time of his resignation from OPA. The threat of grade labeling is a live issue. The leaderS of this movement are zealous and determined. They are using newspaper, magazine and radio publicity to get their message across. They are causing speeches to be made before educators, consumer groups and various civic and social leaders. They are, in fact, using every means at their disposal to win support for their cause. The novement is well organized and has already convinced an alarming number of people that grade labeling is in the public interest. The forces behind grade labeling are not only organized to spread plausible and potent propagenda, but also to bring great political pressure to bear through the labor bloc in Congress, and through the efforts of top renking officiels within the Administration who are sympathetic to their cause. While the leaders of the grade labeling movement are now con- centrating their efforts on the canned goods field, every student of this subject is convinced that they will not be content until compulsory grade - labeling has been imposed on all consumer goods. Source: https:/lwww.industrydocuments.ucsf.edu/docs/xjhl0226 22. Grade labeling has been a perennial threat to the security of trade-marked merchandise for several years. From time to time its pro- ponents muster all of their strength for a concerted drive to get a law enacted which would make grade labeling compulsory. In the summer of 1943 they nearly succeeded. Consumer surveys indicate that the strength of the movement for standardization and grade labeling is gaining rapidly. At the same time they indicate there is a great deal of confusion and misunderstanding in the public mind on the whole subject. In spite of repeated conscientious attempts to do a definitive study of the public's attitude toward grade labeling, no such positive results have yet been achieved. The following charts illustrate the findings of the best available studies to-date on the subject. But it is not possible today to give an authoritative answer to the question, "Do a majority of the people of America want grade labeling?" Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 23. An indication of the strength of the public's faith in government standard- ization is found in Chart L. 1, which shows that nearly 77% think that food would be just as good or better if government standardized all packaged foods by grades. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 IF GOVERNMENT STANDARDIZED PACKAGED FOODS BY GRADES A, B and C, WOULD FOOD GET BETTER OR WORSE ? Total B C % % % Get worse 10.8 13 9 Get better 35.7 34 37 Stay the same 41.2 42 40 Don't Know 12.3 11 14 Total % 100.0 100 100 Total Interviews 1000 500 500 Source- - Link, 1943 Source: https://wvww.industrydocuments.ucsf.edu/docs/xjhl0226 24. It seems apparent (Chart 2) that the publicity given the subject in recent years has resulted in an increased reading of food labels, 72.5% reporting that they do so more than formerly. This has doubtless been further influ- enced by the fact that many people can no longer get the brands that are frmilier to them and are more carefully scrutinizing new brands. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 L.2 A COMPARISON OF THE READING OF FOOD LABELS PRESENT vs. PAST Now read. LESS THAN 1.2% FORMERLY 26.3% ABOUT THE SAME MORE THAN FORMERLY 72.5% Total Answering 1.386.100% Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 25. In the following chart (L.3) the term grade labeling was not used but people were asked if they found the present method of labeling satisfactory. The answer is overwhelmingly in the affirmative. That there is no wide spread dissatis- faction on the part of the public with present food labeling practices is shown by chart L.3, with over 80% finding them satisfactory or ideal. Only 1.7% said the present methods were unsatis- factory. Source:https://www.industrydocuments.ucsf.edu/docs/xjhl0226 L.3 OPINIONS ON THE PRESENT METHOD OF LABELING FOOD PRODUCTS Think method is: UNSATISFACTORY 1.7% FAIRLY SATISFACTORY 18.1% SATISFACTORY 60.0% IDEAL 20.2% Total Answering 1,400.100% Source: ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 26. Some of the misunderstandings on the part of the public as to the values of grade labelling are illustrated by their opinions as to sone of the differences as bstween grades(L.4). Note the majority think that the most important difference between food grades is the nutritional value. Actually nutrition has nothing whatsoever to do with the govern- ment grades. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 WHAT WOULD BE THE IMPORTANT DIFFERENCES BETWEEN A,Band C ? Total B C % % % Nutrition value 52.9 52 52 Taste 12.7 12 15 Purity 25.1 24 26 Size and Shape 21.3 23 19 Other 2.9 4 2 Don't Know 6.1 5 8 Total % 121.0 120 122 Total Answers 1010 600 610 Total Interviews 1000 500 500 Source- Link. 1943 Source: Ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 27. Even when asked for suggestions for label improvements over three-quarters (Chart L.5) had none to offer. Less than 5% suggested grude labelling, while the other suggestions pertained to descriptive labelling. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 L.5 SUGGESTIONS FOR LABELING FOOD PRODUCTS MAKE DESCRIPTIONS MORE COMPLETE 10.2% AND INFORMATIVE GRADE LABELING 4.7% INDICATE NUMBER OF 2.1% SERVINGS OR PORTIONS 5.8% MISCELLANEOUS OFFERED NO SUGGESTIONS 77.2% Total Answering 1,415 -100% Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 28. When asked specifically for their preferences as between grade label- ling and descriptive labelling, the former begins to show up in strength (Chart L.6), yet a majority still express a preference for descriptive labelling. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226

What is the percentage of "Should be done" in the case of B grade?

xjhl0226

xjhl0226_p43, xjhl0226_p44, xjhl0226_p45, xjhl0226_p46, xjhl0226_p47, xjhl0226_p48, xjhl0226_p49, xjhl0226_p50, xjhl0226_p51, xjhl0226_p52, xjhl0226_p53, xjhl0226_p54, xjhl0226_p55, xjhl0226_p56

48

29. But when the issue is put squarely before the public, nearly half (47.7%) think grade labeling should be done. (L.7) Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 DO YOU THINK A, B and C GRADING SHOULD BE DONE ? Total B C % % % Should be done 47.7 48 48 Good idea but not necessary 27.2 28 26 Should not be done 13.7 13 15 Don't Know 11.4 11 11 Total % 100.0 100 100 Total Interviews 1000 500 500 Source-Link, 1943 Source: ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 30. Probably the most convincing proof of the growing strength of the grade labeling movement can be seen by the fact that in the space of two years the forces of standardization have gained 16% in public favor. The comparison of the Roper study, made in 1941, and the Link study, mede in 1943, is illustrated in the chart marked L.g. Note the increase from 32% to 48% of those who think it necessary and should be done. Also the decrease from 51% to 27% among those who are still receptive to the iden, but do not yet feel it necessary. That all the shift in public sentiment is not toward more standardization is shown by the increase from 4% to 14% of those who think it a bad idea and should not be done. But the net change is in the direction of more standard- ization. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 (QUESTION 7) IS ABC GRADE LABELING- - NECESSARY AND 48% SHOULD BE DONE ? 32% A GOOD IDEA BUT 27% NOT NECESSARY? 51% POOR IDEA AND 14% SHOULD NOT BE DONE ? 4% LINK-1943 - 11% ROPER-1941 DON'T KNOW 12% L.8 Source: Ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 31. While the arguments for grade labeling are simpler and more superficially appealing, they are not necessarily more convincing in the long run. The cause of grade labeling has won many converts but industry has not yet adequately presented the arguments for brands, or the reason why grade labeling is not truly in the public interest. These arguments are as old, as sound and as true, as the free enterprise system itself. We believe that if the story of brands and their contribution to the public interest were told, the trend toward standardization could be reversed. The growing, popular strength of grade labeling would indicate that if we do nothing the entire grocery industry will soon be saddled with a law making it mandatory. If, on the other hand, we take an affirmative, constructive stand now we can probably win the firm support of the public to our side. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 32. OPERATING PROCEDURES The nature of the threat will, in large neasure, deternine the method to be used to offset it. The procedures recommended below apply specifically to the handling of the grade labeling problen, but each pro- cedure can readily be adapted to meet other unsound proposals as they arise in the future. The Committee recommends: 1. That G.M.A. carefully watch the activities of the pro- ponents of grade labeling, arranging for a suitable clipping service and other necessary information. 2. That a comprehensive statement of the problem be pre- pared clearly setting forth the arguments on both sides of the question. This statement can then be used as source material for all forms of educational work. 3. That this material be adapted to show how grade labeling would work to the disadvantage of special groups, such as farmers, retailers, stockholders, employers and consumers. 4. That interested members adapt this basic material and distribute it to stockholders, employees, etc. 5. That a bureau be created to arrange speaking engagements and assist in preparing speeches, drawing principally on appropriate representativos of member companies for making addresses. Talks regarding labeling to be made to key groups, such as educators, editors, home economists, consumer groups, etc. 6. That each Senator and Congressman be visited by one or more executives of G.M.A. members - preferably those who reside in his home state - for the purposo of explaining the fallacies of grade labeling and presenting preferable alternatives. 7. That the G.M.A. make a concentrated effort to get its members to review their present labels with a view to adding, as soon as war-time printing difficulties permit, any descriptive copy that will aid consumers in the purchase or use of their products, and that committees be appointed and personnel engaged to vigorously prosecute this policy. (It is suggested that this work might be carried on in close cooperation with the National Canners Association.) Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 33. RESEARCH As a basis for preparing this plan, a careful study was made of all surveys and other information that might have a bearing on the problem. In addition, special surveys were made by G.M.A., as you have already seen, to determine the attitudes of the public towerd the grocery industry and specifically toward grade-labeling. While it is not felt that further survays will alter the basic plan, it is believed that in the detailed execution of the program, Continu- ing research will play an important, integral part. For example, we would like to have in sharper focus the specific things the public likes and dis- likes about the grocery industry. Howover, it is obvious that at the present time, the public does not know as much as it should about the industry, because the story has not been told. No further surveys are needed to prove that point. Hence, it is recommended that any further survey be postponed until the basic plan is approved. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 34. VAYS IN THICH INDIVIDUAL COMPANIES CAN COOPLRATE It is recognized that effective public relations work is now being carried on by individual members of G.M.A. The purpose of this plan is not to interfere with thege activities, but to stimulate them. It is, in fact, specifically proposed that most of the activities be carried on by the individual companies, but necording to the major plan of strategy and co-ordination that will increase their benefits to the sponsoring 'company and the industry as a whole. The following are suggestive of the activities which it is hoped will be carried on by participating companies under this program:- il 1. Devote a portion of their advertising to suggested thenes. 2. Adapt G.M.A. basic material for presentation to stockholders, employees, farmers, etc. 3. Furnish speakers. 4. Call on Congressmen. 5. Present talks, notion pictures and other appropriate material to women's clubs, civic, educational and professional groups. 6. Adopt descriptive labeling. 7. Distribute booklets and other materials showing how nutrition research, increases of supplies, avoidance of waste, aid to the war effort, and other activities of service to the public have been acconplished. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 35. ORGANIZATION To change the ingrained attitudes of a substantial proportion of the population is a major undertaking. This cannot be done in a few days or a few weeks. It must be a carefully planned, integrated and sustained effort over a long period of timo. In order to attain the objectives, all types of media, all forms of adult education and all possible cooperation with other groups will be necessary. It is evident that the necessary organization must be established, and the work undertaken, by a group of the major companies which have a common interest in both the immediate and long-range objectives, and sufficient initiative and resources to bring it into being. To wait for the whole membership, or even a majority, to agree to participate would mean delay and make the project difficult if not impossible, at least so far as coping with present dangers is concerned. Strong leadership now will achieve early and visible results that will rally more and more of the membership to the cause as timo goes on. It is therefore recommended that: 1. A special organization be set up, to be called The Public Information Council of the Grocery Manufacturers of America 2. That the Public Information Council be composed of those manufacturers who are willing to participate. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 36. 3. That it be legally a part of G.M.A. for the handling of accounting and fiduciary matters. 4. That the governing body be a Board of Directors com- posed of the President of G.M.A. and ten chief execu- tives of participating companies selected to represent the various classes or types of business to be desig- nated bv the present Policy Committee. 5. That the Board of Directors elect 8 Chairmen who will be the official head of the Council. That the President of G.M.A. be ex-officio Vice Chairman of the Board. 6. That an Executive Committee, consisting of the Chairman and four other members of the Board of Directors be elected by the Board to administer the Council's affairs within such limits as may be defined by the Board of Directors. 7. That a Planning Committee of nine, drawn from the advertising, sales promotion and public relations personnel of participating companies be set up under the Board of Directors and Executive Committees, to work with the Managing Director and staff in the for- mulation of plans and procedures, and that the Presi- dent of G.M.A. be an ex-officio member of this Committee. 8. That a full-time Managing Director, responsible to the Board of Directors, be employed, together with such staff as may be needed. Source: ttps://www.industrydocuments.ucsf.edu/docs/xjhl0226 37. MANAGEMENT AND STAFF The size and range of this project - looking ahead in terms of years - require something much beyond customary committee handling with its attendant delays, divided responsibility and other handicaps. Responsibility for the successful execution of this plan must be concentrated in the hands of one man who has sufficient stature in the fields of public relations and promotion to inspire his associates and to win the active support of related industries. It is recommended that the Planning Committee, subject to approval by the Policy Committee, be authorized to select and employ such a Menaging Director, at the earliest possible time, and that he be authorized to carry out this plan. The headquarters staff should be recruited by the Managing Director to handle the following functions:- Advertising:- To work with volunteer advertising agencies and with the participating members, in preparing themes and in suggesting and coordinating the public relations advertising of members. Publicity:- To prepare material for speakers, newspapers, magazines, pamphlets, radio programs, motion pictures and other media. Research:- To assemble and study existing date which may have a bearing on the program, to institute special surveys of public opinion, to compile basic statistics and to keep a file of news items, editorials and other information which may affect the progress of the compaign. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 38. Speakers:- To secure competent speakers and make arrangements for their addresses. Descriptive Labeling:- To work with members on improve- mont of labels by adding specifications and descriptive matter. Administration: It is anticipated that necessary personnel be provided to aid the Managing Director in handling matters pertaining to finances, purchasing, personnel, office routine and administrative deteil. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 39. BUDGET A budget of $150,000. will be needed to cover the cost of the organization and the specialized services and assistance required for the first twelve months. The cost of future plans and activities will be provided through additional budgets, as such plans are approved and under- taken. It is recommended that an initial budget be underwritten by contributions of $3,000 apiece from not less than fifty interested companies. When the fund of $150,000. has been thus underwritten, the entire member- ship of G.M.A. (over 200 additional companies) will then be asked to par- ticipate. While the initial budget will be subscribed on a fixed sum basis, ($3,000 each from the underwriting companies) future contributions will be based on the proportionate share the total sales volume of each participating company bears to the total fund subscribed. Future contributions will be limited to a maximum ceiling to be established by the Policy Committee. In other words, future contributions will be determined in approximately the same manner as is now used to fix G.M.A. dues. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 40. FIRST STEPS Once the over-all plan has been approved many first steps can be undertaken immediately after the engaging of a Managing Director. The employment of one or more writers for the proposed Infor- mation Council would increase the present effective output of speeches, special articles and other publicity material. By voluntary action some members may adopt the central themes for part of their own advertising. However, it is not bolioved that grast progress toward carrying out the plan as a whole can be made by committees and volunteers unless there is a special full-time staff at houdquarters to work with members and other groups, prepare material, suggest ideas, follow up plans and see that the objectives are reached. Simple though this plan may appear on paper, it involves E vast amount of work to tronslate it into action. Even though the responsibility for carrying out much of the plan will ultimately rest with the participating members, experience leads us to point out that the extent of such cooperation will be largely determined by the amount of time, thought, energy and leadership exerted by the staff of the new Information Council. This is the critical point in the program and in our judgment will largely determine the scope and effectiveness of the entire effort. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226

What is the percentage of "Should not be done" in the case of C grade?

xjhl0226

xjhl0226_p43, xjhl0226_p44, xjhl0226_p45, xjhl0226_p46, xjhl0226_p47, xjhl0226_p48, xjhl0226_p49, xjhl0226_p50, xjhl0226_p51, xjhl0226_p52, xjhl0226_p53, xjhl0226_p54, xjhl0226_p55, xjhl0226_p56

15

29. But when the issue is put squarely before the public, nearly half (47.7%) think grade labeling should be done. (L.7) Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 DO YOU THINK A, B and C GRADING SHOULD BE DONE ? Total B C % % % Should be done 47.7 48 48 Good idea but not necessary 27.2 28 26 Should not be done 13.7 13 15 Don't Know 11.4 11 11 Total % 100.0 100 100 Total Interviews 1000 500 500 Source-Link, 1943 Source: ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 30. Probably the most convincing proof of the growing strength of the grade labeling movement can be seen by the fact that in the space of two years the forces of standardization have gained 16% in public favor. The comparison of the Roper study, made in 1941, and the Link study, mede in 1943, is illustrated in the chart marked L.g. Note the increase from 32% to 48% of those who think it necessary and should be done. Also the decrease from 51% to 27% among those who are still receptive to the iden, but do not yet feel it necessary. That all the shift in public sentiment is not toward more standardization is shown by the increase from 4% to 14% of those who think it a bad idea and should not be done. But the net change is in the direction of more standard- ization. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 (QUESTION 7) IS ABC GRADE LABELING- - NECESSARY AND 48% SHOULD BE DONE ? 32% A GOOD IDEA BUT 27% NOT NECESSARY? 51% POOR IDEA AND 14% SHOULD NOT BE DONE ? 4% LINK-1943 - 11% ROPER-1941 DON'T KNOW 12% L.8 Source: Ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 31. While the arguments for grade labeling are simpler and more superficially appealing, they are not necessarily more convincing in the long run. The cause of grade labeling has won many converts but industry has not yet adequately presented the arguments for brands, or the reason why grade labeling is not truly in the public interest. These arguments are as old, as sound and as true, as the free enterprise system itself. We believe that if the story of brands and their contribution to the public interest were told, the trend toward standardization could be reversed. The growing, popular strength of grade labeling would indicate that if we do nothing the entire grocery industry will soon be saddled with a law making it mandatory. If, on the other hand, we take an affirmative, constructive stand now we can probably win the firm support of the public to our side. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 32. OPERATING PROCEDURES The nature of the threat will, in large neasure, deternine the method to be used to offset it. The procedures recommended below apply specifically to the handling of the grade labeling problen, but each pro- cedure can readily be adapted to meet other unsound proposals as they arise in the future. The Committee recommends: 1. That G.M.A. carefully watch the activities of the pro- ponents of grade labeling, arranging for a suitable clipping service and other necessary information. 2. That a comprehensive statement of the problem be pre- pared clearly setting forth the arguments on both sides of the question. This statement can then be used as source material for all forms of educational work. 3. That this material be adapted to show how grade labeling would work to the disadvantage of special groups, such as farmers, retailers, stockholders, employers and consumers. 4. That interested members adapt this basic material and distribute it to stockholders, employees, etc. 5. That a bureau be created to arrange speaking engagements and assist in preparing speeches, drawing principally on appropriate representativos of member companies for making addresses. Talks regarding labeling to be made to key groups, such as educators, editors, home economists, consumer groups, etc. 6. That each Senator and Congressman be visited by one or more executives of G.M.A. members - preferably those who reside in his home state - for the purposo of explaining the fallacies of grade labeling and presenting preferable alternatives. 7. That the G.M.A. make a concentrated effort to get its members to review their present labels with a view to adding, as soon as war-time printing difficulties permit, any descriptive copy that will aid consumers in the purchase or use of their products, and that committees be appointed and personnel engaged to vigorously prosecute this policy. (It is suggested that this work might be carried on in close cooperation with the National Canners Association.) Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 33. RESEARCH As a basis for preparing this plan, a careful study was made of all surveys and other information that might have a bearing on the problem. In addition, special surveys were made by G.M.A., as you have already seen, to determine the attitudes of the public towerd the grocery industry and specifically toward grade-labeling. While it is not felt that further survays will alter the basic plan, it is believed that in the detailed execution of the program, Continu- ing research will play an important, integral part. For example, we would like to have in sharper focus the specific things the public likes and dis- likes about the grocery industry. Howover, it is obvious that at the present time, the public does not know as much as it should about the industry, because the story has not been told. No further surveys are needed to prove that point. Hence, it is recommended that any further survey be postponed until the basic plan is approved. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 34. VAYS IN THICH INDIVIDUAL COMPANIES CAN COOPLRATE It is recognized that effective public relations work is now being carried on by individual members of G.M.A. The purpose of this plan is not to interfere with thege activities, but to stimulate them. It is, in fact, specifically proposed that most of the activities be carried on by the individual companies, but necording to the major plan of strategy and co-ordination that will increase their benefits to the sponsoring 'company and the industry as a whole. The following are suggestive of the activities which it is hoped will be carried on by participating companies under this program:- il 1. Devote a portion of their advertising to suggested thenes. 2. Adapt G.M.A. basic material for presentation to stockholders, employees, farmers, etc. 3. Furnish speakers. 4. Call on Congressmen. 5. Present talks, notion pictures and other appropriate material to women's clubs, civic, educational and professional groups. 6. Adopt descriptive labeling. 7. Distribute booklets and other materials showing how nutrition research, increases of supplies, avoidance of waste, aid to the war effort, and other activities of service to the public have been acconplished. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 35. ORGANIZATION To change the ingrained attitudes of a substantial proportion of the population is a major undertaking. This cannot be done in a few days or a few weeks. It must be a carefully planned, integrated and sustained effort over a long period of timo. In order to attain the objectives, all types of media, all forms of adult education and all possible cooperation with other groups will be necessary. It is evident that the necessary organization must be established, and the work undertaken, by a group of the major companies which have a common interest in both the immediate and long-range objectives, and sufficient initiative and resources to bring it into being. To wait for the whole membership, or even a majority, to agree to participate would mean delay and make the project difficult if not impossible, at least so far as coping with present dangers is concerned. Strong leadership now will achieve early and visible results that will rally more and more of the membership to the cause as timo goes on. It is therefore recommended that: 1. A special organization be set up, to be called The Public Information Council of the Grocery Manufacturers of America 2. That the Public Information Council be composed of those manufacturers who are willing to participate. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 36. 3. That it be legally a part of G.M.A. for the handling of accounting and fiduciary matters. 4. That the governing body be a Board of Directors com- posed of the President of G.M.A. and ten chief execu- tives of participating companies selected to represent the various classes or types of business to be desig- nated bv the present Policy Committee. 5. That the Board of Directors elect 8 Chairmen who will be the official head of the Council. That the President of G.M.A. be ex-officio Vice Chairman of the Board. 6. That an Executive Committee, consisting of the Chairman and four other members of the Board of Directors be elected by the Board to administer the Council's affairs within such limits as may be defined by the Board of Directors. 7. That a Planning Committee of nine, drawn from the advertising, sales promotion and public relations personnel of participating companies be set up under the Board of Directors and Executive Committees, to work with the Managing Director and staff in the for- mulation of plans and procedures, and that the Presi- dent of G.M.A. be an ex-officio member of this Committee. 8. That a full-time Managing Director, responsible to the Board of Directors, be employed, together with such staff as may be needed. Source: ttps://www.industrydocuments.ucsf.edu/docs/xjhl0226 37. MANAGEMENT AND STAFF The size and range of this project - looking ahead in terms of years - require something much beyond customary committee handling with its attendant delays, divided responsibility and other handicaps. Responsibility for the successful execution of this plan must be concentrated in the hands of one man who has sufficient stature in the fields of public relations and promotion to inspire his associates and to win the active support of related industries. It is recommended that the Planning Committee, subject to approval by the Policy Committee, be authorized to select and employ such a Menaging Director, at the earliest possible time, and that he be authorized to carry out this plan. The headquarters staff should be recruited by the Managing Director to handle the following functions:- Advertising:- To work with volunteer advertising agencies and with the participating members, in preparing themes and in suggesting and coordinating the public relations advertising of members. Publicity:- To prepare material for speakers, newspapers, magazines, pamphlets, radio programs, motion pictures and other media. Research:- To assemble and study existing date which may have a bearing on the program, to institute special surveys of public opinion, to compile basic statistics and to keep a file of news items, editorials and other information which may affect the progress of the compaign. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 38. Speakers:- To secure competent speakers and make arrangements for their addresses. Descriptive Labeling:- To work with members on improve- mont of labels by adding specifications and descriptive matter. Administration: It is anticipated that necessary personnel be provided to aid the Managing Director in handling matters pertaining to finances, purchasing, personnel, office routine and administrative deteil. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 39. BUDGET A budget of $150,000. will be needed to cover the cost of the organization and the specialized services and assistance required for the first twelve months. The cost of future plans and activities will be provided through additional budgets, as such plans are approved and under- taken. It is recommended that an initial budget be underwritten by contributions of $3,000 apiece from not less than fifty interested companies. When the fund of $150,000. has been thus underwritten, the entire member- ship of G.M.A. (over 200 additional companies) will then be asked to par- ticipate. While the initial budget will be subscribed on a fixed sum basis, ($3,000 each from the underwriting companies) future contributions will be based on the proportionate share the total sales volume of each participating company bears to the total fund subscribed. Future contributions will be limited to a maximum ceiling to be established by the Policy Committee. In other words, future contributions will be determined in approximately the same manner as is now used to fix G.M.A. dues. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 40. FIRST STEPS Once the over-all plan has been approved many first steps can be undertaken immediately after the engaging of a Managing Director. The employment of one or more writers for the proposed Infor- mation Council would increase the present effective output of speeches, special articles and other publicity material. By voluntary action some members may adopt the central themes for part of their own advertising. However, it is not bolioved that grast progress toward carrying out the plan as a whole can be made by committees and volunteers unless there is a special full-time staff at houdquarters to work with members and other groups, prepare material, suggest ideas, follow up plans and see that the objectives are reached. Simple though this plan may appear on paper, it involves E vast amount of work to tronslate it into action. Even though the responsibility for carrying out much of the plan will ultimately rest with the participating members, experience leads us to point out that the extent of such cooperation will be largely determined by the amount of time, thought, energy and leadership exerted by the staff of the new Information Council. This is the critical point in the program and in our judgment will largely determine the scope and effectiveness of the entire effort. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226

What is the percentage of "Good idea but not necessary" in the case of B grade?

xjhl0226

xjhl0226_p43, xjhl0226_p44, xjhl0226_p45, xjhl0226_p46, xjhl0226_p47, xjhl0226_p48, xjhl0226_p49, xjhl0226_p50, xjhl0226_p51, xjhl0226_p52, xjhl0226_p53, xjhl0226_p54, xjhl0226_p55, xjhl0226_p56

28

29. But when the issue is put squarely before the public, nearly half (47.7%) think grade labeling should be done. (L.7) Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 DO YOU THINK A, B and C GRADING SHOULD BE DONE ? Total B C % % % Should be done 47.7 48 48 Good idea but not necessary 27.2 28 26 Should not be done 13.7 13 15 Don't Know 11.4 11 11 Total % 100.0 100 100 Total Interviews 1000 500 500 Source-Link, 1943 Source: ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 30. Probably the most convincing proof of the growing strength of the grade labeling movement can be seen by the fact that in the space of two years the forces of standardization have gained 16% in public favor. The comparison of the Roper study, made in 1941, and the Link study, mede in 1943, is illustrated in the chart marked L.g. Note the increase from 32% to 48% of those who think it necessary and should be done. Also the decrease from 51% to 27% among those who are still receptive to the iden, but do not yet feel it necessary. That all the shift in public sentiment is not toward more standardization is shown by the increase from 4% to 14% of those who think it a bad idea and should not be done. But the net change is in the direction of more standard- ization. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 (QUESTION 7) IS ABC GRADE LABELING- - NECESSARY AND 48% SHOULD BE DONE ? 32% A GOOD IDEA BUT 27% NOT NECESSARY? 51% POOR IDEA AND 14% SHOULD NOT BE DONE ? 4% LINK-1943 - 11% ROPER-1941 DON'T KNOW 12% L.8 Source: Ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 31. While the arguments for grade labeling are simpler and more superficially appealing, they are not necessarily more convincing in the long run. The cause of grade labeling has won many converts but industry has not yet adequately presented the arguments for brands, or the reason why grade labeling is not truly in the public interest. These arguments are as old, as sound and as true, as the free enterprise system itself. We believe that if the story of brands and their contribution to the public interest were told, the trend toward standardization could be reversed. The growing, popular strength of grade labeling would indicate that if we do nothing the entire grocery industry will soon be saddled with a law making it mandatory. If, on the other hand, we take an affirmative, constructive stand now we can probably win the firm support of the public to our side. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 32. OPERATING PROCEDURES The nature of the threat will, in large neasure, deternine the method to be used to offset it. The procedures recommended below apply specifically to the handling of the grade labeling problen, but each pro- cedure can readily be adapted to meet other unsound proposals as they arise in the future. The Committee recommends: 1. That G.M.A. carefully watch the activities of the pro- ponents of grade labeling, arranging for a suitable clipping service and other necessary information. 2. That a comprehensive statement of the problem be pre- pared clearly setting forth the arguments on both sides of the question. This statement can then be used as source material for all forms of educational work. 3. That this material be adapted to show how grade labeling would work to the disadvantage of special groups, such as farmers, retailers, stockholders, employers and consumers. 4. That interested members adapt this basic material and distribute it to stockholders, employees, etc. 5. That a bureau be created to arrange speaking engagements and assist in preparing speeches, drawing principally on appropriate representativos of member companies for making addresses. Talks regarding labeling to be made to key groups, such as educators, editors, home economists, consumer groups, etc. 6. That each Senator and Congressman be visited by one or more executives of G.M.A. members - preferably those who reside in his home state - for the purposo of explaining the fallacies of grade labeling and presenting preferable alternatives. 7. That the G.M.A. make a concentrated effort to get its members to review their present labels with a view to adding, as soon as war-time printing difficulties permit, any descriptive copy that will aid consumers in the purchase or use of their products, and that committees be appointed and personnel engaged to vigorously prosecute this policy. (It is suggested that this work might be carried on in close cooperation with the National Canners Association.) Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 33. RESEARCH As a basis for preparing this plan, a careful study was made of all surveys and other information that might have a bearing on the problem. In addition, special surveys were made by G.M.A., as you have already seen, to determine the attitudes of the public towerd the grocery industry and specifically toward grade-labeling. While it is not felt that further survays will alter the basic plan, it is believed that in the detailed execution of the program, Continu- ing research will play an important, integral part. For example, we would like to have in sharper focus the specific things the public likes and dis- likes about the grocery industry. Howover, it is obvious that at the present time, the public does not know as much as it should about the industry, because the story has not been told. No further surveys are needed to prove that point. Hence, it is recommended that any further survey be postponed until the basic plan is approved. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 34. VAYS IN THICH INDIVIDUAL COMPANIES CAN COOPLRATE It is recognized that effective public relations work is now being carried on by individual members of G.M.A. The purpose of this plan is not to interfere with thege activities, but to stimulate them. It is, in fact, specifically proposed that most of the activities be carried on by the individual companies, but necording to the major plan of strategy and co-ordination that will increase their benefits to the sponsoring 'company and the industry as a whole. The following are suggestive of the activities which it is hoped will be carried on by participating companies under this program:- il 1. Devote a portion of their advertising to suggested thenes. 2. Adapt G.M.A. basic material for presentation to stockholders, employees, farmers, etc. 3. Furnish speakers. 4. Call on Congressmen. 5. Present talks, notion pictures and other appropriate material to women's clubs, civic, educational and professional groups. 6. Adopt descriptive labeling. 7. Distribute booklets and other materials showing how nutrition research, increases of supplies, avoidance of waste, aid to the war effort, and other activities of service to the public have been acconplished. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 35. ORGANIZATION To change the ingrained attitudes of a substantial proportion of the population is a major undertaking. This cannot be done in a few days or a few weeks. It must be a carefully planned, integrated and sustained effort over a long period of timo. In order to attain the objectives, all types of media, all forms of adult education and all possible cooperation with other groups will be necessary. It is evident that the necessary organization must be established, and the work undertaken, by a group of the major companies which have a common interest in both the immediate and long-range objectives, and sufficient initiative and resources to bring it into being. To wait for the whole membership, or even a majority, to agree to participate would mean delay and make the project difficult if not impossible, at least so far as coping with present dangers is concerned. Strong leadership now will achieve early and visible results that will rally more and more of the membership to the cause as timo goes on. It is therefore recommended that: 1. A special organization be set up, to be called The Public Information Council of the Grocery Manufacturers of America 2. That the Public Information Council be composed of those manufacturers who are willing to participate. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 36. 3. That it be legally a part of G.M.A. for the handling of accounting and fiduciary matters. 4. That the governing body be a Board of Directors com- posed of the President of G.M.A. and ten chief execu- tives of participating companies selected to represent the various classes or types of business to be desig- nated bv the present Policy Committee. 5. That the Board of Directors elect 8 Chairmen who will be the official head of the Council. That the President of G.M.A. be ex-officio Vice Chairman of the Board. 6. That an Executive Committee, consisting of the Chairman and four other members of the Board of Directors be elected by the Board to administer the Council's affairs within such limits as may be defined by the Board of Directors. 7. That a Planning Committee of nine, drawn from the advertising, sales promotion and public relations personnel of participating companies be set up under the Board of Directors and Executive Committees, to work with the Managing Director and staff in the for- mulation of plans and procedures, and that the Presi- dent of G.M.A. be an ex-officio member of this Committee. 8. That a full-time Managing Director, responsible to the Board of Directors, be employed, together with such staff as may be needed. Source: ttps://www.industrydocuments.ucsf.edu/docs/xjhl0226 37. MANAGEMENT AND STAFF The size and range of this project - looking ahead in terms of years - require something much beyond customary committee handling with its attendant delays, divided responsibility and other handicaps. Responsibility for the successful execution of this plan must be concentrated in the hands of one man who has sufficient stature in the fields of public relations and promotion to inspire his associates and to win the active support of related industries. It is recommended that the Planning Committee, subject to approval by the Policy Committee, be authorized to select and employ such a Menaging Director, at the earliest possible time, and that he be authorized to carry out this plan. The headquarters staff should be recruited by the Managing Director to handle the following functions:- Advertising:- To work with volunteer advertising agencies and with the participating members, in preparing themes and in suggesting and coordinating the public relations advertising of members. Publicity:- To prepare material for speakers, newspapers, magazines, pamphlets, radio programs, motion pictures and other media. Research:- To assemble and study existing date which may have a bearing on the program, to institute special surveys of public opinion, to compile basic statistics and to keep a file of news items, editorials and other information which may affect the progress of the compaign. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 38. Speakers:- To secure competent speakers and make arrangements for their addresses. Descriptive Labeling:- To work with members on improve- mont of labels by adding specifications and descriptive matter. Administration: It is anticipated that necessary personnel be provided to aid the Managing Director in handling matters pertaining to finances, purchasing, personnel, office routine and administrative deteil. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 39. BUDGET A budget of $150,000. will be needed to cover the cost of the organization and the specialized services and assistance required for the first twelve months. The cost of future plans and activities will be provided through additional budgets, as such plans are approved and under- taken. It is recommended that an initial budget be underwritten by contributions of $3,000 apiece from not less than fifty interested companies. When the fund of $150,000. has been thus underwritten, the entire member- ship of G.M.A. (over 200 additional companies) will then be asked to par- ticipate. While the initial budget will be subscribed on a fixed sum basis, ($3,000 each from the underwriting companies) future contributions will be based on the proportionate share the total sales volume of each participating company bears to the total fund subscribed. Future contributions will be limited to a maximum ceiling to be established by the Policy Committee. In other words, future contributions will be determined in approximately the same manner as is now used to fix G.M.A. dues. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 40. FIRST STEPS Once the over-all plan has been approved many first steps can be undertaken immediately after the engaging of a Managing Director. The employment of one or more writers for the proposed Infor- mation Council would increase the present effective output of speeches, special articles and other publicity material. By voluntary action some members may adopt the central themes for part of their own advertising. However, it is not bolioved that grast progress toward carrying out the plan as a whole can be made by committees and volunteers unless there is a special full-time staff at houdquarters to work with members and other groups, prepare material, suggest ideas, follow up plans and see that the objectives are reached. Simple though this plan may appear on paper, it involves E vast amount of work to tronslate it into action. Even though the responsibility for carrying out much of the plan will ultimately rest with the participating members, experience leads us to point out that the extent of such cooperation will be largely determined by the amount of time, thought, energy and leadership exerted by the staff of the new Information Council. This is the critical point in the program and in our judgment will largely determine the scope and effectiveness of the entire effort. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226

What is the percentage of "Don't Know" in the case of C grade?

xjhl0226

xjhl0226_p43, xjhl0226_p44, xjhl0226_p45, xjhl0226_p46, xjhl0226_p47, xjhl0226_p48, xjhl0226_p49, xjhl0226_p50, xjhl0226_p51, xjhl0226_p52, xjhl0226_p53, xjhl0226_p54, xjhl0226_p55, xjhl0226_p56

11

29. But when the issue is put squarely before the public, nearly half (47.7%) think grade labeling should be done. (L.7) Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 DO YOU THINK A, B and C GRADING SHOULD BE DONE ? Total B C % % % Should be done 47.7 48 48 Good idea but not necessary 27.2 28 26 Should not be done 13.7 13 15 Don't Know 11.4 11 11 Total % 100.0 100 100 Total Interviews 1000 500 500 Source-Link, 1943 Source: ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 30. Probably the most convincing proof of the growing strength of the grade labeling movement can be seen by the fact that in the space of two years the forces of standardization have gained 16% in public favor. The comparison of the Roper study, made in 1941, and the Link study, mede in 1943, is illustrated in the chart marked L.g. Note the increase from 32% to 48% of those who think it necessary and should be done. Also the decrease from 51% to 27% among those who are still receptive to the iden, but do not yet feel it necessary. That all the shift in public sentiment is not toward more standardization is shown by the increase from 4% to 14% of those who think it a bad idea and should not be done. But the net change is in the direction of more standard- ization. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 (QUESTION 7) IS ABC GRADE LABELING- - NECESSARY AND 48% SHOULD BE DONE ? 32% A GOOD IDEA BUT 27% NOT NECESSARY? 51% POOR IDEA AND 14% SHOULD NOT BE DONE ? 4% LINK-1943 - 11% ROPER-1941 DON'T KNOW 12% L.8 Source: Ittps://www.industrydocuments.ucsf.edu/docs/xjhl0226 31. While the arguments for grade labeling are simpler and more superficially appealing, they are not necessarily more convincing in the long run. The cause of grade labeling has won many converts but industry has not yet adequately presented the arguments for brands, or the reason why grade labeling is not truly in the public interest. These arguments are as old, as sound and as true, as the free enterprise system itself. We believe that if the story of brands and their contribution to the public interest were told, the trend toward standardization could be reversed. The growing, popular strength of grade labeling would indicate that if we do nothing the entire grocery industry will soon be saddled with a law making it mandatory. If, on the other hand, we take an affirmative, constructive stand now we can probably win the firm support of the public to our side. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 32. OPERATING PROCEDURES The nature of the threat will, in large neasure, deternine the method to be used to offset it. The procedures recommended below apply specifically to the handling of the grade labeling problen, but each pro- cedure can readily be adapted to meet other unsound proposals as they arise in the future. The Committee recommends: 1. That G.M.A. carefully watch the activities of the pro- ponents of grade labeling, arranging for a suitable clipping service and other necessary information. 2. That a comprehensive statement of the problem be pre- pared clearly setting forth the arguments on both sides of the question. This statement can then be used as source material for all forms of educational work. 3. That this material be adapted to show how grade labeling would work to the disadvantage of special groups, such as farmers, retailers, stockholders, employers and consumers. 4. That interested members adapt this basic material and distribute it to stockholders, employees, etc. 5. That a bureau be created to arrange speaking engagements and assist in preparing speeches, drawing principally on appropriate representativos of member companies for making addresses. Talks regarding labeling to be made to key groups, such as educators, editors, home economists, consumer groups, etc. 6. That each Senator and Congressman be visited by one or more executives of G.M.A. members - preferably those who reside in his home state - for the purposo of explaining the fallacies of grade labeling and presenting preferable alternatives. 7. That the G.M.A. make a concentrated effort to get its members to review their present labels with a view to adding, as soon as war-time printing difficulties permit, any descriptive copy that will aid consumers in the purchase or use of their products, and that committees be appointed and personnel engaged to vigorously prosecute this policy. (It is suggested that this work might be carried on in close cooperation with the National Canners Association.) Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 33. RESEARCH As a basis for preparing this plan, a careful study was made of all surveys and other information that might have a bearing on the problem. In addition, special surveys were made by G.M.A., as you have already seen, to determine the attitudes of the public towerd the grocery industry and specifically toward grade-labeling. While it is not felt that further survays will alter the basic plan, it is believed that in the detailed execution of the program, Continu- ing research will play an important, integral part. For example, we would like to have in sharper focus the specific things the public likes and dis- likes about the grocery industry. Howover, it is obvious that at the present time, the public does not know as much as it should about the industry, because the story has not been told. No further surveys are needed to prove that point. Hence, it is recommended that any further survey be postponed until the basic plan is approved. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 34. VAYS IN THICH INDIVIDUAL COMPANIES CAN COOPLRATE It is recognized that effective public relations work is now being carried on by individual members of G.M.A. The purpose of this plan is not to interfere with thege activities, but to stimulate them. It is, in fact, specifically proposed that most of the activities be carried on by the individual companies, but necording to the major plan of strategy and co-ordination that will increase their benefits to the sponsoring 'company and the industry as a whole. The following are suggestive of the activities which it is hoped will be carried on by participating companies under this program:- il 1. Devote a portion of their advertising to suggested thenes. 2. Adapt G.M.A. basic material for presentation to stockholders, employees, farmers, etc. 3. Furnish speakers. 4. Call on Congressmen. 5. Present talks, notion pictures and other appropriate material to women's clubs, civic, educational and professional groups. 6. Adopt descriptive labeling. 7. Distribute booklets and other materials showing how nutrition research, increases of supplies, avoidance of waste, aid to the war effort, and other activities of service to the public have been acconplished. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 35. ORGANIZATION To change the ingrained attitudes of a substantial proportion of the population is a major undertaking. This cannot be done in a few days or a few weeks. It must be a carefully planned, integrated and sustained effort over a long period of timo. In order to attain the objectives, all types of media, all forms of adult education and all possible cooperation with other groups will be necessary. It is evident that the necessary organization must be established, and the work undertaken, by a group of the major companies which have a common interest in both the immediate and long-range objectives, and sufficient initiative and resources to bring it into being. To wait for the whole membership, or even a majority, to agree to participate would mean delay and make the project difficult if not impossible, at least so far as coping with present dangers is concerned. Strong leadership now will achieve early and visible results that will rally more and more of the membership to the cause as timo goes on. It is therefore recommended that: 1. A special organization be set up, to be called The Public Information Council of the Grocery Manufacturers of America 2. That the Public Information Council be composed of those manufacturers who are willing to participate. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 36. 3. That it be legally a part of G.M.A. for the handling of accounting and fiduciary matters. 4. That the governing body be a Board of Directors com- posed of the President of G.M.A. and ten chief execu- tives of participating companies selected to represent the various classes or types of business to be desig- nated bv the present Policy Committee. 5. That the Board of Directors elect 8 Chairmen who will be the official head of the Council. That the President of G.M.A. be ex-officio Vice Chairman of the Board. 6. That an Executive Committee, consisting of the Chairman and four other members of the Board of Directors be elected by the Board to administer the Council's affairs within such limits as may be defined by the Board of Directors. 7. That a Planning Committee of nine, drawn from the advertising, sales promotion and public relations personnel of participating companies be set up under the Board of Directors and Executive Committees, to work with the Managing Director and staff in the for- mulation of plans and procedures, and that the Presi- dent of G.M.A. be an ex-officio member of this Committee. 8. That a full-time Managing Director, responsible to the Board of Directors, be employed, together with such staff as may be needed. Source: ttps://www.industrydocuments.ucsf.edu/docs/xjhl0226 37. MANAGEMENT AND STAFF The size and range of this project - looking ahead in terms of years - require something much beyond customary committee handling with its attendant delays, divided responsibility and other handicaps. Responsibility for the successful execution of this plan must be concentrated in the hands of one man who has sufficient stature in the fields of public relations and promotion to inspire his associates and to win the active support of related industries. It is recommended that the Planning Committee, subject to approval by the Policy Committee, be authorized to select and employ such a Menaging Director, at the earliest possible time, and that he be authorized to carry out this plan. The headquarters staff should be recruited by the Managing Director to handle the following functions:- Advertising:- To work with volunteer advertising agencies and with the participating members, in preparing themes and in suggesting and coordinating the public relations advertising of members. Publicity:- To prepare material for speakers, newspapers, magazines, pamphlets, radio programs, motion pictures and other media. Research:- To assemble and study existing date which may have a bearing on the program, to institute special surveys of public opinion, to compile basic statistics and to keep a file of news items, editorials and other information which may affect the progress of the compaign. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 38. Speakers:- To secure competent speakers and make arrangements for their addresses. Descriptive Labeling:- To work with members on improve- mont of labels by adding specifications and descriptive matter. Administration: It is anticipated that necessary personnel be provided to aid the Managing Director in handling matters pertaining to finances, purchasing, personnel, office routine and administrative deteil. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 39. BUDGET A budget of $150,000. will be needed to cover the cost of the organization and the specialized services and assistance required for the first twelve months. The cost of future plans and activities will be provided through additional budgets, as such plans are approved and under- taken. It is recommended that an initial budget be underwritten by contributions of $3,000 apiece from not less than fifty interested companies. When the fund of $150,000. has been thus underwritten, the entire member- ship of G.M.A. (over 200 additional companies) will then be asked to par- ticipate. While the initial budget will be subscribed on a fixed sum basis, ($3,000 each from the underwriting companies) future contributions will be based on the proportionate share the total sales volume of each participating company bears to the total fund subscribed. Future contributions will be limited to a maximum ceiling to be established by the Policy Committee. In other words, future contributions will be determined in approximately the same manner as is now used to fix G.M.A. dues. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226 40. FIRST STEPS Once the over-all plan has been approved many first steps can be undertaken immediately after the engaging of a Managing Director. The employment of one or more writers for the proposed Infor- mation Council would increase the present effective output of speeches, special articles and other publicity material. By voluntary action some members may adopt the central themes for part of their own advertising. However, it is not bolioved that grast progress toward carrying out the plan as a whole can be made by committees and volunteers unless there is a special full-time staff at houdquarters to work with members and other groups, prepare material, suggest ideas, follow up plans and see that the objectives are reached. Simple though this plan may appear on paper, it involves E vast amount of work to tronslate it into action. Even though the responsibility for carrying out much of the plan will ultimately rest with the participating members, experience leads us to point out that the extent of such cooperation will be largely determined by the amount of time, thought, energy and leadership exerted by the staff of the new Information Council. This is the critical point in the program and in our judgment will largely determine the scope and effectiveness of the entire effort. Source: https://www.industrydocuments.ucsf.edu/docs/xjhl0226

What is plotted on the y-axis?

pggl0226

pggl0226_p23, pggl0226_p24, pggl0226_p25, pggl0226_p26

Average number of wage earners, AVERAGE NUMBER OF WAGE EARNERS

THE NATIONAL SUGAR HEFINING COMPANY COMPARISON OF WAGE diffrEENtial IN NORTHERN AND SOUTEERN SUGAR REFINERIES, 1930 and 1941 (Basic rate, cents par hour, males) 1930 1941 1942 DIFFERENTIALS 244 366 484 North South North South South 244 37# 4134 From U.S. Dept. of Labor From Union Contracte MORTH: Aversge of Mase., N.Y. and and N.T. only in 1941-2 SOUTH: Averaga of Georgia, Louisiana, and both periods Maroh 26, 1942 Source: https://www.industrydocuments.ucsf.edu/docs/pggl0226 THE MATIONAL SUGAR REFINING COMPANY TREND OF EMPLOYMENT IN CANE SUGAR REFINERIES IN NEW YORK AND LOUISIANA, 1927 - 1939 AS MEASURED BY THE AVERAGE NUMBER OF WAGE EARNERS Average Number of Wage Earners 4,000 HEW YORK LOUISIANA 3,000 2,000 1,000 0 1927 1929 1931 1933 1935 1937 1939 Compiled from statistics of the U. S. Department of Commerce, Burean of the Census March 26, 1942 Source: ittps://www.industrydocuments.ucsf.edu/docs/pggl0226 THES NATIONAL SUGAR REFINING COMP.ANY BOGW OR EXPANDED TRAINING GAMPS - MAY 1941. . . . . of .: 0 SOURCE: Office For Emergeney Management, DEFENSE (1941) p. 24 March 26, 1942 Source: https://www.industrydocuments.ucsf.edu/docs/pggl0226 the HATIONAL SUGAR REFINING COMPANX DAILY APMY BATTOB OF SUGAR DURING SELECTED WAR PERIODS (Ounces) 5.00 4.00 3.20 2.40 2.40 1.92 1838 1860 1898 1917 1928 1941 SOURCE Official etatistica obtained from Mr. A. S. Memir, Foodstaffs Division, U. S. Dept. of Commerce March 26, 1942 Source: https://www.industrydocuments.ucsf.edu/docs/pggl0226

What is the name of the company?

pggl0226

pggl0226_p23, pggl0226_p24, pggl0226_p25, pggl0226_p26

THE NATIONAL SUGAR REFINING COMPANY, The National Sugar Refining Company

THE NATIONAL SUGAR HEFINING COMPANY COMPARISON OF WAGE diffrEENtial IN NORTHERN AND SOUTEERN SUGAR REFINERIES, 1930 and 1941 (Basic rate, cents par hour, males) 1930 1941 1942 DIFFERENTIALS 244 366 484 North South North South South 244 37# 4134 From U.S. Dept. of Labor From Union Contracte MORTH: Aversge of Mase., N.Y. and and N.T. only in 1941-2 SOUTH: Averaga of Georgia, Louisiana, and both periods Maroh 26, 1942 Source: https://www.industrydocuments.ucsf.edu/docs/pggl0226 THE MATIONAL SUGAR REFINING COMPANY TREND OF EMPLOYMENT IN CANE SUGAR REFINERIES IN NEW YORK AND LOUISIANA, 1927 - 1939 AS MEASURED BY THE AVERAGE NUMBER OF WAGE EARNERS Average Number of Wage Earners 4,000 HEW YORK LOUISIANA 3,000 2,000 1,000 0 1927 1929 1931 1933 1935 1937 1939 Compiled from statistics of the U. S. Department of Commerce, Burean of the Census March 26, 1942 Source: ittps://www.industrydocuments.ucsf.edu/docs/pggl0226 THES NATIONAL SUGAR REFINING COMP.ANY BOGW OR EXPANDED TRAINING GAMPS - MAY 1941. . . . . of .: 0 SOURCE: Office For Emergeney Management, DEFENSE (1941) p. 24 March 26, 1942 Source: https://www.industrydocuments.ucsf.edu/docs/pggl0226 the HATIONAL SUGAR REFINING COMPANX DAILY APMY BATTOB OF SUGAR DURING SELECTED WAR PERIODS (Ounces) 5.00 4.00 3.20 2.40 2.40 1.92 1838 1860 1898 1917 1928 1941 SOURCE Official etatistica obtained from Mr. A. S. Memir, Foodstaffs Division, U. S. Dept. of Commerce March 26, 1942 Source: https://www.industrydocuments.ucsf.edu/docs/pggl0226

Who is the Investigator of the meeting publication JAMA (4/12/00)?

rpbw0217

rpbw0217_p0, rpbw0217_p1

Shlipak, shlipak

Premarin Publication/Presentation Planning Meeting April 12, 2000 10:30 AM - 12:00 PM, Conference Room #555-6A AGENDA I. Premarin Study Tracking Update MEETINGS Status Meeting Investigator Study Submitted ASBMR Lane Estrogen and raloxifene on bone microarchitecture Ermer TSE pharmacology Presenting First International Pace/Ke (2 posters) Estrogen and heart rate Conference on Women, variability; estrogen and Heart Disease and Stroke oxidative stress Bakir/Oparil (1 poster/1 Estrogen attenuates osteopontin oral) (vasoprotection); raloxifene not vasoprotective Paganini-Hill Estrogen and stroke Plenary Session Herrington; Manson; ERA; NHS update; estrogen Mendelson; Madori action; public policy Satellite Symposium Harnish; Bakir; Bozkurt, Estrogen mechanisms of action, Rosano review of clinical studies, comparative progestin effects Posters ACC Davidson Zocor/Prempro study Eskin Estrogen and NE in the heart Posters SGI Scharf Estrogen on sleep quality Lane Estrogen and raloxifene on bone microarchitecture Posters ACOG Eskin Estrogen and NE in the heart Archer Prempro bleeding re-analysis PUBLICATIONS Published JAMA (4/12/00) Shlipak Estrogen and lipoprotein(a) Published Arch Fam Med (4/00) McNagny/Frank Counseling and HRT Manuscripts Scharf Estrogen and sleep quality in preparation Birge (2) CNS (1) and Bone (1) Murphy (2) Estrogen and brain serotonin Published JAGS (4/00) Sherwin Estrogen and cognitive function DESIGNWRITE 189 WALL STREET, PRINCETON, NEW JERSEY 08540 609/924-1116 FAX: 609/924-6648 Confidential Pursuant to Confidentiality DUROJ012-001342 Order Source: https://www.industrydocuments.ucsf.edu/docs/rpbw0217 Premarin Publication/Presentation Planning Meeting April 12, 2000 10:30 AM - 12:00 PM, Conference Room #555-6A Status Journal Investigator Study Submitted Br J Menopause Dey Estrogen activity Submitted Urology Nurses On-line Maloney Estrogen and UTIs Submitted Current Atherosclerosis Mosca Atherosclerosis and HRT Reports II. Medical Affairs Updates III. Women's Health Research Institute IV. Prioritizing Meetings V. Poster Template VI. PR Opportunities VII. Upcoming Meetings and Deadlines MEETING DATE DEADLINE ASBMR - American Society for Bone and Mineral Sept 22-26,2000 Apr 12, 2000 Research (Toronto) AHA - American Heart Association (New Orleans, Nov 12-15, 2000 May 5, 2000 LA) ARHP - Association of Reproductive Health Sept 14-16, 2000 May 19, 2000 Professionals (Chicago, IL) NAMS - North American Menopause Society Sept 7-9, 2000 May 31, 2000 (Orlando, FL) 8th World Congress of Gynecological Endocrinology Dec 6-9,2000 Sept 1, 2000 (Florence) DESIGNWRITE . 189 WALL STREET, PRINCETON, NEW JERSEY 08540 609/924-1116 FAX: 609/924-6648 Confidential Pursuant to Confidentiality DUROJ012-001343 Order Source: :ttps://www.industrydocuments.ucsf.edu/docs/rpbw0217

Who is the Investigator of the meeting JAGS (4/00)?

rpbw0217

rpbw0217_p0, rpbw0217_p1

Sherwin, sherwin

Premarin Publication/Presentation Planning Meeting April 12, 2000 10:30 AM - 12:00 PM, Conference Room #555-6A AGENDA I. Premarin Study Tracking Update MEETINGS Status Meeting Investigator Study Submitted ASBMR Lane Estrogen and raloxifene on bone microarchitecture Ermer TSE pharmacology Presenting First International Pace/Ke (2 posters) Estrogen and heart rate Conference on Women, variability; estrogen and Heart Disease and Stroke oxidative stress Bakir/Oparil (1 poster/1 Estrogen attenuates osteopontin oral) (vasoprotection); raloxifene not vasoprotective Paganini-Hill Estrogen and stroke Plenary Session Herrington; Manson; ERA; NHS update; estrogen Mendelson; Madori action; public policy Satellite Symposium Harnish; Bakir; Bozkurt, Estrogen mechanisms of action, Rosano review of clinical studies, comparative progestin effects Posters ACC Davidson Zocor/Prempro study Eskin Estrogen and NE in the heart Posters SGI Scharf Estrogen on sleep quality Lane Estrogen and raloxifene on bone microarchitecture Posters ACOG Eskin Estrogen and NE in the heart Archer Prempro bleeding re-analysis PUBLICATIONS Published JAMA (4/12/00) Shlipak Estrogen and lipoprotein(a) Published Arch Fam Med (4/00) McNagny/Frank Counseling and HRT Manuscripts Scharf Estrogen and sleep quality in preparation Birge (2) CNS (1) and Bone (1) Murphy (2) Estrogen and brain serotonin Published JAGS (4/00) Sherwin Estrogen and cognitive function DESIGNWRITE 189 WALL STREET, PRINCETON, NEW JERSEY 08540 609/924-1116 FAX: 609/924-6648 Confidential Pursuant to Confidentiality DUROJ012-001342 Order Source: https://www.industrydocuments.ucsf.edu/docs/rpbw0217 Premarin Publication/Presentation Planning Meeting April 12, 2000 10:30 AM - 12:00 PM, Conference Room #555-6A Status Journal Investigator Study Submitted Br J Menopause Dey Estrogen activity Submitted Urology Nurses On-line Maloney Estrogen and UTIs Submitted Current Atherosclerosis Mosca Atherosclerosis and HRT Reports II. Medical Affairs Updates III. Women's Health Research Institute IV. Prioritizing Meetings V. Poster Template VI. PR Opportunities VII. Upcoming Meetings and Deadlines MEETING DATE DEADLINE ASBMR - American Society for Bone and Mineral Sept 22-26,2000 Apr 12, 2000 Research (Toronto) AHA - American Heart Association (New Orleans, Nov 12-15, 2000 May 5, 2000 LA) ARHP - Association of Reproductive Health Sept 14-16, 2000 May 19, 2000 Professionals (Chicago, IL) NAMS - North American Menopause Society Sept 7-9, 2000 May 31, 2000 (Orlando, FL) 8th World Congress of Gynecological Endocrinology Dec 6-9,2000 Sept 1, 2000 (Florence) DESIGNWRITE . 189 WALL STREET, PRINCETON, NEW JERSEY 08540 609/924-1116 FAX: 609/924-6648 Confidential Pursuant to Confidentiality DUROJ012-001343 Order Source: :ttps://www.industrydocuments.ucsf.edu/docs/rpbw0217

What is the status of the meeting "ASBMR"?

rpbw0217

rpbw0217_p0, rpbw0217_p1

Submitted, submitted

Premarin Publication/Presentation Planning Meeting April 12, 2000 10:30 AM - 12:00 PM, Conference Room #555-6A AGENDA I. Premarin Study Tracking Update MEETINGS Status Meeting Investigator Study Submitted ASBMR Lane Estrogen and raloxifene on bone microarchitecture Ermer TSE pharmacology Presenting First International Pace/Ke (2 posters) Estrogen and heart rate Conference on Women, variability; estrogen and Heart Disease and Stroke oxidative stress Bakir/Oparil (1 poster/1 Estrogen attenuates osteopontin oral) (vasoprotection); raloxifene not vasoprotective Paganini-Hill Estrogen and stroke Plenary Session Herrington; Manson; ERA; NHS update; estrogen Mendelson; Madori action; public policy Satellite Symposium Harnish; Bakir; Bozkurt, Estrogen mechanisms of action, Rosano review of clinical studies, comparative progestin effects Posters ACC Davidson Zocor/Prempro study Eskin Estrogen and NE in the heart Posters SGI Scharf Estrogen on sleep quality Lane Estrogen and raloxifene on bone microarchitecture Posters ACOG Eskin Estrogen and NE in the heart Archer Prempro bleeding re-analysis PUBLICATIONS Published JAMA (4/12/00) Shlipak Estrogen and lipoprotein(a) Published Arch Fam Med (4/00) McNagny/Frank Counseling and HRT Manuscripts Scharf Estrogen and sleep quality in preparation Birge (2) CNS (1) and Bone (1) Murphy (2) Estrogen and brain serotonin Published JAGS (4/00) Sherwin Estrogen and cognitive function DESIGNWRITE 189 WALL STREET, PRINCETON, NEW JERSEY 08540 609/924-1116 FAX: 609/924-6648 Confidential Pursuant to Confidentiality DUROJ012-001342 Order Source: https://www.industrydocuments.ucsf.edu/docs/rpbw0217 Premarin Publication/Presentation Planning Meeting April 12, 2000 10:30 AM - 12:00 PM, Conference Room #555-6A Status Journal Investigator Study Submitted Br J Menopause Dey Estrogen activity Submitted Urology Nurses On-line Maloney Estrogen and UTIs Submitted Current Atherosclerosis Mosca Atherosclerosis and HRT Reports II. Medical Affairs Updates III. Women's Health Research Institute IV. Prioritizing Meetings V. Poster Template VI. PR Opportunities VII. Upcoming Meetings and Deadlines MEETING DATE DEADLINE ASBMR - American Society for Bone and Mineral Sept 22-26,2000 Apr 12, 2000 Research (Toronto) AHA - American Heart Association (New Orleans, Nov 12-15, 2000 May 5, 2000 LA) ARHP - Association of Reproductive Health Sept 14-16, 2000 May 19, 2000 Professionals (Chicago, IL) NAMS - North American Menopause Society Sept 7-9, 2000 May 31, 2000 (Orlando, FL) 8th World Congress of Gynecological Endocrinology Dec 6-9,2000 Sept 1, 2000 (Florence) DESIGNWRITE . 189 WALL STREET, PRINCETON, NEW JERSEY 08540 609/924-1116 FAX: 609/924-6648 Confidential Pursuant to Confidentiality DUROJ012-001343 Order Source: :ttps://www.industrydocuments.ucsf.edu/docs/rpbw0217

What is the status of the meeting "ACC"?

rpbw0217

rpbw0217_p0, rpbw0217_p1

posters, Posters

Premarin Publication/Presentation Planning Meeting April 12, 2000 10:30 AM - 12:00 PM, Conference Room #555-6A AGENDA I. Premarin Study Tracking Update MEETINGS Status Meeting Investigator Study Submitted ASBMR Lane Estrogen and raloxifene on bone microarchitecture Ermer TSE pharmacology Presenting First International Pace/Ke (2 posters) Estrogen and heart rate Conference on Women, variability; estrogen and Heart Disease and Stroke oxidative stress Bakir/Oparil (1 poster/1 Estrogen attenuates osteopontin oral) (vasoprotection); raloxifene not vasoprotective Paganini-Hill Estrogen and stroke Plenary Session Herrington; Manson; ERA; NHS update; estrogen Mendelson; Madori action; public policy Satellite Symposium Harnish; Bakir; Bozkurt, Estrogen mechanisms of action, Rosano review of clinical studies, comparative progestin effects Posters ACC Davidson Zocor/Prempro study Eskin Estrogen and NE in the heart Posters SGI Scharf Estrogen on sleep quality Lane Estrogen and raloxifene on bone microarchitecture Posters ACOG Eskin Estrogen and NE in the heart Archer Prempro bleeding re-analysis PUBLICATIONS Published JAMA (4/12/00) Shlipak Estrogen and lipoprotein(a) Published Arch Fam Med (4/00) McNagny/Frank Counseling and HRT Manuscripts Scharf Estrogen and sleep quality in preparation Birge (2) CNS (1) and Bone (1) Murphy (2) Estrogen and brain serotonin Published JAGS (4/00) Sherwin Estrogen and cognitive function DESIGNWRITE 189 WALL STREET, PRINCETON, NEW JERSEY 08540 609/924-1116 FAX: 609/924-6648 Confidential Pursuant to Confidentiality DUROJ012-001342 Order Source: https://www.industrydocuments.ucsf.edu/docs/rpbw0217 Premarin Publication/Presentation Planning Meeting April 12, 2000 10:30 AM - 12:00 PM, Conference Room #555-6A Status Journal Investigator Study Submitted Br J Menopause Dey Estrogen activity Submitted Urology Nurses On-line Maloney Estrogen and UTIs Submitted Current Atherosclerosis Mosca Atherosclerosis and HRT Reports II. Medical Affairs Updates III. Women's Health Research Institute IV. Prioritizing Meetings V. Poster Template VI. PR Opportunities VII. Upcoming Meetings and Deadlines MEETING DATE DEADLINE ASBMR - American Society for Bone and Mineral Sept 22-26,2000 Apr 12, 2000 Research (Toronto) AHA - American Heart Association (New Orleans, Nov 12-15, 2000 May 5, 2000 LA) ARHP - Association of Reproductive Health Sept 14-16, 2000 May 19, 2000 Professionals (Chicago, IL) NAMS - North American Menopause Society Sept 7-9, 2000 May 31, 2000 (Orlando, FL) 8th World Congress of Gynecological Endocrinology Dec 6-9,2000 Sept 1, 2000 (Florence) DESIGNWRITE . 189 WALL STREET, PRINCETON, NEW JERSEY 08540 609/924-1116 FAX: 609/924-6648 Confidential Pursuant to Confidentiality DUROJ012-001343 Order Source: :ttps://www.industrydocuments.ucsf.edu/docs/rpbw0217

What is the number of station progress notes?

xmyl0226

xmyl0226_p0

85

Station Progress OCTOBER Notes No. 85 1952 THE USE OF BYPRODUCTS OF TERRITORIAL INDUSTRIES IN SWINE RATIONS by 0. Wayman and K. C. Leong University of Hawaii Collega of Agriculture Agricultural Experiment Station Honolulu, Hawaii Source: https://www.industrydocuments.ucsf.edu/docs/xmyl0226

What is the date mentioned in the document?

xmyl0226

xmyl0226_p0

October 1952, OCTOBER 1952

Station Progress OCTOBER Notes No. 85 1952 THE USE OF BYPRODUCTS OF TERRITORIAL INDUSTRIES IN SWINE RATIONS by 0. Wayman and K. C. Leong University of Hawaii Collega of Agriculture Agricultural Experiment Station Honolulu, Hawaii Source: https://www.industrydocuments.ucsf.edu/docs/xmyl0226

What is the page number?

zxbw0217

zxbw0217_p0, zxbw0217_p1, zxbw0217_p2

2

PROGRESS REPORT 11 Totelle 1mg CLIENT WYETH CONTACTS Wyeth: Richie Lu [email protected]) MJ Roach ([email protected]) Daniele Speilmann ([email protected]) Dave Downey ([email protected]) Current Projects Rick Winneker [email protected]) Jasmine Baleva ([email protected]/ Jim Gurr [email protected] Phil Vinall [email protected]) David Dubinski ([email protected]) DATE 18 October, 2002 PAPERS PROJECT CLASSIFICATION TARGET STATUS/ACTION SUBMISSION DATE/JOURNAL Paper PC(1) Efficacy February 2003 First draft submitted for initial review August 7 A study of the efficacy of continuous Comments received from Daniele October 4 combined regimens of lmg estradiol and trimegestone compared with regimens containing estradiol and norethisterone acetate in postmenopausal women for up to 2 years Paper PC(2) Endometrium/safety March 2003 First draft submitted for initial review August 19 A comparison of the effects of continuous combined regimens of 1 mg estradiol and trimegestone with regimens containing estradiol and norethisterone acetate upon the profiles of endometrial bleeding and safety in postmenopausal women for up to 2 years Paper PC(3) Hemostasis/metabolic impact April 2003 First draft submitted for initial review April 4 Metabolic and hemostatic profile of Comments received from Gary May 13th postmenopausal women receiving a continuous combined regimen of either 1mg estradiol with trimegestone or estradiol and norethisterone acetate over a 1-year period Paper PS(1) Climacteric symptoms March 2003 First draft submitted for initial review August 8 A study of the control of climacteric symptoms in postmenopausal women following sequential regimens of lmg estradiol and trimegestone compared with a regimen containing estradiol and norethisterone over a period of 2 years Paper PS(2) Endometrium/safety March 2003 First draft submitted for initial review August 9 A comparative 2-year study of the effects of sequential regimens of 1 mg estradiol and trimegestone with a regimen containing estradiol and norethisterone upon the patterns of endometrial bleeding and safety in postmenopausal women 1 Confidential Pursuant to Confidentiality OLIVS019-012556 Order Source: https://www.industrydocuments.ucsf.edu/docs/zxbw0217 PROGRESS REPORT 11 Totelle 1mg Client: Wyeth October 18, 2002 PROJECT CLASSIFICATION TARGET STATUS/ACTION SUBMISSION DATE/JOURNAL Paper PS(3) Hemostasis/metabolic impact April 2003 First draft submitted for initial review April 19th Metabolic and hemostatic profile of postmenopausal women receiving a Comments received from Gary May 13th combined sequential regimen of either lmg estradiol and trimegestone or estradiol and norethisterone over a 1-year period PAPERS FOR WMC SYMPOSIUM PROCEEDINGS Paper WMC(1) Preclinical December, 2002 First draft submitted for initial review July 29 The preclinical biology of trimegestone: a new potent and Climacteric Suppl. selective progestin R. Winneker Paper WMC(2) Safety December, 2002 First draft submitted for initial review August 1 An overview of the comparative Bleeding profile Comments received from Gary October 9 efficacy, safety, bleeding profile and Metabolism Climacteric Suppl. effect on lipids of a sequential HRT preparation containing 2 mg estradiol and trimegestone H.P.G. Schneider Paper WMC(3) Bone December, 2002 First draft submitted for initial review July 30 A comparative clinical evaluation of Comments received from Gary October 14 the effect of a new sequential HRT Climacteric Suppl. preparation containing 2 mg estradiol and the progestin trimegestone on postmenopausal bone loss M. Gambacciani Paper WMC(4) Climacteric symptoms December, 2002 First draft submitted for initial review August 9 A comparative clinical evaluation of Efficacy Comments received from Daniele October 9 a continuous HRT preparation Climacteric Suppl. containing 1 mg estradiol and the novel progestin trimegestone P. Bouchard PAPERS FOR PROGESTIN SYMPOSIUM Clinical experience with 2nd International Paper prepared and in review trimegestone as a new progestin in Progestin HRT Symposium Sienna G. Grubb SUPPORTING ACTIVITIES 2 Confidential Pursuant to Confidentiality OLIVS019-012557 Order Source: https://www.industrydocuments.ucsf.edu/docs/zxbw0217 PROGRESS REPORT 11 Totelle 1mg Client: Wyeth October 18, 2002 PROJECT TARGET STATUS/ACTION PUBLICATION DATE Totelle Monograph 1 and 2mg December 2002 Draft manuscript submitted for review February 1st Comments received from Dave Downey. Revised draft submitted to Dave on April 23rd. Formatted and designed document and highlighted refs. submitted for review to Jasmine Totelle 1 mg Slide Set on CD-ROM February 2003 Text written, to be formatted 3 Confidential Pursuant to Confidentiality OLIVS019-012558 Order Source: https://www.industrydocuments.ucsf.edu/docs/zxbw0217

What is the number of participants from the University of Minnesota?

gxxh0227

gxxh0227_p8, gxxh0227_p9, gxxh0227_p10, gxxh0227_p11, gxxh0227_p12

703

TABLE 13A The Ratio Of The Odds of CHD Of The Special Intervention Group To The Usual Care Group By Clinical Center Clinical Center No. of Participants Relative Odds UC SI Of CHD (SI/UC) A. Baltimore 248 261 .589 B. New York 335 342 .639 C. Minneapolis 269 270 :649 D. San Francisco 234 250 .701 E. St. Louis 141 149 .664 F. Boston Harrazd 285 286 .678 G. Davis 221 212 .590 H. Chic. Northwestern 152 154 .536 I. Chic. St. Joseph 141 133 .505 J. Chic. University 90 88 .637 K. Portland 268 263 .710 i . L. Boston University 249 240 .669 M. Dayton 298 288 .636 N. Newark 162 152 .548 o. Philadelphia 178 173 .626 P. Birmingham 132 126 .657 Q. Pittsburgh 240 244 .618 R. Chicago Rush 61 62 .643 S. Rutgers 105 104 .667 T. Columbia 147 140 .551 U. Los Angeles 70 60 .629 v. Miami 51 54 .579 All Combined 4077 4051 .629 Source: https://www.industrydocuments.ucsf.edu/docs/gxxh0227 MULTIPLE RISK FACTOR INTERVENTION TRIAL Contract Renewal Proposals and Contract Extentions for Calendar Year 1977 Total Amt. Overall Total Direct Total Indirect Number Requested/ Cost Per Direct Cost Per Indirect Cost Per Center Randomized Negotiated Participant Costs Participant Costs Participant Rush-Presbyterian St. Luke's 446 410,036 919 337,217 756 72,819 163 Rutgers Medical School 614 460,750 750 405,251 660 55,499 90 U. of South Carolina 618 450,096 728 295,674 478 154,422 250 U. of Southern California 633 421,937 667 318,739 504 103,198 163 Dade-Miami University 414 549,411 1,327 413,710 999 135,701 328 Central Laboratory b 524,099 40 390,939 30 133,160 10 ECG Center b 241,861 19 200,754 16 41,107 3 Proposed b Perform services for all 12,866 participants Source: https://www.industrydocuments.ucsf.edu/docs/gxxh0227 PARTICIPANTS INITIALLY RANDOMIZED AND CURRENT NET TOTAL AS OF AUGUST 16, 1976 Current Number of Men Net Initially Participants Center Recruited SI UC Total Rush-Presbyterian St. Luke's 446 223 222 445 Rutgers Medical School 614 300 306 606 U. of South Carolina 618 305 305 610 U. of Southern California 633 323 327 650 Dade-Miami University 414 214 213 427 Source: https:/lwww.industrydocuments.ucsf.edu/docs/gxxh0227 SUMMARY OF NEGOTIATED CONTRACTS THAT ARE INCREMENTALLY FUNDED BEGINNING CALENDAR YEAR 1976 AND EXTENDING THROUGH CALENDAR YEAR 1977 AND PROPOSED BUDGETS FOR DADE-MIAMI UNIVERSITY 1977-1980 AND THE ECG CENTER AT DALHOUSIE UNIVERSITY FOR 1977-1980 Number Calendar Years Beginning Participants Center 1976 1977 1978 1979 1980 Randomized Rush-Presbyterian St. Luke's 417,685 410,036 412,344 409,216 412,920 446 Rutgers Medical School 482,757 460,750 467,175 477,794 466,497 614 U. of South Carolina 491,870 450,096 457,338 446,068 444,642 618 U. of Southern California 425,403 421,937 424,228 426,651 417,235 633 Dade-Miami University 420,198 549,411a 594,467 650,030 710,950 414 Central Laboratory 484,672 524,099 418,564 --- --- -- ECG Center 197,371 241,861° 259,566 285,521 314,074° --- "Proposed Source: https:/lwww.industrydocuments.ucsf.edu/docs/gxxh0227 SUMMARY OF NEGOTIATED INCREMENTALLY FUNDED CONTRACTS BEGINNING JULY 1976 AND EXTENDING THROUGH JUNE 1980 AND TWO SINGLE YEAR CONTRACTS Number Calendar Years Beginning Participants Center 1976 1977 1978 1979 1980 Randomized University of Minnesota 618,195 632,114 636,165 649,379 649,042 703 b Northwestern 747,952 561,928 523,985 530,261 585,961 892 Cox Heart Institute 471,105 497,014 477,531 454,995 332,234 738 N.J. School of Medicine 497,257 505,336 513,873 520,289 495,544 632 Lankenau Hospital 414,501 418,971 423,917 422,157 421,009 602 University of Alabama 445,093 450,614 454,689 459,897 453,626 606 University of Pittsburgh 476,468 466,352 468,210 468,255 465,080 645 St. Louis Heart Assoc. 399,039 One Year Contract 544 Coordinating Center 1,399,117 One Year Contract --- a Includes ECG Center Budget b Northwestern, St. Joseph's and University of Chicago Units Source: https://www.industrydocuments.ucsf.edu/docs/gxxh0227

What is the number of participants from the University of Pittsburgh?

gxxh0227

gxxh0227_p8, gxxh0227_p9, gxxh0227_p10, gxxh0227_p11, gxxh0227_p12

645

TABLE 13A The Ratio Of The Odds of CHD Of The Special Intervention Group To The Usual Care Group By Clinical Center Clinical Center No. of Participants Relative Odds UC SI Of CHD (SI/UC) A. Baltimore 248 261 .589 B. New York 335 342 .639 C. Minneapolis 269 270 :649 D. San Francisco 234 250 .701 E. St. Louis 141 149 .664 F. Boston Harrazd 285 286 .678 G. Davis 221 212 .590 H. Chic. Northwestern 152 154 .536 I. Chic. St. Joseph 141 133 .505 J. Chic. University 90 88 .637 K. Portland 268 263 .710 i . L. Boston University 249 240 .669 M. Dayton 298 288 .636 N. Newark 162 152 .548 o. Philadelphia 178 173 .626 P. Birmingham 132 126 .657 Q. Pittsburgh 240 244 .618 R. Chicago Rush 61 62 .643 S. Rutgers 105 104 .667 T. Columbia 147 140 .551 U. Los Angeles 70 60 .629 v. Miami 51 54 .579 All Combined 4077 4051 .629 Source: https://www.industrydocuments.ucsf.edu/docs/gxxh0227 MULTIPLE RISK FACTOR INTERVENTION TRIAL Contract Renewal Proposals and Contract Extentions for Calendar Year 1977 Total Amt. Overall Total Direct Total Indirect Number Requested/ Cost Per Direct Cost Per Indirect Cost Per Center Randomized Negotiated Participant Costs Participant Costs Participant Rush-Presbyterian St. Luke's 446 410,036 919 337,217 756 72,819 163 Rutgers Medical School 614 460,750 750 405,251 660 55,499 90 U. of South Carolina 618 450,096 728 295,674 478 154,422 250 U. of Southern California 633 421,937 667 318,739 504 103,198 163 Dade-Miami University 414 549,411 1,327 413,710 999 135,701 328 Central Laboratory b 524,099 40 390,939 30 133,160 10 ECG Center b 241,861 19 200,754 16 41,107 3 Proposed b Perform services for all 12,866 participants Source: https://www.industrydocuments.ucsf.edu/docs/gxxh0227 PARTICIPANTS INITIALLY RANDOMIZED AND CURRENT NET TOTAL AS OF AUGUST 16, 1976 Current Number of Men Net Initially Participants Center Recruited SI UC Total Rush-Presbyterian St. Luke's 446 223 222 445 Rutgers Medical School 614 300 306 606 U. of South Carolina 618 305 305 610 U. of Southern California 633 323 327 650 Dade-Miami University 414 214 213 427 Source: https:/lwww.industrydocuments.ucsf.edu/docs/gxxh0227 SUMMARY OF NEGOTIATED CONTRACTS THAT ARE INCREMENTALLY FUNDED BEGINNING CALENDAR YEAR 1976 AND EXTENDING THROUGH CALENDAR YEAR 1977 AND PROPOSED BUDGETS FOR DADE-MIAMI UNIVERSITY 1977-1980 AND THE ECG CENTER AT DALHOUSIE UNIVERSITY FOR 1977-1980 Number Calendar Years Beginning Participants Center 1976 1977 1978 1979 1980 Randomized Rush-Presbyterian St. Luke's 417,685 410,036 412,344 409,216 412,920 446 Rutgers Medical School 482,757 460,750 467,175 477,794 466,497 614 U. of South Carolina 491,870 450,096 457,338 446,068 444,642 618 U. of Southern California 425,403 421,937 424,228 426,651 417,235 633 Dade-Miami University 420,198 549,411a 594,467 650,030 710,950 414 Central Laboratory 484,672 524,099 418,564 --- --- -- ECG Center 197,371 241,861° 259,566 285,521 314,074° --- "Proposed Source: https:/lwww.industrydocuments.ucsf.edu/docs/gxxh0227 SUMMARY OF NEGOTIATED INCREMENTALLY FUNDED CONTRACTS BEGINNING JULY 1976 AND EXTENDING THROUGH JUNE 1980 AND TWO SINGLE YEAR CONTRACTS Number Calendar Years Beginning Participants Center 1976 1977 1978 1979 1980 Randomized University of Minnesota 618,195 632,114 636,165 649,379 649,042 703 b Northwestern 747,952 561,928 523,985 530,261 585,961 892 Cox Heart Institute 471,105 497,014 477,531 454,995 332,234 738 N.J. School of Medicine 497,257 505,336 513,873 520,289 495,544 632 Lankenau Hospital 414,501 418,971 423,917 422,157 421,009 602 University of Alabama 445,093 450,614 454,689 459,897 453,626 606 University of Pittsburgh 476,468 466,352 468,210 468,255 465,080 645 St. Louis Heart Assoc. 399,039 One Year Contract 544 Coordinating Center 1,399,117 One Year Contract --- a Includes ECG Center Budget b Northwestern, St. Joseph's and University of Chicago Units Source: https://www.industrydocuments.ucsf.edu/docs/gxxh0227

What is the number of participants from the Cox Heart Institute?

gxxh0227

gxxh0227_p8, gxxh0227_p9, gxxh0227_p10, gxxh0227_p11, gxxh0227_p12

738

TABLE 13A The Ratio Of The Odds of CHD Of The Special Intervention Group To The Usual Care Group By Clinical Center Clinical Center No. of Participants Relative Odds UC SI Of CHD (SI/UC) A. Baltimore 248 261 .589 B. New York 335 342 .639 C. Minneapolis 269 270 :649 D. San Francisco 234 250 .701 E. St. Louis 141 149 .664 F. Boston Harrazd 285 286 .678 G. Davis 221 212 .590 H. Chic. Northwestern 152 154 .536 I. Chic. St. Joseph 141 133 .505 J. Chic. University 90 88 .637 K. Portland 268 263 .710 i . L. Boston University 249 240 .669 M. Dayton 298 288 .636 N. Newark 162 152 .548 o. Philadelphia 178 173 .626 P. Birmingham 132 126 .657 Q. Pittsburgh 240 244 .618 R. Chicago Rush 61 62 .643 S. Rutgers 105 104 .667 T. Columbia 147 140 .551 U. Los Angeles 70 60 .629 v. Miami 51 54 .579 All Combined 4077 4051 .629 Source: https://www.industrydocuments.ucsf.edu/docs/gxxh0227 MULTIPLE RISK FACTOR INTERVENTION TRIAL Contract Renewal Proposals and Contract Extentions for Calendar Year 1977 Total Amt. Overall Total Direct Total Indirect Number Requested/ Cost Per Direct Cost Per Indirect Cost Per Center Randomized Negotiated Participant Costs Participant Costs Participant Rush-Presbyterian St. Luke's 446 410,036 919 337,217 756 72,819 163 Rutgers Medical School 614 460,750 750 405,251 660 55,499 90 U. of South Carolina 618 450,096 728 295,674 478 154,422 250 U. of Southern California 633 421,937 667 318,739 504 103,198 163 Dade-Miami University 414 549,411 1,327 413,710 999 135,701 328 Central Laboratory b 524,099 40 390,939 30 133,160 10 ECG Center b 241,861 19 200,754 16 41,107 3 Proposed b Perform services for all 12,866 participants Source: https://www.industrydocuments.ucsf.edu/docs/gxxh0227 PARTICIPANTS INITIALLY RANDOMIZED AND CURRENT NET TOTAL AS OF AUGUST 16, 1976 Current Number of Men Net Initially Participants Center Recruited SI UC Total Rush-Presbyterian St. Luke's 446 223 222 445 Rutgers Medical School 614 300 306 606 U. of South Carolina 618 305 305 610 U. of Southern California 633 323 327 650 Dade-Miami University 414 214 213 427 Source: https:/lwww.industrydocuments.ucsf.edu/docs/gxxh0227 SUMMARY OF NEGOTIATED CONTRACTS THAT ARE INCREMENTALLY FUNDED BEGINNING CALENDAR YEAR 1976 AND EXTENDING THROUGH CALENDAR YEAR 1977 AND PROPOSED BUDGETS FOR DADE-MIAMI UNIVERSITY 1977-1980 AND THE ECG CENTER AT DALHOUSIE UNIVERSITY FOR 1977-1980 Number Calendar Years Beginning Participants Center 1976 1977 1978 1979 1980 Randomized Rush-Presbyterian St. Luke's 417,685 410,036 412,344 409,216 412,920 446 Rutgers Medical School 482,757 460,750 467,175 477,794 466,497 614 U. of South Carolina 491,870 450,096 457,338 446,068 444,642 618 U. of Southern California 425,403 421,937 424,228 426,651 417,235 633 Dade-Miami University 420,198 549,411a 594,467 650,030 710,950 414 Central Laboratory 484,672 524,099 418,564 --- --- -- ECG Center 197,371 241,861° 259,566 285,521 314,074° --- "Proposed Source: https:/lwww.industrydocuments.ucsf.edu/docs/gxxh0227 SUMMARY OF NEGOTIATED INCREMENTALLY FUNDED CONTRACTS BEGINNING JULY 1976 AND EXTENDING THROUGH JUNE 1980 AND TWO SINGLE YEAR CONTRACTS Number Calendar Years Beginning Participants Center 1976 1977 1978 1979 1980 Randomized University of Minnesota 618,195 632,114 636,165 649,379 649,042 703 b Northwestern 747,952 561,928 523,985 530,261 585,961 892 Cox Heart Institute 471,105 497,014 477,531 454,995 332,234 738 N.J. School of Medicine 497,257 505,336 513,873 520,289 495,544 632 Lankenau Hospital 414,501 418,971 423,917 422,157 421,009 602 University of Alabama 445,093 450,614 454,689 459,897 453,626 606 University of Pittsburgh 476,468 466,352 468,210 468,255 465,080 645 St. Louis Heart Assoc. 399,039 One Year Contract 544 Coordinating Center 1,399,117 One Year Contract --- a Includes ECG Center Budget b Northwestern, St. Joseph's and University of Chicago Units Source: https://www.industrydocuments.ucsf.edu/docs/gxxh0227

What is the total service in actual FTE 1981?

sjcf0227

sjcf0227_p0

22,723

VNA OF GREATER ST. LOUIS PRODUCTIVITY REPORT FOR THE MONTH OF SEPTEMBER, 1982 1981 1982 1982 VISIT BREAKDOWN PER ACTUAL ACTUAL BUDGET FULL TIME EQUIVALENT FTE FTE FTE 1. TOTAL VISITS RN/LPN 12,065 13,251 11,739 HHA 6,413 7,131 6,908 Rehab 3,358 3,393 2,953 Social Service 555 677 492 Consultant 332 379 268 Total Service 22,723 24,831 22,360 2. FTE STAFF RN/LPN 104.5 115.8 110.1 HHA 95.6 104.0 106.0 Rehab 26.9 29.5 35.0 Social Service 10.0 10.0 10.0 Consultant 9.0 11.0 11.0 Visiting Staff 246.0 270.3 272.1 Support Staff 130.5 141.0 144.7 Total Staff 376.5 411.3 416.8 3. VISIT PER FWD/FTE RN/LPN 5.5 5.4 5.1 HHA 3.2 3.3 3.1 Rehab 5.9 5.5 4.0 Social Service 2.6 3.2 2.3 Consultant 1.8 1.6 1.2 Visiting Staff 4.4 4.4 3.9 Support Staff 8.3 8.4 7.4 Total Staff 2.9 2.9 2.6 4. AVG. MONTHLY VISITS PER FTE RN/LPN 115.5 114.4 106.6 HHA 67.1 68.6 65.2 Rehab 124.8 115.0 84.4 Social Service 55.5 67.7 49.2 Consultant 36.9 34.5 24.4 Visiting Staff 92.4 91.9 82.2 Support Staff 174.1 176.1 154.5 Total Staff 60.4 60.4 53.6 Source 1. General Revenue Report - September, 1981 and 1982 2. Human Resources Report - August, 1982 Source: https://www.industrydocuments.ucsf.edu/docs/sjcf0227

What is the total FTE staff in 1982 actual FTE?

sjcf0227

sjcf0227_p0

411.3

VNA OF GREATER ST. LOUIS PRODUCTIVITY REPORT FOR THE MONTH OF SEPTEMBER, 1982 1981 1982 1982 VISIT BREAKDOWN PER ACTUAL ACTUAL BUDGET FULL TIME EQUIVALENT FTE FTE FTE 1. TOTAL VISITS RN/LPN 12,065 13,251 11,739 HHA 6,413 7,131 6,908 Rehab 3,358 3,393 2,953 Social Service 555 677 492 Consultant 332 379 268 Total Service 22,723 24,831 22,360 2. FTE STAFF RN/LPN 104.5 115.8 110.1 HHA 95.6 104.0 106.0 Rehab 26.9 29.5 35.0 Social Service 10.0 10.0 10.0 Consultant 9.0 11.0 11.0 Visiting Staff 246.0 270.3 272.1 Support Staff 130.5 141.0 144.7 Total Staff 376.5 411.3 416.8 3. VISIT PER FWD/FTE RN/LPN 5.5 5.4 5.1 HHA 3.2 3.3 3.1 Rehab 5.9 5.5 4.0 Social Service 2.6 3.2 2.3 Consultant 1.8 1.6 1.2 Visiting Staff 4.4 4.4 3.9 Support Staff 8.3 8.4 7.4 Total Staff 2.9 2.9 2.6 4. AVG. MONTHLY VISITS PER FTE RN/LPN 115.5 114.4 106.6 HHA 67.1 68.6 65.2 Rehab 124.8 115.0 84.4 Social Service 55.5 67.7 49.2 Consultant 36.9 34.5 24.4 Visiting Staff 92.4 91.9 82.2 Support Staff 174.1 176.1 154.5 Total Staff 60.4 60.4 53.6 Source 1. General Revenue Report - September, 1981 and 1982 2. Human Resources Report - August, 1982 Source: https://www.industrydocuments.ucsf.edu/docs/sjcf0227

Department of public health is in which division?

nycg0227

nycg0227_p0, nycg0227_p1, nycg0227_p2, nycg0227_p3, nycg0227_p4, nycg0227_p5, nycg0227_p6

Division of Research, DIVISION OF RESEARCH

pull for prof STATE OF CALIFORNIA seak, to Dest to for DEPARTMENT OF PUBLIC HEALTH Division of Research Berkeley, California 1961 SUMMER PROGRAM FOR MEDICAL STUDENTS Information for Applicants Attached is an application and some brief descriptive material concerning the 1961 Medical Student Program of California State Department of Public Health. This program provides orientation to the con- cepts and methods of an operating public health agency and a participating experience in the use of epi- demiologic research methods and in public health practice Each student participates in a number of group activities, but the major portion of his time is devoted to planning, carrying out some part of or com- pleting, if possible, a specific project with a designated staff member responsible as a preceptor Head- quarters for all projects will be Berkeley. The training period extends from June 26 to September 1 inclusive. It would be helpful to know which programs of the Department interest you and why. However, your application will be considered even if you are not interested in a specific project or program. In any event, we would like a statement about your general interests. Perhaps you have some project of your own to suggest - one that might be done in a health department in the time available. This information will be used in selecting participants and in making assignments to projects. In addition to the application, you will find attached a form to be completed by the Office of the Dean of your school. Please have this completed and sent to us. It is a part of t he application. The deadline for submission of applications is March 1. Notification of appointments will be approximat ely April 1. All applicants must be citizens of the United States, possess a bachelor's degree or be eligible ? to receive such degree before July 1, 1961, and must be currently enrolled in, or accepted for admis- sion by, an approved medical school in the United States or Canada. Criteria for Rate of Compensation Range Salary Qualification A $341 per month Equivalent to graduation from college and acceptance by an approved medical school. B $376 per month Completion of one academic year in an ap- proved medical school. C $395 per month Completion of two academic years in an apen proved medical school, or completion of one year plus experience in the California State Service as a Medical Student Assistant for the equivalent of one summer's duration. D $415 per month Completion of three academic years in an apem proved medical school, or completion of two years plus experience in t he California State Service as a Medical Student Assistant f or the equivalent of one summer's duration. E $436 per month Completion of three academic years in an ape proved medical school, plus experience in the California State Service as a Medical Student Assistant for the equivalent of one summer's duration. All correspondence should be addressed to: California State Department of Public Health Division of Research 2151 Berkeley Way Berkeley 4, California FO:ar 021661 Source: https://www.industrydocuments.ucsf.edu/docs/nycg0227 STATE OF CALIFORNIA DEPARTMENT OF PUBLIC HEALTH BERKELEY, CALIFORNIA POSSIBLE PROJECTS FOR MEDICAL STUDENT ASSISTANTS SUMMER, 1961 Health Effects of Air Pollution Studies are in progress to appraise the health effects of air pollution, with emphasis upon changes in pulmonary function. Attention is given to specific pollu- tants such as carbon monoxide and lead. Populations for study may include general population samples, patients in nursing homes or hospitals, and various occupational groups. The Medical Student Assistants will learn epidemiological methods, including laboratory procedures, and will participate in field studies. Cancer The Department operates a Tumor Registry to collect data on cancer cases, makes analyses of these data and performs research related to these analyses. At present, the registry has collected detailed epidemiologic and clinical data on more than 200,000 cases from 40 hospitals in California. In addition, a Tumor Registry encom- passing the entire population of Alameda County, California, is being organized. The Medical Student Assistant will participate in the analyses and study of special data obtained from the central and county registries. Communicable Diseases The Department conducts an extensive program of communicable disease control, including consultation with physicians, hospitals and health departments in the diagnosis and control of communicable disease; formulation of policy and programs for communicable disease control, and for the maintenance of a continuing surveil- lance of communicable diseases. In addition to such problems as tuberculosis, encephalitis, poliomyelitis, infectious hepatitis, enteric diseases, etc., Galifor- nia affords an unusual opportunity to see occasional cases of more exotic infections such as Q-fever, sylvatic plague, tularemia, psittacosis Students may have an oppor- tunity to participate in the investigation of outbreaks of communicable diseases, and may participate in the development of plans for control programs. The changing epide- miologic patterns of primary and secondary syphilis are being studied intensively and control measures for all veneral diseases are being reviewed constantlyo Crippled Children Services By law, the Department is responsible for the maintenance of a program for diagnosis and treatment of physically handicapping conditions in children under 21 years of age. The Bureau of Crippled Children Services is engaged in a review of the need for, adequacy of, and cost of services for several handicapping conditions, such as congenital heart disease and cerebral palsy. Diagnostic and Research Laboratory Procedures The Department's Division of Laboratories provides a wide variety of laboratory services and research activities in chemistry, bacteriology and virology. There may be opportunities f or interested students to obtain combined laboratory and field experience in the study of viral diseases of t he central nervous system and of toxico- logic and bacteriologic problems in the sanitary control of food and drugs. Heart Disease Current studies of causative factors in heart disease are directed toward the role of cigarette smoking, exertion, familial longevity and similar factors in the occurrence of coronary heart disease. The health records of a population of long- shoremen, who were examined in 1951 and again in 1961, are of particular interest. Previous study of these men has shown a surprising lack of relationship between overweight and disease. Students who participate in this S tudy will assist in the collection and evaluation of mortality and morbidity data and in the refinement of epidemiologic methods for studying heart disease. Source:https:liwww.industrydocuments.ucsi.edu/docsmnycg0227, -2- Accidents An epidemiologic study of childhood accidents is being conducted by the Depart- ment in cooperation with the Alameda and Contra Costa County Health Departments, the Berkeley City Health Department and the Alameda=Contra Costa Medical Association. Medical Student Assistants may be employed to assist in the collection and analysis of data on the causes of childhood accidents and to compare the characteristics of families having different frequencies of injuries to children. Reproductive Loss This study is concerned with the epidemiologic investigation of major types of reproductive loss, such as prematurity and congenital malformations Medical Student Assistants will assist in testing and analyzing the adequacy of methods of obtaining detailed information regarding significant events which occur during a series of preg- nancies and the outcome for mother and child. Mental Health Responsibility for community health services for the prevention of mental illness is shared by the State Departments of Public Health and Mental Hygiene. Public Health is concerned with the emotional aspects of traditional public health activities such as immunization, hospitalization of the tuberculous, identification of venereal disease contacts, child health supervision, etc. Public Health also works closely with those individuals and agencies whose major con cern is people with mental illness. In this second category, suicide is a subject of current interest - its frequency, the charm acteristics of individuals attempting and committing suicide, its relationship to other manifestations of a social behavior. Opportunities may be available to participate in this exploration of suicide as a matter of public health concerno Occupational Health The Department regularly conducts field studies in various industries related to the health hazards of working in a variety of environmental circumstances and under unusual physiologic conditions. These studies, as well as consultation to persons in local health departments and industries, employ physicians, engineers, nurses, sani- tarians and chemists. Among the activities in which the Medical Student Assistants might participate are studies of the following problems: use of agricultural chemicals, noise and hearing loss, dusts and respiratory d iseases, allergens, dermatitis, health hazards associated with special fuels, and radiation hazards in industry. These are opportunities to study and evaluate in-plant medical services and to study reported cases of occupational diseases of particular interest to the student. Public Medical Care for Children The Department has been conducting a series of studies of the need, utilization, coordination and quality of community-finance and organized medical care programs for persons under the age 18. This encompasses primarily a dozen local, State and federal tax-supported services. Studies involve observation of services, interviews with selected groups of the public, examination of children and parents, development and testing of new ways of providing better service and evaluation of existing services. Radiological Health Two studies of the Bureau of Radiological Health may provide for participation of Medical Student Assistants. One is an extension of a study begun on a pilot basis in 1960 to determine the status and trends in the voluntary use of protective measures by medical personnel for radiologic diagnostic procedures. Another study of current medical interest is concerned with t he use of mass chest X-ray screening programs throughout the State, with regard to t he criteria for select- ing examiners, the equipment used, the adequacy of follow-up studies, and the yield of the screen o Social Factors in Health Opportunities are available for work with public health social workers, physicians and other professional disciplines on projects aimed at identifying medical-social needs of population groups and how these influence public health programs. These projects are typically carried out in cooperation with local health departments. Source: ttps://www.industrydocuments.ucsf.edu/docs/nycg0227 Current and planned projects include surveys of social problems coming to the attention of local health departments; studies of the social needs of patients in hospitals and nursing homes; case studies of social and health factors associated with economic depen- dency; and case studies of nonparticipants in special health programs Veterinary Public Health Animal diseases transmissible to man have long been of major concern in California. Of particular importance are brucellosis, rabies, encephalitis, psittacosis, leptospirosis, and Q=fever. Opportunities are available to participate in studies of the occurrence and transmission of these diseases and of special problems relating to their incidence in California. Current studies of psittacosis, Q=fever and other animal diseases with pul- monary manifestations in the human may afford participation by Medical Student Assistants. Environmental Health Medical Student Assistants may participate in field surveys and investigations conducted by public health engineers, entomologists, and biologists in the Bureaus of Sanitary Engineering and Vector Control. Of particular interest during the summer months are surveys to determine the impact of recreational activities on the quality of water in the many multi-purpose reservoirs and watersheds of the State and to study potential sources of water=borne disease. The Bureau of Vector Control maintains several field stations for study of the anthropod vectors and wild animal reservoirs of such diseases a.s plague, viral enceph- alitis, tularemia, and Colorado tiok fever. Ecological studies of small mammals and their ectoparasites in t heir natural habitats provide Medical Student Assistants W ith interesting opportunities for experience which combines the use of biologic, epide- miologic and laboratory methods. Hospital Planning Among the several responsibilities and interests in the Department relating to medical care is an expanding program of study and planning aimed toward the orderly development and staffing of hospitals to meet the present and future needs of the rapidly growing population o Medical Student Assistants may participate in the develuo opment and testing of methods for the collection, interpretation and application of information a bout the utilization of hospital facilities and services on a Statewide basis. Prevention of Blindness In its program for the prevention of blindness the Department carties out educa- tional and case=finding activities with particular emphasis upon amblyopia in children and glaucoma in adults. A study is currently being planned to examine the clinical impression that primary glaucoma is associated with diabetes mellitus and certain other chronic diseases. 021761 Source: https://www.industrydocuments.ucsf.edu/docs/nycg0227 ( State of California DO NOT WRITE IN THIS SPACE DEPARTMENT OF PUBLIC HEALTH 2151 Berkeley Way, Berkeley 4, California Number Date Received APPLICATION FOR MEDICAL STUDENT ASSISTANT Action: - Medical Student Program - Summer 1961 Name (please print) - Last First and Initial Birthdate - Month, Day, Year Present Mailing Address Phone Permanent (home) Mailing Address Phone Medical School (attending or accepted to) Medical Class Year to be U.S. Citizenship Completed June, 1961 Yes No 1 2 3 4 EDUCATION: Namos and dates of all college-level institutions attended before entering medical school. NAME DATE DEGREE AND YEAR MAJOR EXPERIENCE: How have you spent your last three summers or vacation periods? YEAR TYPE OF WORK - Organization or Agenoy OTHER (Speoify) (e.g. travel, etc.) Source: https://www.industrydocuments.ucst.edu/docs/nycg0227 Why are you intorested in working in a state health department this summer? Which programs or projects (if any) aro of particular interest to you? (See Information for Applioants) SIGNATURE OF APPLICANT Applications should be returned to: State of California Department of Public Health Division of Research 2151 Berkeley Way (Rev. 1-1-61) Form VS&DP-2229 Berkeley 4, California Source.https://www.industrydocuments.ucsi.edu/docsmnycg0227 To: State of California Department of Public Health (date) Division of Research 2151 Berkeley Way Berkeley 4, California is a student in good standing at the Medical School. He (she) will have completed the year in June, 1961. On the basis of completed work, his (her) relative class standing is in the: highest quarter third quarter second quarter lowest quarter This student's present medical school scholastic record is: satisfactory unsatisfactory Signed Dean, Medical School or if authorized representative give title (Rev. 1-1-61) Form VS&DP-2228 1523 Source: https://www.industrydocuments.ucsf.edu/docs/nycg0227

What is the first topic?

sqmf0227

sqmf0227_p0, sqmf0227_p1, sqmf0227_p2, sqmf0227_p3, sqmf0227_p4, sqmf0227_p5, sqmf0227_p6, sqmf0227_p7, sqmf0227_p8, sqmf0227_p9, sqmf0227_p10, sqmf0227_p11, sqmf0227_p12, sqmf0227_p13, sqmf0227_p14, sqmf0227_p15, sqmf0227_p16

Welcome to our cookbook, Welcome to our Cookbook

Revised 8/31/77 Revised 9/29/77 COOKING WITHOUT YOUR SALT SHAKER AMERICAN HEART ASSOCIATION NORTHEAST OHIO AFFILIATE, INC. in cooperation with the Cleveland Dietetic Association C American Heart Association, Northeast Ohio Affiliate, Inc., 1977 Source: https./lwww.industrydocuments.ucsi.edu/docsisqmf0227 TABLE O F CONTENTS Page Welcome To Our Cookbook When You Go Shopping Flavor Adventures Ingredient Substitutions Recipes and Cooking Tips Entrees and Accompaniments Sandwiches Vegetables Salads and Salad Dressings Breads Soups and Sauces Desserts Happy Snacking! Recipe Index NOTE TO DOCTOR AND DIETITIAN: This cookbook is for the person who must mildly restrict his salt or sodium intake. However, the recipes can easily be adapted to a specific lower level of sodium to correspond with your diet instruction. An analysis for the nutrient composition of the recipes is available free of charge by sending a self-addressed, stamped envelope to the American Heart Association, North- east Ohio Affiliate, Inc. , 1689 East 115th Street, Cleveland, Ohio 44106. Source: https://www.industrydocuments.ucsf.edu/docs/sqmf0227 1 WELCOME TO OUR COOKBOOK Eating is a subject on which most people consider themselves experts because they' 've been doing it all their lives! Yet, many of us have been consuming too much sodium, too much fat and the wrong kind of fat. If you would like to cut down on the amount of sodium and fat in your diet or if your doctor has suggested a "low-salt," modified fat diet, then you'11 find this cookbook an excellent guide. If your doctor has given you specific instructions, you may still use the recipes in this book by adapting them to your own diet. THE WHY'S AND WHEREFORE'S OF SALT AND SODIUM To get down to basics, we need to understand what sodium is and the difference between salt and sodium. We all know what salt is. Sodium, however, is a mineral found in nature and in almost When it IS IN COMBINATION WITH ANOTHER ELEMENT, CHCORINE, all the food we eat. It is not the same as salt. Salt is nearly BECOMES IT USUAL half sodium and most of the sodium we eat comes from ordinary salt TABCE SALT used in cooking or at the table. Confused? You needn't be. Everyone needs some sodium to live. However, our need for sodium can be met without using salt because sodium is found naturally in so many foods. One of the most common reasons a doctor recommends cutting down on salt or sodium in the diet is to control high blood pressure. This is important because high blood pressure increases the risk of heart attack, stroke and kidney failure. There are many other reasons a doctor may advise decreasing salt or sodium intake. While the scientific evidence is not conclusive, studies show that it may be wise for all of us to cut down on our salt intake. For these reasons, none of the recipes in this cookbook contain added salt. WHAT ABOUT FAT AND CHOLESTEROL? In addition to lowering the sodium in your food, recipes and recommended numbers of servings have been chosen for this cookbook with a fat-modified, low-cholesterol diet in mind. The Heart Association recommends decreasing your intake of fat-laden and cholesterol-rich foods and also changing the kind of fat you use. There are two kinds of fat you should be especially concerned about: polyunsaturated and saturated. As you continue reading these pages, you will learn how to use polyunsaturated fats and how to decrease the saturated fat in your diet. You may also be pleasantly surprised to know that by cutting down on fats in your food and serving slightly smaller portions, you will be taking in fewer calories. An approximate calorie content for one serving accompanies each recipe. IN SUMMARY By reducing the amount of sodium in your foods, changing the kind of fat and decreasing the amount of fat and cholesterol in your diet, the American Heart Association believes you can help for reduce your risk of developing heart disease. You may find it difficult to modify eating habits and change some cooking methods 3 that you have followed for many years. The first step is to take the salt shaker off the table. Then use this cookbook. It can help you. Remember that it is not intended to take the place of your doctor's instruction. Should you have any questions, ask your doctor or call your local Heart Association. HAPPY COOKING ! Source.https://www.industrydocuments.ucsi.edu/docsisqmf0227 3-a *IF you HAVE RECEIVED A LOW-SODIUM DIET INSTRUCTION FROM YOUR DOCTOR OR DIETITIAN. check your diet instruction against the recipe ingredients. To help you select the appropriate foods, some recipe ingredients are marked with an asterisk (*). These foods are available in an unsalted form. Follow the recipes using ingredients without salt only when they are specified in your diet instruction sheet. All recipes have been tested with unsalted ingredients. Source:https://www.industrydocuments.ucsi.edu/docsisqmf0227 4 WHEN YOU GO SHOPPING A diet lower in sodium can still taste good and be nutritionally complete. The key is to select a variety of foods which promote good health. Your daily food choices should include: no more than 6 to 8 ounces of lean meat, fish or poultry; other protein foods in place of meat, fish or poultry 4 or more servings of whole grain or enriched bread or cereal products 4 or more servings of fruit or vegetables (include 1 serving of citrus fruit or vegetable high in vitamin C and 1 serving of dark green, leafy or deep yellow vegetables) 2 or more servings of skim milk or low-fat milk products for adults; 3 to 4 servings for children or adolescents 2 to 3 tablespoons polyunsaturated fats and oils in the form of margarine, cooking oil and unsalted salad dressing With a little effort, you can learn to decrease the sodium, change the kind of fat and reduce the amount of fat and cholesterol in your diet. Begin with the recipes in this book. Then, adapt your own favorite recipes by omitting the salt and using the ingredient substitutions listed on pages . To save time later, you may wish to consider doubling the quantity of a recipe and freezing the unused portion. Spices, herbs and other flavorings add zest to a recipe and should be used instead of salt. Be adventurous and try some new flavor ideas. You may also want to ask your doctor about using a Source: https://www.industrydocuments.ucsf.edu/docs/sqm0227 5 salt substitute. If it is allowed, use it sparingly at the table, since salt substitutes tend to be bitter when used heavily. Most of the recipe ingredients called for in this cookbook are readily available in your local grocery store. Some, such as unsalted tomato paste and tomato puree, will be found in the usual section of the grocery store. Other unsalted foods can be found in a special diet section. If they are not in stock, your grocer can probably order them for you. MEAT AND OTHER PROTEIN FOODS For a balanced diet, everyone should eat some protein foods every day. To reduce your salt intake, these foods should include only unsalted fresh, frozen or canned lean meat, fish or poultry. Because even these contain cholesterol, it is especially important that they be limited to 6 to & ounces per day. All meats contain fat, but fish, poultry and veal contain smaller amounts of fat and should be eaten more frequently than other kinds of meat. By carefully selecting the meat you buy and by substituting other protein foods for meat, you can further reduce the fat in your diet. Dried beans, dried peas, soybeans, peanut butter and unsalted nuts may be substituted for meat or used as meat extenders. Dry cottage cheese made without added salt is another good substitute for meat because it is also low in fat. Most other cheeses contain significant amounts of salt, saturated fat and cholesterol. Although it is difficult to find cheese which is low in fat and also unsalted, you may be able to find a local dairy which makes it. ource. https./lwww.industrydocuments.ucsi.edu/docsisqmf0227 6 Surprisingly enough, egg whites may be used as a substitute for meat. Although egg yolks contain very large amounts of choles- terol, the whites contain neither cholesterol nor fat and may be used as often as you like. The American Heart Association recommends that you use no more than 3 egg yolks per week, including those used in cooking or baking. The recipe for No-Cholesterol Egg Substitute on page may be used as a substitute for some of your favorite egg dishes. SHOPPING FOR MEAT The best meats for you are those lean cuts that have less fat around the outside and less marbled fat throughout the meat. Your butcher will be glad to help you select the leanest cuts. The selection of ground beef deserves your special attention. Again, the leanest meat available is the best for you. A medium- to-bright red color signifies a low-fat content, while a light pink color indicates that excess fat has been ground in with the meat. An even better idea is to select a lean cut of meat and ask the butcher to trim it and grind it for you. This is usually done at no extra charge. When selecting chicken, remember that broilers and fryers are preferable because they contain the least amount of fat. We do not recommend the following meats and fish for frequent use because they contain large amounts of sodium, fat and/or cholesterol: 7 luncheon meats shrimp frankfurters smoked, cured or dried sausage meats including bacon spareribs and ham corned beef canned meat, fish or liver and other poultry, unless packed organ meats without salt MILK AND MILK PRODUCTS Everyone should have two or more servings of low-fat milk or milk products every day. Although milk and most milk products do not contain added salt (with the exception of buttermilk and cheese) , whole milk and products made from it contain significant amounts of cholesterol and saturated fats and should be avoided. Products from the following list can be substituted for whole milk products and are recommended because they are lower in fat and cholesterol. You'11 want to choose products fortified with vitamins A and D. skim milk, evaporated skim milk, non-fat dry milk Low-fat milk containing no more than 2 percent fat dry cottage cheese which has no salt added cheese made from skim or partially skim milk with no salt added low-fat yogurt or low-fat frozen yogurt ice milk and sherbets polyunsaturated non-dairy creamers or whiteners (Imitation sour cream, whipped topping and other non-dairy coffee whiteners contain saturated fat and are not recommended.) FRUITS AND VEGETABLES Everyone should have at least four servings of fruits and vegetables daily, including one serving of citrus fruit or vegetable 8 high in vitamin C and one serving of a dark green leafy or deep yellow vegetable. Fruit is great because it contains practically no sodium, no cholesterol and, except for the avocado, no fat. Fruits are low in calories and add vitamins, minerals and fiber to the diet. Plus, they make excellent snacks ! Eat any kind of fruit or juice you like -- fresh, frozen, canned or dried. Vegetables are also good for you because they contain no fat or cholesterol. Fresh vegetables and most frozen ones contain very little sodium and may be eaten as desired. You really should avoid buying canned or frozen vegetables that contain added salt, butter or sauces, but if you enjoy canning or freezing vegetables at home, you can get excellent results by leaving out the salt and following the usual processing directions. Vegetables which have been pickled or packed in brine, such as pickles or sauerkraut, contain extremely large amounts of salt and should not be eaten. BREADS AND CEREAL PRODUCTS Your balanced diet should include four or more servings of whole grain or enriched bread or cereal products. There are so many different kinds of bread on the market that it's really fun to experiment. Breads such as white, whole or cracked wheat, rye, French, Italian, pumpernickel and plain rolls are perfectly acceptable for you to eat although they contain some sodium and small amounts of fat. Soda crackers that don't have salt sprinkled on the top, matzo, melba toast and bread sticks also contain small amounts of sodium and fat but they, too, are acceptable and can 9 be included in your diet. Most other crackers contain large amounts of sodium and fat and you would be wise to avoid them. Commercial baked goods and mixes for muffins, biscuits, sweet rolls, cakes, cookies and pastries contain significant amounts of sodium and/or cholesterol and saturated fat. It would be much better to bake your own. You can either use the recipes in this cookbook or adjust your own favorite recipes by omitting the salt and using the ingredient substitutions on page . Cereals can be great for people trying to following a lower- sodium, fat-modified diet. Most do not contain saturated fat or cholesterol. Read the label and choose only those which contain recommended fats, page . Many cold cereals and instant hot cereals do contain some sodium, but they may be used in your diet. Other hot cereals as well as rice and pastas, such as spaghetti and macaroni, contain practically no sodium and are certainly acceptable; but do remember to omit the salt from the cooking water when preparing these foods. FATS AND OILS Polyunsaturated fats and oils are important elements in your One to two daily diet. Two to three tablespoons of polyunsaturated fat should be used daily. This can be in the form of unsalted salad dressing or margarine or oil used in cooking. Oils are cholesterol-free and do not contain sodium. Although low in cholesterol, mayonnaise and most margarines do contain some salt, but they are still acceptable for use. Other commercial salad dressings should be avoided because they contain large amounts of salt. Source: https://www.industrydocuments.ucsi.edu/docsisqmi0227 10 It is generally agreed that we all eat too much fat. It is, however, important to make changes not only in the amount of fat but in the kind of fat eaten. The chart below lists those fats which are recommended and those which are not recommended. RECOMMENDED Polyunsaturated: NOT RECOMMENDED Saturated : Safflower oil butter corn oil vegetable shortening cottonseed oil vegetable fat soybean oil bacon, salt pork sesame seed oil suet, lard sunflower seed oil chicken fat, meat fat polyunsaturated margarine coconut oil mayonnaise hydrogenated vegetable oil unsalted salad dressing palm kernel oil Foroccasionaluseonly: peanut oil olive oil What is a polyunsaturated margarine? Read the label to decide. SAMPLE LABEL BRAND X POLYUNSATURATED MARGARINE Nutrition Information Per Serving Serving size 14 grams (about 1 tbsp.) Servings per container 32 (per pound container) Calories 100 Protein 0 Carbohydrate 0 Fat 11 grams Percent of calories from fat over 99% Polyunsaturated 4 grams Saturated 2 grams Cholesterol 0 (0 per 100 grams) Here is how to use this information. Look at the amount of polyunsaturated and saturated fats: Source: https://www.industrydocuments.ucsi.edu/docsisqmi0227 11 IF THE MARGARINE CONTAINS THEN IT IS At least twice as much Recommended polyunsaturated as saturated fat Less than twice as much Not Recommended polyunsaturated as saturated fat To determine if the margarine is recommended or not recommended, divide the number of grams of polyunsaturated fat by the number of grams of saturated fat. If the answer is 2 or higher, the margarine is recommended. If a margarine does not contain a nutrition label, look for one that does. Manufacturers occasionally change product ingredients so read the label each time you select a product -- even if it's one you've used before. Label-reading can be helpful with many other products, too! BEVERAGES The following beverages are satisfactory for use since they contain insignificant amounts of fat or cholesterol and little or no sodium: water, skim milk, fruit juices, fruit drinks, coffee, tea, carbonated beverages, beer, table wine and alcohol. However, if you are trying to lose weight and need to limit calories, you may wish to avoid those beverages which give you calories without giving you nutritional value. Such drinks include: sugared carbonated beverages and fruit drinks, beer, wine and alcohol. Source. https://www.industrydocuments.ucsi.edu/docsisqmf0227 12 MISCELLANEOUS FOODS AND FLAVORINGS Many commonly used commercial seasonings and sauces contain significant amounts of sodium or salt and should not be used. These include flavorings such as soy sauce, Worcestershire sauce, steak sauce, catsup, chili sauce, monosodium glutamate, meat tenderizer, flavored seasoning salts and bouillon cubes. Commer- cial soups, olives, relishes, pickles and many snack foods also contain large amounts of salt and should not be used. Some of these products are made without salt and and are available commercially. Recipes are provided in this cookbook for catsup, chili sauce, soups, relish and pickles. Two common food ingredients which should be avoided because of their saturated fat content include chocolate candy and cocoa butter found in baking chocolate and chocolate chips. Unsweetened cocoa powder, however, may be used because most of the fat has been removed. Source: https://www.industrydocuments.ucsi.edu/docsisqmi0227 13 FLAVOR ADVENTURES Because most herbs, spices and table wines do not contain sodium, cholesterol or fat, they can be used in place of salt as seasonings. You will find that flavoring substances such as black pepper, onion, green pepper, garlic, lemon juice and vinegar complement and enhance the natural goodness of food. A word of caution, however, when using herbs and spices: use them sparingly because a little goes a long way. Remember, however, if you use fresh rather than dried herbs, use twice the amount. To keep a ready supply of seasonings on hand, try using a combination of herbs instead of salt in your salt shaker. You can make your own herb shaker by combining one-half teaspoon of cayenne pepper, one tablespoon of garlic powder and one teaspoon of each of the following ground seasonings: basil, marjoram, thyme, parsley, savory, mace, onion powder, black pepper and sage. You'11 find this combination of flavors a delightful enhancer of meats and vegetables in the kitchen or on the table. Table wines are fine to use in cooking but avoid flavoring your meats with "cooking wines" as they contain added salt. As with herbs, a little wine goes a long way. You can devise your own flavorful marinades by using wine, vinegar and oil or unsalted salad dressings. Lemon juice, Source: https://www.industrydocuments.ucsi.edu/docsisqmf0227 14 vinegar, Tabasco sauce or unsalted liquid smoke are also great for adding flavor to meats, soups and vegetables. You'11 find the following chart an excellent guide for flavor combinations MEAT Beef: Bay leaf, dry mustard powder, & FISH green pepper, marjoram, fresh & POULTRY mushrooms, nutmeg, onion, pepper, sage, thyme. Chicken : Green pepper, lemon juice, marjoram, fresh mushrooms, paprika, parsley, poultry seasoning, sage, thyme. Fish : Bay leaf, curry powder, dry mustard powder, green pepper, lemon juice, marjoram, fresh mushrooms, paprika. Lamb : Curry powder, garlic, mint, mint jelly, pineapple, rosemary. Pork: Apple, applesauce, garlic, onion, sage. Veal: Apricot, bay leaf, curry powder, ginger, marjoram, oregano. VEGETABLES Asparagus : Garlic, lemon juice, onion, vinegar. Corn: Green pepper, pimiento, fresh tomato. Cucumbers : Chives, dill, garlic, vinegar. Source.https:/iwww.industrydocuments.ucsi.edu/docsisqmf0227

What is the second topic?

sqmf0227

sqmf0227_p0, sqmf0227_p1, sqmf0227_p2, sqmf0227_p3, sqmf0227_p4, sqmf0227_p5, sqmf0227_p6, sqmf0227_p7, sqmf0227_p8, sqmf0227_p9, sqmf0227_p10, sqmf0227_p11, sqmf0227_p12, sqmf0227_p13, sqmf0227_p14, sqmf0227_p15, sqmf0227_p16

When you go shopping, When you go Shopping

Revised 8/31/77 Revised 9/29/77 COOKING WITHOUT YOUR SALT SHAKER AMERICAN HEART ASSOCIATION NORTHEAST OHIO AFFILIATE, INC. in cooperation with the Cleveland Dietetic Association C American Heart Association, Northeast Ohio Affiliate, Inc., 1977 Source: https./lwww.industrydocuments.ucsi.edu/docsisqmf0227 TABLE O F CONTENTS Page Welcome To Our Cookbook When You Go Shopping Flavor Adventures Ingredient Substitutions Recipes and Cooking Tips Entrees and Accompaniments Sandwiches Vegetables Salads and Salad Dressings Breads Soups and Sauces Desserts Happy Snacking! Recipe Index NOTE TO DOCTOR AND DIETITIAN: This cookbook is for the person who must mildly restrict his salt or sodium intake. However, the recipes can easily be adapted to a specific lower level of sodium to correspond with your diet instruction. An analysis for the nutrient composition of the recipes is available free of charge by sending a self-addressed, stamped envelope to the American Heart Association, North- east Ohio Affiliate, Inc. , 1689 East 115th Street, Cleveland, Ohio 44106. Source: https://www.industrydocuments.ucsf.edu/docs/sqmf0227 1 WELCOME TO OUR COOKBOOK Eating is a subject on which most people consider themselves experts because they' 've been doing it all their lives! Yet, many of us have been consuming too much sodium, too much fat and the wrong kind of fat. If you would like to cut down on the amount of sodium and fat in your diet or if your doctor has suggested a "low-salt," modified fat diet, then you'11 find this cookbook an excellent guide. If your doctor has given you specific instructions, you may still use the recipes in this book by adapting them to your own diet. THE WHY'S AND WHEREFORE'S OF SALT AND SODIUM To get down to basics, we need to understand what sodium is and the difference between salt and sodium. We all know what salt is. Sodium, however, is a mineral found in nature and in almost When it IS IN COMBINATION WITH ANOTHER ELEMENT, CHCORINE, all the food we eat. It is not the same as salt. Salt is nearly BECOMES IT USUAL half sodium and most of the sodium we eat comes from ordinary salt TABCE SALT used in cooking or at the table. Confused? You needn't be. Everyone needs some sodium to live. However, our need for sodium can be met without using salt because sodium is found naturally in so many foods. One of the most common reasons a doctor recommends cutting down on salt or sodium in the diet is to control high blood pressure. This is important because high blood pressure increases the risk of heart attack, stroke and kidney failure. There are many other reasons a doctor may advise decreasing salt or sodium intake. While the scientific evidence is not conclusive, studies show that it may be wise for all of us to cut down on our salt intake. For these reasons, none of the recipes in this cookbook contain added salt. WHAT ABOUT FAT AND CHOLESTEROL? In addition to lowering the sodium in your food, recipes and recommended numbers of servings have been chosen for this cookbook with a fat-modified, low-cholesterol diet in mind. The Heart Association recommends decreasing your intake of fat-laden and cholesterol-rich foods and also changing the kind of fat you use. There are two kinds of fat you should be especially concerned about: polyunsaturated and saturated. As you continue reading these pages, you will learn how to use polyunsaturated fats and how to decrease the saturated fat in your diet. You may also be pleasantly surprised to know that by cutting down on fats in your food and serving slightly smaller portions, you will be taking in fewer calories. An approximate calorie content for one serving accompanies each recipe. IN SUMMARY By reducing the amount of sodium in your foods, changing the kind of fat and decreasing the amount of fat and cholesterol in your diet, the American Heart Association believes you can help for reduce your risk of developing heart disease. You may find it difficult to modify eating habits and change some cooking methods 3 that you have followed for many years. The first step is to take the salt shaker off the table. Then use this cookbook. It can help you. Remember that it is not intended to take the place of your doctor's instruction. Should you have any questions, ask your doctor or call your local Heart Association. HAPPY COOKING ! Source.https://www.industrydocuments.ucsi.edu/docsisqmf0227 3-a *IF you HAVE RECEIVED A LOW-SODIUM DIET INSTRUCTION FROM YOUR DOCTOR OR DIETITIAN. check your diet instruction against the recipe ingredients. To help you select the appropriate foods, some recipe ingredients are marked with an asterisk (*). These foods are available in an unsalted form. Follow the recipes using ingredients without salt only when they are specified in your diet instruction sheet. All recipes have been tested with unsalted ingredients. Source:https://www.industrydocuments.ucsi.edu/docsisqmf0227 4 WHEN YOU GO SHOPPING A diet lower in sodium can still taste good and be nutritionally complete. The key is to select a variety of foods which promote good health. Your daily food choices should include: no more than 6 to 8 ounces of lean meat, fish or poultry; other protein foods in place of meat, fish or poultry 4 or more servings of whole grain or enriched bread or cereal products 4 or more servings of fruit or vegetables (include 1 serving of citrus fruit or vegetable high in vitamin C and 1 serving of dark green, leafy or deep yellow vegetables) 2 or more servings of skim milk or low-fat milk products for adults; 3 to 4 servings for children or adolescents 2 to 3 tablespoons polyunsaturated fats and oils in the form of margarine, cooking oil and unsalted salad dressing With a little effort, you can learn to decrease the sodium, change the kind of fat and reduce the amount of fat and cholesterol in your diet. Begin with the recipes in this book. Then, adapt your own favorite recipes by omitting the salt and using the ingredient substitutions listed on pages . To save time later, you may wish to consider doubling the quantity of a recipe and freezing the unused portion. Spices, herbs and other flavorings add zest to a recipe and should be used instead of salt. Be adventurous and try some new flavor ideas. You may also want to ask your doctor about using a Source: https://www.industrydocuments.ucsf.edu/docs/sqm0227 5 salt substitute. If it is allowed, use it sparingly at the table, since salt substitutes tend to be bitter when used heavily. Most of the recipe ingredients called for in this cookbook are readily available in your local grocery store. Some, such as unsalted tomato paste and tomato puree, will be found in the usual section of the grocery store. Other unsalted foods can be found in a special diet section. If they are not in stock, your grocer can probably order them for you. MEAT AND OTHER PROTEIN FOODS For a balanced diet, everyone should eat some protein foods every day. To reduce your salt intake, these foods should include only unsalted fresh, frozen or canned lean meat, fish or poultry. Because even these contain cholesterol, it is especially important that they be limited to 6 to & ounces per day. All meats contain fat, but fish, poultry and veal contain smaller amounts of fat and should be eaten more frequently than other kinds of meat. By carefully selecting the meat you buy and by substituting other protein foods for meat, you can further reduce the fat in your diet. Dried beans, dried peas, soybeans, peanut butter and unsalted nuts may be substituted for meat or used as meat extenders. Dry cottage cheese made without added salt is another good substitute for meat because it is also low in fat. Most other cheeses contain significant amounts of salt, saturated fat and cholesterol. Although it is difficult to find cheese which is low in fat and also unsalted, you may be able to find a local dairy which makes it. ource. https./lwww.industrydocuments.ucsi.edu/docsisqmf0227 6 Surprisingly enough, egg whites may be used as a substitute for meat. Although egg yolks contain very large amounts of choles- terol, the whites contain neither cholesterol nor fat and may be used as often as you like. The American Heart Association recommends that you use no more than 3 egg yolks per week, including those used in cooking or baking. The recipe for No-Cholesterol Egg Substitute on page may be used as a substitute for some of your favorite egg dishes. SHOPPING FOR MEAT The best meats for you are those lean cuts that have less fat around the outside and less marbled fat throughout the meat. Your butcher will be glad to help you select the leanest cuts. The selection of ground beef deserves your special attention. Again, the leanest meat available is the best for you. A medium- to-bright red color signifies a low-fat content, while a light pink color indicates that excess fat has been ground in with the meat. An even better idea is to select a lean cut of meat and ask the butcher to trim it and grind it for you. This is usually done at no extra charge. When selecting chicken, remember that broilers and fryers are preferable because they contain the least amount of fat. We do not recommend the following meats and fish for frequent use because they contain large amounts of sodium, fat and/or cholesterol: 7 luncheon meats shrimp frankfurters smoked, cured or dried sausage meats including bacon spareribs and ham corned beef canned meat, fish or liver and other poultry, unless packed organ meats without salt MILK AND MILK PRODUCTS Everyone should have two or more servings of low-fat milk or milk products every day. Although milk and most milk products do not contain added salt (with the exception of buttermilk and cheese) , whole milk and products made from it contain significant amounts of cholesterol and saturated fats and should be avoided. Products from the following list can be substituted for whole milk products and are recommended because they are lower in fat and cholesterol. You'11 want to choose products fortified with vitamins A and D. skim milk, evaporated skim milk, non-fat dry milk Low-fat milk containing no more than 2 percent fat dry cottage cheese which has no salt added cheese made from skim or partially skim milk with no salt added low-fat yogurt or low-fat frozen yogurt ice milk and sherbets polyunsaturated non-dairy creamers or whiteners (Imitation sour cream, whipped topping and other non-dairy coffee whiteners contain saturated fat and are not recommended.) FRUITS AND VEGETABLES Everyone should have at least four servings of fruits and vegetables daily, including one serving of citrus fruit or vegetable 8 high in vitamin C and one serving of a dark green leafy or deep yellow vegetable. Fruit is great because it contains practically no sodium, no cholesterol and, except for the avocado, no fat. Fruits are low in calories and add vitamins, minerals and fiber to the diet. Plus, they make excellent snacks ! Eat any kind of fruit or juice you like -- fresh, frozen, canned or dried. Vegetables are also good for you because they contain no fat or cholesterol. Fresh vegetables and most frozen ones contain very little sodium and may be eaten as desired. You really should avoid buying canned or frozen vegetables that contain added salt, butter or sauces, but if you enjoy canning or freezing vegetables at home, you can get excellent results by leaving out the salt and following the usual processing directions. Vegetables which have been pickled or packed in brine, such as pickles or sauerkraut, contain extremely large amounts of salt and should not be eaten. BREADS AND CEREAL PRODUCTS Your balanced diet should include four or more servings of whole grain or enriched bread or cereal products. There are so many different kinds of bread on the market that it's really fun to experiment. Breads such as white, whole or cracked wheat, rye, French, Italian, pumpernickel and plain rolls are perfectly acceptable for you to eat although they contain some sodium and small amounts of fat. Soda crackers that don't have salt sprinkled on the top, matzo, melba toast and bread sticks also contain small amounts of sodium and fat but they, too, are acceptable and can 9 be included in your diet. Most other crackers contain large amounts of sodium and fat and you would be wise to avoid them. Commercial baked goods and mixes for muffins, biscuits, sweet rolls, cakes, cookies and pastries contain significant amounts of sodium and/or cholesterol and saturated fat. It would be much better to bake your own. You can either use the recipes in this cookbook or adjust your own favorite recipes by omitting the salt and using the ingredient substitutions on page . Cereals can be great for people trying to following a lower- sodium, fat-modified diet. Most do not contain saturated fat or cholesterol. Read the label and choose only those which contain recommended fats, page . Many cold cereals and instant hot cereals do contain some sodium, but they may be used in your diet. Other hot cereals as well as rice and pastas, such as spaghetti and macaroni, contain practically no sodium and are certainly acceptable; but do remember to omit the salt from the cooking water when preparing these foods. FATS AND OILS Polyunsaturated fats and oils are important elements in your One to two daily diet. Two to three tablespoons of polyunsaturated fat should be used daily. This can be in the form of unsalted salad dressing or margarine or oil used in cooking. Oils are cholesterol-free and do not contain sodium. Although low in cholesterol, mayonnaise and most margarines do contain some salt, but they are still acceptable for use. Other commercial salad dressings should be avoided because they contain large amounts of salt. Source: https://www.industrydocuments.ucsi.edu/docsisqmi0227 10 It is generally agreed that we all eat too much fat. It is, however, important to make changes not only in the amount of fat but in the kind of fat eaten. The chart below lists those fats which are recommended and those which are not recommended. RECOMMENDED Polyunsaturated: NOT RECOMMENDED Saturated : Safflower oil butter corn oil vegetable shortening cottonseed oil vegetable fat soybean oil bacon, salt pork sesame seed oil suet, lard sunflower seed oil chicken fat, meat fat polyunsaturated margarine coconut oil mayonnaise hydrogenated vegetable oil unsalted salad dressing palm kernel oil Foroccasionaluseonly: peanut oil olive oil What is a polyunsaturated margarine? Read the label to decide. SAMPLE LABEL BRAND X POLYUNSATURATED MARGARINE Nutrition Information Per Serving Serving size 14 grams (about 1 tbsp.) Servings per container 32 (per pound container) Calories 100 Protein 0 Carbohydrate 0 Fat 11 grams Percent of calories from fat over 99% Polyunsaturated 4 grams Saturated 2 grams Cholesterol 0 (0 per 100 grams) Here is how to use this information. Look at the amount of polyunsaturated and saturated fats: Source: https://www.industrydocuments.ucsi.edu/docsisqmi0227 11 IF THE MARGARINE CONTAINS THEN IT IS At least twice as much Recommended polyunsaturated as saturated fat Less than twice as much Not Recommended polyunsaturated as saturated fat To determine if the margarine is recommended or not recommended, divide the number of grams of polyunsaturated fat by the number of grams of saturated fat. If the answer is 2 or higher, the margarine is recommended. If a margarine does not contain a nutrition label, look for one that does. Manufacturers occasionally change product ingredients so read the label each time you select a product -- even if it's one you've used before. Label-reading can be helpful with many other products, too! BEVERAGES The following beverages are satisfactory for use since they contain insignificant amounts of fat or cholesterol and little or no sodium: water, skim milk, fruit juices, fruit drinks, coffee, tea, carbonated beverages, beer, table wine and alcohol. However, if you are trying to lose weight and need to limit calories, you may wish to avoid those beverages which give you calories without giving you nutritional value. Such drinks include: sugared carbonated beverages and fruit drinks, beer, wine and alcohol. Source. https://www.industrydocuments.ucsi.edu/docsisqmf0227 12 MISCELLANEOUS FOODS AND FLAVORINGS Many commonly used commercial seasonings and sauces contain significant amounts of sodium or salt and should not be used. These include flavorings such as soy sauce, Worcestershire sauce, steak sauce, catsup, chili sauce, monosodium glutamate, meat tenderizer, flavored seasoning salts and bouillon cubes. Commer- cial soups, olives, relishes, pickles and many snack foods also contain large amounts of salt and should not be used. Some of these products are made without salt and and are available commercially. Recipes are provided in this cookbook for catsup, chili sauce, soups, relish and pickles. Two common food ingredients which should be avoided because of their saturated fat content include chocolate candy and cocoa butter found in baking chocolate and chocolate chips. Unsweetened cocoa powder, however, may be used because most of the fat has been removed. Source: https://www.industrydocuments.ucsi.edu/docsisqmi0227 13 FLAVOR ADVENTURES Because most herbs, spices and table wines do not contain sodium, cholesterol or fat, they can be used in place of salt as seasonings. You will find that flavoring substances such as black pepper, onion, green pepper, garlic, lemon juice and vinegar complement and enhance the natural goodness of food. A word of caution, however, when using herbs and spices: use them sparingly because a little goes a long way. Remember, however, if you use fresh rather than dried herbs, use twice the amount. To keep a ready supply of seasonings on hand, try using a combination of herbs instead of salt in your salt shaker. You can make your own herb shaker by combining one-half teaspoon of cayenne pepper, one tablespoon of garlic powder and one teaspoon of each of the following ground seasonings: basil, marjoram, thyme, parsley, savory, mace, onion powder, black pepper and sage. You'11 find this combination of flavors a delightful enhancer of meats and vegetables in the kitchen or on the table. Table wines are fine to use in cooking but avoid flavoring your meats with "cooking wines" as they contain added salt. As with herbs, a little wine goes a long way. You can devise your own flavorful marinades by using wine, vinegar and oil or unsalted salad dressings. Lemon juice, Source: https://www.industrydocuments.ucsi.edu/docsisqmf0227 14 vinegar, Tabasco sauce or unsalted liquid smoke are also great for adding flavor to meats, soups and vegetables. You'11 find the following chart an excellent guide for flavor combinations MEAT Beef: Bay leaf, dry mustard powder, & FISH green pepper, marjoram, fresh & POULTRY mushrooms, nutmeg, onion, pepper, sage, thyme. Chicken : Green pepper, lemon juice, marjoram, fresh mushrooms, paprika, parsley, poultry seasoning, sage, thyme. Fish : Bay leaf, curry powder, dry mustard powder, green pepper, lemon juice, marjoram, fresh mushrooms, paprika. Lamb : Curry powder, garlic, mint, mint jelly, pineapple, rosemary. Pork: Apple, applesauce, garlic, onion, sage. Veal: Apricot, bay leaf, curry powder, ginger, marjoram, oregano. VEGETABLES Asparagus : Garlic, lemon juice, onion, vinegar. Corn: Green pepper, pimiento, fresh tomato. Cucumbers : Chives, dill, garlic, vinegar. Source.https:/iwww.industrydocuments.ucsi.edu/docsisqmf0227

What is the third topic?

sqmf0227

sqmf0227_p0, sqmf0227_p1, sqmf0227_p2, sqmf0227_p3, sqmf0227_p4, sqmf0227_p5, sqmf0227_p6, sqmf0227_p7, sqmf0227_p8, sqmf0227_p9, sqmf0227_p10, sqmf0227_p11, sqmf0227_p12, sqmf0227_p13, sqmf0227_p14, sqmf0227_p15, sqmf0227_p16

Flavor Adventures

Revised 8/31/77 Revised 9/29/77 COOKING WITHOUT YOUR SALT SHAKER AMERICAN HEART ASSOCIATION NORTHEAST OHIO AFFILIATE, INC. in cooperation with the Cleveland Dietetic Association C American Heart Association, Northeast Ohio Affiliate, Inc., 1977 Source: https./lwww.industrydocuments.ucsi.edu/docsisqmf0227 TABLE O F CONTENTS Page Welcome To Our Cookbook When You Go Shopping Flavor Adventures Ingredient Substitutions Recipes and Cooking Tips Entrees and Accompaniments Sandwiches Vegetables Salads and Salad Dressings Breads Soups and Sauces Desserts Happy Snacking! Recipe Index NOTE TO DOCTOR AND DIETITIAN: This cookbook is for the person who must mildly restrict his salt or sodium intake. However, the recipes can easily be adapted to a specific lower level of sodium to correspond with your diet instruction. An analysis for the nutrient composition of the recipes is available free of charge by sending a self-addressed, stamped envelope to the American Heart Association, North- east Ohio Affiliate, Inc. , 1689 East 115th Street, Cleveland, Ohio 44106. Source: https://www.industrydocuments.ucsf.edu/docs/sqmf0227 1 WELCOME TO OUR COOKBOOK Eating is a subject on which most people consider themselves experts because they' 've been doing it all their lives! Yet, many of us have been consuming too much sodium, too much fat and the wrong kind of fat. If you would like to cut down on the amount of sodium and fat in your diet or if your doctor has suggested a "low-salt," modified fat diet, then you'11 find this cookbook an excellent guide. If your doctor has given you specific instructions, you may still use the recipes in this book by adapting them to your own diet. THE WHY'S AND WHEREFORE'S OF SALT AND SODIUM To get down to basics, we need to understand what sodium is and the difference between salt and sodium. We all know what salt is. Sodium, however, is a mineral found in nature and in almost When it IS IN COMBINATION WITH ANOTHER ELEMENT, CHCORINE, all the food we eat. It is not the same as salt. Salt is nearly BECOMES IT USUAL half sodium and most of the sodium we eat comes from ordinary salt TABCE SALT used in cooking or at the table. Confused? You needn't be. Everyone needs some sodium to live. However, our need for sodium can be met without using salt because sodium is found naturally in so many foods. One of the most common reasons a doctor recommends cutting down on salt or sodium in the diet is to control high blood pressure. This is important because high blood pressure increases the risk of heart attack, stroke and kidney failure. There are many other reasons a doctor may advise decreasing salt or sodium intake. While the scientific evidence is not conclusive, studies show that it may be wise for all of us to cut down on our salt intake. For these reasons, none of the recipes in this cookbook contain added salt. WHAT ABOUT FAT AND CHOLESTEROL? In addition to lowering the sodium in your food, recipes and recommended numbers of servings have been chosen for this cookbook with a fat-modified, low-cholesterol diet in mind. The Heart Association recommends decreasing your intake of fat-laden and cholesterol-rich foods and also changing the kind of fat you use. There are two kinds of fat you should be especially concerned about: polyunsaturated and saturated. As you continue reading these pages, you will learn how to use polyunsaturated fats and how to decrease the saturated fat in your diet. You may also be pleasantly surprised to know that by cutting down on fats in your food and serving slightly smaller portions, you will be taking in fewer calories. An approximate calorie content for one serving accompanies each recipe. IN SUMMARY By reducing the amount of sodium in your foods, changing the kind of fat and decreasing the amount of fat and cholesterol in your diet, the American Heart Association believes you can help for reduce your risk of developing heart disease. You may find it difficult to modify eating habits and change some cooking methods 3 that you have followed for many years. The first step is to take the salt shaker off the table. Then use this cookbook. It can help you. Remember that it is not intended to take the place of your doctor's instruction. Should you have any questions, ask your doctor or call your local Heart Association. HAPPY COOKING ! Source.https://www.industrydocuments.ucsi.edu/docsisqmf0227 3-a *IF you HAVE RECEIVED A LOW-SODIUM DIET INSTRUCTION FROM YOUR DOCTOR OR DIETITIAN. check your diet instruction against the recipe ingredients. To help you select the appropriate foods, some recipe ingredients are marked with an asterisk (*). These foods are available in an unsalted form. Follow the recipes using ingredients without salt only when they are specified in your diet instruction sheet. All recipes have been tested with unsalted ingredients. Source:https://www.industrydocuments.ucsi.edu/docsisqmf0227 4 WHEN YOU GO SHOPPING A diet lower in sodium can still taste good and be nutritionally complete. The key is to select a variety of foods which promote good health. Your daily food choices should include: no more than 6 to 8 ounces of lean meat, fish or poultry; other protein foods in place of meat, fish or poultry 4 or more servings of whole grain or enriched bread or cereal products 4 or more servings of fruit or vegetables (include 1 serving of citrus fruit or vegetable high in vitamin C and 1 serving of dark green, leafy or deep yellow vegetables) 2 or more servings of skim milk or low-fat milk products for adults; 3 to 4 servings for children or adolescents 2 to 3 tablespoons polyunsaturated fats and oils in the form of margarine, cooking oil and unsalted salad dressing With a little effort, you can learn to decrease the sodium, change the kind of fat and reduce the amount of fat and cholesterol in your diet. Begin with the recipes in this book. Then, adapt your own favorite recipes by omitting the salt and using the ingredient substitutions listed on pages . To save time later, you may wish to consider doubling the quantity of a recipe and freezing the unused portion. Spices, herbs and other flavorings add zest to a recipe and should be used instead of salt. Be adventurous and try some new flavor ideas. You may also want to ask your doctor about using a Source: https://www.industrydocuments.ucsf.edu/docs/sqm0227 5 salt substitute. If it is allowed, use it sparingly at the table, since salt substitutes tend to be bitter when used heavily. Most of the recipe ingredients called for in this cookbook are readily available in your local grocery store. Some, such as unsalted tomato paste and tomato puree, will be found in the usual section of the grocery store. Other unsalted foods can be found in a special diet section. If they are not in stock, your grocer can probably order them for you. MEAT AND OTHER PROTEIN FOODS For a balanced diet, everyone should eat some protein foods every day. To reduce your salt intake, these foods should include only unsalted fresh, frozen or canned lean meat, fish or poultry. Because even these contain cholesterol, it is especially important that they be limited to 6 to & ounces per day. All meats contain fat, but fish, poultry and veal contain smaller amounts of fat and should be eaten more frequently than other kinds of meat. By carefully selecting the meat you buy and by substituting other protein foods for meat, you can further reduce the fat in your diet. Dried beans, dried peas, soybeans, peanut butter and unsalted nuts may be substituted for meat or used as meat extenders. Dry cottage cheese made without added salt is another good substitute for meat because it is also low in fat. Most other cheeses contain significant amounts of salt, saturated fat and cholesterol. Although it is difficult to find cheese which is low in fat and also unsalted, you may be able to find a local dairy which makes it. ource. https./lwww.industrydocuments.ucsi.edu/docsisqmf0227 6 Surprisingly enough, egg whites may be used as a substitute for meat. Although egg yolks contain very large amounts of choles- terol, the whites contain neither cholesterol nor fat and may be used as often as you like. The American Heart Association recommends that you use no more than 3 egg yolks per week, including those used in cooking or baking. The recipe for No-Cholesterol Egg Substitute on page may be used as a substitute for some of your favorite egg dishes. SHOPPING FOR MEAT The best meats for you are those lean cuts that have less fat around the outside and less marbled fat throughout the meat. Your butcher will be glad to help you select the leanest cuts. The selection of ground beef deserves your special attention. Again, the leanest meat available is the best for you. A medium- to-bright red color signifies a low-fat content, while a light pink color indicates that excess fat has been ground in with the meat. An even better idea is to select a lean cut of meat and ask the butcher to trim it and grind it for you. This is usually done at no extra charge. When selecting chicken, remember that broilers and fryers are preferable because they contain the least amount of fat. We do not recommend the following meats and fish for frequent use because they contain large amounts of sodium, fat and/or cholesterol: 7 luncheon meats shrimp frankfurters smoked, cured or dried sausage meats including bacon spareribs and ham corned beef canned meat, fish or liver and other poultry, unless packed organ meats without salt MILK AND MILK PRODUCTS Everyone should have two or more servings of low-fat milk or milk products every day. Although milk and most milk products do not contain added salt (with the exception of buttermilk and cheese) , whole milk and products made from it contain significant amounts of cholesterol and saturated fats and should be avoided. Products from the following list can be substituted for whole milk products and are recommended because they are lower in fat and cholesterol. You'11 want to choose products fortified with vitamins A and D. skim milk, evaporated skim milk, non-fat dry milk Low-fat milk containing no more than 2 percent fat dry cottage cheese which has no salt added cheese made from skim or partially skim milk with no salt added low-fat yogurt or low-fat frozen yogurt ice milk and sherbets polyunsaturated non-dairy creamers or whiteners (Imitation sour cream, whipped topping and other non-dairy coffee whiteners contain saturated fat and are not recommended.) FRUITS AND VEGETABLES Everyone should have at least four servings of fruits and vegetables daily, including one serving of citrus fruit or vegetable 8 high in vitamin C and one serving of a dark green leafy or deep yellow vegetable. Fruit is great because it contains practically no sodium, no cholesterol and, except for the avocado, no fat. Fruits are low in calories and add vitamins, minerals and fiber to the diet. Plus, they make excellent snacks ! Eat any kind of fruit or juice you like -- fresh, frozen, canned or dried. Vegetables are also good for you because they contain no fat or cholesterol. Fresh vegetables and most frozen ones contain very little sodium and may be eaten as desired. You really should avoid buying canned or frozen vegetables that contain added salt, butter or sauces, but if you enjoy canning or freezing vegetables at home, you can get excellent results by leaving out the salt and following the usual processing directions. Vegetables which have been pickled or packed in brine, such as pickles or sauerkraut, contain extremely large amounts of salt and should not be eaten. BREADS AND CEREAL PRODUCTS Your balanced diet should include four or more servings of whole grain or enriched bread or cereal products. There are so many different kinds of bread on the market that it's really fun to experiment. Breads such as white, whole or cracked wheat, rye, French, Italian, pumpernickel and plain rolls are perfectly acceptable for you to eat although they contain some sodium and small amounts of fat. Soda crackers that don't have salt sprinkled on the top, matzo, melba toast and bread sticks also contain small amounts of sodium and fat but they, too, are acceptable and can 9 be included in your diet. Most other crackers contain large amounts of sodium and fat and you would be wise to avoid them. Commercial baked goods and mixes for muffins, biscuits, sweet rolls, cakes, cookies and pastries contain significant amounts of sodium and/or cholesterol and saturated fat. It would be much better to bake your own. You can either use the recipes in this cookbook or adjust your own favorite recipes by omitting the salt and using the ingredient substitutions on page . Cereals can be great for people trying to following a lower- sodium, fat-modified diet. Most do not contain saturated fat or cholesterol. Read the label and choose only those which contain recommended fats, page . Many cold cereals and instant hot cereals do contain some sodium, but they may be used in your diet. Other hot cereals as well as rice and pastas, such as spaghetti and macaroni, contain practically no sodium and are certainly acceptable; but do remember to omit the salt from the cooking water when preparing these foods. FATS AND OILS Polyunsaturated fats and oils are important elements in your One to two daily diet. Two to three tablespoons of polyunsaturated fat should be used daily. This can be in the form of unsalted salad dressing or margarine or oil used in cooking. Oils are cholesterol-free and do not contain sodium. Although low in cholesterol, mayonnaise and most margarines do contain some salt, but they are still acceptable for use. Other commercial salad dressings should be avoided because they contain large amounts of salt. Source: https://www.industrydocuments.ucsi.edu/docsisqmi0227 10 It is generally agreed that we all eat too much fat. It is, however, important to make changes not only in the amount of fat but in the kind of fat eaten. The chart below lists those fats which are recommended and those which are not recommended. RECOMMENDED Polyunsaturated: NOT RECOMMENDED Saturated : Safflower oil butter corn oil vegetable shortening cottonseed oil vegetable fat soybean oil bacon, salt pork sesame seed oil suet, lard sunflower seed oil chicken fat, meat fat polyunsaturated margarine coconut oil mayonnaise hydrogenated vegetable oil unsalted salad dressing palm kernel oil Foroccasionaluseonly: peanut oil olive oil What is a polyunsaturated margarine? Read the label to decide. SAMPLE LABEL BRAND X POLYUNSATURATED MARGARINE Nutrition Information Per Serving Serving size 14 grams (about 1 tbsp.) Servings per container 32 (per pound container) Calories 100 Protein 0 Carbohydrate 0 Fat 11 grams Percent of calories from fat over 99% Polyunsaturated 4 grams Saturated 2 grams Cholesterol 0 (0 per 100 grams) Here is how to use this information. Look at the amount of polyunsaturated and saturated fats: Source: https://www.industrydocuments.ucsi.edu/docsisqmi0227 11 IF THE MARGARINE CONTAINS THEN IT IS At least twice as much Recommended polyunsaturated as saturated fat Less than twice as much Not Recommended polyunsaturated as saturated fat To determine if the margarine is recommended or not recommended, divide the number of grams of polyunsaturated fat by the number of grams of saturated fat. If the answer is 2 or higher, the margarine is recommended. If a margarine does not contain a nutrition label, look for one that does. Manufacturers occasionally change product ingredients so read the label each time you select a product -- even if it's one you've used before. Label-reading can be helpful with many other products, too! BEVERAGES The following beverages are satisfactory for use since they contain insignificant amounts of fat or cholesterol and little or no sodium: water, skim milk, fruit juices, fruit drinks, coffee, tea, carbonated beverages, beer, table wine and alcohol. However, if you are trying to lose weight and need to limit calories, you may wish to avoid those beverages which give you calories without giving you nutritional value. Such drinks include: sugared carbonated beverages and fruit drinks, beer, wine and alcohol. Source. https://www.industrydocuments.ucsi.edu/docsisqmf0227 12 MISCELLANEOUS FOODS AND FLAVORINGS Many commonly used commercial seasonings and sauces contain significant amounts of sodium or salt and should not be used. These include flavorings such as soy sauce, Worcestershire sauce, steak sauce, catsup, chili sauce, monosodium glutamate, meat tenderizer, flavored seasoning salts and bouillon cubes. Commer- cial soups, olives, relishes, pickles and many snack foods also contain large amounts of salt and should not be used. Some of these products are made without salt and and are available commercially. Recipes are provided in this cookbook for catsup, chili sauce, soups, relish and pickles. Two common food ingredients which should be avoided because of their saturated fat content include chocolate candy and cocoa butter found in baking chocolate and chocolate chips. Unsweetened cocoa powder, however, may be used because most of the fat has been removed. Source: https://www.industrydocuments.ucsi.edu/docsisqmi0227 13 FLAVOR ADVENTURES Because most herbs, spices and table wines do not contain sodium, cholesterol or fat, they can be used in place of salt as seasonings. You will find that flavoring substances such as black pepper, onion, green pepper, garlic, lemon juice and vinegar complement and enhance the natural goodness of food. A word of caution, however, when using herbs and spices: use them sparingly because a little goes a long way. Remember, however, if you use fresh rather than dried herbs, use twice the amount. To keep a ready supply of seasonings on hand, try using a combination of herbs instead of salt in your salt shaker. You can make your own herb shaker by combining one-half teaspoon of cayenne pepper, one tablespoon of garlic powder and one teaspoon of each of the following ground seasonings: basil, marjoram, thyme, parsley, savory, mace, onion powder, black pepper and sage. You'11 find this combination of flavors a delightful enhancer of meats and vegetables in the kitchen or on the table. Table wines are fine to use in cooking but avoid flavoring your meats with "cooking wines" as they contain added salt. As with herbs, a little wine goes a long way. You can devise your own flavorful marinades by using wine, vinegar and oil or unsalted salad dressings. Lemon juice, Source: https://www.industrydocuments.ucsi.edu/docsisqmf0227 14 vinegar, Tabasco sauce or unsalted liquid smoke are also great for adding flavor to meats, soups and vegetables. You'11 find the following chart an excellent guide for flavor combinations MEAT Beef: Bay leaf, dry mustard powder, & FISH green pepper, marjoram, fresh & POULTRY mushrooms, nutmeg, onion, pepper, sage, thyme. Chicken : Green pepper, lemon juice, marjoram, fresh mushrooms, paprika, parsley, poultry seasoning, sage, thyme. Fish : Bay leaf, curry powder, dry mustard powder, green pepper, lemon juice, marjoram, fresh mushrooms, paprika. Lamb : Curry powder, garlic, mint, mint jelly, pineapple, rosemary. Pork: Apple, applesauce, garlic, onion, sage. Veal: Apricot, bay leaf, curry powder, ginger, marjoram, oregano. VEGETABLES Asparagus : Garlic, lemon juice, onion, vinegar. Corn: Green pepper, pimiento, fresh tomato. Cucumbers : Chives, dill, garlic, vinegar. Source.https:/iwww.industrydocuments.ucsi.edu/docsisqmf0227

What is the date mentioned at the bottom of the document?

yrvg0227

yrvg0227_p0

3/17/77

MISSOURI MEDICAID Prior to September 1, 1974, the Visiting Nurse Association was paid as follows: RN visit $10.00 - Both subject to a 12 visit maximum LPN visit 8.00 in a 90 day period. No other service covered. Did not pay for supplies or equipment. September 1, 1974 until November 23, 1976. RN/LPN visit - our nursing visit cost per the most recent Medicare cost report, with a maximum of 24 visits in a 90 day period. No other service covered. Did not pay for supplies or equipment. November 23, 1976 RN/LPN - our most recent Medicare cost HHA - now covered at our most recent Medicare cost. Both of the above are subject to a maximum of 24 total visits in a 90 day period. Supplies and equipment - now covered providing we have prior approval from the state. The details and the form are "still at the printer". Receipts by VNA 1973 10,464 1974 7,847 1975 15,425 1976 67,171 Obviously the program has drastically improved for VNA, however, 27% of service rendered Medicaid patients in 1976 was not paid for by Medicaid. Of those services covered, only 78% were paid for by Medicaid because of the 24 visit limitation. If Medicaid was a total service it is estimated that the VNA would received some additional $75,000 thereby decreasing the need for United Way monies. WNJ:rp 3/17/77 Source: https://www.industrydocuments.ucst.edu/docs/yrvg227

What is the first date mentioned in the document?

yrvg0227

yrvg0227_p0

September 1, 1974

MISSOURI MEDICAID Prior to September 1, 1974, the Visiting Nurse Association was paid as follows: RN visit $10.00 - Both subject to a 12 visit maximum LPN visit 8.00 in a 90 day period. No other service covered. Did not pay for supplies or equipment. September 1, 1974 until November 23, 1976. RN/LPN visit - our nursing visit cost per the most recent Medicare cost report, with a maximum of 24 visits in a 90 day period. No other service covered. Did not pay for supplies or equipment. November 23, 1976 RN/LPN - our most recent Medicare cost HHA - now covered at our most recent Medicare cost. Both of the above are subject to a maximum of 24 total visits in a 90 day period. Supplies and equipment - now covered providing we have prior approval from the state. The details and the form are "still at the printer". Receipts by VNA 1973 10,464 1974 7,847 1975 15,425 1976 67,171 Obviously the program has drastically improved for VNA, however, 27% of service rendered Medicaid patients in 1976 was not paid for by Medicaid. Of those services covered, only 78% were paid for by Medicaid because of the 24 visit limitation. If Medicaid was a total service it is estimated that the VNA would received some additional $75,000 thereby decreasing the need for United Way monies. WNJ:rp 3/17/77 Source: https://www.industrydocuments.ucst.edu/docs/yrvg227

What is the full form of OTA?

rlnf0227

rlnf0227_p0, rlnf0227_p1, rlnf0227_p2, rlnf0227_p3, rlnf0227_p4, rlnf0227_p5, rlnf0227_p6, rlnf0227_p7, rlnf0227_p8, rlnf0227_p9, rlnf0227_p10, rlnf0227_p11, rlnf0227_p12, rlnf0227_p13, rlnf0227_p14, rlnf0227_p15, rlnf0227_p16, rlnf0227_p17, rlnf0227_p18, rlnf0227_p19, rlnf0227_p20

Office of Technology Assessment

Research Allemalives 880 III CONGRESS OF THE UNITED STATES Office of Technology Assessment WASHINGTON D. C. 20510 Source: https://www.industrydocuments.ucsf.edu/docs/rInf0227 Nuirition Research Alternatives DLA CONGRESS OF THE UNITED STATES Office of Technology Assessment WASHINGTON. D. C. 20510 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Library of Congress Catalog Card Number 78-600116 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, D.C. 20402 Stock No. 052-003-00596-4 ii Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 FOREWORD This assessment is an analysis of nutrition research alternatives- alternative goals and priorities, alternative definitions and funding, and alter- native research personnel requirements. Its principal finding is that Federal human nutrition research programs have failed to deal with the changing health problems of the American people. Possibly the most productive and important area of nutrition research will be the identification of specific dietary links to chronic diseases, leading to methods for prevention. The late Senator Hubert H. Humphrey, member of the Technology Assess- ment Board, requested the assessment to provide guidance to Congress in over- sight of the executive agencies conducting human nutrition research. The study was conducted by the staff of the OTA food program with the assistance of the OTA Food Advisory Committee and the Advisory Panel on Human Nutrition Research. The resulting report is a synthesis and does not necessarily reflect the position of any individual. Russell W. Peterson RUSSELL W. PETERSON Director Office of Technology Assessment iii Source: ttps://wvww.industrydocuments.ucsf.edu/docs/rinf0227 OTA Food Program Staff J.B. Cordaro, Food Program Manager Catherine E. Woteki, Nutrition Cluster Leader Phyllis Balan, Administrative Secretary Reita Crossen, Secretary Ann Woodbridge, Administrative Assistant OTA Publishing Staff John C. Holmes, Publishing Officer Kathie S. Boss Joanne Heming V Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 OTA Food Advisory Committee Martin E. Abel, Chairman Senior Vice President, Schnittker Associates Johanna Dwyer, Vice Chairman Frances Stern Nutrition Center, New England Medical Center David Call Laura Heuser R. Dennis Rouse Director of Cooperative Member, Board of Directors Dean, School of Agriculture Extension Agricultural Council of America Auburn University Cornell University Arnold Mayer Lauren Soth Cy Carpenter Legislative Representative Agricultural Consultant President Amalgamated Meat Cutters and Thomas Sporleder Minnesota Farmers Union Butcher Workmen of North Professor of Agricultural Eliot Coleman America Economics Director, Coolidge Center for the Max Milner Texas A&M University Study of Agriculture Associate Director Sylvan Wittwer Almeta Edwards Fleming International Nutrition Planning Director and Assistant Dean Social Program Coordinator Program College of Agriculture and Florence County, S.C. Massachusetts Institute of Natural Resources Technology Michigan State University Lorne Greene Chairman of the Board Robert O. Nesheim American Freedom From Vice President, Science and Hunger Foundation Technology The Quaker Oats Company Richard L. Hall Vice President, Science and Kathleen O'Reilly Technology Director McCormick & Company, Inc. Consumer Federation of America OTA Steering Panel on Human Nutrition Research Johanna Dwyer, Chairman Frances Stern Nutrition Center, New England Medical Center Howard Bauman Robert Harkins Margaret McConnell Science and Technology Grocery Manufacturers of Society for Nutrition Education The Pillsbury Company America, Inc. Mark Hegsted Malden C. Nesheim Ellen Haas School of Public Health Division of Nutritional Sciences Community Nutrition Institute Harvard University Cornell University vi Source: https://lwww.industrydocuments.ucsf.edu/docs/rinf0227 Manuscript Review Panel Sol Chafkin Hamish Munro Bernard Schweigert Office of Social Development Department of Nutrition and Department of Food Science Ford Foundation Food Science and Technology Massachusetts Institute of University of California at Joan Gussow Technology Davis Program in Nutrition Teachers College Columbia University Consultants Alice Lichtenstein Patricia Kearney Samuel Iker Department of Nutrition Frances Stern Nutrition Center Iker Associates. Inc. Harvard University New England Medical Center vii Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Workshop Participants M Dale F. Anderson* Ruth Hueneman* Arnold Schaefer* F: Quality Control Public Health Nutrition Swanson Center for N. General Mills University of California at Nutrition, Inc. Berkeley jo Jane Armstrong* Kenneth Schlossberg* L Consumer Affairs Jacob Jacoby* ** Schlossberg-Cassidy Associates Jewell Companies, Inc. Psychological Sciences O: Purdue University Kathleene D. Sheekey* James Carroll* Consumer Federation of America El Department of Public Norge Jerome** Ci Administration Community Health Sheila Sidles* Syracuse University University of Kansas Medical Iowa Consumers League U Center Gerald Cassidy* ** Bruce Stillings*: T Schlosberg-Cassidy Associates Ogden C. Johnson* * Corporate Research A Hershey Foods Activities Samuel J. Fomon*: U. Nabisco, Inc. Pediatrics Department Paul Lachance* * University of Iowa Food Science Department Albert Stunkard*1 Rutgers University Department of Psychiatry D. James D. Grant** University of Pennsylvania Research and Development Alex Malaspina* Medical School CPC International Inc. External Technical Affairs The Coca-Cola Company Janet Tenney* ** Harry L. Greene** Office of Consumer Affairs Pediatrics, Biochemistry, Josephine Martin* Giant Food, Inc. and Nutrition School Food & Nutrition Section Vanderbilt Medical Center Georgia District of Reinhardt Thiessen, Jr.* C: Vanderbilt University Education Nutrition General Foods Helen Guthrie* Robert) J. McEwen, S.J. * Nutrition Department Economics Department Ed Traisman* Pennsylvania State University Boston College McDonald's, Inc. Richard Hall* Max Milner* James Turner, Esq.* McCormick & Company, Inc. International Nutrition Planning Swankin & Turner Program James Halpin Stanley Wilson* Massachusetts Institute of Southern Region Alabama Agricultural Technology Agricultural Experiment Station Experiment Station Clemson University Robert Nesheim* Beverly Winikoff* Science and Technology Gaurth Hansen* Rockefeller Foundation The Quaker Oats Company Biochemistry & Nutrition Utah State University S. J. Ritchey* * Virginia Polytechnic Institute La Vell Henderson* and State University Department of Biochemistry University of Minnesota Arthur J. Salisbury* National Foundation March of Dimes *Newport News Workshop, Nov. 28-29, 1977 *Boston Workshop, Sept. 28-30, 1977 viii Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Agency Personnel Responding to Questionnaires or Interviewed by OTA Staff Myrtle Brown James H. Iacono Dorothy Pringle Food and Nutrition Board Agricultural Research Service Cooperative State Research National Academy of Sciences U.S. Department of Agriculture Service U.S. Department of John E. Canham Evelyn Johnson Agriculture Letterman Army Institute of Extension Service Research U.S. Department of Agriculture Miloslave Rechcigl Office of the Surgeon General Bureau for Technical Samuel Kahn Assistance Elizabeth Davis Bureau of Technical Agency for International Cooperative State Research Assistance Development Service Agency for International Department of State U.S. Department of Agriculture Development Department of State Howerde E. Sauberlich T.M. Edminister Letterman Army Institute of Agricultural Research Service Nancy Leidenfrost Research U.S. Department of Agriculture Extension Service Office of the Surgeon General U.S. Department of Agriculture Mary Egan Neil Schaller Health Services Administration Robert Leyton Extension Service Department of Health, Education, Medical Research Service U.S. Department of and Welfare Veterans Administration Agriculture Allan Forbes Charles U. Lowe Ruth Schultz Food and Drug Administration Public Health Service Medical Research Service Department of Health, Education, Department of Health, Education, and Welfare Veterans Administration and Welfare Ralph McCracken Fred Shank Carol Foreman U.S. Department of Agriculture Agricultural Research Service Food and Nutrition Service U.S. Department of Agriculture U.S. Department of Martin Forman Agriculture Bureau of Technical Assistance James Nielson Agency for International Research and Education Daniel Shaughnessy Development U.S. Department of Agriculture Office of Food for Peace Department of State Patti Okura-Leiberg Agency for International Thomas Grumbly Food and Agriculture Development Food and Drug Administration Organization Department of State Department of Health, Education, Grace Ostenso Artemis Simopoulos and Welfare Food and Nutrition Service National Institutes of Health Linda Haverberg U.S. Department of Department of Health, Bureau for Latin America Agriculture Education, and Welfare Agency for International Michael) J. Pallansch Evelyn Spindler Development Department of State Agricultural Research Service Extension Service U.S. Department of U.S. Department of Irwin Hornstein Agriculture Agriculture Bureau of Technical Assistance Albert A. Pawlowski Paul E. Tyler Agency for International Alcohol, Drug Abuse, and Mental Medical Research and Development Health Administration Development Department of State Department of Health, U.S. Navy Robert H. Herman Education, and Welfare Fred Welz Letterman Army Institute of Research Seymour Perry Bureau for Latin America National Institutes of Health Agency for International Office of the Surgeon Department of Health, Development General Education, and Welfare Department of State Col. Hickman U.S. Army Medical Research and Dan C. Popma Development Bio-Environmental Systems Command Office of the Surgeon National Aeronautics and General Space Administration ix Source: https://www.industrydocuments.ucsf.edu/docs/rInf0227 Workshop Observers Thelma Arnold Arthur McDowell Arlette Rasmussen Walter Reed National Cancer for Health Food Science and Nutrition University of Health Science Statistics Department U.S. Army Department of Health, University of Delaware Education. and Welfare Beverly Cullen Artemis Simopoulos Nutrition Department Robert McGandy National Institutes of Health Boston University Medical Center Department of Health, Elizabeth Davis Tufts University Education. and Welfare Cooperative State Research Lucille McLaughlin Service Nutrition Department Evelyn Spindler U.S. Department of Boston University Cooperate Extension Service Agriculture U.S. Department of Max Milner Agriculture Yolan L. Harsany International Nutrition Food and Drug Administration Planning Program Geraldine Thompkins Office of Health Information Department of Health. Massachusetts Institute of Eduçation. and Welfare Technology and Health Promotion Department of Health, James Hicks George Parman Education. and Welfare Center for Disease Control Trade and Development Department of Health. Corporation Edith Weir Education, and Welfare Isabelle Patterson National Agricultural Library U.S. Department of Robert Leyton Department of Health, Agriculture Field Operations Division Education, and Welfare Medical Research Service Dorothy Pringle Veterans Administration Cooperative State Research Marshall Matz Service Subcommittee on Nutrition U.S. Department of Senate Committee on Agriculture Agriculture, Nutrition, and Forestry x Source: https://www.industrydocuments.ucsf.edu/docs/rInf0227 Contents Chapter Page EXECUTIVE SUMMARY 3 Congressional Options 4 I. OVERVIEW 9 What Research Cannot Do To Solve Nutrition Problems 11 II. KEY ISSUES 15 Issue 1 -Goals and Priorities of Human Nutrition Research 15 Issue -Definition and Funding of Human Nutrition Research 17 Issue -Personnel Resource Requirements 22 III. NUTRITION RESEARCH STRATEGIES 27 The Status Quo: Nutrition Research in the Federal Government 27 Goals and Priorities 27 Definition and Funding 30 Personnel Resource Requirements 30 New Directions in Federally Supported Human Nutrition Research: The OSTP Report 30 Goals and Priorities 30 Definition and Funding 32 Personnel Resource Requirements 32 Federal Human Nutrition Research Needs a Coordinated Approach To Advance Nutrition Knowledge: The GAO Report 32 Goals and Priorities 32 Definition and Funding 33 Personnel Resource Requirements 33 A Comprehensive Nutrition Research Strategy 34 Goals and Priorities 34 Definition and Funding 36 Personnel Resource Requirements 37 IV. CONGRESSIONAL OPTIONS 41 Option 1: Congress Could Choose To Maintain the Overall Status Quo. 41 Option 2: Congress Could Choose To Pursue a Human Nutrition Research Strategy Different From That of the Status Quo. 42 APPENDIX 47 xi Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 LIST OF TABLES Table No. Page 1. Alternative Human Nutrition Research Strategies 5 2. Death Rates Per 100,000 Population for Leading Causes, by Sex and Age: 1974 10 3. Federal Government Agencies Active in Food and Nutrition Programs and Their Nutrition Research Priorities 18 4. Federal Expenditures for Human Nutrition Research 21 5. A Seven-Point Nutrition Research Strategy 35 6. Criteria Used for Assessing Research Priorities 48 xii Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 EXECUTIVE SUMMARY vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 EXECUTIVE SUMMARY During this century, particularly since World War II, Americans have markedly altered their eating habits and lifestyles. Simultaneously there has been an equally significant change in the major causes of death. Fifty to seventy-five years ago illnesses during infancy and infectious diseases. such as tuberculosis and pneumonia, dominated the mortality tables. Nutrient deficiency diseases, such as rickets and pellagra. were also signifi- cant public health concerns. Today we find that most Americans die from degenerative illnesses such as heart disease and cancer. At the same time few Americans show any overt evi- dence of nutritional deficiency. Unlike the infectious diseases, degenerative illness appears to result from the complex interaction of multiple factors. Although diet is one of the factors in- volved. to date there has been relatively little research into the direct relationship of diet to chronic disease. However, epidemiological studies indicate that overcon- sumption of food. especially certain kinds of foods, contributes to the incidence of and mortality from degenerative diseases such as heart disease, some cancers, stroke. hypertension, and diabetes. The United States has gradually shifted its nutrition research focus away from domestic nutrient deficiency questions, and toward biochemical functions of nutrients and undernutrition in developing countries. This shift has left a vacuum in domestic human nutrition research. Today we need to know the answers to several key questions, such as: What specific elements in the American diet con- tribute to the physiological or biochemical changes which lead to the development of degenerative illnesses? By reorienting Federal nutrition research efforts, the links between diet and these diseases may soon be discovered. Obtaining better knowledge, and conveying it to the public, could reduce or delay the incidence of a number of major ailments. Research on the links between diet and heart disease has brought widely publicized recommendations to reduce consumption of cholesterol and saturated animal fats. These recommendations have changed the eating habits of many Americans. We are eating more polyunsaturated fats and less saturated fat and cholesterol. In the last 10 years, the mortality rate from cor- onary heart disease has gone down over 20 percent, although heart disease still remains the leading cause of death. No conclusive cause and effect have been established, but diet, along with exercise and improved medical care, is considered a factor in this decline. Most human nutrition research in the United States is conducted or spon- sored by the Federal Government, primarily through the Department of Agri- culture (USDA), the State agriculture experiment stations, and the Department of Health, Education, and Welfare (HEW). Alternatives for redefining and refocusing Government nutrition research have been put forward in recent legislation and several studies. This report assesses these alternatives, along with the state of Federal nutrition research. 3 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 The principal finding of this OTA assessment report is that the Federal Government has failed to adjust the emphasis of its human nutrition research activities to deal with the changing health problems of the people of the United States. The consequences of continuing to pursue the present preoc- cupation with nutritional deficiency diseases will seriously affect the quality of life of present and future generations into the 21st century. OTA's assessment explores several optional paths that the U.S. Congress might consider to deal with this finding. Each of these options are discussed from the perspective of the three issue areas critical to the assessment's prin- cipal finding. These are: 1) Goals and priorities of human nutrition research, 2) Definition and funding of human nutrition research, and 3) Personnel resource requirements. CONGRESSIONAL OPTIONS Congress can elect to maintain the status quo with or without minor shifts or choose among the strategies and options offered by OTA, the General Ac- counting Office (GAO), and the Office of Science & Technology Policy (OSTP). These alternatives are outlined in table 1. Either alternative has economic, in- stitutional, and health implications. Congress could choose to maintain the overall status quo by refraining from any action, awaiting the recommendations of the President's Reorganiza- tion Project. Congress could also choose to make small alterations to the existing system without changing its overall priorities and structure. This could be accomplished by amending the Food and Agriculture Act of 1977 to clarify the designation of lead agency for human nutrition research, by developing nutri- tion research goals and priorities for HEW that complement the goals and pri- orities outlined for USDA in the Food and Agriculture Act of 1977, by enacting legislation establishing a coordinating mechanism for Federal human nutrition research activities, or by considering legislation to improve data storage and retrieval systems currently in use. If Congress chooses to change the emphasis of federally funded nutrition research, such change could be based on the strategies and options put for- ward by OSTP, GAO, or OTA. Before any path is chosen, however, more in- formation is required on Federal expenditures and nutrition research person- nel. This could be gained through a GAO audit of Federal expenditures for human nutrition research and a census of research personnel. Based on these findings, Congress could consider increased training grants and fellowships to fill any existing gaps in research personnel. 4 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 Table 1. - -Alternative Human Nutrition Research Strategies Components of Office of Technology General Accounting Office of Science and strategy Assessment Office Technology Policy Research Role of diet in prevention of Research gaps: Effects of nutrition on priorities chronic disease and obesity Knowledge of dietary human health and per- Role of nutrition in treat- nutrients required to pro- formance ment of disease and sup- mote or maintain growth or Food sciences port of therapy well-being at various stages Nutrition education research Requirements for essential and conditions of life Diet and nutritional status nutrients Information on the com- surveillance Nutrition education and position of the current consumer information U.S. food supply and the Nutritional aspects of food extent that nutrients are science and food safety biologically available Monitoring nutritional Evaluation of long-term status health consequences of the Nutrition policy and modern diet management Assessment of the Nation's current nutritional status in terms of dietary excesses and imbalances, as well as deficiencies Research needs: Long-term studies of human subjects across the full range of both health and disease Comparative studies of populations of differing geographic, cultural, and genetic backgrounds Basic investigations of the functions and interactions of dietary components Updated and expanded food composition data Improved techniques for assessing long-term tox- icological risks Definition Definition should recognize Does not define nutrition Definition includes basic and funding degree of relationship to research. Instability of fed- physiological and biochemical stated goals. Before Congress erally funded extramural re- research. Establishes FY 1977 considers appropriations search is a barrier to research spending at $116.6 for nutrition research, an progress. Endorses develop- million. Recommends no in- audit of Federal expenditures ment of federally funded creases in funding with reallo- should be performed using a regional research centers in cation of resources to the constant definition. conjunction with universities. higher priority areas. Personnel No reliable figures are There is a shortage of nutri- Not considered. requirements available for numbers of nutri- tion research scientists. tion research scientists in the laboratory or in training. Before a comprehensive research program is estab- lished, must consider ability of the field to implement and sustain a program. Research Maintain pluralistic ap- Assign each area to a lead Coordinate agency activities organization proach with well-defined Federal agency through the Federal Coordi- agency responsibilities Eliminate unnecessary re- nating Council on Science Initiate an interagency search Engineering, & Technology committee with rotating Promote Government-wide Conduct external reviews of chairmanship research planning, coor- intramural programs Implement a uniform data dination, and reporting Improve intra-agency coor- storage and retrieval dination system Establish an ad hoc inter- Improve congressional agency nutrition education oversight through joint research committee planning and hearings 5 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter I OVERVIEW vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter I OVERVIEW Modern nutrition science dates from the turn of the century when vita- mins were first discovered. Since that time, nearly all elements in foods essential for health have been dentified-vitamins, amino acids, minerals, and fatty acids. Indeed, a patient can be maintained for a long period by in- travenous feeding with a purified diet that contains the known necessary nutrients. This indicates that few essential nutrients remain to be found. Early nutrition research was spurred by the finding that many severe diseases such as rickets, pellagra, beriberi, and scurvy were caused by vitamin deficiencies. These nutrition deficiency diseases were practically eliminated in the United States by the 1940's as a result of better nutritional knowledge, food enrichment, agricultural advances, and socioeconomic changes. Consequently, a belief spread among scientists that little of prac- tical importance for the United States would result from further research in human nutrition. Attention was instead shifted increasingly to the biochemical functions of essential nutrients and infant and childhood malnutrition in developing nations. Over the past 50 years, the basic goal of sion share the common risk factor of obes- nutrition strategy in the United States has ity, which is caused by overeating and lack been to ensure an adequate intake of all of exercise. About 30 percent of men and essential nutrients for the population. Nutri- 40 percent of women in the United States tional advice to the public has consistently between the ages of 40 and 49 are over- stressed a balanced diet that provides nec- weight. Many are technically "obese"- essary protein, minerals, and vitamins. This more than 20 percent above desirable strategy has been largely successful. How- weight. This fact is reflected in disease ever, it was developed and carried out with statistics. Some 23 million Americans suffer little understanding of the long-term effects from hypertension and 10 million from dia- of the abundant diet currently consumed by betes. Diabetics are twice as prone to heart the majority of Americans. disease and stroke. Every year, 850,000 Americans suffer fatal heart attacks. Studies during the past decade have in- dicated that overconsumption of food and Five of the leading causes of death are relative overconsumption of certain kinds of believed to be diet-related. These are heart food are important contributing factors in disease, cancer, stroke, diabetes, and cir- heart disease, stroke, hypertension, cancer, rhosis of the liver. The mortality statistics diabetes, osteoporosis, and dental disease. for these diseases are shown in table 2. The Increased research into the role of diet in impact of chronic diseases extends beyond causing and preventing such major chronic the obvious mortality figures. Chronic dis- diseases may lead to findings which could eases account for many days of work lost, reduce their incidence or delay their onset. major hospitalization costs, and personal suffering because of activity limitation. These diet-related diseases take a heavy toll in the United States. For example, car- The links between diet and these diseases diovascular disease, diabetes, and hyperten- are based on epidemiological studies, and 9 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 2. - Death Rates Per 100,000 Population for Leading Causes, by Sex and Age: 1974 (Excludes deaths of nonresidents of the United States) Sex and age Heart Cirrhosis Emphy- group (in years) disease Cancer Stroke Accidents Pneumoniaa Homicide Suicide Diabetes of liver sema Male 400 191 87.8 71.1 28.9 16.3 18.1 14.7 21.2 15.3 15-24 3 8 1.5 99.1 1.9 22.1 17.1 0.5 0.5 0.1 25-44 44 29 7.7 69.6 4.8 29.5 23.1 3.2 13.7 0.5 45-64 591 338 73.1 71.0 24.9 16.9 28.2 20.8 60.9 18.4 65 and over 3,081 1,293 810.7 144.2 233.7 8.9 36.7 110.4 61.9 131.8 Female 301 151 107.9 29.0 23.0 4.4 6.5 20.5 10.6 3.8 15-24 2 5 1.3 23.9 1.5 6.3 4.6 0.6 0.3 0 25-44 15 35 7.9 17.4 3.1 7.0 9.5 2.7 7.4 0.2 45-64 195 261 56.2 24.9 12.5 3.7 11.8 20.3 28.8 5.7 65 and over 2,159 723 791.8 94.6 150.7 3.2 7.3 130.1 22.7 21.4 ancludes influenza. Source: U.S. National Center for Health Statistics, Vital Statistics of the United States, annual. 1 direct cause-and-effect relationships have decade. The causes of this favorable trend not been established. It is therefore impossi- are not conclusively known, but better nutri- ble to estimate the economic benefits to be tion education, changes in formulation of derived from funding research in this area. processed food, and changing eating habits This does not imply that attention should appear to have played an important role. not be directed to this research. Clearly, The statistics are consistent with reported reducing the incidence and severity of these per capita reductions in the consumption of diseases or preventing the early expression saturated animal fats and cholesterol, in- of them would reap large economic and creases in the consumption of vegetable oils, social benefits. alterations of the ratio of polyunsaturated to saturated fats in the diet, a decrease in There is evidence that nutrition research smoking, and the attention of many Ameri- cans to exercise. These shifts belie the can make an impact on chronic diseases. In- tensive studies on the relationship of diet to widespread assumption that it is impossible heart disease, the greatest cause of death in to change American habits, including eating the United States, have yielded results. As habits, for the better. They also indicate the connections have become clearer, at that a major chronic disease can be com- least 16 national and international groups bated by modifying dietary behavior. have developed similar dietary recommen- dations to combat cardiovascular disease. With varying degrees of emphasis, these These findings are significant to future recommendations have urged reduced in- nutrition research in light of growing take of cholesterol and fats, especially epidemiological evidence linking diet to saturated animal fats. In addition, they other chronic and degenerative diseases have stressed weight control, more physical such as cancer, diabetes, hypertension, and activity, and a halt to smoking. osteoporosis. There has been little direct research, however, into the dietary factors involved in these diseases. Specific aspects These recommendations, widely and of diet that contribute to physical or bio- repeatedly publicized, have had an impact chemical changes leading to the onset of on Americans. Recent reports indicate that such diseases are still unknown. Current while the age adjusted mortality rate from knowledge is now at the point where knowl- coronary heart disease rose 19 percent be- edge of diet and heart disease was in the tween 1950 and 1963, the rate has declined late 1950's, when intense research began to more than 20 percent during the past establish the relationship. Possibly the most 10 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rlnf0227 productive and important area of nutrition patients with chronic diseases or special research will be the identification of metabolic problems of genetic origin. specific dietary links to other chronic dis- eases. Such research will inevitably require The identification of all or nearly all of the development of new techniques and ap- the essential nutrients has opened up new proaches. areas of clinical patient care. The develop- There are other areas where more nutri- ment of purified diets allows complete nutri- tion research is needed. While severe mal- tion by intravenous feeding. Diets can now nutrition is now relatively rare in the United be tailored. to meet the needs of a wide States, moderate degrees of iron deficiency, variety of patients. It is clear that many folic acid deficiency, and possibly other patients-those with chronic disease, deficiencies remain relatively common. For trauma, genetic defects, and others-have a variety of social, economic, or physiologi- not received adequate nutrition in the past. cal reasons, some groups in the population Since developments in this field are still in are particularly prone to nutritional defi- their infancy, further research support will ciencies. These groups include the poor, the be needed to ensure continued improve- elderly, pregnant women, alcoholics, and ments in patient care. WHAT RESEARCH CANNOT DO TO SOLVE NUTRITION PROBLEMS Increased nutrition research can help utilized, the failure may lie in the inade- solve some of the nutrition problems of quate design and administration of public American society. Research, however, can- nutrition education and food programs. Peo- not solve all such problems. Some of our ple may fail to respond to existing pro- most pressing needs involve the application grams. They may be confused by the profu- of existing knowledge rather than the sion of sometimes contradictory recommen- search for new knowledge. If it is unclear dations and urgings from various experts how to make use of existing knowledge, re- and authorities. It is the Government's chal- search indeed can help. If both the knowl- lenge to remedy such problems and reach edge and means are available but are not people with needed nutrition services. 11 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter II KEY ISSUES vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227

What is the table number?

xglg0227

xglg0227_p0, xglg0227_p1, xglg0227_p2, xglg0227_p3, xglg0227_p4, xglg0227_p5, xglg0227_p6, xglg0227_p7

1, Table 1

ABSTRACT AD NO. Accession No. 1. Preparing Institution: Western Reserve University School of Medicine (Cleveland Metropolitan General Hospital) Cleveland, Ohio 2. Title of Report: Metabolism of Protein, Anino Acids and Ammonia in Patients with Liver Disease 3. Principal Investigator: George J. Gabuzda, M.D. 4. Number of pages; date: six pages, three tables; April, 1961 5. Contract Number: DA-49-007-MD-749 6. Supported by: Research and Development Division Office of the Surgeon General, Department of Army Washington 25, D.C. The metabolic effects of administering single emino acids are being investigated in patients. The administration of L-arginine orally or intravenously was consistently accompanied by increases in urinary potassium and bicarbonate excretions, urine pH and decreases in titratable acid and emmonium excretions. When arginino hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloride acid alone. No alterations in blood electrolytes occurred. L-lysine resulted in changes similar to those noted with Laaginine. The administration of Laggutamic acid or L-aspartic acid had no effect on urine or blood electrolytes. Thus the metabolic effects observed occurred with basic (cationic) but not with acidie (anionic) amino acids. L-arginine feeding with hydrochloride acid resulted in less decrease in serum bicarbonate concentration and less excretion of hydrogen ion in the urine than when the hydrochloric acid was given alone. In addition, a patient with chronic renal disease maintained in a progressively acidotic state by the oral administration of hydrochloric acid stabilized serum bicarbonate concentration and pH without changing hydrogen ion excretion when L=arginine was fed, These data are interpreted as follows Basic amino acids behave as cations in the body and probably displace some intracellular potassium. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some mechanism increase total body buffering capacity Other investigations in progress include: 1) the role of the upper gastro intestinal tract as a source of blood ammonium and as a possible aite for removal of ammonium; 2) the relation of blood ammonium levels to renal ammonium production and excretion; and 3) alterations in urinary amino acid excretions that may occur in potassium deficiency states. Data available is at this time insufficient to warrant presentation or interpretation of the findings in these areas. Copies of this report are filed with the Armed Services Technical Information Agency. Arlington Hall Station, Arlington 12, Virginia, and may be obtained from that agency by qualified investigators working under Government Contract. Source: https://www.industrydocuments.ucsf.edu/docsixglg022 PROGRESS REPORT - TO THE SURGEON GENERAL DEPARTMENT OF THE ARMY Contract No. DA-49-007-M0-749 May 1, 1960 - April 30, 1961 Metabolism of Protein, Amino Acids and Ammonia in Patients with Liver Disease Responsible Investigator: George J. Gabuzda, M.D. Associate Professor of Medicine Western Reserve University School of Medicine at Cleveland Matropolitan General Hospital Cleveland, Oh1o Supported by: Research and Development Division Office of the Surgeon General Department of the Anny Washington 25, D.C. April, 1961 Source: https://www.industrydocuments.ucsf.edu/docsixgg0227 Introduction Metabolism of ammonium amino acids and protein in patients with liver disease is the primary subject of investigations conducted under this contract. These studies have been oriented to the relation of disordered nitrogen meta- bolism to hepatic coma and to the responses of these patients to metabolic loads. The current status of investigations dealing with the role of the ugper gastrointestinal tract and of the kidney in ammonium matabolism is outlined below in perspective to past work from this laboratory. The effect of adminis- cering single amino acids on acid base balance has been a prominent subject of investigation during the past year. Accordingly, the findings resulting from these studies are presented in more detail. Although the amino acid studies were accomplished primarily in patients with cirrhosis of the liver, the results may well have pertinence to more general problems of protein nutrition and the responses of undernourished subjects, including chose with liver disease, to various metabolic altezations such as acidosis, alkalosis and potassium deficiency. I. METABOLISM OF AMMONIUM A. The Upper Gastrointestinal Tract The role of the upper gastrointestinal tract in ammonium metabolism has been approached from two points of view. 1) The upper gastrointestinal tract as a source of ammonium, and 2) the upper gastrointestinal tract as a possible site for removal of ammonium from the body. In conjunction with these studies several observations have been made that may be pertinent to normal gastric physiology. Based on previous work from these laboratories, the hypothesis has been made that nonbacterial "amidase", present in the upper gastrointestinal tract, may account for release of ammonium (amide nitrogen) from glutamine. In several patients serial aspirates of duodenal juice obtained after glutamine feeding demonstrated by qualitative bidimensional paper chromatography in- creased amounts of glutamic acid. Interpretation of this finding has been held in reservation since there was uncertainty about the adequacy of the separation procedure for glutamine and glutamic acid by the method employed. In addition, attempts to recover increased ammonium resulting fxom the deamidation of glutamine were not consistently successful. During the past year some effort has been directed at improving the technology involved in these studies. It is difficult to do adequate ammonium determinations on raw gastric or duodenal aspirate by the Conway method. This method has now been modified to involve the collection of the aspirates directly into trichlor= acetic acid. This is centrifuged and appropriate dilutions of the supernates then taken for analysis. The latter procedure permits more accurate and consistent analyses. In addition a method (Waelsh, et. al.) is being set up for the separation of glutamic acid and glutemine utilizing a magnesium ozide ion exchange column. The latter should provide a mich more adequate method for these determinations. After this methodology is established, studies will continue attempting to demonstrate that when glutamine is fed glutamic acid and amonium can be recovered from the upper gastrointestinal tract in appropriate quantities. One observation that provides some encouragement to the hypothesis stated is as follows Duodenal aspirate passed through a Seits filter released from glutamine the same amount of ammonium as was released by Source: https://www.industrydocuments.ucst.edu/docs/xglg227 - 2 - unfiltered aspirate, indicating that aspirate rendered free of bacteria by filtration still retains enzyme activity. Gastric juice contains significant quentities of ammonium under some circumstances. It seemed conceivable that the stomach may extract ammonium from arterial blood by trapping it in the acid gastric juice. If this were the case, one would expect to find large arteriovenous differences across the stomach. To determine whether or not this is the case two experiments were done in dogs. In these animals no arteriovenous difference was detected across the stomach. These experiments, however, were not considered entirely adequate because of difficulties concerning the adequacy of blood sampling from gastric veins in the dog, and obtaining large enough volumes of blood to provide for adequate replicate analyses. It may be possible to make similar observations on the arteriovenous difference for ammonium across the stomach in patients undergoing gastric surgery Since gastric juice does contain ammonium, it seemed worthwhile to determine what effect continuous gastric suction might have on arterial ammonium content. If arterial blood ammonium level could be reduced by this means, gastric suction would provide a method for removing ammonium from the body and conceivably might be of benefit to patients with hepatic coma. To date three patients have undergone continuous gastric suction following histamine induced secretion. In both these patients arterial blood emmonium levels decreased, although in these particular instances the levels were not markedly elevated to begin with. It is planned to determine the effects of gastric suction following histamine adminstration to patients with elevated blood ammonium levels. As an incidental observation it was noted that with histamine induced gastric secretion, volume of gastric juice increased while ammonium concentra- tion decreased. This suggests that total ammonium output into the gastric juice was unaltered by volume of secretion and appeared in gastric juice as a reciprocal of pH. These observations are of interest because they suggest that for gastric juice ammonium concentration is not related to the pH diffusion gradient between blood and juice. Studies dealing with the source and significance of ammonium in gastric juice are continuing B. The Kidney 1. Effect of Blood Ammonium Level on Renal Ammonium Production. The effect of elevated blood ammonium levels on renal ammonium production and excretion are being evaluated. These studies are based on the idea that increased levels of ammonium in arterial blood may inhibit renal production of ammonium from glutamine and other sources. Less ammonia might than be available for diffusion and excretion in the urine with hydrogen 1on and possibly account for the apparent susceptibility of patients with liver disease to the development of acidosis. To date, two patients with hepatic disease have been maintained on constant dietary regimens. Their ability to excrete acid loads (orally administered hydrochloric acid) was determined on two occasions in each patient at two levels of dietary protein intake. In one of these patients response to the acid load at both levels of protein intake Source: https://www.industrydocuments.ucsf.edu/docsixglg22 - 3 - were comparable, although blood ammonium level increased. The second patient study was unsatisfactory because increasing protein intake failed to produce elevated blood ammonium level. Additional selected patients will be similarly studied. In contrast to the hypothesis presented here, Owe et. al. (3. Clin. Invest. 40: 215, 1961) present evidence that hypexammonemia is associated with a decreased arterial-renal venous ammonium difference and increased excretion of ammonium in the urine indicating that arterial ammonium concentration significantly influences urinary ammonium excretion. From previous studies we have reason to doubt this finding. The studies outlined here should provide additional evidence that will help to clarify these opposing points of view concerning the influence of arterial ammonium level on urinary ammonium excretion. II. AMINO ACID METABOLISM A. Effects of Single Amino Acide on Metabolism of Potassium and Hydrogen Ion. These studies concern the effect of administering single amino acids on acid base balance. They were prompted by the observation that patients with liver disease given arginine orally or intravenously excrete increased quanti- ties of potassium in the urine. Two possible explanations for this potassium diuresis have been considered: 1) that arginine displaces extrarenal cellular potassium in a manner analogous to that demonstrated in vitro in which lysine displaced potassium from rat diaphragm, and 2) that arginine influences the handling of electrolytes at the renal level. Six subjects were studied in a metabolic ward. 155 millimoles of Laarginine or Laglutamic acid or L-arginine-L-glutamate was given daily for three days. The three days of amino acid administration were preceded and followed by con- trol periods of from six to twelve days. The arginine (free=base) and glutanic acid were given orally. Arginine hydrochloride, arginine-glutamate and sodium glutamate were administered intravenously . Daily urinary excretions of sodium, potassium, chloride, phosphorus, bicarbonate, ammonium, titratable acid and pH were determined, and blood electrolytes were measured serially. Illustrative data for one of the patients are shown in table 1. The administration of arginine, as free amino acid orally or as hydro- chloride or glutamate salt intravenously, was consistently accompanied by increases in potassium excretion ranging from 10-65% above control values. Arginine administration (except when given as hydrochloride) was also accompanied by increases in urine pH and by bicarbonate and decreases in titratable acid and ammonium excretion. Even when arginine hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloric acid alone. Alterations in blood electrolytes occurred only with arginine hydrochloride which induced decreases in pH and carbon dioxide content. Urinary potassium excretion was unaltered by sodium glutamate given intra- venously or glutamic acid given orally. Increases in urine pH and a large excre- tion of bicarbonate occurred with sodium glutamate. Glutamic acid per se did not effect the blood or urine constituents measured. Glutamic acid given as Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 - a - arginine-glutamate did not negate the effect of arginine on potassium excretion. When L-lysine was given, changes similer to those noted with L-arginine occurred L-aspartic acid feeding, like glutemic acid feeding had no effect on urine or blood electrolytes. Thus the matabolic effects noted occurred with basic (cationic) but not with acidic (anionic) amino acids. The results of these studies are illustrated in Table 2. Subsequent studies were designed to determine whether the cationic amino acids exerted these effects prinarily by influencing renal or extrarenal mechanisms. To this end the responses of three patients of 100 mEq of hydro- chloric acid given orally daily for three days, with and without simultaneous L-arginine administration, were determined. When the acid load was given with L-arginine there was approximately 50% less decrease in serun bicarbonate concentration and 40% less hydrogen 1on excreted in the urine than when hydro- chloric acid was given alone (Table 3). Urinary potassium excretions resulting from L-arginine were comparable to those resulting from hydrochloric acid administration. An additional study was done in a patient with chronic renal disease. A slowly progressive acidosis was induced in this patient by administration of hydrochloric acid orally. (25 mBq daily). Feeding L-arginine in addition to this acid resulted in a stabilization of serum bicarbonate concentration and pH without change in hydrogen ion excretion. If in this circumstance arginine was acting at the renal level to enhance urinary potassium excretion at the expense of hydrogen ion excretion, one would expect the acidosis to have become more profound. This did not occur, and on the contrary the developing acidosis was halted. When L-arginine was discontinued, serum bicarbonate concentration promptly decreased further indicating that the arginine had some effect within the body that controlled the developing acidosis. The current interpretation of these data is as follows Basic amino acids seem to behave as cations in the body and probably displace some intracellular potassium. The site of this displacement is not known. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some unknown mechanism increase total body buffering capacity Additional metabolic studies on patients are in progress to further elucidate the findings outlined above. In addition, mutritional experiments are being conducted in rats who are fed single anino acids in addition to a diet. If rats demonstrate responses similar to those observed in the patients, these animals will be utilized to further define the metabolic effects of single amino acids at the tissue level. Analysis of tissues Obtained from the rats should permit evaluation of the concept that cationic amino acids displace potassium. The site of this potassium displacement might also be established In addition, analysis of urine and preparations of tissues for amino acid content by the automatic amino acid analyzer will provide information con- cerning the effect of single amino acid administration upon tissue content of other amino acids. These studies may have pertinence to problems involved with "amino acid imbalance", may contribute to knowledge concerning the role of amino acids in Source: https://www.industrydocuments.ucsf.edu/docsixglg0221 - 5 - acid base balance, and may be pertinent to the responses of undernourished patients, including those with hepatic cirrhosis, to various metabolic alterations, such as acidosis, alkalosis, and potassium deficiency B. Amino Acid Excretion in Potassium Deficiency Because of reports indicating that in animals rendered potassium deficient, lysine content increased intracellularly, qualitative amino acid patterns were determined by circular paper chromstography on the urines obtained from patients who were rendered potassium deficient by diuretics. On each occasion when total urine potassium excretion decreased below 5 mEq, qualitative changes in free amino acid patterns were detectable in the urine. These changes are characterized by disappearance of basic amino acids which include lysine, arginine and histadine and the disappearance of a band corresponding most probably to glutamine, and the appearance of a cystine band. The interpretation of these qualitative paper chromatograms has limitations Accordingly, it is planned to confirm and quantitate these changes on the Spinco Automatic Acid Analyzer by analysis of urine and blood obtained from potassium deficient sub- jects. The quantitative amino acid data needed to evaluate the potential of this project should be forthcoming. Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 Effect of Arginine and Glutamic Acid on Urinary Electrolyte Excretion Patient G Male, 37 Yr. STUDY PERIOD URINARY EXCRETIONS - mEq/day T.A. NH3 Net H° R pH Control 23 33 56 67 5.71 Arginine P.O. 0 29 29 90 6.31 Control 23 37 60 57 5.53 Glutamic Acid p.o. 22 37 59 72 5.70 Control 17 33 50 75 5.97 Arginine-Glutemate P.O. 11 26 37 91 6.34 Control 21 34 55 65 5.75 Arginine-Glutemate i.v. 0 29 29 90 6.48 Control 23 37 60 57 5.76 T.A. = titratable acid Net H+ ma titratable acid plus ammonia Table 1 Source: https://www.industrydocuments.ucst.edu/docsixglgo227

What is the full form of TA?

xglg0227

xglg0227_p0, xglg0227_p1, xglg0227_p2, xglg0227_p3, xglg0227_p4, xglg0227_p5, xglg0227_p6, xglg0227_p7

Titratable acid, titratable acid

ABSTRACT AD NO. Accession No. 1. Preparing Institution: Western Reserve University School of Medicine (Cleveland Metropolitan General Hospital) Cleveland, Ohio 2. Title of Report: Metabolism of Protein, Anino Acids and Ammonia in Patients with Liver Disease 3. Principal Investigator: George J. Gabuzda, M.D. 4. Number of pages; date: six pages, three tables; April, 1961 5. Contract Number: DA-49-007-MD-749 6. Supported by: Research and Development Division Office of the Surgeon General, Department of Army Washington 25, D.C. The metabolic effects of administering single emino acids are being investigated in patients. The administration of L-arginine orally or intravenously was consistently accompanied by increases in urinary potassium and bicarbonate excretions, urine pH and decreases in titratable acid and emmonium excretions. When arginino hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloride acid alone. No alterations in blood electrolytes occurred. L-lysine resulted in changes similar to those noted with Laaginine. The administration of Laggutamic acid or L-aspartic acid had no effect on urine or blood electrolytes. Thus the metabolic effects observed occurred with basic (cationic) but not with acidie (anionic) amino acids. L-arginine feeding with hydrochloride acid resulted in less decrease in serum bicarbonate concentration and less excretion of hydrogen ion in the urine than when the hydrochloric acid was given alone. In addition, a patient with chronic renal disease maintained in a progressively acidotic state by the oral administration of hydrochloric acid stabilized serum bicarbonate concentration and pH without changing hydrogen ion excretion when L=arginine was fed, These data are interpreted as follows Basic amino acids behave as cations in the body and probably displace some intracellular potassium. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some mechanism increase total body buffering capacity Other investigations in progress include: 1) the role of the upper gastro intestinal tract as a source of blood ammonium and as a possible aite for removal of ammonium; 2) the relation of blood ammonium levels to renal ammonium production and excretion; and 3) alterations in urinary amino acid excretions that may occur in potassium deficiency states. Data available is at this time insufficient to warrant presentation or interpretation of the findings in these areas. Copies of this report are filed with the Armed Services Technical Information Agency. Arlington Hall Station, Arlington 12, Virginia, and may be obtained from that agency by qualified investigators working under Government Contract. Source: https://www.industrydocuments.ucsf.edu/docsixglg022 PROGRESS REPORT - TO THE SURGEON GENERAL DEPARTMENT OF THE ARMY Contract No. DA-49-007-M0-749 May 1, 1960 - April 30, 1961 Metabolism of Protein, Amino Acids and Ammonia in Patients with Liver Disease Responsible Investigator: George J. Gabuzda, M.D. Associate Professor of Medicine Western Reserve University School of Medicine at Cleveland Matropolitan General Hospital Cleveland, Oh1o Supported by: Research and Development Division Office of the Surgeon General Department of the Anny Washington 25, D.C. April, 1961 Source: https://www.industrydocuments.ucsf.edu/docsixgg0227 Introduction Metabolism of ammonium amino acids and protein in patients with liver disease is the primary subject of investigations conducted under this contract. These studies have been oriented to the relation of disordered nitrogen meta- bolism to hepatic coma and to the responses of these patients to metabolic loads. The current status of investigations dealing with the role of the ugper gastrointestinal tract and of the kidney in ammonium matabolism is outlined below in perspective to past work from this laboratory. The effect of adminis- cering single amino acids on acid base balance has been a prominent subject of investigation during the past year. Accordingly, the findings resulting from these studies are presented in more detail. Although the amino acid studies were accomplished primarily in patients with cirrhosis of the liver, the results may well have pertinence to more general problems of protein nutrition and the responses of undernourished subjects, including chose with liver disease, to various metabolic altezations such as acidosis, alkalosis and potassium deficiency. I. METABOLISM OF AMMONIUM A. The Upper Gastrointestinal Tract The role of the upper gastrointestinal tract in ammonium metabolism has been approached from two points of view. 1) The upper gastrointestinal tract as a source of ammonium, and 2) the upper gastrointestinal tract as a possible site for removal of ammonium from the body. In conjunction with these studies several observations have been made that may be pertinent to normal gastric physiology. Based on previous work from these laboratories, the hypothesis has been made that nonbacterial "amidase", present in the upper gastrointestinal tract, may account for release of ammonium (amide nitrogen) from glutamine. In several patients serial aspirates of duodenal juice obtained after glutamine feeding demonstrated by qualitative bidimensional paper chromatography in- creased amounts of glutamic acid. Interpretation of this finding has been held in reservation since there was uncertainty about the adequacy of the separation procedure for glutamine and glutamic acid by the method employed. In addition, attempts to recover increased ammonium resulting fxom the deamidation of glutamine were not consistently successful. During the past year some effort has been directed at improving the technology involved in these studies. It is difficult to do adequate ammonium determinations on raw gastric or duodenal aspirate by the Conway method. This method has now been modified to involve the collection of the aspirates directly into trichlor= acetic acid. This is centrifuged and appropriate dilutions of the supernates then taken for analysis. The latter procedure permits more accurate and consistent analyses. In addition a method (Waelsh, et. al.) is being set up for the separation of glutamic acid and glutemine utilizing a magnesium ozide ion exchange column. The latter should provide a mich more adequate method for these determinations. After this methodology is established, studies will continue attempting to demonstrate that when glutamine is fed glutamic acid and amonium can be recovered from the upper gastrointestinal tract in appropriate quantities. One observation that provides some encouragement to the hypothesis stated is as follows Duodenal aspirate passed through a Seits filter released from glutamine the same amount of ammonium as was released by Source: https://www.industrydocuments.ucst.edu/docs/xglg227 - 2 - unfiltered aspirate, indicating that aspirate rendered free of bacteria by filtration still retains enzyme activity. Gastric juice contains significant quentities of ammonium under some circumstances. It seemed conceivable that the stomach may extract ammonium from arterial blood by trapping it in the acid gastric juice. If this were the case, one would expect to find large arteriovenous differences across the stomach. To determine whether or not this is the case two experiments were done in dogs. In these animals no arteriovenous difference was detected across the stomach. These experiments, however, were not considered entirely adequate because of difficulties concerning the adequacy of blood sampling from gastric veins in the dog, and obtaining large enough volumes of blood to provide for adequate replicate analyses. It may be possible to make similar observations on the arteriovenous difference for ammonium across the stomach in patients undergoing gastric surgery Since gastric juice does contain ammonium, it seemed worthwhile to determine what effect continuous gastric suction might have on arterial ammonium content. If arterial blood ammonium level could be reduced by this means, gastric suction would provide a method for removing ammonium from the body and conceivably might be of benefit to patients with hepatic coma. To date three patients have undergone continuous gastric suction following histamine induced secretion. In both these patients arterial blood emmonium levels decreased, although in these particular instances the levels were not markedly elevated to begin with. It is planned to determine the effects of gastric suction following histamine adminstration to patients with elevated blood ammonium levels. As an incidental observation it was noted that with histamine induced gastric secretion, volume of gastric juice increased while ammonium concentra- tion decreased. This suggests that total ammonium output into the gastric juice was unaltered by volume of secretion and appeared in gastric juice as a reciprocal of pH. These observations are of interest because they suggest that for gastric juice ammonium concentration is not related to the pH diffusion gradient between blood and juice. Studies dealing with the source and significance of ammonium in gastric juice are continuing B. The Kidney 1. Effect of Blood Ammonium Level on Renal Ammonium Production. The effect of elevated blood ammonium levels on renal ammonium production and excretion are being evaluated. These studies are based on the idea that increased levels of ammonium in arterial blood may inhibit renal production of ammonium from glutamine and other sources. Less ammonia might than be available for diffusion and excretion in the urine with hydrogen 1on and possibly account for the apparent susceptibility of patients with liver disease to the development of acidosis. To date, two patients with hepatic disease have been maintained on constant dietary regimens. Their ability to excrete acid loads (orally administered hydrochloric acid) was determined on two occasions in each patient at two levels of dietary protein intake. In one of these patients response to the acid load at both levels of protein intake Source: https://www.industrydocuments.ucsf.edu/docsixglg22 - 3 - were comparable, although blood ammonium level increased. The second patient study was unsatisfactory because increasing protein intake failed to produce elevated blood ammonium level. Additional selected patients will be similarly studied. In contrast to the hypothesis presented here, Owe et. al. (3. Clin. Invest. 40: 215, 1961) present evidence that hypexammonemia is associated with a decreased arterial-renal venous ammonium difference and increased excretion of ammonium in the urine indicating that arterial ammonium concentration significantly influences urinary ammonium excretion. From previous studies we have reason to doubt this finding. The studies outlined here should provide additional evidence that will help to clarify these opposing points of view concerning the influence of arterial ammonium level on urinary ammonium excretion. II. AMINO ACID METABOLISM A. Effects of Single Amino Acide on Metabolism of Potassium and Hydrogen Ion. These studies concern the effect of administering single amino acids on acid base balance. They were prompted by the observation that patients with liver disease given arginine orally or intravenously excrete increased quanti- ties of potassium in the urine. Two possible explanations for this potassium diuresis have been considered: 1) that arginine displaces extrarenal cellular potassium in a manner analogous to that demonstrated in vitro in which lysine displaced potassium from rat diaphragm, and 2) that arginine influences the handling of electrolytes at the renal level. Six subjects were studied in a metabolic ward. 155 millimoles of Laarginine or Laglutamic acid or L-arginine-L-glutamate was given daily for three days. The three days of amino acid administration were preceded and followed by con- trol periods of from six to twelve days. The arginine (free=base) and glutanic acid were given orally. Arginine hydrochloride, arginine-glutamate and sodium glutamate were administered intravenously . Daily urinary excretions of sodium, potassium, chloride, phosphorus, bicarbonate, ammonium, titratable acid and pH were determined, and blood electrolytes were measured serially. Illustrative data for one of the patients are shown in table 1. The administration of arginine, as free amino acid orally or as hydro- chloride or glutamate salt intravenously, was consistently accompanied by increases in potassium excretion ranging from 10-65% above control values. Arginine administration (except when given as hydrochloride) was also accompanied by increases in urine pH and by bicarbonate and decreases in titratable acid and ammonium excretion. Even when arginine hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloric acid alone. Alterations in blood electrolytes occurred only with arginine hydrochloride which induced decreases in pH and carbon dioxide content. Urinary potassium excretion was unaltered by sodium glutamate given intra- venously or glutamic acid given orally. Increases in urine pH and a large excre- tion of bicarbonate occurred with sodium glutamate. Glutamic acid per se did not effect the blood or urine constituents measured. Glutamic acid given as Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 - a - arginine-glutamate did not negate the effect of arginine on potassium excretion. When L-lysine was given, changes similer to those noted with L-arginine occurred L-aspartic acid feeding, like glutemic acid feeding had no effect on urine or blood electrolytes. Thus the matabolic effects noted occurred with basic (cationic) but not with acidic (anionic) amino acids. The results of these studies are illustrated in Table 2. Subsequent studies were designed to determine whether the cationic amino acids exerted these effects prinarily by influencing renal or extrarenal mechanisms. To this end the responses of three patients of 100 mEq of hydro- chloric acid given orally daily for three days, with and without simultaneous L-arginine administration, were determined. When the acid load was given with L-arginine there was approximately 50% less decrease in serun bicarbonate concentration and 40% less hydrogen 1on excreted in the urine than when hydro- chloric acid was given alone (Table 3). Urinary potassium excretions resulting from L-arginine were comparable to those resulting from hydrochloric acid administration. An additional study was done in a patient with chronic renal disease. A slowly progressive acidosis was induced in this patient by administration of hydrochloric acid orally. (25 mBq daily). Feeding L-arginine in addition to this acid resulted in a stabilization of serum bicarbonate concentration and pH without change in hydrogen ion excretion. If in this circumstance arginine was acting at the renal level to enhance urinary potassium excretion at the expense of hydrogen ion excretion, one would expect the acidosis to have become more profound. This did not occur, and on the contrary the developing acidosis was halted. When L-arginine was discontinued, serum bicarbonate concentration promptly decreased further indicating that the arginine had some effect within the body that controlled the developing acidosis. The current interpretation of these data is as follows Basic amino acids seem to behave as cations in the body and probably displace some intracellular potassium. The site of this displacement is not known. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some unknown mechanism increase total body buffering capacity Additional metabolic studies on patients are in progress to further elucidate the findings outlined above. In addition, mutritional experiments are being conducted in rats who are fed single anino acids in addition to a diet. If rats demonstrate responses similar to those observed in the patients, these animals will be utilized to further define the metabolic effects of single amino acids at the tissue level. Analysis of tissues Obtained from the rats should permit evaluation of the concept that cationic amino acids displace potassium. The site of this potassium displacement might also be established In addition, analysis of urine and preparations of tissues for amino acid content by the automatic amino acid analyzer will provide information con- cerning the effect of single amino acid administration upon tissue content of other amino acids. These studies may have pertinence to problems involved with "amino acid imbalance", may contribute to knowledge concerning the role of amino acids in Source: https://www.industrydocuments.ucsf.edu/docsixglg0221 - 5 - acid base balance, and may be pertinent to the responses of undernourished patients, including those with hepatic cirrhosis, to various metabolic alterations, such as acidosis, alkalosis, and potassium deficiency B. Amino Acid Excretion in Potassium Deficiency Because of reports indicating that in animals rendered potassium deficient, lysine content increased intracellularly, qualitative amino acid patterns were determined by circular paper chromstography on the urines obtained from patients who were rendered potassium deficient by diuretics. On each occasion when total urine potassium excretion decreased below 5 mEq, qualitative changes in free amino acid patterns were detectable in the urine. These changes are characterized by disappearance of basic amino acids which include lysine, arginine and histadine and the disappearance of a band corresponding most probably to glutamine, and the appearance of a cystine band. The interpretation of these qualitative paper chromatograms has limitations Accordingly, it is planned to confirm and quantitate these changes on the Spinco Automatic Acid Analyzer by analysis of urine and blood obtained from potassium deficient sub- jects. The quantitative amino acid data needed to evaluate the potential of this project should be forthcoming. Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 Effect of Arginine and Glutamic Acid on Urinary Electrolyte Excretion Patient G Male, 37 Yr. STUDY PERIOD URINARY EXCRETIONS - mEq/day T.A. NH3 Net H° R pH Control 23 33 56 67 5.71 Arginine P.O. 0 29 29 90 6.31 Control 23 37 60 57 5.53 Glutamic Acid p.o. 22 37 59 72 5.70 Control 17 33 50 75 5.97 Arginine-Glutemate P.O. 11 26 37 91 6.34 Control 21 34 55 65 5.75 Arginine-Glutemate i.v. 0 29 29 90 6.48 Control 23 37 60 57 5.76 T.A. = titratable acid Net H+ ma titratable acid plus ammonia Table 1 Source: https://www.industrydocuments.ucst.edu/docsixglgo227

What is the age of the patient?

xglg0227

xglg0227_p0, xglg0227_p1, xglg0227_p2, xglg0227_p3, xglg0227_p4, xglg0227_p5, xglg0227_p6, xglg0227_p7

37, 37 yr, 37 Yr.

ABSTRACT AD NO. Accession No. 1. Preparing Institution: Western Reserve University School of Medicine (Cleveland Metropolitan General Hospital) Cleveland, Ohio 2. Title of Report: Metabolism of Protein, Anino Acids and Ammonia in Patients with Liver Disease 3. Principal Investigator: George J. Gabuzda, M.D. 4. Number of pages; date: six pages, three tables; April, 1961 5. Contract Number: DA-49-007-MD-749 6. Supported by: Research and Development Division Office of the Surgeon General, Department of Army Washington 25, D.C. The metabolic effects of administering single emino acids are being investigated in patients. The administration of L-arginine orally or intravenously was consistently accompanied by increases in urinary potassium and bicarbonate excretions, urine pH and decreases in titratable acid and emmonium excretions. When arginino hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloride acid alone. No alterations in blood electrolytes occurred. L-lysine resulted in changes similar to those noted with Laaginine. The administration of Laggutamic acid or L-aspartic acid had no effect on urine or blood electrolytes. Thus the metabolic effects observed occurred with basic (cationic) but not with acidie (anionic) amino acids. L-arginine feeding with hydrochloride acid resulted in less decrease in serum bicarbonate concentration and less excretion of hydrogen ion in the urine than when the hydrochloric acid was given alone. In addition, a patient with chronic renal disease maintained in a progressively acidotic state by the oral administration of hydrochloric acid stabilized serum bicarbonate concentration and pH without changing hydrogen ion excretion when L=arginine was fed, These data are interpreted as follows Basic amino acids behave as cations in the body and probably displace some intracellular potassium. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some mechanism increase total body buffering capacity Other investigations in progress include: 1) the role of the upper gastro intestinal tract as a source of blood ammonium and as a possible aite for removal of ammonium; 2) the relation of blood ammonium levels to renal ammonium production and excretion; and 3) alterations in urinary amino acid excretions that may occur in potassium deficiency states. Data available is at this time insufficient to warrant presentation or interpretation of the findings in these areas. Copies of this report are filed with the Armed Services Technical Information Agency. Arlington Hall Station, Arlington 12, Virginia, and may be obtained from that agency by qualified investigators working under Government Contract. Source: https://www.industrydocuments.ucsf.edu/docsixglg022 PROGRESS REPORT - TO THE SURGEON GENERAL DEPARTMENT OF THE ARMY Contract No. DA-49-007-M0-749 May 1, 1960 - April 30, 1961 Metabolism of Protein, Amino Acids and Ammonia in Patients with Liver Disease Responsible Investigator: George J. Gabuzda, M.D. Associate Professor of Medicine Western Reserve University School of Medicine at Cleveland Matropolitan General Hospital Cleveland, Oh1o Supported by: Research and Development Division Office of the Surgeon General Department of the Anny Washington 25, D.C. April, 1961 Source: https://www.industrydocuments.ucsf.edu/docsixgg0227 Introduction Metabolism of ammonium amino acids and protein in patients with liver disease is the primary subject of investigations conducted under this contract. These studies have been oriented to the relation of disordered nitrogen meta- bolism to hepatic coma and to the responses of these patients to metabolic loads. The current status of investigations dealing with the role of the ugper gastrointestinal tract and of the kidney in ammonium matabolism is outlined below in perspective to past work from this laboratory. The effect of adminis- cering single amino acids on acid base balance has been a prominent subject of investigation during the past year. Accordingly, the findings resulting from these studies are presented in more detail. Although the amino acid studies were accomplished primarily in patients with cirrhosis of the liver, the results may well have pertinence to more general problems of protein nutrition and the responses of undernourished subjects, including chose with liver disease, to various metabolic altezations such as acidosis, alkalosis and potassium deficiency. I. METABOLISM OF AMMONIUM A. The Upper Gastrointestinal Tract The role of the upper gastrointestinal tract in ammonium metabolism has been approached from two points of view. 1) The upper gastrointestinal tract as a source of ammonium, and 2) the upper gastrointestinal tract as a possible site for removal of ammonium from the body. In conjunction with these studies several observations have been made that may be pertinent to normal gastric physiology. Based on previous work from these laboratories, the hypothesis has been made that nonbacterial "amidase", present in the upper gastrointestinal tract, may account for release of ammonium (amide nitrogen) from glutamine. In several patients serial aspirates of duodenal juice obtained after glutamine feeding demonstrated by qualitative bidimensional paper chromatography in- creased amounts of glutamic acid. Interpretation of this finding has been held in reservation since there was uncertainty about the adequacy of the separation procedure for glutamine and glutamic acid by the method employed. In addition, attempts to recover increased ammonium resulting fxom the deamidation of glutamine were not consistently successful. During the past year some effort has been directed at improving the technology involved in these studies. It is difficult to do adequate ammonium determinations on raw gastric or duodenal aspirate by the Conway method. This method has now been modified to involve the collection of the aspirates directly into trichlor= acetic acid. This is centrifuged and appropriate dilutions of the supernates then taken for analysis. The latter procedure permits more accurate and consistent analyses. In addition a method (Waelsh, et. al.) is being set up for the separation of glutamic acid and glutemine utilizing a magnesium ozide ion exchange column. The latter should provide a mich more adequate method for these determinations. After this methodology is established, studies will continue attempting to demonstrate that when glutamine is fed glutamic acid and amonium can be recovered from the upper gastrointestinal tract in appropriate quantities. One observation that provides some encouragement to the hypothesis stated is as follows Duodenal aspirate passed through a Seits filter released from glutamine the same amount of ammonium as was released by Source: https://www.industrydocuments.ucst.edu/docs/xglg227 - 2 - unfiltered aspirate, indicating that aspirate rendered free of bacteria by filtration still retains enzyme activity. Gastric juice contains significant quentities of ammonium under some circumstances. It seemed conceivable that the stomach may extract ammonium from arterial blood by trapping it in the acid gastric juice. If this were the case, one would expect to find large arteriovenous differences across the stomach. To determine whether or not this is the case two experiments were done in dogs. In these animals no arteriovenous difference was detected across the stomach. These experiments, however, were not considered entirely adequate because of difficulties concerning the adequacy of blood sampling from gastric veins in the dog, and obtaining large enough volumes of blood to provide for adequate replicate analyses. It may be possible to make similar observations on the arteriovenous difference for ammonium across the stomach in patients undergoing gastric surgery Since gastric juice does contain ammonium, it seemed worthwhile to determine what effect continuous gastric suction might have on arterial ammonium content. If arterial blood ammonium level could be reduced by this means, gastric suction would provide a method for removing ammonium from the body and conceivably might be of benefit to patients with hepatic coma. To date three patients have undergone continuous gastric suction following histamine induced secretion. In both these patients arterial blood emmonium levels decreased, although in these particular instances the levels were not markedly elevated to begin with. It is planned to determine the effects of gastric suction following histamine adminstration to patients with elevated blood ammonium levels. As an incidental observation it was noted that with histamine induced gastric secretion, volume of gastric juice increased while ammonium concentra- tion decreased. This suggests that total ammonium output into the gastric juice was unaltered by volume of secretion and appeared in gastric juice as a reciprocal of pH. These observations are of interest because they suggest that for gastric juice ammonium concentration is not related to the pH diffusion gradient between blood and juice. Studies dealing with the source and significance of ammonium in gastric juice are continuing B. The Kidney 1. Effect of Blood Ammonium Level on Renal Ammonium Production. The effect of elevated blood ammonium levels on renal ammonium production and excretion are being evaluated. These studies are based on the idea that increased levels of ammonium in arterial blood may inhibit renal production of ammonium from glutamine and other sources. Less ammonia might than be available for diffusion and excretion in the urine with hydrogen 1on and possibly account for the apparent susceptibility of patients with liver disease to the development of acidosis. To date, two patients with hepatic disease have been maintained on constant dietary regimens. Their ability to excrete acid loads (orally administered hydrochloric acid) was determined on two occasions in each patient at two levels of dietary protein intake. In one of these patients response to the acid load at both levels of protein intake Source: https://www.industrydocuments.ucsf.edu/docsixglg22 - 3 - were comparable, although blood ammonium level increased. The second patient study was unsatisfactory because increasing protein intake failed to produce elevated blood ammonium level. Additional selected patients will be similarly studied. In contrast to the hypothesis presented here, Owe et. al. (3. Clin. Invest. 40: 215, 1961) present evidence that hypexammonemia is associated with a decreased arterial-renal venous ammonium difference and increased excretion of ammonium in the urine indicating that arterial ammonium concentration significantly influences urinary ammonium excretion. From previous studies we have reason to doubt this finding. The studies outlined here should provide additional evidence that will help to clarify these opposing points of view concerning the influence of arterial ammonium level on urinary ammonium excretion. II. AMINO ACID METABOLISM A. Effects of Single Amino Acide on Metabolism of Potassium and Hydrogen Ion. These studies concern the effect of administering single amino acids on acid base balance. They were prompted by the observation that patients with liver disease given arginine orally or intravenously excrete increased quanti- ties of potassium in the urine. Two possible explanations for this potassium diuresis have been considered: 1) that arginine displaces extrarenal cellular potassium in a manner analogous to that demonstrated in vitro in which lysine displaced potassium from rat diaphragm, and 2) that arginine influences the handling of electrolytes at the renal level. Six subjects were studied in a metabolic ward. 155 millimoles of Laarginine or Laglutamic acid or L-arginine-L-glutamate was given daily for three days. The three days of amino acid administration were preceded and followed by con- trol periods of from six to twelve days. The arginine (free=base) and glutanic acid were given orally. Arginine hydrochloride, arginine-glutamate and sodium glutamate were administered intravenously . Daily urinary excretions of sodium, potassium, chloride, phosphorus, bicarbonate, ammonium, titratable acid and pH were determined, and blood electrolytes were measured serially. Illustrative data for one of the patients are shown in table 1. The administration of arginine, as free amino acid orally or as hydro- chloride or glutamate salt intravenously, was consistently accompanied by increases in potassium excretion ranging from 10-65% above control values. Arginine administration (except when given as hydrochloride) was also accompanied by increases in urine pH and by bicarbonate and decreases in titratable acid and ammonium excretion. Even when arginine hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloric acid alone. Alterations in blood electrolytes occurred only with arginine hydrochloride which induced decreases in pH and carbon dioxide content. Urinary potassium excretion was unaltered by sodium glutamate given intra- venously or glutamic acid given orally. Increases in urine pH and a large excre- tion of bicarbonate occurred with sodium glutamate. Glutamic acid per se did not effect the blood or urine constituents measured. Glutamic acid given as Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 - a - arginine-glutamate did not negate the effect of arginine on potassium excretion. When L-lysine was given, changes similer to those noted with L-arginine occurred L-aspartic acid feeding, like glutemic acid feeding had no effect on urine or blood electrolytes. Thus the matabolic effects noted occurred with basic (cationic) but not with acidic (anionic) amino acids. The results of these studies are illustrated in Table 2. Subsequent studies were designed to determine whether the cationic amino acids exerted these effects prinarily by influencing renal or extrarenal mechanisms. To this end the responses of three patients of 100 mEq of hydro- chloric acid given orally daily for three days, with and without simultaneous L-arginine administration, were determined. When the acid load was given with L-arginine there was approximately 50% less decrease in serun bicarbonate concentration and 40% less hydrogen 1on excreted in the urine than when hydro- chloric acid was given alone (Table 3). Urinary potassium excretions resulting from L-arginine were comparable to those resulting from hydrochloric acid administration. An additional study was done in a patient with chronic renal disease. A slowly progressive acidosis was induced in this patient by administration of hydrochloric acid orally. (25 mBq daily). Feeding L-arginine in addition to this acid resulted in a stabilization of serum bicarbonate concentration and pH without change in hydrogen ion excretion. If in this circumstance arginine was acting at the renal level to enhance urinary potassium excretion at the expense of hydrogen ion excretion, one would expect the acidosis to have become more profound. This did not occur, and on the contrary the developing acidosis was halted. When L-arginine was discontinued, serum bicarbonate concentration promptly decreased further indicating that the arginine had some effect within the body that controlled the developing acidosis. The current interpretation of these data is as follows Basic amino acids seem to behave as cations in the body and probably displace some intracellular potassium. The site of this displacement is not known. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some unknown mechanism increase total body buffering capacity Additional metabolic studies on patients are in progress to further elucidate the findings outlined above. In addition, mutritional experiments are being conducted in rats who are fed single anino acids in addition to a diet. If rats demonstrate responses similar to those observed in the patients, these animals will be utilized to further define the metabolic effects of single amino acids at the tissue level. Analysis of tissues Obtained from the rats should permit evaluation of the concept that cationic amino acids displace potassium. The site of this potassium displacement might also be established In addition, analysis of urine and preparations of tissues for amino acid content by the automatic amino acid analyzer will provide information con- cerning the effect of single amino acid administration upon tissue content of other amino acids. These studies may have pertinence to problems involved with "amino acid imbalance", may contribute to knowledge concerning the role of amino acids in Source: https://www.industrydocuments.ucsf.edu/docsixglg0221 - 5 - acid base balance, and may be pertinent to the responses of undernourished patients, including those with hepatic cirrhosis, to various metabolic alterations, such as acidosis, alkalosis, and potassium deficiency B. Amino Acid Excretion in Potassium Deficiency Because of reports indicating that in animals rendered potassium deficient, lysine content increased intracellularly, qualitative amino acid patterns were determined by circular paper chromstography on the urines obtained from patients who were rendered potassium deficient by diuretics. On each occasion when total urine potassium excretion decreased below 5 mEq, qualitative changes in free amino acid patterns were detectable in the urine. These changes are characterized by disappearance of basic amino acids which include lysine, arginine and histadine and the disappearance of a band corresponding most probably to glutamine, and the appearance of a cystine band. The interpretation of these qualitative paper chromatograms has limitations Accordingly, it is planned to confirm and quantitate these changes on the Spinco Automatic Acid Analyzer by analysis of urine and blood obtained from potassium deficient sub- jects. The quantitative amino acid data needed to evaluate the potential of this project should be forthcoming. Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 Effect of Arginine and Glutamic Acid on Urinary Electrolyte Excretion Patient G Male, 37 Yr. STUDY PERIOD URINARY EXCRETIONS - mEq/day T.A. NH3 Net H° R pH Control 23 33 56 67 5.71 Arginine P.O. 0 29 29 90 6.31 Control 23 37 60 57 5.53 Glutamic Acid p.o. 22 37 59 72 5.70 Control 17 33 50 75 5.97 Arginine-Glutemate P.O. 11 26 37 91 6.34 Control 21 34 55 65 5.75 Arginine-Glutemate i.v. 0 29 29 90 6.48 Control 23 37 60 57 5.76 T.A. = titratable acid Net H+ ma titratable acid plus ammonia Table 1 Source: https://www.industrydocuments.ucst.edu/docsixglgo227

What is the sex of the patient?

xglg0227

xglg0227_p0, xglg0227_p1, xglg0227_p2, xglg0227_p3, xglg0227_p4, xglg0227_p5, xglg0227_p6, xglg0227_p7

Male

ABSTRACT AD NO. Accession No. 1. Preparing Institution: Western Reserve University School of Medicine (Cleveland Metropolitan General Hospital) Cleveland, Ohio 2. Title of Report: Metabolism of Protein, Anino Acids and Ammonia in Patients with Liver Disease 3. Principal Investigator: George J. Gabuzda, M.D. 4. Number of pages; date: six pages, three tables; April, 1961 5. Contract Number: DA-49-007-MD-749 6. Supported by: Research and Development Division Office of the Surgeon General, Department of Army Washington 25, D.C. The metabolic effects of administering single emino acids are being investigated in patients. The administration of L-arginine orally or intravenously was consistently accompanied by increases in urinary potassium and bicarbonate excretions, urine pH and decreases in titratable acid and emmonium excretions. When arginino hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloride acid alone. No alterations in blood electrolytes occurred. L-lysine resulted in changes similar to those noted with Laaginine. The administration of Laggutamic acid or L-aspartic acid had no effect on urine or blood electrolytes. Thus the metabolic effects observed occurred with basic (cationic) but not with acidie (anionic) amino acids. L-arginine feeding with hydrochloride acid resulted in less decrease in serum bicarbonate concentration and less excretion of hydrogen ion in the urine than when the hydrochloric acid was given alone. In addition, a patient with chronic renal disease maintained in a progressively acidotic state by the oral administration of hydrochloric acid stabilized serum bicarbonate concentration and pH without changing hydrogen ion excretion when L=arginine was fed, These data are interpreted as follows Basic amino acids behave as cations in the body and probably displace some intracellular potassium. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some mechanism increase total body buffering capacity Other investigations in progress include: 1) the role of the upper gastro intestinal tract as a source of blood ammonium and as a possible aite for removal of ammonium; 2) the relation of blood ammonium levels to renal ammonium production and excretion; and 3) alterations in urinary amino acid excretions that may occur in potassium deficiency states. Data available is at this time insufficient to warrant presentation or interpretation of the findings in these areas. Copies of this report are filed with the Armed Services Technical Information Agency. Arlington Hall Station, Arlington 12, Virginia, and may be obtained from that agency by qualified investigators working under Government Contract. Source: https://www.industrydocuments.ucsf.edu/docsixglg022 PROGRESS REPORT - TO THE SURGEON GENERAL DEPARTMENT OF THE ARMY Contract No. DA-49-007-M0-749 May 1, 1960 - April 30, 1961 Metabolism of Protein, Amino Acids and Ammonia in Patients with Liver Disease Responsible Investigator: George J. Gabuzda, M.D. Associate Professor of Medicine Western Reserve University School of Medicine at Cleveland Matropolitan General Hospital Cleveland, Oh1o Supported by: Research and Development Division Office of the Surgeon General Department of the Anny Washington 25, D.C. April, 1961 Source: https://www.industrydocuments.ucsf.edu/docsixgg0227 Introduction Metabolism of ammonium amino acids and protein in patients with liver disease is the primary subject of investigations conducted under this contract. These studies have been oriented to the relation of disordered nitrogen meta- bolism to hepatic coma and to the responses of these patients to metabolic loads. The current status of investigations dealing with the role of the ugper gastrointestinal tract and of the kidney in ammonium matabolism is outlined below in perspective to past work from this laboratory. The effect of adminis- cering single amino acids on acid base balance has been a prominent subject of investigation during the past year. Accordingly, the findings resulting from these studies are presented in more detail. Although the amino acid studies were accomplished primarily in patients with cirrhosis of the liver, the results may well have pertinence to more general problems of protein nutrition and the responses of undernourished subjects, including chose with liver disease, to various metabolic altezations such as acidosis, alkalosis and potassium deficiency. I. METABOLISM OF AMMONIUM A. The Upper Gastrointestinal Tract The role of the upper gastrointestinal tract in ammonium metabolism has been approached from two points of view. 1) The upper gastrointestinal tract as a source of ammonium, and 2) the upper gastrointestinal tract as a possible site for removal of ammonium from the body. In conjunction with these studies several observations have been made that may be pertinent to normal gastric physiology. Based on previous work from these laboratories, the hypothesis has been made that nonbacterial "amidase", present in the upper gastrointestinal tract, may account for release of ammonium (amide nitrogen) from glutamine. In several patients serial aspirates of duodenal juice obtained after glutamine feeding demonstrated by qualitative bidimensional paper chromatography in- creased amounts of glutamic acid. Interpretation of this finding has been held in reservation since there was uncertainty about the adequacy of the separation procedure for glutamine and glutamic acid by the method employed. In addition, attempts to recover increased ammonium resulting fxom the deamidation of glutamine were not consistently successful. During the past year some effort has been directed at improving the technology involved in these studies. It is difficult to do adequate ammonium determinations on raw gastric or duodenal aspirate by the Conway method. This method has now been modified to involve the collection of the aspirates directly into trichlor= acetic acid. This is centrifuged and appropriate dilutions of the supernates then taken for analysis. The latter procedure permits more accurate and consistent analyses. In addition a method (Waelsh, et. al.) is being set up for the separation of glutamic acid and glutemine utilizing a magnesium ozide ion exchange column. The latter should provide a mich more adequate method for these determinations. After this methodology is established, studies will continue attempting to demonstrate that when glutamine is fed glutamic acid and amonium can be recovered from the upper gastrointestinal tract in appropriate quantities. One observation that provides some encouragement to the hypothesis stated is as follows Duodenal aspirate passed through a Seits filter released from glutamine the same amount of ammonium as was released by Source: https://www.industrydocuments.ucst.edu/docs/xglg227 - 2 - unfiltered aspirate, indicating that aspirate rendered free of bacteria by filtration still retains enzyme activity. Gastric juice contains significant quentities of ammonium under some circumstances. It seemed conceivable that the stomach may extract ammonium from arterial blood by trapping it in the acid gastric juice. If this were the case, one would expect to find large arteriovenous differences across the stomach. To determine whether or not this is the case two experiments were done in dogs. In these animals no arteriovenous difference was detected across the stomach. These experiments, however, were not considered entirely adequate because of difficulties concerning the adequacy of blood sampling from gastric veins in the dog, and obtaining large enough volumes of blood to provide for adequate replicate analyses. It may be possible to make similar observations on the arteriovenous difference for ammonium across the stomach in patients undergoing gastric surgery Since gastric juice does contain ammonium, it seemed worthwhile to determine what effect continuous gastric suction might have on arterial ammonium content. If arterial blood ammonium level could be reduced by this means, gastric suction would provide a method for removing ammonium from the body and conceivably might be of benefit to patients with hepatic coma. To date three patients have undergone continuous gastric suction following histamine induced secretion. In both these patients arterial blood emmonium levels decreased, although in these particular instances the levels were not markedly elevated to begin with. It is planned to determine the effects of gastric suction following histamine adminstration to patients with elevated blood ammonium levels. As an incidental observation it was noted that with histamine induced gastric secretion, volume of gastric juice increased while ammonium concentra- tion decreased. This suggests that total ammonium output into the gastric juice was unaltered by volume of secretion and appeared in gastric juice as a reciprocal of pH. These observations are of interest because they suggest that for gastric juice ammonium concentration is not related to the pH diffusion gradient between blood and juice. Studies dealing with the source and significance of ammonium in gastric juice are continuing B. The Kidney 1. Effect of Blood Ammonium Level on Renal Ammonium Production. The effect of elevated blood ammonium levels on renal ammonium production and excretion are being evaluated. These studies are based on the idea that increased levels of ammonium in arterial blood may inhibit renal production of ammonium from glutamine and other sources. Less ammonia might than be available for diffusion and excretion in the urine with hydrogen 1on and possibly account for the apparent susceptibility of patients with liver disease to the development of acidosis. To date, two patients with hepatic disease have been maintained on constant dietary regimens. Their ability to excrete acid loads (orally administered hydrochloric acid) was determined on two occasions in each patient at two levels of dietary protein intake. In one of these patients response to the acid load at both levels of protein intake Source: https://www.industrydocuments.ucsf.edu/docsixglg22 - 3 - were comparable, although blood ammonium level increased. The second patient study was unsatisfactory because increasing protein intake failed to produce elevated blood ammonium level. Additional selected patients will be similarly studied. In contrast to the hypothesis presented here, Owe et. al. (3. Clin. Invest. 40: 215, 1961) present evidence that hypexammonemia is associated with a decreased arterial-renal venous ammonium difference and increased excretion of ammonium in the urine indicating that arterial ammonium concentration significantly influences urinary ammonium excretion. From previous studies we have reason to doubt this finding. The studies outlined here should provide additional evidence that will help to clarify these opposing points of view concerning the influence of arterial ammonium level on urinary ammonium excretion. II. AMINO ACID METABOLISM A. Effects of Single Amino Acide on Metabolism of Potassium and Hydrogen Ion. These studies concern the effect of administering single amino acids on acid base balance. They were prompted by the observation that patients with liver disease given arginine orally or intravenously excrete increased quanti- ties of potassium in the urine. Two possible explanations for this potassium diuresis have been considered: 1) that arginine displaces extrarenal cellular potassium in a manner analogous to that demonstrated in vitro in which lysine displaced potassium from rat diaphragm, and 2) that arginine influences the handling of electrolytes at the renal level. Six subjects were studied in a metabolic ward. 155 millimoles of Laarginine or Laglutamic acid or L-arginine-L-glutamate was given daily for three days. The three days of amino acid administration were preceded and followed by con- trol periods of from six to twelve days. The arginine (free=base) and glutanic acid were given orally. Arginine hydrochloride, arginine-glutamate and sodium glutamate were administered intravenously . Daily urinary excretions of sodium, potassium, chloride, phosphorus, bicarbonate, ammonium, titratable acid and pH were determined, and blood electrolytes were measured serially. Illustrative data for one of the patients are shown in table 1. The administration of arginine, as free amino acid orally or as hydro- chloride or glutamate salt intravenously, was consistently accompanied by increases in potassium excretion ranging from 10-65% above control values. Arginine administration (except when given as hydrochloride) was also accompanied by increases in urine pH and by bicarbonate and decreases in titratable acid and ammonium excretion. Even when arginine hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloric acid alone. Alterations in blood electrolytes occurred only with arginine hydrochloride which induced decreases in pH and carbon dioxide content. Urinary potassium excretion was unaltered by sodium glutamate given intra- venously or glutamic acid given orally. Increases in urine pH and a large excre- tion of bicarbonate occurred with sodium glutamate. Glutamic acid per se did not effect the blood or urine constituents measured. Glutamic acid given as Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 - a - arginine-glutamate did not negate the effect of arginine on potassium excretion. When L-lysine was given, changes similer to those noted with L-arginine occurred L-aspartic acid feeding, like glutemic acid feeding had no effect on urine or blood electrolytes. Thus the matabolic effects noted occurred with basic (cationic) but not with acidic (anionic) amino acids. The results of these studies are illustrated in Table 2. Subsequent studies were designed to determine whether the cationic amino acids exerted these effects prinarily by influencing renal or extrarenal mechanisms. To this end the responses of three patients of 100 mEq of hydro- chloric acid given orally daily for three days, with and without simultaneous L-arginine administration, were determined. When the acid load was given with L-arginine there was approximately 50% less decrease in serun bicarbonate concentration and 40% less hydrogen 1on excreted in the urine than when hydro- chloric acid was given alone (Table 3). Urinary potassium excretions resulting from L-arginine were comparable to those resulting from hydrochloric acid administration. An additional study was done in a patient with chronic renal disease. A slowly progressive acidosis was induced in this patient by administration of hydrochloric acid orally. (25 mBq daily). Feeding L-arginine in addition to this acid resulted in a stabilization of serum bicarbonate concentration and pH without change in hydrogen ion excretion. If in this circumstance arginine was acting at the renal level to enhance urinary potassium excretion at the expense of hydrogen ion excretion, one would expect the acidosis to have become more profound. This did not occur, and on the contrary the developing acidosis was halted. When L-arginine was discontinued, serum bicarbonate concentration promptly decreased further indicating that the arginine had some effect within the body that controlled the developing acidosis. The current interpretation of these data is as follows Basic amino acids seem to behave as cations in the body and probably displace some intracellular potassium. The site of this displacement is not known. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some unknown mechanism increase total body buffering capacity Additional metabolic studies on patients are in progress to further elucidate the findings outlined above. In addition, mutritional experiments are being conducted in rats who are fed single anino acids in addition to a diet. If rats demonstrate responses similar to those observed in the patients, these animals will be utilized to further define the metabolic effects of single amino acids at the tissue level. Analysis of tissues Obtained from the rats should permit evaluation of the concept that cationic amino acids displace potassium. The site of this potassium displacement might also be established In addition, analysis of urine and preparations of tissues for amino acid content by the automatic amino acid analyzer will provide information con- cerning the effect of single amino acid administration upon tissue content of other amino acids. These studies may have pertinence to problems involved with "amino acid imbalance", may contribute to knowledge concerning the role of amino acids in Source: https://www.industrydocuments.ucsf.edu/docsixglg0221 - 5 - acid base balance, and may be pertinent to the responses of undernourished patients, including those with hepatic cirrhosis, to various metabolic alterations, such as acidosis, alkalosis, and potassium deficiency B. Amino Acid Excretion in Potassium Deficiency Because of reports indicating that in animals rendered potassium deficient, lysine content increased intracellularly, qualitative amino acid patterns were determined by circular paper chromstography on the urines obtained from patients who were rendered potassium deficient by diuretics. On each occasion when total urine potassium excretion decreased below 5 mEq, qualitative changes in free amino acid patterns were detectable in the urine. These changes are characterized by disappearance of basic amino acids which include lysine, arginine and histadine and the disappearance of a band corresponding most probably to glutamine, and the appearance of a cystine band. The interpretation of these qualitative paper chromatograms has limitations Accordingly, it is planned to confirm and quantitate these changes on the Spinco Automatic Acid Analyzer by analysis of urine and blood obtained from potassium deficient sub- jects. The quantitative amino acid data needed to evaluate the potential of this project should be forthcoming. Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 Effect of Arginine and Glutamic Acid on Urinary Electrolyte Excretion Patient G Male, 37 Yr. STUDY PERIOD URINARY EXCRETIONS - mEq/day T.A. NH3 Net H° R pH Control 23 33 56 67 5.71 Arginine P.O. 0 29 29 90 6.31 Control 23 37 60 57 5.53 Glutamic Acid p.o. 22 37 59 72 5.70 Control 17 33 50 75 5.97 Arginine-Glutemate P.O. 11 26 37 91 6.34 Control 21 34 55 65 5.75 Arginine-Glutemate i.v. 0 29 29 90 6.48 Control 23 37 60 57 5.76 T.A. = titratable acid Net H+ ma titratable acid plus ammonia Table 1 Source: https://www.industrydocuments.ucst.edu/docsixglgo227

What is the pH of Arginine p.o.?

xglg0227

xglg0227_p0, xglg0227_p1, xglg0227_p2, xglg0227_p3, xglg0227_p4, xglg0227_p5, xglg0227_p6, xglg0227_p7

6.31

ABSTRACT AD NO. Accession No. 1. Preparing Institution: Western Reserve University School of Medicine (Cleveland Metropolitan General Hospital) Cleveland, Ohio 2. Title of Report: Metabolism of Protein, Anino Acids and Ammonia in Patients with Liver Disease 3. Principal Investigator: George J. Gabuzda, M.D. 4. Number of pages; date: six pages, three tables; April, 1961 5. Contract Number: DA-49-007-MD-749 6. Supported by: Research and Development Division Office of the Surgeon General, Department of Army Washington 25, D.C. The metabolic effects of administering single emino acids are being investigated in patients. The administration of L-arginine orally or intravenously was consistently accompanied by increases in urinary potassium and bicarbonate excretions, urine pH and decreases in titratable acid and emmonium excretions. When arginino hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloride acid alone. No alterations in blood electrolytes occurred. L-lysine resulted in changes similar to those noted with Laaginine. The administration of Laggutamic acid or L-aspartic acid had no effect on urine or blood electrolytes. Thus the metabolic effects observed occurred with basic (cationic) but not with acidie (anionic) amino acids. L-arginine feeding with hydrochloride acid resulted in less decrease in serum bicarbonate concentration and less excretion of hydrogen ion in the urine than when the hydrochloric acid was given alone. In addition, a patient with chronic renal disease maintained in a progressively acidotic state by the oral administration of hydrochloric acid stabilized serum bicarbonate concentration and pH without changing hydrogen ion excretion when L=arginine was fed, These data are interpreted as follows Basic amino acids behave as cations in the body and probably displace some intracellular potassium. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some mechanism increase total body buffering capacity Other investigations in progress include: 1) the role of the upper gastro intestinal tract as a source of blood ammonium and as a possible aite for removal of ammonium; 2) the relation of blood ammonium levels to renal ammonium production and excretion; and 3) alterations in urinary amino acid excretions that may occur in potassium deficiency states. Data available is at this time insufficient to warrant presentation or interpretation of the findings in these areas. Copies of this report are filed with the Armed Services Technical Information Agency. Arlington Hall Station, Arlington 12, Virginia, and may be obtained from that agency by qualified investigators working under Government Contract. Source: https://www.industrydocuments.ucsf.edu/docsixglg022 PROGRESS REPORT - TO THE SURGEON GENERAL DEPARTMENT OF THE ARMY Contract No. DA-49-007-M0-749 May 1, 1960 - April 30, 1961 Metabolism of Protein, Amino Acids and Ammonia in Patients with Liver Disease Responsible Investigator: George J. Gabuzda, M.D. Associate Professor of Medicine Western Reserve University School of Medicine at Cleveland Matropolitan General Hospital Cleveland, Oh1o Supported by: Research and Development Division Office of the Surgeon General Department of the Anny Washington 25, D.C. April, 1961 Source: https://www.industrydocuments.ucsf.edu/docsixgg0227 Introduction Metabolism of ammonium amino acids and protein in patients with liver disease is the primary subject of investigations conducted under this contract. These studies have been oriented to the relation of disordered nitrogen meta- bolism to hepatic coma and to the responses of these patients to metabolic loads. The current status of investigations dealing with the role of the ugper gastrointestinal tract and of the kidney in ammonium matabolism is outlined below in perspective to past work from this laboratory. The effect of adminis- cering single amino acids on acid base balance has been a prominent subject of investigation during the past year. Accordingly, the findings resulting from these studies are presented in more detail. Although the amino acid studies were accomplished primarily in patients with cirrhosis of the liver, the results may well have pertinence to more general problems of protein nutrition and the responses of undernourished subjects, including chose with liver disease, to various metabolic altezations such as acidosis, alkalosis and potassium deficiency. I. METABOLISM OF AMMONIUM A. The Upper Gastrointestinal Tract The role of the upper gastrointestinal tract in ammonium metabolism has been approached from two points of view. 1) The upper gastrointestinal tract as a source of ammonium, and 2) the upper gastrointestinal tract as a possible site for removal of ammonium from the body. In conjunction with these studies several observations have been made that may be pertinent to normal gastric physiology. Based on previous work from these laboratories, the hypothesis has been made that nonbacterial "amidase", present in the upper gastrointestinal tract, may account for release of ammonium (amide nitrogen) from glutamine. In several patients serial aspirates of duodenal juice obtained after glutamine feeding demonstrated by qualitative bidimensional paper chromatography in- creased amounts of glutamic acid. Interpretation of this finding has been held in reservation since there was uncertainty about the adequacy of the separation procedure for glutamine and glutamic acid by the method employed. In addition, attempts to recover increased ammonium resulting fxom the deamidation of glutamine were not consistently successful. During the past year some effort has been directed at improving the technology involved in these studies. It is difficult to do adequate ammonium determinations on raw gastric or duodenal aspirate by the Conway method. This method has now been modified to involve the collection of the aspirates directly into trichlor= acetic acid. This is centrifuged and appropriate dilutions of the supernates then taken for analysis. The latter procedure permits more accurate and consistent analyses. In addition a method (Waelsh, et. al.) is being set up for the separation of glutamic acid and glutemine utilizing a magnesium ozide ion exchange column. The latter should provide a mich more adequate method for these determinations. After this methodology is established, studies will continue attempting to demonstrate that when glutamine is fed glutamic acid and amonium can be recovered from the upper gastrointestinal tract in appropriate quantities. One observation that provides some encouragement to the hypothesis stated is as follows Duodenal aspirate passed through a Seits filter released from glutamine the same amount of ammonium as was released by Source: https://www.industrydocuments.ucst.edu/docs/xglg227 - 2 - unfiltered aspirate, indicating that aspirate rendered free of bacteria by filtration still retains enzyme activity. Gastric juice contains significant quentities of ammonium under some circumstances. It seemed conceivable that the stomach may extract ammonium from arterial blood by trapping it in the acid gastric juice. If this were the case, one would expect to find large arteriovenous differences across the stomach. To determine whether or not this is the case two experiments were done in dogs. In these animals no arteriovenous difference was detected across the stomach. These experiments, however, were not considered entirely adequate because of difficulties concerning the adequacy of blood sampling from gastric veins in the dog, and obtaining large enough volumes of blood to provide for adequate replicate analyses. It may be possible to make similar observations on the arteriovenous difference for ammonium across the stomach in patients undergoing gastric surgery Since gastric juice does contain ammonium, it seemed worthwhile to determine what effect continuous gastric suction might have on arterial ammonium content. If arterial blood ammonium level could be reduced by this means, gastric suction would provide a method for removing ammonium from the body and conceivably might be of benefit to patients with hepatic coma. To date three patients have undergone continuous gastric suction following histamine induced secretion. In both these patients arterial blood emmonium levels decreased, although in these particular instances the levels were not markedly elevated to begin with. It is planned to determine the effects of gastric suction following histamine adminstration to patients with elevated blood ammonium levels. As an incidental observation it was noted that with histamine induced gastric secretion, volume of gastric juice increased while ammonium concentra- tion decreased. This suggests that total ammonium output into the gastric juice was unaltered by volume of secretion and appeared in gastric juice as a reciprocal of pH. These observations are of interest because they suggest that for gastric juice ammonium concentration is not related to the pH diffusion gradient between blood and juice. Studies dealing with the source and significance of ammonium in gastric juice are continuing B. The Kidney 1. Effect of Blood Ammonium Level on Renal Ammonium Production. The effect of elevated blood ammonium levels on renal ammonium production and excretion are being evaluated. These studies are based on the idea that increased levels of ammonium in arterial blood may inhibit renal production of ammonium from glutamine and other sources. Less ammonia might than be available for diffusion and excretion in the urine with hydrogen 1on and possibly account for the apparent susceptibility of patients with liver disease to the development of acidosis. To date, two patients with hepatic disease have been maintained on constant dietary regimens. Their ability to excrete acid loads (orally administered hydrochloric acid) was determined on two occasions in each patient at two levels of dietary protein intake. In one of these patients response to the acid load at both levels of protein intake Source: https://www.industrydocuments.ucsf.edu/docsixglg22 - 3 - were comparable, although blood ammonium level increased. The second patient study was unsatisfactory because increasing protein intake failed to produce elevated blood ammonium level. Additional selected patients will be similarly studied. In contrast to the hypothesis presented here, Owe et. al. (3. Clin. Invest. 40: 215, 1961) present evidence that hypexammonemia is associated with a decreased arterial-renal venous ammonium difference and increased excretion of ammonium in the urine indicating that arterial ammonium concentration significantly influences urinary ammonium excretion. From previous studies we have reason to doubt this finding. The studies outlined here should provide additional evidence that will help to clarify these opposing points of view concerning the influence of arterial ammonium level on urinary ammonium excretion. II. AMINO ACID METABOLISM A. Effects of Single Amino Acide on Metabolism of Potassium and Hydrogen Ion. These studies concern the effect of administering single amino acids on acid base balance. They were prompted by the observation that patients with liver disease given arginine orally or intravenously excrete increased quanti- ties of potassium in the urine. Two possible explanations for this potassium diuresis have been considered: 1) that arginine displaces extrarenal cellular potassium in a manner analogous to that demonstrated in vitro in which lysine displaced potassium from rat diaphragm, and 2) that arginine influences the handling of electrolytes at the renal level. Six subjects were studied in a metabolic ward. 155 millimoles of Laarginine or Laglutamic acid or L-arginine-L-glutamate was given daily for three days. The three days of amino acid administration were preceded and followed by con- trol periods of from six to twelve days. The arginine (free=base) and glutanic acid were given orally. Arginine hydrochloride, arginine-glutamate and sodium glutamate were administered intravenously . Daily urinary excretions of sodium, potassium, chloride, phosphorus, bicarbonate, ammonium, titratable acid and pH were determined, and blood electrolytes were measured serially. Illustrative data for one of the patients are shown in table 1. The administration of arginine, as free amino acid orally or as hydro- chloride or glutamate salt intravenously, was consistently accompanied by increases in potassium excretion ranging from 10-65% above control values. Arginine administration (except when given as hydrochloride) was also accompanied by increases in urine pH and by bicarbonate and decreases in titratable acid and ammonium excretion. Even when arginine hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloric acid alone. Alterations in blood electrolytes occurred only with arginine hydrochloride which induced decreases in pH and carbon dioxide content. Urinary potassium excretion was unaltered by sodium glutamate given intra- venously or glutamic acid given orally. Increases in urine pH and a large excre- tion of bicarbonate occurred with sodium glutamate. Glutamic acid per se did not effect the blood or urine constituents measured. Glutamic acid given as Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 - a - arginine-glutamate did not negate the effect of arginine on potassium excretion. When L-lysine was given, changes similer to those noted with L-arginine occurred L-aspartic acid feeding, like glutemic acid feeding had no effect on urine or blood electrolytes. Thus the matabolic effects noted occurred with basic (cationic) but not with acidic (anionic) amino acids. The results of these studies are illustrated in Table 2. Subsequent studies were designed to determine whether the cationic amino acids exerted these effects prinarily by influencing renal or extrarenal mechanisms. To this end the responses of three patients of 100 mEq of hydro- chloric acid given orally daily for three days, with and without simultaneous L-arginine administration, were determined. When the acid load was given with L-arginine there was approximately 50% less decrease in serun bicarbonate concentration and 40% less hydrogen 1on excreted in the urine than when hydro- chloric acid was given alone (Table 3). Urinary potassium excretions resulting from L-arginine were comparable to those resulting from hydrochloric acid administration. An additional study was done in a patient with chronic renal disease. A slowly progressive acidosis was induced in this patient by administration of hydrochloric acid orally. (25 mBq daily). Feeding L-arginine in addition to this acid resulted in a stabilization of serum bicarbonate concentration and pH without change in hydrogen ion excretion. If in this circumstance arginine was acting at the renal level to enhance urinary potassium excretion at the expense of hydrogen ion excretion, one would expect the acidosis to have become more profound. This did not occur, and on the contrary the developing acidosis was halted. When L-arginine was discontinued, serum bicarbonate concentration promptly decreased further indicating that the arginine had some effect within the body that controlled the developing acidosis. The current interpretation of these data is as follows Basic amino acids seem to behave as cations in the body and probably displace some intracellular potassium. The site of this displacement is not known. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some unknown mechanism increase total body buffering capacity Additional metabolic studies on patients are in progress to further elucidate the findings outlined above. In addition, mutritional experiments are being conducted in rats who are fed single anino acids in addition to a diet. If rats demonstrate responses similar to those observed in the patients, these animals will be utilized to further define the metabolic effects of single amino acids at the tissue level. Analysis of tissues Obtained from the rats should permit evaluation of the concept that cationic amino acids displace potassium. The site of this potassium displacement might also be established In addition, analysis of urine and preparations of tissues for amino acid content by the automatic amino acid analyzer will provide information con- cerning the effect of single amino acid administration upon tissue content of other amino acids. These studies may have pertinence to problems involved with "amino acid imbalance", may contribute to knowledge concerning the role of amino acids in Source: https://www.industrydocuments.ucsf.edu/docsixglg0221 - 5 - acid base balance, and may be pertinent to the responses of undernourished patients, including those with hepatic cirrhosis, to various metabolic alterations, such as acidosis, alkalosis, and potassium deficiency B. Amino Acid Excretion in Potassium Deficiency Because of reports indicating that in animals rendered potassium deficient, lysine content increased intracellularly, qualitative amino acid patterns were determined by circular paper chromstography on the urines obtained from patients who were rendered potassium deficient by diuretics. On each occasion when total urine potassium excretion decreased below 5 mEq, qualitative changes in free amino acid patterns were detectable in the urine. These changes are characterized by disappearance of basic amino acids which include lysine, arginine and histadine and the disappearance of a band corresponding most probably to glutamine, and the appearance of a cystine band. The interpretation of these qualitative paper chromatograms has limitations Accordingly, it is planned to confirm and quantitate these changes on the Spinco Automatic Acid Analyzer by analysis of urine and blood obtained from potassium deficient sub- jects. The quantitative amino acid data needed to evaluate the potential of this project should be forthcoming. Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 Effect of Arginine and Glutamic Acid on Urinary Electrolyte Excretion Patient G Male, 37 Yr. STUDY PERIOD URINARY EXCRETIONS - mEq/day T.A. NH3 Net H° R pH Control 23 33 56 67 5.71 Arginine P.O. 0 29 29 90 6.31 Control 23 37 60 57 5.53 Glutamic Acid p.o. 22 37 59 72 5.70 Control 17 33 50 75 5.97 Arginine-Glutemate P.O. 11 26 37 91 6.34 Control 21 34 55 65 5.75 Arginine-Glutemate i.v. 0 29 29 90 6.48 Control 23 37 60 57 5.76 T.A. = titratable acid Net H+ ma titratable acid plus ammonia Table 1 Source: https://www.industrydocuments.ucst.edu/docsixglgo227

What is the pH of Arginine-Glutamate p.o.?

xglg0227

xglg0227_p0, xglg0227_p1, xglg0227_p2, xglg0227_p3, xglg0227_p4, xglg0227_p5, xglg0227_p6, xglg0227_p7

6.34

ABSTRACT AD NO. Accession No. 1. Preparing Institution: Western Reserve University School of Medicine (Cleveland Metropolitan General Hospital) Cleveland, Ohio 2. Title of Report: Metabolism of Protein, Anino Acids and Ammonia in Patients with Liver Disease 3. Principal Investigator: George J. Gabuzda, M.D. 4. Number of pages; date: six pages, three tables; April, 1961 5. Contract Number: DA-49-007-MD-749 6. Supported by: Research and Development Division Office of the Surgeon General, Department of Army Washington 25, D.C. The metabolic effects of administering single emino acids are being investigated in patients. The administration of L-arginine orally or intravenously was consistently accompanied by increases in urinary potassium and bicarbonate excretions, urine pH and decreases in titratable acid and emmonium excretions. When arginino hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloride acid alone. No alterations in blood electrolytes occurred. L-lysine resulted in changes similar to those noted with Laaginine. The administration of Laggutamic acid or L-aspartic acid had no effect on urine or blood electrolytes. Thus the metabolic effects observed occurred with basic (cationic) but not with acidie (anionic) amino acids. L-arginine feeding with hydrochloride acid resulted in less decrease in serum bicarbonate concentration and less excretion of hydrogen ion in the urine than when the hydrochloric acid was given alone. In addition, a patient with chronic renal disease maintained in a progressively acidotic state by the oral administration of hydrochloric acid stabilized serum bicarbonate concentration and pH without changing hydrogen ion excretion when L=arginine was fed, These data are interpreted as follows Basic amino acids behave as cations in the body and probably displace some intracellular potassium. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some mechanism increase total body buffering capacity Other investigations in progress include: 1) the role of the upper gastro intestinal tract as a source of blood ammonium and as a possible aite for removal of ammonium; 2) the relation of blood ammonium levels to renal ammonium production and excretion; and 3) alterations in urinary amino acid excretions that may occur in potassium deficiency states. Data available is at this time insufficient to warrant presentation or interpretation of the findings in these areas. Copies of this report are filed with the Armed Services Technical Information Agency. Arlington Hall Station, Arlington 12, Virginia, and may be obtained from that agency by qualified investigators working under Government Contract. Source: https://www.industrydocuments.ucsf.edu/docsixglg022 PROGRESS REPORT - TO THE SURGEON GENERAL DEPARTMENT OF THE ARMY Contract No. DA-49-007-M0-749 May 1, 1960 - April 30, 1961 Metabolism of Protein, Amino Acids and Ammonia in Patients with Liver Disease Responsible Investigator: George J. Gabuzda, M.D. Associate Professor of Medicine Western Reserve University School of Medicine at Cleveland Matropolitan General Hospital Cleveland, Oh1o Supported by: Research and Development Division Office of the Surgeon General Department of the Anny Washington 25, D.C. April, 1961 Source: https://www.industrydocuments.ucsf.edu/docsixgg0227 Introduction Metabolism of ammonium amino acids and protein in patients with liver disease is the primary subject of investigations conducted under this contract. These studies have been oriented to the relation of disordered nitrogen meta- bolism to hepatic coma and to the responses of these patients to metabolic loads. The current status of investigations dealing with the role of the ugper gastrointestinal tract and of the kidney in ammonium matabolism is outlined below in perspective to past work from this laboratory. The effect of adminis- cering single amino acids on acid base balance has been a prominent subject of investigation during the past year. Accordingly, the findings resulting from these studies are presented in more detail. Although the amino acid studies were accomplished primarily in patients with cirrhosis of the liver, the results may well have pertinence to more general problems of protein nutrition and the responses of undernourished subjects, including chose with liver disease, to various metabolic altezations such as acidosis, alkalosis and potassium deficiency. I. METABOLISM OF AMMONIUM A. The Upper Gastrointestinal Tract The role of the upper gastrointestinal tract in ammonium metabolism has been approached from two points of view. 1) The upper gastrointestinal tract as a source of ammonium, and 2) the upper gastrointestinal tract as a possible site for removal of ammonium from the body. In conjunction with these studies several observations have been made that may be pertinent to normal gastric physiology. Based on previous work from these laboratories, the hypothesis has been made that nonbacterial "amidase", present in the upper gastrointestinal tract, may account for release of ammonium (amide nitrogen) from glutamine. In several patients serial aspirates of duodenal juice obtained after glutamine feeding demonstrated by qualitative bidimensional paper chromatography in- creased amounts of glutamic acid. Interpretation of this finding has been held in reservation since there was uncertainty about the adequacy of the separation procedure for glutamine and glutamic acid by the method employed. In addition, attempts to recover increased ammonium resulting fxom the deamidation of glutamine were not consistently successful. During the past year some effort has been directed at improving the technology involved in these studies. It is difficult to do adequate ammonium determinations on raw gastric or duodenal aspirate by the Conway method. This method has now been modified to involve the collection of the aspirates directly into trichlor= acetic acid. This is centrifuged and appropriate dilutions of the supernates then taken for analysis. The latter procedure permits more accurate and consistent analyses. In addition a method (Waelsh, et. al.) is being set up for the separation of glutamic acid and glutemine utilizing a magnesium ozide ion exchange column. The latter should provide a mich more adequate method for these determinations. After this methodology is established, studies will continue attempting to demonstrate that when glutamine is fed glutamic acid and amonium can be recovered from the upper gastrointestinal tract in appropriate quantities. One observation that provides some encouragement to the hypothesis stated is as follows Duodenal aspirate passed through a Seits filter released from glutamine the same amount of ammonium as was released by Source: https://www.industrydocuments.ucst.edu/docs/xglg227 - 2 - unfiltered aspirate, indicating that aspirate rendered free of bacteria by filtration still retains enzyme activity. Gastric juice contains significant quentities of ammonium under some circumstances. It seemed conceivable that the stomach may extract ammonium from arterial blood by trapping it in the acid gastric juice. If this were the case, one would expect to find large arteriovenous differences across the stomach. To determine whether or not this is the case two experiments were done in dogs. In these animals no arteriovenous difference was detected across the stomach. These experiments, however, were not considered entirely adequate because of difficulties concerning the adequacy of blood sampling from gastric veins in the dog, and obtaining large enough volumes of blood to provide for adequate replicate analyses. It may be possible to make similar observations on the arteriovenous difference for ammonium across the stomach in patients undergoing gastric surgery Since gastric juice does contain ammonium, it seemed worthwhile to determine what effect continuous gastric suction might have on arterial ammonium content. If arterial blood ammonium level could be reduced by this means, gastric suction would provide a method for removing ammonium from the body and conceivably might be of benefit to patients with hepatic coma. To date three patients have undergone continuous gastric suction following histamine induced secretion. In both these patients arterial blood emmonium levels decreased, although in these particular instances the levels were not markedly elevated to begin with. It is planned to determine the effects of gastric suction following histamine adminstration to patients with elevated blood ammonium levels. As an incidental observation it was noted that with histamine induced gastric secretion, volume of gastric juice increased while ammonium concentra- tion decreased. This suggests that total ammonium output into the gastric juice was unaltered by volume of secretion and appeared in gastric juice as a reciprocal of pH. These observations are of interest because they suggest that for gastric juice ammonium concentration is not related to the pH diffusion gradient between blood and juice. Studies dealing with the source and significance of ammonium in gastric juice are continuing B. The Kidney 1. Effect of Blood Ammonium Level on Renal Ammonium Production. The effect of elevated blood ammonium levels on renal ammonium production and excretion are being evaluated. These studies are based on the idea that increased levels of ammonium in arterial blood may inhibit renal production of ammonium from glutamine and other sources. Less ammonia might than be available for diffusion and excretion in the urine with hydrogen 1on and possibly account for the apparent susceptibility of patients with liver disease to the development of acidosis. To date, two patients with hepatic disease have been maintained on constant dietary regimens. Their ability to excrete acid loads (orally administered hydrochloric acid) was determined on two occasions in each patient at two levels of dietary protein intake. In one of these patients response to the acid load at both levels of protein intake Source: https://www.industrydocuments.ucsf.edu/docsixglg22 - 3 - were comparable, although blood ammonium level increased. The second patient study was unsatisfactory because increasing protein intake failed to produce elevated blood ammonium level. Additional selected patients will be similarly studied. In contrast to the hypothesis presented here, Owe et. al. (3. Clin. Invest. 40: 215, 1961) present evidence that hypexammonemia is associated with a decreased arterial-renal venous ammonium difference and increased excretion of ammonium in the urine indicating that arterial ammonium concentration significantly influences urinary ammonium excretion. From previous studies we have reason to doubt this finding. The studies outlined here should provide additional evidence that will help to clarify these opposing points of view concerning the influence of arterial ammonium level on urinary ammonium excretion. II. AMINO ACID METABOLISM A. Effects of Single Amino Acide on Metabolism of Potassium and Hydrogen Ion. These studies concern the effect of administering single amino acids on acid base balance. They were prompted by the observation that patients with liver disease given arginine orally or intravenously excrete increased quanti- ties of potassium in the urine. Two possible explanations for this potassium diuresis have been considered: 1) that arginine displaces extrarenal cellular potassium in a manner analogous to that demonstrated in vitro in which lysine displaced potassium from rat diaphragm, and 2) that arginine influences the handling of electrolytes at the renal level. Six subjects were studied in a metabolic ward. 155 millimoles of Laarginine or Laglutamic acid or L-arginine-L-glutamate was given daily for three days. The three days of amino acid administration were preceded and followed by con- trol periods of from six to twelve days. The arginine (free=base) and glutanic acid were given orally. Arginine hydrochloride, arginine-glutamate and sodium glutamate were administered intravenously . Daily urinary excretions of sodium, potassium, chloride, phosphorus, bicarbonate, ammonium, titratable acid and pH were determined, and blood electrolytes were measured serially. Illustrative data for one of the patients are shown in table 1. The administration of arginine, as free amino acid orally or as hydro- chloride or glutamate salt intravenously, was consistently accompanied by increases in potassium excretion ranging from 10-65% above control values. Arginine administration (except when given as hydrochloride) was also accompanied by increases in urine pH and by bicarbonate and decreases in titratable acid and ammonium excretion. Even when arginine hydrochloride was given, acidification of the urine and ammonium production were delayed as compared to the renal response to hydrochloric acid alone. Alterations in blood electrolytes occurred only with arginine hydrochloride which induced decreases in pH and carbon dioxide content. Urinary potassium excretion was unaltered by sodium glutamate given intra- venously or glutamic acid given orally. Increases in urine pH and a large excre- tion of bicarbonate occurred with sodium glutamate. Glutamic acid per se did not effect the blood or urine constituents measured. Glutamic acid given as Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 - a - arginine-glutamate did not negate the effect of arginine on potassium excretion. When L-lysine was given, changes similer to those noted with L-arginine occurred L-aspartic acid feeding, like glutemic acid feeding had no effect on urine or blood electrolytes. Thus the matabolic effects noted occurred with basic (cationic) but not with acidic (anionic) amino acids. The results of these studies are illustrated in Table 2. Subsequent studies were designed to determine whether the cationic amino acids exerted these effects prinarily by influencing renal or extrarenal mechanisms. To this end the responses of three patients of 100 mEq of hydro- chloric acid given orally daily for three days, with and without simultaneous L-arginine administration, were determined. When the acid load was given with L-arginine there was approximately 50% less decrease in serun bicarbonate concentration and 40% less hydrogen 1on excreted in the urine than when hydro- chloric acid was given alone (Table 3). Urinary potassium excretions resulting from L-arginine were comparable to those resulting from hydrochloric acid administration. An additional study was done in a patient with chronic renal disease. A slowly progressive acidosis was induced in this patient by administration of hydrochloric acid orally. (25 mBq daily). Feeding L-arginine in addition to this acid resulted in a stabilization of serum bicarbonate concentration and pH without change in hydrogen ion excretion. If in this circumstance arginine was acting at the renal level to enhance urinary potassium excretion at the expense of hydrogen ion excretion, one would expect the acidosis to have become more profound. This did not occur, and on the contrary the developing acidosis was halted. When L-arginine was discontinued, serum bicarbonate concentration promptly decreased further indicating that the arginine had some effect within the body that controlled the developing acidosis. The current interpretation of these data is as follows Basic amino acids seem to behave as cations in the body and probably displace some intracellular potassium. The site of this displacement is not known. Basic amino acids also either decrease the production of hydrogen ion requiring excretion or by some unknown mechanism increase total body buffering capacity Additional metabolic studies on patients are in progress to further elucidate the findings outlined above. In addition, mutritional experiments are being conducted in rats who are fed single anino acids in addition to a diet. If rats demonstrate responses similar to those observed in the patients, these animals will be utilized to further define the metabolic effects of single amino acids at the tissue level. Analysis of tissues Obtained from the rats should permit evaluation of the concept that cationic amino acids displace potassium. The site of this potassium displacement might also be established In addition, analysis of urine and preparations of tissues for amino acid content by the automatic amino acid analyzer will provide information con- cerning the effect of single amino acid administration upon tissue content of other amino acids. These studies may have pertinence to problems involved with "amino acid imbalance", may contribute to knowledge concerning the role of amino acids in Source: https://www.industrydocuments.ucsf.edu/docsixglg0221 - 5 - acid base balance, and may be pertinent to the responses of undernourished patients, including those with hepatic cirrhosis, to various metabolic alterations, such as acidosis, alkalosis, and potassium deficiency B. Amino Acid Excretion in Potassium Deficiency Because of reports indicating that in animals rendered potassium deficient, lysine content increased intracellularly, qualitative amino acid patterns were determined by circular paper chromstography on the urines obtained from patients who were rendered potassium deficient by diuretics. On each occasion when total urine potassium excretion decreased below 5 mEq, qualitative changes in free amino acid patterns were detectable in the urine. These changes are characterized by disappearance of basic amino acids which include lysine, arginine and histadine and the disappearance of a band corresponding most probably to glutamine, and the appearance of a cystine band. The interpretation of these qualitative paper chromatograms has limitations Accordingly, it is planned to confirm and quantitate these changes on the Spinco Automatic Acid Analyzer by analysis of urine and blood obtained from potassium deficient sub- jects. The quantitative amino acid data needed to evaluate the potential of this project should be forthcoming. Source: https://www.industrydocuments.ucsf.edu/docs/xglg0227 Effect of Arginine and Glutamic Acid on Urinary Electrolyte Excretion Patient G Male, 37 Yr. STUDY PERIOD URINARY EXCRETIONS - mEq/day T.A. NH3 Net H° R pH Control 23 33 56 67 5.71 Arginine P.O. 0 29 29 90 6.31 Control 23 37 60 57 5.53 Glutamic Acid p.o. 22 37 59 72 5.70 Control 17 33 50 75 5.97 Arginine-Glutemate P.O. 11 26 37 91 6.34 Control 21 34 55 65 5.75 Arginine-Glutemate i.v. 0 29 29 90 6.48 Control 23 37 60 57 5.76 T.A. = titratable acid Net H+ ma titratable acid plus ammonia Table 1 Source: https://www.industrydocuments.ucst.edu/docsixglgo227

What is the name of the person?

xklg0227

xklg0227_p0

Irene Karl

Name Title Amount de Dates 02 28 46148 IRENE KARL 223235110064117 Res. Ass't 500.00 100.00 3510 2/1/63 * 2/28/63 * 18.13 500.00 18.13 Source: https://www.industrydocuments.ucsf.edu/docs/xklg0227

What is the title?

xklg0227

xklg0227_p0

"Res. Asst"

Name Title Amount de Dates 02 28 46148 IRENE KARL 223235110064117 Res. Ass't 500.00 100.00 3510 2/1/63 * 2/28/63 * 18.13 500.00 18.13 Source: https://www.industrydocuments.ucsf.edu/docs/xklg0227

What is the amount?

xklg0227

xklg0227_p0

500.00

Name Title Amount de Dates 02 28 46148 IRENE KARL 223235110064117 Res. Ass't 500.00 100.00 3510 2/1/63 * 2/28/63 * 18.13 500.00 18.13 Source: https://www.industrydocuments.ucsf.edu/docs/xklg0227

The first image represents which nutrient?

rlnf0227

rlnf0227_p22, rlnf0227_p23, rlnf0227_p24, rlnf0227_p25, rlnf0227_p26, rlnf0227_p27, rlnf0227_p28, rlnf0227_p29, rlnf0227_p30, rlnf0227_p31, rlnf0227_p32, rlnf0227_p33, rlnf0227_p34, rlnf0227_p35, rlnf0227_p36, rlnf0227_p37, rlnf0227_p38, rlnf0227_p39, rlnf0227_p40, rlnf0227_p41, rlnf0227_p42, rlnf0227_p43

Vitamins

lating research findings. Because of a general noted that this language is ambiguous. It does lack of accessibility, it is often extremely dif- not specify "lead," and it leaves cooperation ficult for agencies to communicate research to the goodwill of HEW. information to the public or Congress. The need for improved coordination in Of course, some overlap in interests is in- nutrition research extends beyond the execu- evitable in similar areas of research, and tive agencies to Congress. At present 14 con- duplication of research results is a necessary gressional committees and 20 subcommittees part of scientific research. But unnecessary are concerned with nutrition matters. The duplication should be avoided. Minimizing principals include the Senate Committees on duplication by developing more efficient Agriculture, Nutrition, and Forestry (Sub- means of sharing information on planned, on- committee on Nutrition); Appropriations going, and completed research is an achiev- (Subcommittees on Labor-Health, Education able goal. and Welfare, and Agriculture); the House In the same sense that some duplication is Agriculture Committee (Subcommittee on a necessary part of scientific research, Domestic Marketing, Consumer Relations, healthy competition among agencies may and Nutrition); the House Appropriations stimulate greater effort and ultimately bene- Committee (Subcommittees on Agriculture fit the public. But the proprietary stance and Labor-Health, Education, and Welfare); taken by some agencies is wasteful and in- House Interstate and Foreign Commerce hibits joint planning. Internecine struggles at Committee (Subcommittees on Oversight and higher levels of Government apparently fos- Investigations, and Health and Environment); ter such attitudes. However, career civil serv- and the House Science and Technology Com- ants and the public, as well as the overall mittee (Subcommittee on Domestic and Inter- Federal research effort, suffer as a result. national Scientific Planning, Analysis, and The turf battles that lead agencies to work at Cooperation, and the Subcommittee on Sci- cross purposes should be eliminated. Agen- ence, Research, and Technology). Since some cies involved in nutrition research should duplication of interest exists, joint sessions of demonstrate a commitment to coordination relevant congressional subcommittees to con- and the avoidance of unnecessary duplica- sider plans and hearings for oversight pur- tion. This commitment needs to be built in, not poses should be considered. only at the "political" level of the higher There is a strong relationship between echelons of Government but also in the career human nutrition research conducted abroad civil service. and research needs in the United States. The The establishment at USDA of the Human research goals identified in this report can be Nutrition Center and the Human Nutrition best achieved if international and domestic Policy Committee and at HEW of the Nutrition research activities are tuned together. Coordinating Committee are two positive Nutrition research in other countries may steps toward intra-agency coordination. They help in solving domestic nutrition problems. not only indicate a commitment to nutrition For example, epidemiological investigations research but also can serve as mechanisms of certain chronic diseases require good in- for interagency coordination and information formation about disease incidence. This may exchange. be obtained from studies of societies with The Food and Agriculture Act of 1977 lifestyles and food habits very different from specifies that the Secretary of Agriculture our own. The high incidence of malnutrition shall "periodically consult with the adminis- in some developing nations also provides an trators of other Federal departments and opportunity to investigate relationships be- agencies that have responsibility for coor- tween the nutritional status and functional dinating Federal nutrition research activ- performance of individuals in a way that ities." However without the support and in- would be impossible in the United States. It volvement of the Secretary of HEW, unilat- may be possible to extrapolate the results of eral USDA efforts to coordinate research studies of severe malnutrition abroad to may not be effective. Likewise, it should be margina! nutritional areas in this country. 16 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 The study of worldwide populations and will have a dual reward-assistance to mal- food patterns is essential to the better under- nourished peoples abroad and increased standing of some of the priority research knowledge of human nutrient needs and areas of nutrition. Thus any effort to increase health status under changing environmental international nutrition research capabilities conditions. ISSUE 2 - Definition and Funding of Human Nutrition Research If one accepts that the goals of human genetics, animal nutrition, plant nutrition, nutrition research are twofold-(1) the pro- and plant genetics comes under this classi- motion of optimum health and performance, fication. While there is need to integrate such and (2) the treatment of diseases through diet agricultural research with human nutrition therapy and the support of other medical concerns, these areas should not be consid- therapies-th definition of human nutrition ered human nutrition research. Similarly, research flows from these stated goals. If all basic research on metabolism of nutrients, if the research areas involving nutrition are not directly applicable to people, should not listed, from basic studies on the metabolism be considered human nutrition research. of nutrients to genetic studies on the develop- Basic research on metabolism should be con- ment of foods with specific nutrient charac- sidered as basic research underlying all of teristics, it is clear that some areas of the biomedical and life sciences. Human research are more closely related to these nutrition research builds upon this knowl- stated goals than others. Accordingly, the edge base, but the apparent commitment to definition of human nutrition research must and budget for human nutrition research take into account these relationships to should not be inflated by its inclusion. stated goals. Throughout this assessment, a recurrent In terms of this assessment, nutrition problem has been that of definition of human research falls into three broad categories. nutrition research. Agencies report as human Most closely related to the stated goals is nutrition research studies that appear to research into the biochemical and physiologi- have little to do with human nutrition. Ex- cal effects of food on the body in health and amples are "Catalytic Functions and Metab- disease. This category includes research on olism of Vitamin B6 in Bacteria and Fungi," nutritional management of disease, nutrient "Nutritional Imbalance and Metabolic Alter- needs and interactions, and research which ations in Fungi," or "Hepatoma Incidence in promotes optimum health and disease pre- Trout on Dietary Aflatoxin and PCB." Such vention through diet. studies are worthwhile and contribute to our understanding of basic biochemistry but are Research on food and nutrition quality not directly applicable to humans. determinants is also related to the stated The almost unanimous consensus of the goals, but less directly so than the previous category. Under this heading would be re- participants in the OTA study was that at- search into food composition, especially the tribution of these Federal expenditures to nutritive components and changes in nutrient "human nutrition research" was improper. composition that occur from point of origin to Fourteen different Federal agencies are point of consumption; food safety; social, cul- engaged in some sort of nutrition research. tural, and economic aspects of food habits; Each agency has developed its own definition feeding programs; nutrition education; con- of human nutrition research and set priorities sumer information; and nutrition surveillance on the basis of how it interprets its legislation and monitoring. mandate. The agencies and their priorities are shown in table 3. The third category of research involves basic research on sources of human food and Federal expenditures for human nutrition basic biochemistry. Research into animal research in FY 1977 (shown in table 4) were 17 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3. - Federal Government Agencies Active in Food and Nutrition Programs and Their Nutrition Research Priorities Food and nutrition Department Agency programs Research priorities Health, Edu- National National Institute of Arthritis, Metabolism, and Digestive Diseases cation, & Institutes (NIAMDD).Basic hysiological studies of nutrients; basic metabolism Welfare of Health studies; obesit, trace elements nutrition support of patients; fiber; anemias. National Institute of Child Health and Human Development (NICHHD). Nutrition and fetal development; metabolic capacities of normal, low- birthweight, and premature infants; diet modification for low-birth- weight and premature infants; optimum nutrition in developmental years; nutrition and reproductive potential; genetic variability-nuti tional interaction; prevention- - metabolic antecedents of adult disease. National Cancer Institute (NCI). Nutrition support of cancer patient; nu- trition in cancer etiology; host-tumor interactions and competition for nutrients; prevention strategies based on nutrition; diet and nutrition in the rehabilitation of cancer patients. National Heart, Lung, and Blood Institute (NHLBI). Nutrition in etiology of arteriosclerosis and hypertension; achieving and maintaining dietary change; development of food composition tables; methodology-col lecting, recording, and evaluating dietary data. National Institute of General Medical Sciences (NIGMS). Trauma- tized/burned patients and nutrition. National Institute of Environmental Health Sciences (NIEHS). Neuro- toxicity; mutagenesis; teratology; environmental contaminants in food. National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Protein-calorie malnutrition, B-vitamin deficiencies and the nervous system; genetic disorders and the nervous system; specific nutritional problems in the central nervous system; stroke. National Institute of Dental Research (NIDR). Sucrose and caries; poor nutrition and periodontal disease; poor nutrition and oral mucus mem- branes; nutrition in craniofacial malformations and oral-facial struc- tures; nutrition and salivary gland development. National Institute of Allergy and Infectious Disease (NIAID). Interrelated factors hearing on malnutrition, infection, and the immune system. National Eye Institute (NEI). Vitamins A, B-12, and other nutrients in visual processes; diseases of visual system, e.g., keratomalacia; metab- olism of visual cells; protein changes in the lens. National Institute on Aging (NIA). Nutritional status of the elderly; aspects of increase in life span including dietary manipulations; vitamin supplementation in elderly; nutrient intake as a consequence of econ- omic status in elderly; relationship among nutrition, cellular structure, and function in elderly. Division of Research Resources (DRR). Nutrient requirements for growth, gestation, lactation in primates and laboratory rodents; stand- ard diets for specific objectives; interaction of various nutrients on physiological function in laboratory animals; differences in nutrient re- quirements among strains of animals within a species. Food & Regulatory activities Nutrient efficacy and safety; nutrient interrelationships as concerned Drug related to: nutrition with disease prevention; nutrient bioavailability for food fortification Admin- labeling, ingredient purposes; nutrient quality assessment of processed foods; medical istration labeling, food for food assessment; food composition and nutrient analysis as related to special dietary use, FDA mission; and consumer studies of perceptions about food values food advertising, nutri- and nutritional quality and educational models to help correct tion quality of foods misconceptions about them. Health Re- Health and Nutrition Assessment of the nutritional status of the American people. sources Examination Survey Admin- istration 18 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3 - -continued Food and nutrition Department Agency programs Research priorities Center for Epidemiological surveillance studies in cooperation with State Disease agencies assistance to AID in similar international areas. Control Health Collaborative research and screening program for phenylketonuria. Services Admin- istration Alcohol, Effects of alcohol consumption on nutrient metabolism and nutritional Drug deficiencies; study of food additive consumption and hyperactivity Abuse, & in children. Mental 5 Health Admin- istration Agriculture Agricul- Human Requirements for Nutrients tural Re- Determine the requirements for lipid intake and identification of the search forms of these nutrients in foods that may be useful in meeting Service* these requirements. Determine the requirements for mineral intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for vitamin intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for protein and amino acid intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for carbohydrate and energy intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Food Composition and Improvement To provide accurate, up-to-date, and comprehensive information in a readily usable form on the composition of all important foods for those nutrients required by and biologically useful to man. To provide the technology for the nutritional improvement of foods when enhanced levels of certain nutrients in the diet are needed to correct possible dietary faults. Food Consumption and Use To provide accurate, up-to-date, and comprehensive information in a readily usable form on food consumption and dietary levels. To provide consultative assistance on food and nutrition problems and provide sound guidance materials on nutrition for the consumer and for nutrition educators, program leaders, and food program man- agers; to identify techniques which will assist people in selecting nu- tritionally adequate diets within different budget limitations; to iden- tify means to modify undesirable food habits; to strengthen nutri- tionally desirable food choice. To identify and develop suitable and safe procedures for food man- agement and preparation for home and institutional consumers, for best retention of both nutritional and eating qualities and to avoid food-borne illness. Coopera- Nutrient requirements; nutritional status of special population groups tive State including children, low income, and aging; metabolic function of Research nutrients in the diet and their interactions; nutrient content of foods; Service* effects of processing on nutrients; food delivery systems; food habits and use); dietary patterns. 19 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table -continued Food and nutrition Department Agency programs Research priorities Economic Economic and social research relating to domestic food programs; Research nutrition policy in LDCs; food choices (demand); nutritional programs Service' for the elderly. Defense Determination of nutritional and dietary standards for Armed Forces personnel subsisted under normal and special operating conditions; evaluation of nutritional adequacy of food as consumed; evaluation of the nutritional status of Armed Forces personnel; establishment of sanitary and food hygiene standards for all food program activities; food aspects of preventive medicine. National Nutritional control of neurotransmitters; role of dietary protein and Aeronautics specific amino acids in optimizing human performance under stress. & Space Ad- ministration Veterans Depart- Research in disease and diet: nutrition and disease or clinical nutrition, Adminis- ment of dietary therapy; effect of disease on nutrition; environmental toxicants, tration Medicine alcohol, and nutrition; nutrition and cancer; nutrition and vision re- & Surgery search; nutrition-related therapy. Metabolic effects: Investigations on or related to malabsorption syn- dromes, inborn errors of metabolism, and familial or inherited nutri- tional defects. Nutrition requirements: Studies of nutrient metabolism, malnutrition, neuroendocrine nutrient interactions, fundamental intermediary metab- olism involving the role of one or more nutrients. State Agency Development of new low-cost nutritious foods; development and for Inter- dissemination of new appropriate technologies; understanding national nutritional needs and requirements; testing and evaluation of nutrition Develop- program alternatives; research on methodologies for improving national ment nutrition planning and programing. National Basic research in the behavioral, education, and social sciences in Science areas applicable to foods and nutrition. Foundation Under USDA's recent reorganization, ARS is now called Federal Research, and is housed within the Science and Education Administration. Under USDA S recent reorganization, CRS is called Cooperative Research and is housed within the Science and Education Administration Under USDA S recent reorganization, ERS is called Economics and is housed within the Economics, Statistics. and Cooperatives Service. Under USDA recent reorganization, ES is called Extension and is housed within the Science and Education Administration estimated at between $50 million and $117 tion research. Seventy-five percent of Federal million, depending on how "nutrition re- nutrition research is conducted outside of the search' was defined. If for example, the NIH two departments through competitive grants definition is used, NIH appears to be spend- and contracts. Using the more realistic fund- ing $80 million for human nutrition research. ing figure of $50 million for FY 1977, NIH at This broad definition takes in studies of basic HEW funded 44 percent of the total, and the biochemistry, studies which are not focused Science and Education Administration (SEA) on nutrition but have a nutrition aspect, as at USDA funded 43 percent of the total. The well as studies of primary nutrition. If a nar- Science and Education Administration en- row definition is used, one encompassing only compasses what were formerly known as the those studies of direct clinical applications Agricultural Research Service and the Coop- and disease prevention, the NIH nutrition erative State Research Service. Under research funding falls in the annual range of USDA's new reorganization, most human nu- $20 million. Even the higher $80 million trition research will be coordinated by SEA's figure, incidentally, amounts to less than 3 Human Nutrition Center. percent of the NIH research budget. The Science and Education Administration HEW and USDA are responsible for the Cooperative Research (SEA-CR) of USDA is majority of federally supported human nutri- unique among Federal agencies in that it links 20 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 Table 4. - Federal Expenditures for Human Nutrition Research An Approximation of FY '77 Expenditures (millions of dollars) Office of Science & Office of Management Agency Technology Policy & Budgetb Department of Health, Education, & Welfare $ 88.6 $22.0 National Institutes of Health 80.4C 22.0d Food and Drug Administration 3.9 National Center for Health Statistics 2.4 Alcohol, Drug Abuse, and Mental Health Administration 1.1 Health Services Administration 0.5* Center for Disease Control 0.3* Department of Agriculture 22.0 21.8 Agricultural Research Service 14.0 13.2 Cooperative State Research Service 7.5 8.1 Economic Research Service 0.5 0.5 Agency for International Development 2.9 0 Department of Defense 2.3* 2.2 Veterans Administration 0.5* 4.1 National Science Foundation 0.3* 0 Grand total. $116.6 $50.2 affice of Science and Technology Policy, New Directions in Federally Supported Human Nutrition Research, December 1977. Poffice of Management and Budget, Special Analyses-Budget of the U.S. Government FY 1979. This figure includes studies designed to assess the mechanisms and the consequences of food or nutrient intake in the intact organism. particularly man: investigations involving nutrient variables at the cellular or subcellular level, including metabolic studies in animals and man: research designed to elucidate the metabolic role or function of an essential nutrient in both animal models and man, as appropriate; all studies concerned with genetic-nutrient-environmental interactions; dietary studies ex- pected to produce changes in health status, including the maintenance of health and the treatment of disease in man. This figure includes biochemical, physiological, and clinical studies of nutritional needs for normal growth, development, and health: nutritional needs of patients with specific common diseases: and experimental assessments of feeding programs. *Estimates of FY 1976 expenditures provided by draft Government Accounting Office report, Human Nutrition Research- Need for a Coordinated Approach to Advance Our Knowledge, 1977. Federal and State research efforts. SEA-CR levels could be made since current estimates administers funds that Congress appropri- of Federal spending for human nutrition ates to the States for agricultural research. research are questionable. Estimates for FY This work is conducted at the State agricul- 1977 range from $50 million to $117 million tural experiment stations, land-grant colleges (table 4). The lower figure, based on agency and universities, approved schools of for- responses to a standard questionnaire, was estry, colleges of 1890, and Tuskegee In- developed by the Office of Management and stitute. In FY 1977, the States used $7.5 Budget (OMB) for the FY 1979 budget. The million of the Federal money available to higher figure came from an OSTP working them for human nutrition research. The group and appeared in the December 1977 States themselves provided $11.7 million for report "New Directions in Human Nutrition human nutrition research in 1976. Most of Research." the Federal money came from funds author- ized by the Hatch Act, as amended, and P.L. Neither is reliable. The $50 million, for ex- 89-106 (an act to amend the Agriculture Act ample, fails to include certain nutrition of 1954). The funds are accounted for under research activities within HEW, AID, and the the Hatch Act research program called Peo- National Science Foundation. The $117 mil- ple, Communities, and Institutions, which lion, on the other hand, includes $80.4 million comprised 12 percent of total Hatch Act of NIH spending-much of it of tenuous con- research funds in 1977. nection to human nutrition research. In testi- mony before the Senate Select Committee on Federal human nutrition research may be Nutrition and Human Needs on October 17, financially undernourished. However, no 1977, NIH Director Dr. Donald Fredrickson analysis of the adequacy of present funding conceded that, based on a strict definition, 21 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 his agency devoted only around $20 million to whether any of these funds are devoted to human nutrition research in FY 1977 (a fig- research on which methods are most effeo- ure reported to OMB). tive for reaching people. Another statistic which raised questions OTA concluded that most estimates of came from the Veterans Administration (VA). human nutrition research funding were ques- GAO put the VA's FY 1976 nutrition research tionable and that total funding fell con- spending at $0.5 million. In FY 1977, the VA siderably short of the reported $117 million reported sharply increased expenditures of level. Regardless of which overall figure is $4.1 million, even though nutrition research more nearly accurate, certain areas iden- was not recognized as a high priority by the tified by OTA are not now receiving sufficient agency. Federal support, the result of a lack of recognition of their importance and zero or In some cases, it was difficult to determine almost no funds. Those areas most in need of how much (if any) money was being spent for increased funding are the role of diet in the certain types of important nutrition research. prevention of chronic disease and obesity, For instance, the Federal Government is now nutrition education and consumer informa- annually spending about $70 million on nutri- tion, monitoring nutritional status, and nutri- tion education programs. It is unclear tion policy and management. ISSUE 3 - Personnel Resource Requirements Estimates of the number of scientists they are engaged in research activities. This engaged in human nutrition research also does not indicate the degree of involvement proved elusive. and, of course, neglects those outside of dietetics engaged in nutrition research. In an attempt to determine the current number of scientists engaged in human-nutri- The two Government agencies that fund tion research and the numbers of research the largest portion of nutrition research, scientists being trained, OTA contacted five HEW and USDA, do maintain figures on sci- professional societies and six Government entist-years devoted to nutrition research agencies. Of the professional societies, the and 5-year projections of personnel needs. At American Public Health Association, Insti- USDA in FY 1976, 193.5 scientist years were tute of Food Technologists, and American devoted to human nutrition research as de- Chemical Society make no attempt to distin- fined by the agency. The 5-year projection of guish between members engaged in research need for nutrition research scientists at versus other career orientations and USDA is for 260.7 scientist years, a 20-per- therefore could not supply information on the cent increase. proportion of their membership engaged in In a written response to an OTA question- human nutrition research or training of nutri- naire, NIH informed OTA that 70 scientists tion research scientists. Membership in the were employed in human nutrition research American Institute of Nutrition (AIN) is in 1977. But NIH Director Fredrickson sub- limited to those who have made significant mitted a written statement to the Senate contributions to the field of nutrition re- Select Committee on Nutrition and Human search. By definition, all of AIN's 1,730 mem- Needs that during that same time period 180 bers are nutrition research scientists. This intramural investigators in NIH were directly number seriously underestimates the total involved in human nutrition research. Of that number of scientists in the field, since junior number, 20 were defined as "classical nutri- people are not eligible for membership and tionists" when nutrition research was de- very few behavior and education researchers fined as "the study of food and nutrients." In are included. AIN does not keep any figures FY 1977, 20 lead scientists, those holding on training. Of the American Dietetic Asso- M.D., Ph.D., or D.V.M. degrees, and 50 junior ciation's 21,751 members in 1977, 764 state scientists were conducting nutrition research 22 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 at Letterman Army Institute of Research of professional nutrition training programs as the Department of Defense. well as increased training support. For grad- uate students in nutrition and food science, Before a comprehensive nutrition research program is established, consideration must such changes might include greater stress on be given to the ability of the field to sustain nutritional pharmacology, food science prin- such a program. No accurate figures exist on ciples, nutrition education, nutritional status evaluation, and nutrition-related diseases. how many scientists are currently engaged in human nutrition research. Furthermore, few Training would be further strengthened by reports on nutrition research mention this postdoctoral research work with either hu- aspect of planning. mans or experimental animals. Greater em- phasis on nutritional biochemistry and clini- Implementation of the research priority cal nutrition in undergraduate medical edu- areas identified in this report may require cation may help attract physicians to the changes of emphasis in existing graduate and field. 23 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES Accumulating the fragmented research activities of the 14 Federal agen- cies supporting human nutrition research does not, as a whole, constitute a coherent strategy for the solution of current diet-related health problems. A goód understanding of the status quo can be gained by analysis of the Food and Agriculture Act of 1977 which established research goals and priorities for the Department of Agriculture (USDA). The picture of the present situation can be completed by reviewing the research goals and priorities at the Na- tional Institutes of Health (NIH). Alternatives to the status quo can be found in the recently published reports of the Office of Science and Technology Policy (OSTP) and the General Accounting Office (GAO). These two alter- natives, plus an alternative developed by OTA, are examined here and provide Congress with several alternative strategies that may be pursued. Each of the alternatives are examined from three perspectives: Do the stated goals and priorities adequately address current U.S. health problems? Is nutrition research defined clearly to permit realistic estimation of Federal expend- itures? Is consideration given to the personnel requirements to fulfill pro- posed research priorities? THE STATUS QUO: NUTRITION RESEARCH IN THE FEDERAL GOVERNMENT Goals and Priorities The Food and Agriculture Act of 1977 rec- fants, children, adolescents, elderly men and ognized the relationship between diet and the women, and pregnant women; and that there general health of the population. The legis- is a critical need for objective data concern- lation states "that there is increasing evi- ing food safety, the potential of food enrich- dence of a relationship between diet and ment, and means to encourage better nutri- many of the leading causes of death in the tional practices." United States; that improved nutrition is an integral component of preventive health care; The legislation declares that the Secretary that there is a serious need for research on of Agriculture shall develop and implement a the chronic effects of diet on degenerative national food and human nutrition research diseases and related disorders; that nutrition program that shall include, but not be limited and health considerations are important to to, five areas: U.S. agricultural policy; that there is insuffi- cient knowledge concerning precise human 1. Research on human nutritional require- nutritional requirements, the interaction of ments. the various nutritional constituents of food, and differences in nutritional requirements 2. Research on nutrient composition of among different population groups such as in- foods and the effects of agricultural 27 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 practices, handling, food processing, "Reviewing the policies, plans, and goals and cooking on the nutrients they con- of programs within USDA involving the tain. food and agricultural sciences, and 3. Surveillance of the nutritional benefits related programs in other Federal and provided to participants in the food pro- State departments and agencies and in grams administered by USDA. the colleges and universities developed by the Secretary under this title; 4. Research on the factors affecting food preference and habits. Reviewing and ssessing the extent of agricultural research and extension be- 5. The development of techniques and ing conducted by private foundations equipment to assist consumers in the and businesses, and the relationships of home or in institutions in selecting food such research and extension to federally that supplies a nutritionally adequate supported agricultural research and ex- diet. tension; Reviewing and providing consultation to Although the legislation points up the rela- the Secretary on national policies, prior- tionship between diet and leading causes of ities, and strategies for agricultural death in the United States, the research pri- research and extension for both the ority areas spelled out do not pursue this line short and long term; of inquiry. Since the legislation pertains almost exclusively to USDA, it lays out what Assessing the overall adequacy of, and could be considered a partial strategy to making recommendations to the Secre- solve the problems of diet and chronic de- tary with regard to, the distribution of generative diseases-research on nutrient resources and the allocation of funds au- needs, on the composition of the food supply, thorized by this title; on ways to help consumers select a healthful Preparing and submitting to the diet, and surveillance of the population. Fur- Secretary, not later than October 31 of thermore, funding proposed in the FY 1979 sch year, a statement of recommenda- budget does not match the ambitious wording tions as to allocations of responsibilities of the legislation. and levels of funding among federally supported agricultural research and ex- The Food and Agriculture Act of 1977 tension programs; and designated the Secretary of Agriculture to "establish jointly with the Secretary of Not later than March 1 of each year sub- Health, Education, and Welfare procedures mitting a report on its appraisal of the for coordination with respect to nutrition President's proposed budget for the food research in areas of mutual interest." Sec- and agricultural sciences for the fiscal tion 1406 amends the National Science and year beginning in such year and the Technology Policy, Organization, and Priori- recommendations of the Secretary con- ties Act of 1976 (90 Stat. 471; 42 U.S.C. 6651 tained in the annual report.' (h)), by creating a standing subcommittee to be known as the Subcommittee on Food and As indicated earlier, the Food and Agricul- Renewable Resources. ture Act of 1977 does not clearly give USDA the lead responsibility for human nutrition The legislation also established a National research. Section 1405 declares "the Depart- Agricultural Research and Extension Users ment of Agriculture is designated as the lead Advisory Board composed of 21 members rep- agency of the Federal Government for agri- resenting a wide variety of agricultural pro- cultural research (except with respect to the ducer, consumer, marketing, and environ- biomedical aspects of human nutrition con- mental interests. Two members must be en- cerned with diagnosis or treatment of dis- gaged in human nutrition work. The Advisory easc). Human nutrition is one of the Board has the responsibilities for: areas included in the definition of "food and 28 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 agricultural sciences (section 1404). But the long-range goals of the AID nutri- Section 1409 states that "*t is the intent of tion program are: to have developing coun- Congress in enacting this title to augment, tries incorporate nutrition considerations in- coordinate, and supplement the planning, ini- to their social and economic development tiation, and conduct of agricultural research plans; to create the methodologies for assess- ing needs, determining causes, and selecting programs existing prior to the enactment of interventions: and to have available the most this title, except that it is not the intent of cost-effective interventions with information Congress in enacting this title to limit the on when they are most appropriate to apply, authority of the Secretary of Health, Educa- the cost and other requirements for imple- tion, and Welfare under any Act which the menting them, the best methods for imple- Secretary of Health, Education, and Welfare menting them, and information on expected administers." Thus a clear mandate is not results. given to USDA to be the lead agency for The AID nutrition research program is human nutrition research. designed to provide new knowledge that will Section 1423 (b) requires the Secretary of help implement programs to attain these Agriculture to "periodically consult with the goals. The AID nutrition research program administrators of the other Federal depart- attempts to assess the functional signifi- cance of improvements in nutrition; it seeks ments and agencies." As discussed earlier, to establish whether nutritional needs can be this unilateral approach to coordination satisfied with locally available foods; it relies on the goodwill of other agencies to evaluates the effectiveness of nutrition in- cooperate with USDA in the goal of research tervention; and it seeks to inform govern- coordination. ments about the potential impact of policies in food and nutrition. Research priorities at NIH are summarized in table 3. A wide range of basic and applied It is therefore apparent that the AID nutri- research are embodied in these priorities. tion research program is not and should not The major emphasis is on basic and curative- be designed to address the research needs oriented disease research rather than dis- outlined in this report. The AID program is ease prevention. This becomes more clear as designed to meet the needs of host countries. allocations of funds to the different areas are Should a research project yield results ap- studied. The Nutrition Study Section at NIH plicable to problems discussed in this report, reviewed a total of 181 grant proposals in FY it is serendipitous. There is a clear need to en- 1977, and approved 119, totaling $4.7 million. courage international research, much of Only four other study sections recommended which would be epidemiological, to identify for approval grants totaling less than $4.7 and explore dietary and lifestyle factors con- million in this period of time. Two of these tributing to the major chronic diseases. sections have been disbanded, their work be- In theory, AID's nutrition research ac- ing referred to other study sections. Since tivities undergo peer review. Research funds research in nutrition involves many different are publicized through the distribution of a disciplines and crosses traditional discipli- brochure, and information on AID's research nary lines, NIH maintains that many grant needs are circulated among professional applications with nutrition components are groups and announced at professional meet- referred to other study sections. It can there- ings. 'Projects that are awarded on the basis fore be assumed that $4.7 million is what NIH of predominant capability are very carefully clearly defined as human nutrition research, reviewed before approval. Fewer and fewer and the remainder of the $80.4 million of projects follow this latter nutrition research funded by NIH if FY 1977 was basic and disease-oriented research In practice, the system seems to have func- with nutrition components of varying degrees tioned somewhat differently. Human nutri- of relevance. ¹Irwin Hornstein, Deputy Director, Office of Nutri- The Agency for International Development tion, Agency for International Development, June 8, (AID) is the Federal agency primarily respon- 1978. sible for international nutrition research. ²Ibid. 29 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research received an estimated $2.7 mil- human nutrition research is made in the Act. lion from AID in FY 1977. Most of this re- search was conceived by agency staff who In response to these requirements, USDA requested $43 million for human nutrition then had a scientific research group develop research in its FY 1979 budget proposal. This study proposals. The proposals were is a 95-percent increase over its FY 1977 screened by AID staff members before being spending of $22 million. submitted to the Research Advisory Commit- tee for technical feasibility evaluation. The At NIH, nutrition research support has re- agency does not widely advertise requests for mained relatively constant over the last sev- proposals, and few unsolicited proposals are eral years, constituting less than 3 percent of received. Some panel participants felt that the total research budget. Estimates of actual this system reduces the scientific base of ex- dollar outlays for human nutrition research pertise on which the agency can draw and vary from $20 million to $80 million for FY leads to an inbreeding of research ideas. 1977. Definition and Funding Personnel Resource Requirements The Food and Agriculture Act of 1977 does not explicitly define the term "nutrition" nor Both the USDA and HEW support under- the scope of "nutrition research." It implies graduate, predoctoral, and postdoctoral that "nutrition research" includes research students through a variety of tuition grants, on diet and disease, certain aspects of agri- loans, fellowships, and training grants. The cultural policy, nutritional requirements, Food and Agriculture Act establishes grants food composition and nutrient interactions, and fellowships for food and agricultural food safety, food enrichment, and means of sciences education at the undergraduate encouraging better nutritional practices. through postdoctoral levels. The program is There is no reference in the legislation to in- authorized in FY 1978 for $25 million, ex- ternational nutrition research. panding to $50 million by FY 1982. The pro- Section 1423 (a) of the Food and portion of this money to be devoted to training Agriculture Act of 1977 states that the Secre- nutrition researchers is not specified. tary of Agriculture "shall increase support The Department of Health, Education, and for such research [research into food and Welfare has traditionally supported training human nutrition] to a level that provides of research scientists through training grants resources adequate to meet the policy of this and fellowships. In FY 1977 these totaled subtitle." No specific authorization for $2.3 million for human nutrition research. NEW DIRECTIONS IN FEDERALLY SUPPORTED HUMAN NUTRITION RESEARCH: THE OSTP REPORT Goals and Priorities eral nutrition research activities. Although the report focused only on domestic research, it encouraged various Federal agencies in- In December 1977, OSTP published a re- volved in such activities to assess the poten- port on Government nutrition research. The tial international benefits from current and report defined the scope of human nutrition plonned projects. research, described existing Federal pro- grams, identified research areas that need he working groups of the OSTP inter- more attention, and suggested means for en- agency senior nutrition research staff recom- hancing the coordination and quality of Fed- mended four priority research activities: 30 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 1. Effects of nutrition on human health and In HEW, the programs of the Food and performance in pregnancy, infancy and Drug Administration (FDA), the National early childhood, old age, obesity, iron Center for Health Statistics (NCHS), the deficiency, nutrient toxicity, and in- Center for Disease Control (CDC), and NIH must be coordinated in the high-priority ac- teractions; tivities identified. At NIH, it is essential 2. Food sciences (methodology for analyz- for the NIH Director and for the Nutrition ing food composition, nutrient bio-avail- Coordinating Committee under his direction ability in foods, updating national to have the authority to prioritize nutrition nutrient data bank, expanding food com- research needs. The Director of NIH, has a position measurements); relationship to the several Institutes which 3. Nutrition education research (factors permits allocation of funds for nutrition research in the absence of specific statutory determining dietary practices, identifi- authorities for reprogramming between In- cation of good nutritional practices, ad stitute appropriations. hoc <educational research committee); In USDA, it is essential that the nutrition and research activities of the Agricultural Re- 4. Diet and nutritional status surveillance search Service (ARS), the Cooperative State (food composition, survey methodology, Research Service (CSRS), the Food and Nutri- measurements of nutritional status, tion Service (FNS), and the Economic Re- analysis of the Health and Nutrition Ex- search Service (ERS) be coordinated through amination Survey (HANES) data, epi- the Secretary of Agriculture." demiological studies). Finally, the establishment of an ad hoc in- The criteria used by the working group in teragency nutrition education research com- mittee is recommended. This committee selecting research areas for greater attention were impact, substantial existing knowledge would: identify and summarize research find- ings related to nutrition education research gap. and researchability. The priority areas and summarize pertinent findings from other chosen reflect the narrowness of these cri- areas of education research, establish priori- teria. The priorities tend toward short-term ties, and develop a plan for conducting nutri- projects that lack long-term commitments tion education research. needed to identify the nutrition elements of major health problems facing adult Ameri- It is doubtful that OSTP through FCCSET cans-the chronic degenerative diseases and would be able to adequately oversee coordi- obesity. nation of nutrition research activities. The staff of the Office is small, and their respon- In the OSTP report several recommenda- sibilities large. With a budget of $50 million tions are made for coordination within and to $117 million per year, nutrition research is among the departments conducting nutrition a very small component of the FY 1977 $3.6 research. First of all, the participants in the billion research budget for health and agri- study requested OSTP "to continue to take a culture. lead role in coordinating and monitoring External reviews by teams of nonagency nutrition research activities." OSTP could scientists may improve the quality of intra- serve as a focal point for interagency plan- mural human nutrition research activities, ning through the Federal Coordinating Coun- but they cannot be expected to improve re- cil on Science, Engineering, and Technology search coordination. This recommendation (FCCSET), chaired by the Director of OSTP. calls for the external reviews to be conducted Secondly, external reviews of the intramural within 12 months of the report's publication grants process in both NIH and USDA with by an unspecified number of multidiscipli- joint participation of Federal agencies in nary teams. Scientists from agencies con- developing requests for proposals and in ducting nutrition research would also par- reviewing research in progress. ticipate. The report suggests that this would To improve coordination and communica- be expected to increase communication and tion within HEW and USDA, the report rec- understanding of Federal programs. Since ommends: the review would only be conducted once and 31 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 no provisions are made for improving bad Food consumption patterns and nutri- situations if they are found, it is doubtful that tional status of the general population it would be of any lasting use in improving in- and of special high-risk subgroups with- teragency communication or the quality of in- in the population; evaluation of the nutri- tramural research. tional impacts of various intervention The proposal that Federal agencies jointly strategies and public policies. participate in developing requests for re- The OSTP report established Federal ex- search proposals and in reviewing research penditures for nutrition research for FY 1977 in progress has merit, as does the proposal at $116.6 million. The report stated that no for an ad hoc interagency nutrition education specific funding levels would be recommend- research committee. The ideas could be fur- ther explored by USDA and HEW and pro- ed, but that the report's objectives could be met "at least in part by reallocation of posals for implementation developed. resources from existing programs to the higher priority areas identified." It is highly unlikely that this could be accomplished Definition and Funding without outside intervention. It is also ques- tionable whether such a strategy makes good The scope of human nutrition research, as sense, since the amount of human nutrition defined by the OSTP study, included in- research conducted in this country is so small vestigation of: in comparison to our $3.6 billion in health and Basic physiological and biochemical agriculture research expenditures and our mechanisms for the digestion, absorp- $160.6 billion in health costs. Furthermore: at tion, metabolism, and transport of nutri- least $60 million of the $117 million is basic ents; the role of food ingredients in research on metabolism which underlies human health and performance and in many of the biological and health sciences. A the prevention and treatment of disease; cut in this funding would severely constrain progress in basic research. Nutrient composition of foods; the ef- fects of storage, processing, and packag- ing; and the biological availability of nu- trients in the foods at the time of con- Personnel Resource Requirements sumption; Determinants of dietary practices and The OSTP report does not consider the per- methods for educating the public about sonnel resources needed to fulfill the re- dietary practices; and search priorities contained in the report. FEDERAL HUMAN NUTRITION RESEARCH NEEDS A COORDINATED APPROACH TO ADVANCE NUTRITION KNOWLEDGE: THE GAO REPORT Goals and Priorities Knowledge of dietary nutrients required to promote or maintain growth or well- The General Accounting Office was asked being at various stages and conditions of to identify research gaps and needs in the life: field of human nutrition. The scope of the Information on the composition of the report was restricted to the domestic situa- current U.S. food supply and the extent tion. Gaps identified by GAO included: that nutrients are biologically available; 32 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Evaluation of long-term health conse- Eliminate unnecessary research that quences of the modern diet; and may exist among Federal agencies. Promote Government-wide human nutri- Assessment of the Nation's current tion research planning, coordination, nutritional status in terms of dietary ex- and reporting." cesses and imbalances, as well as defi- ciencies. These recommendations are not suffi- ciently specific to be considered a strategy GAO recommended research along the for organizing nutrition research. Further- following lines to overcome these research more, in an early draft of their report, OSTP gaps: assigned lead and support agency respon- sibilities for specific nutrition research Long-term studies of human subjects areas. This approach was abandoned in the across the full range of both health and final report because of agency objections. A disease; general goal of improved research planning, coordination, and reporting is commendable, Comparative studies of populations of but without specifics probably will not be at- tained. differing geographic, cultural, and genetic backgrounds; Basic investigations of the functions and Definition and Funding interactions of dietary components; GAO identifies the third barrier to prog- Updated and expanded food composition ress in nutrition research as "instability of data; and federally funded extramural research." The report does not make specific recommenda- Improved techniques for assessing long- tions as to how to improve this situation. term toxicological risks. However, it endorses the development of fed- erally funded regional research centers in conjunction with universities and colleges. The priorities set out in the GAO report in- GAO estimates U.S. Government expend- volve the types of research that will probably itures for human nutrition research at $73 provide the most information on the role of million to $117 million annually. It makes no diet in disease. However, work is also needed attempt to define nutrition research or to on how best to convey the research findings analyze agency reports on nutrition research to the public so they can be translated into expenditures. daily life. The GAO report cites "lack of central focus and coordination" and "shortage of nu- Personnel Resource Requirements trition scientists" as two of the three prin- cipal barriers to progress in human nutrition The GAO report highlights the concern of research. To remedy the first of these, the re- the scientific community that there is a short- port recommends that the Director of OSTP age of nutrition research scientists. If this "work with the Federal agencies to further situation exists, it holds significant implica- define the subject areas comprising human tions for the ability of the research commun- nutrition research and make recommenda- ity to absorb research funds should large in- tions to the Director of OMB to: creases be made in the future. Since no accu- rate information exists on the numbers and expertise of nutrition research scientists out- Assign where practicable, each area to side Government laboratories, analysis of re- a lead Federal agency. search capabilities is impossible. 33 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 A COMPREHENSIVE NUTRITION RESEARCH STRATEGY Goals and Priorities points are outlined in table 5. The rationale for the selection of each is contained in the The focus now lacking in Federal nutrition appendix. research could be achieved by defining the Several mechanisms for coordinating Fed- scope of human nutrition research, defining eral nutrition research activities have been general goals for Federal agencies that con- suggested. These include assigning respon- duct such research, and specifying research sibilities for research areas to various agen- priority areas that are in line with the gen- cies, making one agency the lead agency, eral goals. A reorientation of Federal nutri- placing coordination responsibility under a tion research efforts should recognize the third party, assigning coordination respon- changing nature of our food supply by placing sibility to the assistant secretary level, and greater emphasis on the role of diet in concentrating all nutrition research activities preventing chronic diseases. At the same in either USDA or HEW. time, Government programs must continue The first alternative (assigning respon- striving to eliminate hunger and malnutrition sibilities for research areas to various agen- through intervention programs and research. cies) would make USDA and HEW the two lead agencies in human nutrition research. Such a reoriented research strategy re- This approach is similar to the one taken in quires an increased focus on today's complex the Food and Agriculture Act of 1977 in food supply. especially on the effects of proc- which the legitimate roles of both agencies in essed food, food additives and contaminants, nutrition research are recognized. Under and similar problems that concern consum- such a system of joint responsibility, the con- ers, food producers, and health profession- cerns of each agency would have to be de- als. Research in the food sciences would fined to minimize duplication of effort. An ef- enable us to evaluate the adequacy of the fective system of intra-agency cooperation food supply and to develop recommendations would also be necessary. However, since it for needed changes. Such changes might in- may not be possible to clearly separate the clude new processing techniques, fortifica- concerns of nutrition and disease from those tion, reformulation, or selection of alternative of "normal nutrition," some overlap would food items by consumers. probably be inevitable. Broader information and intervention ef- The second alternative assigns one agency forts outside of the health care system are main responsibility for nutrition research. also necessary. The public should know what Since USDA and HEW fund 87 percent of the scientific community has learned about Federal human nutrition research, they are the relationships among lifestyles, food con- the most likely candidates for the lead agency sumption, and health. Developing improved role. There are arguments both for and ways of conveying such knowledge would en- against giving such responsibility to one or courage the public to adopt better eating the other agency. habits and other health-promoting behavior. Currently USDA plays the major role in OTA working group participants felt that carrying out food intervention programs in neither the existing legislation nor the priori- the United States. By giving it primary re- ties suggested in the OSTP and GAO reports sponsibility for funding and coordinating provided the holistic, integrated research nutrition research efforts, the Government's strategy needed to meet current and pro- research and food intervention activities jected diet-related problems in the United might be better coordinated. At the same States. Seven elements of a comprehensive time, Federal research activities might research strategy to define the role of nutri- become more responsive to consumer views tion in the prevention of chronic disease and and needs because of USDA's major involve- to improve management of current nutrition- ment in food and nutrition education pro- related problems were discussed. The seven grams. 34 Source: https://www.industrydocuments.ucsf.edu/docs/rInf0227 Table 5.-A Seven-Point Nutrition Research Strategy The role of diet in the prevention of chronic disease and obesity Major health problems and diet-related risk factors Diet, aging, and disease Methods for preventing obesity Nutrition and mental development The role of nutrition in the treatment of disease and support of therapy Nutritional support of patients with severe disease and injury Other disease states Technology for delivery of nutrients to patients Behavioral and emotional problems Nutrition education and consumer information Factors affecting lifetime eating habits and identification of critical points for education Development and evaluation of nutrition education and communication methods Methods for simplifying consumer information utilization Requirements for essential nutrients Methods for determining nutrient needs Interactions among nutrient requirements based on functional criteria Pharmacologic and toxicologic effects of on nutritions Bioavailability of nutrients in foods Nutritional aspects of food science and food safety Food composition New food processing and handling procedures to maintain nutrient content Better methods of assuring food safety Monitoring nutritional status Methods for improving integration of food consumption and nutritional status surveillance Evaluation of the effects of food and nutrition education programs Nutrition policy and management Food-related interventions Other interventions USDA now coordinates research in the ments for giving HEW, the agency concerned area of food production with the State agri- with health, the lead responsibility for direct- culture experiment stations and other coop- ing nutrition research. However, such re- erating institutions. Some link between the search has not been a main HEW concern in nutritional concerns of consumers and the the past. Disease-prevention research has food production system seems to be essential. generally received much less support than But USDA has traditionally had little respon- specific disease-oriented or curative-oriented sibility or expertise in the area of human research. Moreover, HEW has not been con- health and disease. One of the major needs in cerned with the nutrient requirements of Federal nutrition research activities is a healthy people, food consumption patterns, or reorientation of priorities to stress the role of food composition. In addition, HEW has no nutrition in the prevention of disease. Thus nationwide programs of nutrition and health separating health-related nutrition research education comparable to those developed by from the overall direction of health research USDA. may not be wise. If health-related nutrition research fell exclusively under USDA, poten- tial conflicts might arise. The research might The report by OSTP recommended that the produce recommendations for substantial lead role in nutrition research be given to a shifts in food practices. Such findings and third party which would formulate policy and recommendations could conflict with the coordinate and monitor programs. Under this traditional interests of producer groups. arrangement, various agencies would retain their existing nutrition research respon- Many of the research priorities identified sibilities, but their activities would be over- by OTA as well as other groups involve the seen by the third party. The concept offers relationship of human health to nutritional some positive features. It would focus atten- practices. Therefore, there are strong argu- tion on nutrition while retaining the healthy 35 Source: https://www.industrydocuments.ucsf.edu/docs/rlnf0227 competition among agencies involved in nutri- A pluralistic approach to human nutrition tion research. research, with well-defined agency respon- sibilities for HEW and USDA, appears to be However, such a third-party concept also the best means of coordinating Federal raises several problems. It involves another research efforts. Such an approach could layer of Federal bureaucracy. A third-party produce the kind of creative competition that oversight body might have no real power to would likely enhance human nutrition influence budgets and allocate resources research. It would also result in some within and among agencies, especially since overlapping of efforts, which should be it would lack a political constituency. These minimized by the coordinating process. potential deficiencies would be further mag- The coordinating function might best be nified by inadequate staff and expertise. In carried out by an interagency committee with the end, such a coordinating mechanism would probably only serve as a means to ex- a rotating chairmanship. This arrangement change information, much as the nutrition would be consistent with a pluralistic ap- proach to research. At the same time, it coordinating committee does within NIH and the Current Research Information System would help ensure against any one agency (CRIS) does for USDA. building a "most-favored" relationship with the coordinating committee. Another alternative would give assistant Coordination of Federal nutrition activities secretaries in HEW and USDA responsibility extends beyond specific mechanisms for for coordinating nutrition research policy intra- and inter-agency coordination. It also within and between their respective agen- includes information storage, retrieval, and cies. Lack of high-level commitment to nutri- integration. No uniform system presently ex- tion research has been a problem in the past. ists among the various agencies involved in Placing responsibility for nutrition at the nutrition research. Computerized systems assistant secretary level might create the that permit information integration and re- visibility and commitment needed to effec- trieval need to be explored. At the very least, tively coordinate nutrition research efforts. relevant branches of HEW and USDA should Such an arrangement would require adminis- have a common indexing and data retrieval trative changes within both agencies. At pre- system for this type of information. Since sent, it is unclear if the USDA reorganization federally supported research accounts for that created a Human Nutrition Center the major share of research in the nutrition within SEA will accomplish this goal. and health maintenance areas, integration among these agencies is essential. Integration A final option would consolidate nutrition of nutrition research data is also desirable programs in one agency, either USDA or among the public, private, and voluntary sec- HEW. These activities would include re- tors. search, education, regulation, training, serv- ice delivery, monitoring and surveillance, and food and other intervention programs. Both Definition and Funding USDA and HEW have recently shown interest in this concept in papers entitled USDA's Commitment to Food and Nutrition Policy and As outlined under issue 2, OTA could not The Role of HEW in Human Nutrition: Future perform an analysis of the present Federal Directions. However, the wisdom of such a human nutrition research budget, since pres- consolidation is debatable. Although both ent expenditure estimates are so disparate. agencies currently have a number of nutri- Federal spending on human nutrition tion programs, the expertise involved is quite research should be precisely determined. By specialized. Whether this approach would eliminating the present confusion, Congress solve coordination problems probably will be better able to judge appropriate levels depends on the agency's commitment to the of funding for nutrition research. Congress field of nutrition. could request GAO to audit the human nutri- 36 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research expenditures of Federal agen- facilitate future congressional oversight cies. The GAO audit, based on a constant hearings. definition, should determine total Federal spending for human nutrition research, the number of scientist years involved, and Personnel Resource Requirements Federal expenditures in the seven priority areas set out in this report. If Congress were to choose to implement On the basis of such information, Congress the OTA comprehensive nutrition research would have several options. The first would strategy, there is a clear need to establish be to maintain the status quo in nutrition how many scientists are both presently in- research funding, with possible reallocation volved in, or training for, nutrition research. of some funds to areas not now receiving sup- This census would include a breakdown in port. As a second option, Congress could ap- terms of various research areas, such as propriate, additional funds to specific nutri- Government facilities, universities, medical tion research areas that are not getting facilities, private institutes, and industry. enough support. Finally, Congress could ear- This kind of census would identify where nu- mark a percentage of Hatch funds for human trition research personnel gaps exist and nutrition research. Such an audit, together where greater support is necessary. To fill with a uniform system for reporting human such gaps, expanded Federal support should nutrition research spending, could also be considered. 37 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONCRESSIONAL OPTIONS vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONGRESSIONAL OPTIONS OTA found that three key issues underlie the basic finding that the Fed- eral Government has failed to adjust the emphasis of its human nutrition research activities to meet the changing health problems of the American people. Alternative approaches of dealing with these issues have been ex- plored. Congress can elect to maintain the status quo, with or without minor shifts, or choose among the strategies and options offered by OTA, the General Accounting Office (GAO), and the Office of Science and Technology Policy (OSTP), (see chapter III). Either alternative has economic, institutional, and health implications. Option 1: Congress Could Choose To Maintain the Overall Status Quo Maintaining the status quo could mean itoring nutrition status, and nutrition policy refraining from any action. In a broader and management. sense, it also could involve minor im- provements in the present system-without If Congress chooses to refrain from any ac- making substantial changes. tion to await the recommendations of the President's Reorganization Project, no ad- A. Congress could refrain from any action, verse effects would be expected. awaiting the recommendations of the President's Reorganization Project. B. Congress could amend the Food and Agri- culture Act of 1977 to clarify the desig- In August of 1977, President Carter nation of lead agency for human nutrition directed the Reorganization Project staff at research. the Office of Management and Budget to thor- oughly review the organization and structure At the present time, the Department of of Federal food and nutrition programs. Food Agriculture (USDA) interprets the Food and and nutrition research is one of the seven ma- Agriculture Act of 1977 to mean that USDA is jor areas under review. A final report to the the lead agency for human nutrition re- President, expected in January of 1979, will search, an interpretation not shared by the include recommendations that may signifi- Department of Health, Education, and Wel- cantly alter the organization, and thus the fare (HEW). If Congress intended USDA to course, of nutrition research activities. have primary responsibility for this research area, the Act will require amendment. Since significant strides have been made in nutrition research, there is no reason to ex- C. Congress could develop nutrition research pect a decline in research productivity if cur- goals and priorities for HEW that comple- rent funding levels are maintained. However, ment the goals and priorities outlined for since several important areas of nutrition USDA in the Food and Agriculture Act of research receive little support at present, 1977. progress in these areas would be slow. These areas include the role of nutrition in the pre- The legislation contains strong language on vention of disease, nutrition education, mon- the relationship of diet to many of the leading 41 Source: https://lwww.industrydocuments.ucsf.edu/docs/rinf0227

The second image represents which nutrient?

rlnf0227

rlnf0227_p22, rlnf0227_p23, rlnf0227_p24, rlnf0227_p25, rlnf0227_p26, rlnf0227_p27, rlnf0227_p28, rlnf0227_p29, rlnf0227_p30, rlnf0227_p31, rlnf0227_p32, rlnf0227_p33, rlnf0227_p34, rlnf0227_p35, rlnf0227_p36, rlnf0227_p37, rlnf0227_p38, rlnf0227_p39, rlnf0227_p40, rlnf0227_p41, rlnf0227_p42, rlnf0227_p43

fats, Fats

lating research findings. Because of a general noted that this language is ambiguous. It does lack of accessibility, it is often extremely dif- not specify "lead," and it leaves cooperation ficult for agencies to communicate research to the goodwill of HEW. information to the public or Congress. The need for improved coordination in Of course, some overlap in interests is in- nutrition research extends beyond the execu- evitable in similar areas of research, and tive agencies to Congress. At present 14 con- duplication of research results is a necessary gressional committees and 20 subcommittees part of scientific research. But unnecessary are concerned with nutrition matters. The duplication should be avoided. Minimizing principals include the Senate Committees on duplication by developing more efficient Agriculture, Nutrition, and Forestry (Sub- means of sharing information on planned, on- committee on Nutrition); Appropriations going, and completed research is an achiev- (Subcommittees on Labor-Health, Education able goal. and Welfare, and Agriculture); the House In the same sense that some duplication is Agriculture Committee (Subcommittee on a necessary part of scientific research, Domestic Marketing, Consumer Relations, healthy competition among agencies may and Nutrition); the House Appropriations stimulate greater effort and ultimately bene- Committee (Subcommittees on Agriculture fit the public. But the proprietary stance and Labor-Health, Education, and Welfare); taken by some agencies is wasteful and in- House Interstate and Foreign Commerce hibits joint planning. Internecine struggles at Committee (Subcommittees on Oversight and higher levels of Government apparently fos- Investigations, and Health and Environment); ter such attitudes. However, career civil serv- and the House Science and Technology Com- ants and the public, as well as the overall mittee (Subcommittee on Domestic and Inter- Federal research effort, suffer as a result. national Scientific Planning, Analysis, and The turf battles that lead agencies to work at Cooperation, and the Subcommittee on Sci- cross purposes should be eliminated. Agen- ence, Research, and Technology). Since some cies involved in nutrition research should duplication of interest exists, joint sessions of demonstrate a commitment to coordination relevant congressional subcommittees to con- and the avoidance of unnecessary duplica- sider plans and hearings for oversight pur- tion. This commitment needs to be built in, not poses should be considered. only at the "political" level of the higher There is a strong relationship between echelons of Government but also in the career human nutrition research conducted abroad civil service. and research needs in the United States. The The establishment at USDA of the Human research goals identified in this report can be Nutrition Center and the Human Nutrition best achieved if international and domestic Policy Committee and at HEW of the Nutrition research activities are tuned together. Coordinating Committee are two positive Nutrition research in other countries may steps toward intra-agency coordination. They help in solving domestic nutrition problems. not only indicate a commitment to nutrition For example, epidemiological investigations research but also can serve as mechanisms of certain chronic diseases require good in- for interagency coordination and information formation about disease incidence. This may exchange. be obtained from studies of societies with The Food and Agriculture Act of 1977 lifestyles and food habits very different from specifies that the Secretary of Agriculture our own. The high incidence of malnutrition shall "periodically consult with the adminis- in some developing nations also provides an trators of other Federal departments and opportunity to investigate relationships be- agencies that have responsibility for coor- tween the nutritional status and functional dinating Federal nutrition research activ- performance of individuals in a way that ities." However without the support and in- would be impossible in the United States. It volvement of the Secretary of HEW, unilat- may be possible to extrapolate the results of eral USDA efforts to coordinate research studies of severe malnutrition abroad to may not be effective. Likewise, it should be margina! nutritional areas in this country. 16 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 The study of worldwide populations and will have a dual reward-assistance to mal- food patterns is essential to the better under- nourished peoples abroad and increased standing of some of the priority research knowledge of human nutrient needs and areas of nutrition. Thus any effort to increase health status under changing environmental international nutrition research capabilities conditions. ISSUE 2 - Definition and Funding of Human Nutrition Research If one accepts that the goals of human genetics, animal nutrition, plant nutrition, nutrition research are twofold-(1) the pro- and plant genetics comes under this classi- motion of optimum health and performance, fication. While there is need to integrate such and (2) the treatment of diseases through diet agricultural research with human nutrition therapy and the support of other medical concerns, these areas should not be consid- therapies-th definition of human nutrition ered human nutrition research. Similarly, research flows from these stated goals. If all basic research on metabolism of nutrients, if the research areas involving nutrition are not directly applicable to people, should not listed, from basic studies on the metabolism be considered human nutrition research. of nutrients to genetic studies on the develop- Basic research on metabolism should be con- ment of foods with specific nutrient charac- sidered as basic research underlying all of teristics, it is clear that some areas of the biomedical and life sciences. Human research are more closely related to these nutrition research builds upon this knowl- stated goals than others. Accordingly, the edge base, but the apparent commitment to definition of human nutrition research must and budget for human nutrition research take into account these relationships to should not be inflated by its inclusion. stated goals. Throughout this assessment, a recurrent In terms of this assessment, nutrition problem has been that of definition of human research falls into three broad categories. nutrition research. Agencies report as human Most closely related to the stated goals is nutrition research studies that appear to research into the biochemical and physiologi- have little to do with human nutrition. Ex- cal effects of food on the body in health and amples are "Catalytic Functions and Metab- disease. This category includes research on olism of Vitamin B6 in Bacteria and Fungi," nutritional management of disease, nutrient "Nutritional Imbalance and Metabolic Alter- needs and interactions, and research which ations in Fungi," or "Hepatoma Incidence in promotes optimum health and disease pre- Trout on Dietary Aflatoxin and PCB." Such vention through diet. studies are worthwhile and contribute to our understanding of basic biochemistry but are Research on food and nutrition quality not directly applicable to humans. determinants is also related to the stated The almost unanimous consensus of the goals, but less directly so than the previous category. Under this heading would be re- participants in the OTA study was that at- search into food composition, especially the tribution of these Federal expenditures to nutritive components and changes in nutrient "human nutrition research" was improper. composition that occur from point of origin to Fourteen different Federal agencies are point of consumption; food safety; social, cul- engaged in some sort of nutrition research. tural, and economic aspects of food habits; Each agency has developed its own definition feeding programs; nutrition education; con- of human nutrition research and set priorities sumer information; and nutrition surveillance on the basis of how it interprets its legislation and monitoring. mandate. The agencies and their priorities are shown in table 3. The third category of research involves basic research on sources of human food and Federal expenditures for human nutrition basic biochemistry. Research into animal research in FY 1977 (shown in table 4) were 17 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3. - Federal Government Agencies Active in Food and Nutrition Programs and Their Nutrition Research Priorities Food and nutrition Department Agency programs Research priorities Health, Edu- National National Institute of Arthritis, Metabolism, and Digestive Diseases cation, & Institutes (NIAMDD).Basic hysiological studies of nutrients; basic metabolism Welfare of Health studies; obesit, trace elements nutrition support of patients; fiber; anemias. National Institute of Child Health and Human Development (NICHHD). Nutrition and fetal development; metabolic capacities of normal, low- birthweight, and premature infants; diet modification for low-birth- weight and premature infants; optimum nutrition in developmental years; nutrition and reproductive potential; genetic variability-nuti tional interaction; prevention- - metabolic antecedents of adult disease. National Cancer Institute (NCI). Nutrition support of cancer patient; nu- trition in cancer etiology; host-tumor interactions and competition for nutrients; prevention strategies based on nutrition; diet and nutrition in the rehabilitation of cancer patients. National Heart, Lung, and Blood Institute (NHLBI). Nutrition in etiology of arteriosclerosis and hypertension; achieving and maintaining dietary change; development of food composition tables; methodology-col lecting, recording, and evaluating dietary data. National Institute of General Medical Sciences (NIGMS). Trauma- tized/burned patients and nutrition. National Institute of Environmental Health Sciences (NIEHS). Neuro- toxicity; mutagenesis; teratology; environmental contaminants in food. National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Protein-calorie malnutrition, B-vitamin deficiencies and the nervous system; genetic disorders and the nervous system; specific nutritional problems in the central nervous system; stroke. National Institute of Dental Research (NIDR). Sucrose and caries; poor nutrition and periodontal disease; poor nutrition and oral mucus mem- branes; nutrition in craniofacial malformations and oral-facial struc- tures; nutrition and salivary gland development. National Institute of Allergy and Infectious Disease (NIAID). Interrelated factors hearing on malnutrition, infection, and the immune system. National Eye Institute (NEI). Vitamins A, B-12, and other nutrients in visual processes; diseases of visual system, e.g., keratomalacia; metab- olism of visual cells; protein changes in the lens. National Institute on Aging (NIA). Nutritional status of the elderly; aspects of increase in life span including dietary manipulations; vitamin supplementation in elderly; nutrient intake as a consequence of econ- omic status in elderly; relationship among nutrition, cellular structure, and function in elderly. Division of Research Resources (DRR). Nutrient requirements for growth, gestation, lactation in primates and laboratory rodents; stand- ard diets for specific objectives; interaction of various nutrients on physiological function in laboratory animals; differences in nutrient re- quirements among strains of animals within a species. Food & Regulatory activities Nutrient efficacy and safety; nutrient interrelationships as concerned Drug related to: nutrition with disease prevention; nutrient bioavailability for food fortification Admin- labeling, ingredient purposes; nutrient quality assessment of processed foods; medical istration labeling, food for food assessment; food composition and nutrient analysis as related to special dietary use, FDA mission; and consumer studies of perceptions about food values food advertising, nutri- and nutritional quality and educational models to help correct tion quality of foods misconceptions about them. Health Re- Health and Nutrition Assessment of the nutritional status of the American people. sources Examination Survey Admin- istration 18 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3 - -continued Food and nutrition Department Agency programs Research priorities Center for Epidemiological surveillance studies in cooperation with State Disease agencies assistance to AID in similar international areas. Control Health Collaborative research and screening program for phenylketonuria. Services Admin- istration Alcohol, Effects of alcohol consumption on nutrient metabolism and nutritional Drug deficiencies; study of food additive consumption and hyperactivity Abuse, & in children. Mental 5 Health Admin- istration Agriculture Agricul- Human Requirements for Nutrients tural Re- Determine the requirements for lipid intake and identification of the search forms of these nutrients in foods that may be useful in meeting Service* these requirements. Determine the requirements for mineral intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for vitamin intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for protein and amino acid intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for carbohydrate and energy intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Food Composition and Improvement To provide accurate, up-to-date, and comprehensive information in a readily usable form on the composition of all important foods for those nutrients required by and biologically useful to man. To provide the technology for the nutritional improvement of foods when enhanced levels of certain nutrients in the diet are needed to correct possible dietary faults. Food Consumption and Use To provide accurate, up-to-date, and comprehensive information in a readily usable form on food consumption and dietary levels. To provide consultative assistance on food and nutrition problems and provide sound guidance materials on nutrition for the consumer and for nutrition educators, program leaders, and food program man- agers; to identify techniques which will assist people in selecting nu- tritionally adequate diets within different budget limitations; to iden- tify means to modify undesirable food habits; to strengthen nutri- tionally desirable food choice. To identify and develop suitable and safe procedures for food man- agement and preparation for home and institutional consumers, for best retention of both nutritional and eating qualities and to avoid food-borne illness. Coopera- Nutrient requirements; nutritional status of special population groups tive State including children, low income, and aging; metabolic function of Research nutrients in the diet and their interactions; nutrient content of foods; Service* effects of processing on nutrients; food delivery systems; food habits and use); dietary patterns. 19 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table -continued Food and nutrition Department Agency programs Research priorities Economic Economic and social research relating to domestic food programs; Research nutrition policy in LDCs; food choices (demand); nutritional programs Service' for the elderly. Defense Determination of nutritional and dietary standards for Armed Forces personnel subsisted under normal and special operating conditions; evaluation of nutritional adequacy of food as consumed; evaluation of the nutritional status of Armed Forces personnel; establishment of sanitary and food hygiene standards for all food program activities; food aspects of preventive medicine. National Nutritional control of neurotransmitters; role of dietary protein and Aeronautics specific amino acids in optimizing human performance under stress. & Space Ad- ministration Veterans Depart- Research in disease and diet: nutrition and disease or clinical nutrition, Adminis- ment of dietary therapy; effect of disease on nutrition; environmental toxicants, tration Medicine alcohol, and nutrition; nutrition and cancer; nutrition and vision re- & Surgery search; nutrition-related therapy. Metabolic effects: Investigations on or related to malabsorption syn- dromes, inborn errors of metabolism, and familial or inherited nutri- tional defects. Nutrition requirements: Studies of nutrient metabolism, malnutrition, neuroendocrine nutrient interactions, fundamental intermediary metab- olism involving the role of one or more nutrients. State Agency Development of new low-cost nutritious foods; development and for Inter- dissemination of new appropriate technologies; understanding national nutritional needs and requirements; testing and evaluation of nutrition Develop- program alternatives; research on methodologies for improving national ment nutrition planning and programing. National Basic research in the behavioral, education, and social sciences in Science areas applicable to foods and nutrition. Foundation Under USDA's recent reorganization, ARS is now called Federal Research, and is housed within the Science and Education Administration. Under USDA S recent reorganization, CRS is called Cooperative Research and is housed within the Science and Education Administration Under USDA S recent reorganization, ERS is called Economics and is housed within the Economics, Statistics. and Cooperatives Service. Under USDA recent reorganization, ES is called Extension and is housed within the Science and Education Administration estimated at between $50 million and $117 tion research. Seventy-five percent of Federal million, depending on how "nutrition re- nutrition research is conducted outside of the search' was defined. If for example, the NIH two departments through competitive grants definition is used, NIH appears to be spend- and contracts. Using the more realistic fund- ing $80 million for human nutrition research. ing figure of $50 million for FY 1977, NIH at This broad definition takes in studies of basic HEW funded 44 percent of the total, and the biochemistry, studies which are not focused Science and Education Administration (SEA) on nutrition but have a nutrition aspect, as at USDA funded 43 percent of the total. The well as studies of primary nutrition. If a nar- Science and Education Administration en- row definition is used, one encompassing only compasses what were formerly known as the those studies of direct clinical applications Agricultural Research Service and the Coop- and disease prevention, the NIH nutrition erative State Research Service. Under research funding falls in the annual range of USDA's new reorganization, most human nu- $20 million. Even the higher $80 million trition research will be coordinated by SEA's figure, incidentally, amounts to less than 3 Human Nutrition Center. percent of the NIH research budget. The Science and Education Administration HEW and USDA are responsible for the Cooperative Research (SEA-CR) of USDA is majority of federally supported human nutri- unique among Federal agencies in that it links 20 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 Table 4. - Federal Expenditures for Human Nutrition Research An Approximation of FY '77 Expenditures (millions of dollars) Office of Science & Office of Management Agency Technology Policy & Budgetb Department of Health, Education, & Welfare $ 88.6 $22.0 National Institutes of Health 80.4C 22.0d Food and Drug Administration 3.9 National Center for Health Statistics 2.4 Alcohol, Drug Abuse, and Mental Health Administration 1.1 Health Services Administration 0.5* Center for Disease Control 0.3* Department of Agriculture 22.0 21.8 Agricultural Research Service 14.0 13.2 Cooperative State Research Service 7.5 8.1 Economic Research Service 0.5 0.5 Agency for International Development 2.9 0 Department of Defense 2.3* 2.2 Veterans Administration 0.5* 4.1 National Science Foundation 0.3* 0 Grand total. $116.6 $50.2 affice of Science and Technology Policy, New Directions in Federally Supported Human Nutrition Research, December 1977. Poffice of Management and Budget, Special Analyses-Budget of the U.S. Government FY 1979. This figure includes studies designed to assess the mechanisms and the consequences of food or nutrient intake in the intact organism. particularly man: investigations involving nutrient variables at the cellular or subcellular level, including metabolic studies in animals and man: research designed to elucidate the metabolic role or function of an essential nutrient in both animal models and man, as appropriate; all studies concerned with genetic-nutrient-environmental interactions; dietary studies ex- pected to produce changes in health status, including the maintenance of health and the treatment of disease in man. This figure includes biochemical, physiological, and clinical studies of nutritional needs for normal growth, development, and health: nutritional needs of patients with specific common diseases: and experimental assessments of feeding programs. *Estimates of FY 1976 expenditures provided by draft Government Accounting Office report, Human Nutrition Research- Need for a Coordinated Approach to Advance Our Knowledge, 1977. Federal and State research efforts. SEA-CR levels could be made since current estimates administers funds that Congress appropri- of Federal spending for human nutrition ates to the States for agricultural research. research are questionable. Estimates for FY This work is conducted at the State agricul- 1977 range from $50 million to $117 million tural experiment stations, land-grant colleges (table 4). The lower figure, based on agency and universities, approved schools of for- responses to a standard questionnaire, was estry, colleges of 1890, and Tuskegee In- developed by the Office of Management and stitute. In FY 1977, the States used $7.5 Budget (OMB) for the FY 1979 budget. The million of the Federal money available to higher figure came from an OSTP working them for human nutrition research. The group and appeared in the December 1977 States themselves provided $11.7 million for report "New Directions in Human Nutrition human nutrition research in 1976. Most of Research." the Federal money came from funds author- ized by the Hatch Act, as amended, and P.L. Neither is reliable. The $50 million, for ex- 89-106 (an act to amend the Agriculture Act ample, fails to include certain nutrition of 1954). The funds are accounted for under research activities within HEW, AID, and the the Hatch Act research program called Peo- National Science Foundation. The $117 mil- ple, Communities, and Institutions, which lion, on the other hand, includes $80.4 million comprised 12 percent of total Hatch Act of NIH spending-much of it of tenuous con- research funds in 1977. nection to human nutrition research. In testi- mony before the Senate Select Committee on Federal human nutrition research may be Nutrition and Human Needs on October 17, financially undernourished. However, no 1977, NIH Director Dr. Donald Fredrickson analysis of the adequacy of present funding conceded that, based on a strict definition, 21 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 his agency devoted only around $20 million to whether any of these funds are devoted to human nutrition research in FY 1977 (a fig- research on which methods are most effeo- ure reported to OMB). tive for reaching people. Another statistic which raised questions OTA concluded that most estimates of came from the Veterans Administration (VA). human nutrition research funding were ques- GAO put the VA's FY 1976 nutrition research tionable and that total funding fell con- spending at $0.5 million. In FY 1977, the VA siderably short of the reported $117 million reported sharply increased expenditures of level. Regardless of which overall figure is $4.1 million, even though nutrition research more nearly accurate, certain areas iden- was not recognized as a high priority by the tified by OTA are not now receiving sufficient agency. Federal support, the result of a lack of recognition of their importance and zero or In some cases, it was difficult to determine almost no funds. Those areas most in need of how much (if any) money was being spent for increased funding are the role of diet in the certain types of important nutrition research. prevention of chronic disease and obesity, For instance, the Federal Government is now nutrition education and consumer informa- annually spending about $70 million on nutri- tion, monitoring nutritional status, and nutri- tion education programs. It is unclear tion policy and management. ISSUE 3 - Personnel Resource Requirements Estimates of the number of scientists they are engaged in research activities. This engaged in human nutrition research also does not indicate the degree of involvement proved elusive. and, of course, neglects those outside of dietetics engaged in nutrition research. In an attempt to determine the current number of scientists engaged in human-nutri- The two Government agencies that fund tion research and the numbers of research the largest portion of nutrition research, scientists being trained, OTA contacted five HEW and USDA, do maintain figures on sci- professional societies and six Government entist-years devoted to nutrition research agencies. Of the professional societies, the and 5-year projections of personnel needs. At American Public Health Association, Insti- USDA in FY 1976, 193.5 scientist years were tute of Food Technologists, and American devoted to human nutrition research as de- Chemical Society make no attempt to distin- fined by the agency. The 5-year projection of guish between members engaged in research need for nutrition research scientists at versus other career orientations and USDA is for 260.7 scientist years, a 20-per- therefore could not supply information on the cent increase. proportion of their membership engaged in In a written response to an OTA question- human nutrition research or training of nutri- naire, NIH informed OTA that 70 scientists tion research scientists. Membership in the were employed in human nutrition research American Institute of Nutrition (AIN) is in 1977. But NIH Director Fredrickson sub- limited to those who have made significant mitted a written statement to the Senate contributions to the field of nutrition re- Select Committee on Nutrition and Human search. By definition, all of AIN's 1,730 mem- Needs that during that same time period 180 bers are nutrition research scientists. This intramural investigators in NIH were directly number seriously underestimates the total involved in human nutrition research. Of that number of scientists in the field, since junior number, 20 were defined as "classical nutri- people are not eligible for membership and tionists" when nutrition research was de- very few behavior and education researchers fined as "the study of food and nutrients." In are included. AIN does not keep any figures FY 1977, 20 lead scientists, those holding on training. Of the American Dietetic Asso- M.D., Ph.D., or D.V.M. degrees, and 50 junior ciation's 21,751 members in 1977, 764 state scientists were conducting nutrition research 22 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 at Letterman Army Institute of Research of professional nutrition training programs as the Department of Defense. well as increased training support. For grad- uate students in nutrition and food science, Before a comprehensive nutrition research program is established, consideration must such changes might include greater stress on be given to the ability of the field to sustain nutritional pharmacology, food science prin- such a program. No accurate figures exist on ciples, nutrition education, nutritional status evaluation, and nutrition-related diseases. how many scientists are currently engaged in human nutrition research. Furthermore, few Training would be further strengthened by reports on nutrition research mention this postdoctoral research work with either hu- aspect of planning. mans or experimental animals. Greater em- phasis on nutritional biochemistry and clini- Implementation of the research priority cal nutrition in undergraduate medical edu- areas identified in this report may require cation may help attract physicians to the changes of emphasis in existing graduate and field. 23 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES Accumulating the fragmented research activities of the 14 Federal agen- cies supporting human nutrition research does not, as a whole, constitute a coherent strategy for the solution of current diet-related health problems. A goód understanding of the status quo can be gained by analysis of the Food and Agriculture Act of 1977 which established research goals and priorities for the Department of Agriculture (USDA). The picture of the present situation can be completed by reviewing the research goals and priorities at the Na- tional Institutes of Health (NIH). Alternatives to the status quo can be found in the recently published reports of the Office of Science and Technology Policy (OSTP) and the General Accounting Office (GAO). These two alter- natives, plus an alternative developed by OTA, are examined here and provide Congress with several alternative strategies that may be pursued. Each of the alternatives are examined from three perspectives: Do the stated goals and priorities adequately address current U.S. health problems? Is nutrition research defined clearly to permit realistic estimation of Federal expend- itures? Is consideration given to the personnel requirements to fulfill pro- posed research priorities? THE STATUS QUO: NUTRITION RESEARCH IN THE FEDERAL GOVERNMENT Goals and Priorities The Food and Agriculture Act of 1977 rec- fants, children, adolescents, elderly men and ognized the relationship between diet and the women, and pregnant women; and that there general health of the population. The legis- is a critical need for objective data concern- lation states "that there is increasing evi- ing food safety, the potential of food enrich- dence of a relationship between diet and ment, and means to encourage better nutri- many of the leading causes of death in the tional practices." United States; that improved nutrition is an integral component of preventive health care; The legislation declares that the Secretary that there is a serious need for research on of Agriculture shall develop and implement a the chronic effects of diet on degenerative national food and human nutrition research diseases and related disorders; that nutrition program that shall include, but not be limited and health considerations are important to to, five areas: U.S. agricultural policy; that there is insuffi- cient knowledge concerning precise human 1. Research on human nutritional require- nutritional requirements, the interaction of ments. the various nutritional constituents of food, and differences in nutritional requirements 2. Research on nutrient composition of among different population groups such as in- foods and the effects of agricultural 27 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 practices, handling, food processing, "Reviewing the policies, plans, and goals and cooking on the nutrients they con- of programs within USDA involving the tain. food and agricultural sciences, and 3. Surveillance of the nutritional benefits related programs in other Federal and provided to participants in the food pro- State departments and agencies and in grams administered by USDA. the colleges and universities developed by the Secretary under this title; 4. Research on the factors affecting food preference and habits. Reviewing and ssessing the extent of agricultural research and extension be- 5. The development of techniques and ing conducted by private foundations equipment to assist consumers in the and businesses, and the relationships of home or in institutions in selecting food such research and extension to federally that supplies a nutritionally adequate supported agricultural research and ex- diet. tension; Reviewing and providing consultation to Although the legislation points up the rela- the Secretary on national policies, prior- tionship between diet and leading causes of ities, and strategies for agricultural death in the United States, the research pri- research and extension for both the ority areas spelled out do not pursue this line short and long term; of inquiry. Since the legislation pertains almost exclusively to USDA, it lays out what Assessing the overall adequacy of, and could be considered a partial strategy to making recommendations to the Secre- solve the problems of diet and chronic de- tary with regard to, the distribution of generative diseases-research on nutrient resources and the allocation of funds au- needs, on the composition of the food supply, thorized by this title; on ways to help consumers select a healthful Preparing and submitting to the diet, and surveillance of the population. Fur- Secretary, not later than October 31 of thermore, funding proposed in the FY 1979 sch year, a statement of recommenda- budget does not match the ambitious wording tions as to allocations of responsibilities of the legislation. and levels of funding among federally supported agricultural research and ex- The Food and Agriculture Act of 1977 tension programs; and designated the Secretary of Agriculture to "establish jointly with the Secretary of Not later than March 1 of each year sub- Health, Education, and Welfare procedures mitting a report on its appraisal of the for coordination with respect to nutrition President's proposed budget for the food research in areas of mutual interest." Sec- and agricultural sciences for the fiscal tion 1406 amends the National Science and year beginning in such year and the Technology Policy, Organization, and Priori- recommendations of the Secretary con- ties Act of 1976 (90 Stat. 471; 42 U.S.C. 6651 tained in the annual report.' (h)), by creating a standing subcommittee to be known as the Subcommittee on Food and As indicated earlier, the Food and Agricul- Renewable Resources. ture Act of 1977 does not clearly give USDA the lead responsibility for human nutrition The legislation also established a National research. Section 1405 declares "the Depart- Agricultural Research and Extension Users ment of Agriculture is designated as the lead Advisory Board composed of 21 members rep- agency of the Federal Government for agri- resenting a wide variety of agricultural pro- cultural research (except with respect to the ducer, consumer, marketing, and environ- biomedical aspects of human nutrition con- mental interests. Two members must be en- cerned with diagnosis or treatment of dis- gaged in human nutrition work. The Advisory easc). Human nutrition is one of the Board has the responsibilities for: areas included in the definition of "food and 28 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 agricultural sciences (section 1404). But the long-range goals of the AID nutri- Section 1409 states that "*t is the intent of tion program are: to have developing coun- Congress in enacting this title to augment, tries incorporate nutrition considerations in- coordinate, and supplement the planning, ini- to their social and economic development tiation, and conduct of agricultural research plans; to create the methodologies for assess- ing needs, determining causes, and selecting programs existing prior to the enactment of interventions: and to have available the most this title, except that it is not the intent of cost-effective interventions with information Congress in enacting this title to limit the on when they are most appropriate to apply, authority of the Secretary of Health, Educa- the cost and other requirements for imple- tion, and Welfare under any Act which the menting them, the best methods for imple- Secretary of Health, Education, and Welfare menting them, and information on expected administers." Thus a clear mandate is not results. given to USDA to be the lead agency for The AID nutrition research program is human nutrition research. designed to provide new knowledge that will Section 1423 (b) requires the Secretary of help implement programs to attain these Agriculture to "periodically consult with the goals. The AID nutrition research program administrators of the other Federal depart- attempts to assess the functional signifi- cance of improvements in nutrition; it seeks ments and agencies." As discussed earlier, to establish whether nutritional needs can be this unilateral approach to coordination satisfied with locally available foods; it relies on the goodwill of other agencies to evaluates the effectiveness of nutrition in- cooperate with USDA in the goal of research tervention; and it seeks to inform govern- coordination. ments about the potential impact of policies in food and nutrition. Research priorities at NIH are summarized in table 3. A wide range of basic and applied It is therefore apparent that the AID nutri- research are embodied in these priorities. tion research program is not and should not The major emphasis is on basic and curative- be designed to address the research needs oriented disease research rather than dis- outlined in this report. The AID program is ease prevention. This becomes more clear as designed to meet the needs of host countries. allocations of funds to the different areas are Should a research project yield results ap- studied. The Nutrition Study Section at NIH plicable to problems discussed in this report, reviewed a total of 181 grant proposals in FY it is serendipitous. There is a clear need to en- 1977, and approved 119, totaling $4.7 million. courage international research, much of Only four other study sections recommended which would be epidemiological, to identify for approval grants totaling less than $4.7 and explore dietary and lifestyle factors con- million in this period of time. Two of these tributing to the major chronic diseases. sections have been disbanded, their work be- In theory, AID's nutrition research ac- ing referred to other study sections. Since tivities undergo peer review. Research funds research in nutrition involves many different are publicized through the distribution of a disciplines and crosses traditional discipli- brochure, and information on AID's research nary lines, NIH maintains that many grant needs are circulated among professional applications with nutrition components are groups and announced at professional meet- referred to other study sections. It can there- ings. 'Projects that are awarded on the basis fore be assumed that $4.7 million is what NIH of predominant capability are very carefully clearly defined as human nutrition research, reviewed before approval. Fewer and fewer and the remainder of the $80.4 million of projects follow this latter nutrition research funded by NIH if FY 1977 was basic and disease-oriented research In practice, the system seems to have func- with nutrition components of varying degrees tioned somewhat differently. Human nutri- of relevance. ¹Irwin Hornstein, Deputy Director, Office of Nutri- The Agency for International Development tion, Agency for International Development, June 8, (AID) is the Federal agency primarily respon- 1978. sible for international nutrition research. ²Ibid. 29 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research received an estimated $2.7 mil- human nutrition research is made in the Act. lion from AID in FY 1977. Most of this re- search was conceived by agency staff who In response to these requirements, USDA requested $43 million for human nutrition then had a scientific research group develop research in its FY 1979 budget proposal. This study proposals. The proposals were is a 95-percent increase over its FY 1977 screened by AID staff members before being spending of $22 million. submitted to the Research Advisory Commit- tee for technical feasibility evaluation. The At NIH, nutrition research support has re- agency does not widely advertise requests for mained relatively constant over the last sev- proposals, and few unsolicited proposals are eral years, constituting less than 3 percent of received. Some panel participants felt that the total research budget. Estimates of actual this system reduces the scientific base of ex- dollar outlays for human nutrition research pertise on which the agency can draw and vary from $20 million to $80 million for FY leads to an inbreeding of research ideas. 1977. Definition and Funding Personnel Resource Requirements The Food and Agriculture Act of 1977 does not explicitly define the term "nutrition" nor Both the USDA and HEW support under- the scope of "nutrition research." It implies graduate, predoctoral, and postdoctoral that "nutrition research" includes research students through a variety of tuition grants, on diet and disease, certain aspects of agri- loans, fellowships, and training grants. The cultural policy, nutritional requirements, Food and Agriculture Act establishes grants food composition and nutrient interactions, and fellowships for food and agricultural food safety, food enrichment, and means of sciences education at the undergraduate encouraging better nutritional practices. through postdoctoral levels. The program is There is no reference in the legislation to in- authorized in FY 1978 for $25 million, ex- ternational nutrition research. panding to $50 million by FY 1982. The pro- Section 1423 (a) of the Food and portion of this money to be devoted to training Agriculture Act of 1977 states that the Secre- nutrition researchers is not specified. tary of Agriculture "shall increase support The Department of Health, Education, and for such research [research into food and Welfare has traditionally supported training human nutrition] to a level that provides of research scientists through training grants resources adequate to meet the policy of this and fellowships. In FY 1977 these totaled subtitle." No specific authorization for $2.3 million for human nutrition research. NEW DIRECTIONS IN FEDERALLY SUPPORTED HUMAN NUTRITION RESEARCH: THE OSTP REPORT Goals and Priorities eral nutrition research activities. Although the report focused only on domestic research, it encouraged various Federal agencies in- In December 1977, OSTP published a re- volved in such activities to assess the poten- port on Government nutrition research. The tial international benefits from current and report defined the scope of human nutrition plonned projects. research, described existing Federal pro- grams, identified research areas that need he working groups of the OSTP inter- more attention, and suggested means for en- agency senior nutrition research staff recom- hancing the coordination and quality of Fed- mended four priority research activities: 30 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 1. Effects of nutrition on human health and In HEW, the programs of the Food and performance in pregnancy, infancy and Drug Administration (FDA), the National early childhood, old age, obesity, iron Center for Health Statistics (NCHS), the deficiency, nutrient toxicity, and in- Center for Disease Control (CDC), and NIH must be coordinated in the high-priority ac- teractions; tivities identified. At NIH, it is essential 2. Food sciences (methodology for analyz- for the NIH Director and for the Nutrition ing food composition, nutrient bio-avail- Coordinating Committee under his direction ability in foods, updating national to have the authority to prioritize nutrition nutrient data bank, expanding food com- research needs. The Director of NIH, has a position measurements); relationship to the several Institutes which 3. Nutrition education research (factors permits allocation of funds for nutrition research in the absence of specific statutory determining dietary practices, identifi- authorities for reprogramming between In- cation of good nutritional practices, ad stitute appropriations. hoc <educational research committee); In USDA, it is essential that the nutrition and research activities of the Agricultural Re- 4. Diet and nutritional status surveillance search Service (ARS), the Cooperative State (food composition, survey methodology, Research Service (CSRS), the Food and Nutri- measurements of nutritional status, tion Service (FNS), and the Economic Re- analysis of the Health and Nutrition Ex- search Service (ERS) be coordinated through amination Survey (HANES) data, epi- the Secretary of Agriculture." demiological studies). Finally, the establishment of an ad hoc in- The criteria used by the working group in teragency nutrition education research com- mittee is recommended. This committee selecting research areas for greater attention were impact, substantial existing knowledge would: identify and summarize research find- ings related to nutrition education research gap. and researchability. The priority areas and summarize pertinent findings from other chosen reflect the narrowness of these cri- areas of education research, establish priori- teria. The priorities tend toward short-term ties, and develop a plan for conducting nutri- projects that lack long-term commitments tion education research. needed to identify the nutrition elements of major health problems facing adult Ameri- It is doubtful that OSTP through FCCSET cans-the chronic degenerative diseases and would be able to adequately oversee coordi- obesity. nation of nutrition research activities. The staff of the Office is small, and their respon- In the OSTP report several recommenda- sibilities large. With a budget of $50 million tions are made for coordination within and to $117 million per year, nutrition research is among the departments conducting nutrition a very small component of the FY 1977 $3.6 research. First of all, the participants in the billion research budget for health and agri- study requested OSTP "to continue to take a culture. lead role in coordinating and monitoring External reviews by teams of nonagency nutrition research activities." OSTP could scientists may improve the quality of intra- serve as a focal point for interagency plan- mural human nutrition research activities, ning through the Federal Coordinating Coun- but they cannot be expected to improve re- cil on Science, Engineering, and Technology search coordination. This recommendation (FCCSET), chaired by the Director of OSTP. calls for the external reviews to be conducted Secondly, external reviews of the intramural within 12 months of the report's publication grants process in both NIH and USDA with by an unspecified number of multidiscipli- joint participation of Federal agencies in nary teams. Scientists from agencies con- developing requests for proposals and in ducting nutrition research would also par- reviewing research in progress. ticipate. The report suggests that this would To improve coordination and communica- be expected to increase communication and tion within HEW and USDA, the report rec- understanding of Federal programs. Since ommends: the review would only be conducted once and 31 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 no provisions are made for improving bad Food consumption patterns and nutri- situations if they are found, it is doubtful that tional status of the general population it would be of any lasting use in improving in- and of special high-risk subgroups with- teragency communication or the quality of in- in the population; evaluation of the nutri- tramural research. tional impacts of various intervention The proposal that Federal agencies jointly strategies and public policies. participate in developing requests for re- The OSTP report established Federal ex- search proposals and in reviewing research penditures for nutrition research for FY 1977 in progress has merit, as does the proposal at $116.6 million. The report stated that no for an ad hoc interagency nutrition education specific funding levels would be recommend- research committee. The ideas could be fur- ther explored by USDA and HEW and pro- ed, but that the report's objectives could be met "at least in part by reallocation of posals for implementation developed. resources from existing programs to the higher priority areas identified." It is highly unlikely that this could be accomplished Definition and Funding without outside intervention. It is also ques- tionable whether such a strategy makes good The scope of human nutrition research, as sense, since the amount of human nutrition defined by the OSTP study, included in- research conducted in this country is so small vestigation of: in comparison to our $3.6 billion in health and Basic physiological and biochemical agriculture research expenditures and our mechanisms for the digestion, absorp- $160.6 billion in health costs. Furthermore: at tion, metabolism, and transport of nutri- least $60 million of the $117 million is basic ents; the role of food ingredients in research on metabolism which underlies human health and performance and in many of the biological and health sciences. A the prevention and treatment of disease; cut in this funding would severely constrain progress in basic research. Nutrient composition of foods; the ef- fects of storage, processing, and packag- ing; and the biological availability of nu- trients in the foods at the time of con- Personnel Resource Requirements sumption; Determinants of dietary practices and The OSTP report does not consider the per- methods for educating the public about sonnel resources needed to fulfill the re- dietary practices; and search priorities contained in the report. FEDERAL HUMAN NUTRITION RESEARCH NEEDS A COORDINATED APPROACH TO ADVANCE NUTRITION KNOWLEDGE: THE GAO REPORT Goals and Priorities Knowledge of dietary nutrients required to promote or maintain growth or well- The General Accounting Office was asked being at various stages and conditions of to identify research gaps and needs in the life: field of human nutrition. The scope of the Information on the composition of the report was restricted to the domestic situa- current U.S. food supply and the extent tion. Gaps identified by GAO included: that nutrients are biologically available; 32 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Evaluation of long-term health conse- Eliminate unnecessary research that quences of the modern diet; and may exist among Federal agencies. Promote Government-wide human nutri- Assessment of the Nation's current tion research planning, coordination, nutritional status in terms of dietary ex- and reporting." cesses and imbalances, as well as defi- ciencies. These recommendations are not suffi- ciently specific to be considered a strategy GAO recommended research along the for organizing nutrition research. Further- following lines to overcome these research more, in an early draft of their report, OSTP gaps: assigned lead and support agency respon- sibilities for specific nutrition research Long-term studies of human subjects areas. This approach was abandoned in the across the full range of both health and final report because of agency objections. A disease; general goal of improved research planning, coordination, and reporting is commendable, Comparative studies of populations of but without specifics probably will not be at- tained. differing geographic, cultural, and genetic backgrounds; Basic investigations of the functions and Definition and Funding interactions of dietary components; GAO identifies the third barrier to prog- Updated and expanded food composition ress in nutrition research as "instability of data; and federally funded extramural research." The report does not make specific recommenda- Improved techniques for assessing long- tions as to how to improve this situation. term toxicological risks. However, it endorses the development of fed- erally funded regional research centers in conjunction with universities and colleges. The priorities set out in the GAO report in- GAO estimates U.S. Government expend- volve the types of research that will probably itures for human nutrition research at $73 provide the most information on the role of million to $117 million annually. It makes no diet in disease. However, work is also needed attempt to define nutrition research or to on how best to convey the research findings analyze agency reports on nutrition research to the public so they can be translated into expenditures. daily life. The GAO report cites "lack of central focus and coordination" and "shortage of nu- Personnel Resource Requirements trition scientists" as two of the three prin- cipal barriers to progress in human nutrition The GAO report highlights the concern of research. To remedy the first of these, the re- the scientific community that there is a short- port recommends that the Director of OSTP age of nutrition research scientists. If this "work with the Federal agencies to further situation exists, it holds significant implica- define the subject areas comprising human tions for the ability of the research commun- nutrition research and make recommenda- ity to absorb research funds should large in- tions to the Director of OMB to: creases be made in the future. Since no accu- rate information exists on the numbers and expertise of nutrition research scientists out- Assign where practicable, each area to side Government laboratories, analysis of re- a lead Federal agency. search capabilities is impossible. 33 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 A COMPREHENSIVE NUTRITION RESEARCH STRATEGY Goals and Priorities points are outlined in table 5. The rationale for the selection of each is contained in the The focus now lacking in Federal nutrition appendix. research could be achieved by defining the Several mechanisms for coordinating Fed- scope of human nutrition research, defining eral nutrition research activities have been general goals for Federal agencies that con- suggested. These include assigning respon- duct such research, and specifying research sibilities for research areas to various agen- priority areas that are in line with the gen- cies, making one agency the lead agency, eral goals. A reorientation of Federal nutri- placing coordination responsibility under a tion research efforts should recognize the third party, assigning coordination respon- changing nature of our food supply by placing sibility to the assistant secretary level, and greater emphasis on the role of diet in concentrating all nutrition research activities preventing chronic diseases. At the same in either USDA or HEW. time, Government programs must continue The first alternative (assigning respon- striving to eliminate hunger and malnutrition sibilities for research areas to various agen- through intervention programs and research. cies) would make USDA and HEW the two lead agencies in human nutrition research. Such a reoriented research strategy re- This approach is similar to the one taken in quires an increased focus on today's complex the Food and Agriculture Act of 1977 in food supply. especially on the effects of proc- which the legitimate roles of both agencies in essed food, food additives and contaminants, nutrition research are recognized. Under and similar problems that concern consum- such a system of joint responsibility, the con- ers, food producers, and health profession- cerns of each agency would have to be de- als. Research in the food sciences would fined to minimize duplication of effort. An ef- enable us to evaluate the adequacy of the fective system of intra-agency cooperation food supply and to develop recommendations would also be necessary. However, since it for needed changes. Such changes might in- may not be possible to clearly separate the clude new processing techniques, fortifica- concerns of nutrition and disease from those tion, reformulation, or selection of alternative of "normal nutrition," some overlap would food items by consumers. probably be inevitable. Broader information and intervention ef- The second alternative assigns one agency forts outside of the health care system are main responsibility for nutrition research. also necessary. The public should know what Since USDA and HEW fund 87 percent of the scientific community has learned about Federal human nutrition research, they are the relationships among lifestyles, food con- the most likely candidates for the lead agency sumption, and health. Developing improved role. There are arguments both for and ways of conveying such knowledge would en- against giving such responsibility to one or courage the public to adopt better eating the other agency. habits and other health-promoting behavior. Currently USDA plays the major role in OTA working group participants felt that carrying out food intervention programs in neither the existing legislation nor the priori- the United States. By giving it primary re- ties suggested in the OSTP and GAO reports sponsibility for funding and coordinating provided the holistic, integrated research nutrition research efforts, the Government's strategy needed to meet current and pro- research and food intervention activities jected diet-related problems in the United might be better coordinated. At the same States. Seven elements of a comprehensive time, Federal research activities might research strategy to define the role of nutri- become more responsive to consumer views tion in the prevention of chronic disease and and needs because of USDA's major involve- to improve management of current nutrition- ment in food and nutrition education pro- related problems were discussed. The seven grams. 34 Source: https://www.industrydocuments.ucsf.edu/docs/rInf0227 Table 5.-A Seven-Point Nutrition Research Strategy The role of diet in the prevention of chronic disease and obesity Major health problems and diet-related risk factors Diet, aging, and disease Methods for preventing obesity Nutrition and mental development The role of nutrition in the treatment of disease and support of therapy Nutritional support of patients with severe disease and injury Other disease states Technology for delivery of nutrients to patients Behavioral and emotional problems Nutrition education and consumer information Factors affecting lifetime eating habits and identification of critical points for education Development and evaluation of nutrition education and communication methods Methods for simplifying consumer information utilization Requirements for essential nutrients Methods for determining nutrient needs Interactions among nutrient requirements based on functional criteria Pharmacologic and toxicologic effects of on nutritions Bioavailability of nutrients in foods Nutritional aspects of food science and food safety Food composition New food processing and handling procedures to maintain nutrient content Better methods of assuring food safety Monitoring nutritional status Methods for improving integration of food consumption and nutritional status surveillance Evaluation of the effects of food and nutrition education programs Nutrition policy and management Food-related interventions Other interventions USDA now coordinates research in the ments for giving HEW, the agency concerned area of food production with the State agri- with health, the lead responsibility for direct- culture experiment stations and other coop- ing nutrition research. However, such re- erating institutions. Some link between the search has not been a main HEW concern in nutritional concerns of consumers and the the past. Disease-prevention research has food production system seems to be essential. generally received much less support than But USDA has traditionally had little respon- specific disease-oriented or curative-oriented sibility or expertise in the area of human research. Moreover, HEW has not been con- health and disease. One of the major needs in cerned with the nutrient requirements of Federal nutrition research activities is a healthy people, food consumption patterns, or reorientation of priorities to stress the role of food composition. In addition, HEW has no nutrition in the prevention of disease. Thus nationwide programs of nutrition and health separating health-related nutrition research education comparable to those developed by from the overall direction of health research USDA. may not be wise. If health-related nutrition research fell exclusively under USDA, poten- tial conflicts might arise. The research might The report by OSTP recommended that the produce recommendations for substantial lead role in nutrition research be given to a shifts in food practices. Such findings and third party which would formulate policy and recommendations could conflict with the coordinate and monitor programs. Under this traditional interests of producer groups. arrangement, various agencies would retain their existing nutrition research respon- Many of the research priorities identified sibilities, but their activities would be over- by OTA as well as other groups involve the seen by the third party. The concept offers relationship of human health to nutritional some positive features. It would focus atten- practices. Therefore, there are strong argu- tion on nutrition while retaining the healthy 35 Source: https://www.industrydocuments.ucsf.edu/docs/rlnf0227 competition among agencies involved in nutri- A pluralistic approach to human nutrition tion research. research, with well-defined agency respon- sibilities for HEW and USDA, appears to be However, such a third-party concept also the best means of coordinating Federal raises several problems. It involves another research efforts. Such an approach could layer of Federal bureaucracy. A third-party produce the kind of creative competition that oversight body might have no real power to would likely enhance human nutrition influence budgets and allocate resources research. It would also result in some within and among agencies, especially since overlapping of efforts, which should be it would lack a political constituency. These minimized by the coordinating process. potential deficiencies would be further mag- The coordinating function might best be nified by inadequate staff and expertise. In carried out by an interagency committee with the end, such a coordinating mechanism would probably only serve as a means to ex- a rotating chairmanship. This arrangement change information, much as the nutrition would be consistent with a pluralistic ap- proach to research. At the same time, it coordinating committee does within NIH and the Current Research Information System would help ensure against any one agency (CRIS) does for USDA. building a "most-favored" relationship with the coordinating committee. Another alternative would give assistant Coordination of Federal nutrition activities secretaries in HEW and USDA responsibility extends beyond specific mechanisms for for coordinating nutrition research policy intra- and inter-agency coordination. It also within and between their respective agen- includes information storage, retrieval, and cies. Lack of high-level commitment to nutri- integration. No uniform system presently ex- tion research has been a problem in the past. ists among the various agencies involved in Placing responsibility for nutrition at the nutrition research. Computerized systems assistant secretary level might create the that permit information integration and re- visibility and commitment needed to effec- trieval need to be explored. At the very least, tively coordinate nutrition research efforts. relevant branches of HEW and USDA should Such an arrangement would require adminis- have a common indexing and data retrieval trative changes within both agencies. At pre- system for this type of information. Since sent, it is unclear if the USDA reorganization federally supported research accounts for that created a Human Nutrition Center the major share of research in the nutrition within SEA will accomplish this goal. and health maintenance areas, integration among these agencies is essential. Integration A final option would consolidate nutrition of nutrition research data is also desirable programs in one agency, either USDA or among the public, private, and voluntary sec- HEW. These activities would include re- tors. search, education, regulation, training, serv- ice delivery, monitoring and surveillance, and food and other intervention programs. Both Definition and Funding USDA and HEW have recently shown interest in this concept in papers entitled USDA's Commitment to Food and Nutrition Policy and As outlined under issue 2, OTA could not The Role of HEW in Human Nutrition: Future perform an analysis of the present Federal Directions. However, the wisdom of such a human nutrition research budget, since pres- consolidation is debatable. Although both ent expenditure estimates are so disparate. agencies currently have a number of nutri- Federal spending on human nutrition tion programs, the expertise involved is quite research should be precisely determined. By specialized. Whether this approach would eliminating the present confusion, Congress solve coordination problems probably will be better able to judge appropriate levels depends on the agency's commitment to the of funding for nutrition research. Congress field of nutrition. could request GAO to audit the human nutri- 36 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research expenditures of Federal agen- facilitate future congressional oversight cies. The GAO audit, based on a constant hearings. definition, should determine total Federal spending for human nutrition research, the number of scientist years involved, and Personnel Resource Requirements Federal expenditures in the seven priority areas set out in this report. If Congress were to choose to implement On the basis of such information, Congress the OTA comprehensive nutrition research would have several options. The first would strategy, there is a clear need to establish be to maintain the status quo in nutrition how many scientists are both presently in- research funding, with possible reallocation volved in, or training for, nutrition research. of some funds to areas not now receiving sup- This census would include a breakdown in port. As a second option, Congress could ap- terms of various research areas, such as propriate, additional funds to specific nutri- Government facilities, universities, medical tion research areas that are not getting facilities, private institutes, and industry. enough support. Finally, Congress could ear- This kind of census would identify where nu- mark a percentage of Hatch funds for human trition research personnel gaps exist and nutrition research. Such an audit, together where greater support is necessary. To fill with a uniform system for reporting human such gaps, expanded Federal support should nutrition research spending, could also be considered. 37 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONCRESSIONAL OPTIONS vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONGRESSIONAL OPTIONS OTA found that three key issues underlie the basic finding that the Fed- eral Government has failed to adjust the emphasis of its human nutrition research activities to meet the changing health problems of the American people. Alternative approaches of dealing with these issues have been ex- plored. Congress can elect to maintain the status quo, with or without minor shifts, or choose among the strategies and options offered by OTA, the General Accounting Office (GAO), and the Office of Science and Technology Policy (OSTP), (see chapter III). Either alternative has economic, institutional, and health implications. Option 1: Congress Could Choose To Maintain the Overall Status Quo Maintaining the status quo could mean itoring nutrition status, and nutrition policy refraining from any action. In a broader and management. sense, it also could involve minor im- provements in the present system-without If Congress chooses to refrain from any ac- making substantial changes. tion to await the recommendations of the President's Reorganization Project, no ad- A. Congress could refrain from any action, verse effects would be expected. awaiting the recommendations of the President's Reorganization Project. B. Congress could amend the Food and Agri- culture Act of 1977 to clarify the desig- In August of 1977, President Carter nation of lead agency for human nutrition directed the Reorganization Project staff at research. the Office of Management and Budget to thor- oughly review the organization and structure At the present time, the Department of of Federal food and nutrition programs. Food Agriculture (USDA) interprets the Food and and nutrition research is one of the seven ma- Agriculture Act of 1977 to mean that USDA is jor areas under review. A final report to the the lead agency for human nutrition re- President, expected in January of 1979, will search, an interpretation not shared by the include recommendations that may signifi- Department of Health, Education, and Wel- cantly alter the organization, and thus the fare (HEW). If Congress intended USDA to course, of nutrition research activities. have primary responsibility for this research area, the Act will require amendment. Since significant strides have been made in nutrition research, there is no reason to ex- C. Congress could develop nutrition research pect a decline in research productivity if cur- goals and priorities for HEW that comple- rent funding levels are maintained. However, ment the goals and priorities outlined for since several important areas of nutrition USDA in the Food and Agriculture Act of research receive little support at present, 1977. progress in these areas would be slow. These areas include the role of nutrition in the pre- The legislation contains strong language on vention of disease, nutrition education, mon- the relationship of diet to many of the leading 41 Source: https://lwww.industrydocuments.ucsf.edu/docs/rinf0227

The third image represents which nutrient?

rlnf0227

rlnf0227_p22, rlnf0227_p23, rlnf0227_p24, rlnf0227_p25, rlnf0227_p26, rlnf0227_p27, rlnf0227_p28, rlnf0227_p29, rlnf0227_p30, rlnf0227_p31, rlnf0227_p32, rlnf0227_p33, rlnf0227_p34, rlnf0227_p35, rlnf0227_p36, rlnf0227_p37, rlnf0227_p38, rlnf0227_p39, rlnf0227_p40, rlnf0227_p41, rlnf0227_p42, rlnf0227_p43

minerals, Minerals

lating research findings. Because of a general noted that this language is ambiguous. It does lack of accessibility, it is often extremely dif- not specify "lead," and it leaves cooperation ficult for agencies to communicate research to the goodwill of HEW. information to the public or Congress. The need for improved coordination in Of course, some overlap in interests is in- nutrition research extends beyond the execu- evitable in similar areas of research, and tive agencies to Congress. At present 14 con- duplication of research results is a necessary gressional committees and 20 subcommittees part of scientific research. But unnecessary are concerned with nutrition matters. The duplication should be avoided. Minimizing principals include the Senate Committees on duplication by developing more efficient Agriculture, Nutrition, and Forestry (Sub- means of sharing information on planned, on- committee on Nutrition); Appropriations going, and completed research is an achiev- (Subcommittees on Labor-Health, Education able goal. and Welfare, and Agriculture); the House In the same sense that some duplication is Agriculture Committee (Subcommittee on a necessary part of scientific research, Domestic Marketing, Consumer Relations, healthy competition among agencies may and Nutrition); the House Appropriations stimulate greater effort and ultimately bene- Committee (Subcommittees on Agriculture fit the public. But the proprietary stance and Labor-Health, Education, and Welfare); taken by some agencies is wasteful and in- House Interstate and Foreign Commerce hibits joint planning. Internecine struggles at Committee (Subcommittees on Oversight and higher levels of Government apparently fos- Investigations, and Health and Environment); ter such attitudes. However, career civil serv- and the House Science and Technology Com- ants and the public, as well as the overall mittee (Subcommittee on Domestic and Inter- Federal research effort, suffer as a result. national Scientific Planning, Analysis, and The turf battles that lead agencies to work at Cooperation, and the Subcommittee on Sci- cross purposes should be eliminated. Agen- ence, Research, and Technology). Since some cies involved in nutrition research should duplication of interest exists, joint sessions of demonstrate a commitment to coordination relevant congressional subcommittees to con- and the avoidance of unnecessary duplica- sider plans and hearings for oversight pur- tion. This commitment needs to be built in, not poses should be considered. only at the "political" level of the higher There is a strong relationship between echelons of Government but also in the career human nutrition research conducted abroad civil service. and research needs in the United States. The The establishment at USDA of the Human research goals identified in this report can be Nutrition Center and the Human Nutrition best achieved if international and domestic Policy Committee and at HEW of the Nutrition research activities are tuned together. Coordinating Committee are two positive Nutrition research in other countries may steps toward intra-agency coordination. They help in solving domestic nutrition problems. not only indicate a commitment to nutrition For example, epidemiological investigations research but also can serve as mechanisms of certain chronic diseases require good in- for interagency coordination and information formation about disease incidence. This may exchange. be obtained from studies of societies with The Food and Agriculture Act of 1977 lifestyles and food habits very different from specifies that the Secretary of Agriculture our own. The high incidence of malnutrition shall "periodically consult with the adminis- in some developing nations also provides an trators of other Federal departments and opportunity to investigate relationships be- agencies that have responsibility for coor- tween the nutritional status and functional dinating Federal nutrition research activ- performance of individuals in a way that ities." However without the support and in- would be impossible in the United States. It volvement of the Secretary of HEW, unilat- may be possible to extrapolate the results of eral USDA efforts to coordinate research studies of severe malnutrition abroad to may not be effective. Likewise, it should be margina! nutritional areas in this country. 16 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 The study of worldwide populations and will have a dual reward-assistance to mal- food patterns is essential to the better under- nourished peoples abroad and increased standing of some of the priority research knowledge of human nutrient needs and areas of nutrition. Thus any effort to increase health status under changing environmental international nutrition research capabilities conditions. ISSUE 2 - Definition and Funding of Human Nutrition Research If one accepts that the goals of human genetics, animal nutrition, plant nutrition, nutrition research are twofold-(1) the pro- and plant genetics comes under this classi- motion of optimum health and performance, fication. While there is need to integrate such and (2) the treatment of diseases through diet agricultural research with human nutrition therapy and the support of other medical concerns, these areas should not be consid- therapies-th definition of human nutrition ered human nutrition research. Similarly, research flows from these stated goals. If all basic research on metabolism of nutrients, if the research areas involving nutrition are not directly applicable to people, should not listed, from basic studies on the metabolism be considered human nutrition research. of nutrients to genetic studies on the develop- Basic research on metabolism should be con- ment of foods with specific nutrient charac- sidered as basic research underlying all of teristics, it is clear that some areas of the biomedical and life sciences. Human research are more closely related to these nutrition research builds upon this knowl- stated goals than others. Accordingly, the edge base, but the apparent commitment to definition of human nutrition research must and budget for human nutrition research take into account these relationships to should not be inflated by its inclusion. stated goals. Throughout this assessment, a recurrent In terms of this assessment, nutrition problem has been that of definition of human research falls into three broad categories. nutrition research. Agencies report as human Most closely related to the stated goals is nutrition research studies that appear to research into the biochemical and physiologi- have little to do with human nutrition. Ex- cal effects of food on the body in health and amples are "Catalytic Functions and Metab- disease. This category includes research on olism of Vitamin B6 in Bacteria and Fungi," nutritional management of disease, nutrient "Nutritional Imbalance and Metabolic Alter- needs and interactions, and research which ations in Fungi," or "Hepatoma Incidence in promotes optimum health and disease pre- Trout on Dietary Aflatoxin and PCB." Such vention through diet. studies are worthwhile and contribute to our understanding of basic biochemistry but are Research on food and nutrition quality not directly applicable to humans. determinants is also related to the stated The almost unanimous consensus of the goals, but less directly so than the previous category. Under this heading would be re- participants in the OTA study was that at- search into food composition, especially the tribution of these Federal expenditures to nutritive components and changes in nutrient "human nutrition research" was improper. composition that occur from point of origin to Fourteen different Federal agencies are point of consumption; food safety; social, cul- engaged in some sort of nutrition research. tural, and economic aspects of food habits; Each agency has developed its own definition feeding programs; nutrition education; con- of human nutrition research and set priorities sumer information; and nutrition surveillance on the basis of how it interprets its legislation and monitoring. mandate. The agencies and their priorities are shown in table 3. The third category of research involves basic research on sources of human food and Federal expenditures for human nutrition basic biochemistry. Research into animal research in FY 1977 (shown in table 4) were 17 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3. - Federal Government Agencies Active in Food and Nutrition Programs and Their Nutrition Research Priorities Food and nutrition Department Agency programs Research priorities Health, Edu- National National Institute of Arthritis, Metabolism, and Digestive Diseases cation, & Institutes (NIAMDD).Basic hysiological studies of nutrients; basic metabolism Welfare of Health studies; obesit, trace elements nutrition support of patients; fiber; anemias. National Institute of Child Health and Human Development (NICHHD). Nutrition and fetal development; metabolic capacities of normal, low- birthweight, and premature infants; diet modification for low-birth- weight and premature infants; optimum nutrition in developmental years; nutrition and reproductive potential; genetic variability-nuti tional interaction; prevention- - metabolic antecedents of adult disease. National Cancer Institute (NCI). Nutrition support of cancer patient; nu- trition in cancer etiology; host-tumor interactions and competition for nutrients; prevention strategies based on nutrition; diet and nutrition in the rehabilitation of cancer patients. National Heart, Lung, and Blood Institute (NHLBI). Nutrition in etiology of arteriosclerosis and hypertension; achieving and maintaining dietary change; development of food composition tables; methodology-col lecting, recording, and evaluating dietary data. National Institute of General Medical Sciences (NIGMS). Trauma- tized/burned patients and nutrition. National Institute of Environmental Health Sciences (NIEHS). Neuro- toxicity; mutagenesis; teratology; environmental contaminants in food. National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Protein-calorie malnutrition, B-vitamin deficiencies and the nervous system; genetic disorders and the nervous system; specific nutritional problems in the central nervous system; stroke. National Institute of Dental Research (NIDR). Sucrose and caries; poor nutrition and periodontal disease; poor nutrition and oral mucus mem- branes; nutrition in craniofacial malformations and oral-facial struc- tures; nutrition and salivary gland development. National Institute of Allergy and Infectious Disease (NIAID). Interrelated factors hearing on malnutrition, infection, and the immune system. National Eye Institute (NEI). Vitamins A, B-12, and other nutrients in visual processes; diseases of visual system, e.g., keratomalacia; metab- olism of visual cells; protein changes in the lens. National Institute on Aging (NIA). Nutritional status of the elderly; aspects of increase in life span including dietary manipulations; vitamin supplementation in elderly; nutrient intake as a consequence of econ- omic status in elderly; relationship among nutrition, cellular structure, and function in elderly. Division of Research Resources (DRR). Nutrient requirements for growth, gestation, lactation in primates and laboratory rodents; stand- ard diets for specific objectives; interaction of various nutrients on physiological function in laboratory animals; differences in nutrient re- quirements among strains of animals within a species. Food & Regulatory activities Nutrient efficacy and safety; nutrient interrelationships as concerned Drug related to: nutrition with disease prevention; nutrient bioavailability for food fortification Admin- labeling, ingredient purposes; nutrient quality assessment of processed foods; medical istration labeling, food for food assessment; food composition and nutrient analysis as related to special dietary use, FDA mission; and consumer studies of perceptions about food values food advertising, nutri- and nutritional quality and educational models to help correct tion quality of foods misconceptions about them. Health Re- Health and Nutrition Assessment of the nutritional status of the American people. sources Examination Survey Admin- istration 18 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3 - -continued Food and nutrition Department Agency programs Research priorities Center for Epidemiological surveillance studies in cooperation with State Disease agencies assistance to AID in similar international areas. Control Health Collaborative research and screening program for phenylketonuria. Services Admin- istration Alcohol, Effects of alcohol consumption on nutrient metabolism and nutritional Drug deficiencies; study of food additive consumption and hyperactivity Abuse, & in children. Mental 5 Health Admin- istration Agriculture Agricul- Human Requirements for Nutrients tural Re- Determine the requirements for lipid intake and identification of the search forms of these nutrients in foods that may be useful in meeting Service* these requirements. Determine the requirements for mineral intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for vitamin intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for protein and amino acid intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for carbohydrate and energy intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Food Composition and Improvement To provide accurate, up-to-date, and comprehensive information in a readily usable form on the composition of all important foods for those nutrients required by and biologically useful to man. To provide the technology for the nutritional improvement of foods when enhanced levels of certain nutrients in the diet are needed to correct possible dietary faults. Food Consumption and Use To provide accurate, up-to-date, and comprehensive information in a readily usable form on food consumption and dietary levels. To provide consultative assistance on food and nutrition problems and provide sound guidance materials on nutrition for the consumer and for nutrition educators, program leaders, and food program man- agers; to identify techniques which will assist people in selecting nu- tritionally adequate diets within different budget limitations; to iden- tify means to modify undesirable food habits; to strengthen nutri- tionally desirable food choice. To identify and develop suitable and safe procedures for food man- agement and preparation for home and institutional consumers, for best retention of both nutritional and eating qualities and to avoid food-borne illness. Coopera- Nutrient requirements; nutritional status of special population groups tive State including children, low income, and aging; metabolic function of Research nutrients in the diet and their interactions; nutrient content of foods; Service* effects of processing on nutrients; food delivery systems; food habits and use); dietary patterns. 19 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table -continued Food and nutrition Department Agency programs Research priorities Economic Economic and social research relating to domestic food programs; Research nutrition policy in LDCs; food choices (demand); nutritional programs Service' for the elderly. Defense Determination of nutritional and dietary standards for Armed Forces personnel subsisted under normal and special operating conditions; evaluation of nutritional adequacy of food as consumed; evaluation of the nutritional status of Armed Forces personnel; establishment of sanitary and food hygiene standards for all food program activities; food aspects of preventive medicine. National Nutritional control of neurotransmitters; role of dietary protein and Aeronautics specific amino acids in optimizing human performance under stress. & Space Ad- ministration Veterans Depart- Research in disease and diet: nutrition and disease or clinical nutrition, Adminis- ment of dietary therapy; effect of disease on nutrition; environmental toxicants, tration Medicine alcohol, and nutrition; nutrition and cancer; nutrition and vision re- & Surgery search; nutrition-related therapy. Metabolic effects: Investigations on or related to malabsorption syn- dromes, inborn errors of metabolism, and familial or inherited nutri- tional defects. Nutrition requirements: Studies of nutrient metabolism, malnutrition, neuroendocrine nutrient interactions, fundamental intermediary metab- olism involving the role of one or more nutrients. State Agency Development of new low-cost nutritious foods; development and for Inter- dissemination of new appropriate technologies; understanding national nutritional needs and requirements; testing and evaluation of nutrition Develop- program alternatives; research on methodologies for improving national ment nutrition planning and programing. National Basic research in the behavioral, education, and social sciences in Science areas applicable to foods and nutrition. Foundation Under USDA's recent reorganization, ARS is now called Federal Research, and is housed within the Science and Education Administration. Under USDA S recent reorganization, CRS is called Cooperative Research and is housed within the Science and Education Administration Under USDA S recent reorganization, ERS is called Economics and is housed within the Economics, Statistics. and Cooperatives Service. Under USDA recent reorganization, ES is called Extension and is housed within the Science and Education Administration estimated at between $50 million and $117 tion research. Seventy-five percent of Federal million, depending on how "nutrition re- nutrition research is conducted outside of the search' was defined. If for example, the NIH two departments through competitive grants definition is used, NIH appears to be spend- and contracts. Using the more realistic fund- ing $80 million for human nutrition research. ing figure of $50 million for FY 1977, NIH at This broad definition takes in studies of basic HEW funded 44 percent of the total, and the biochemistry, studies which are not focused Science and Education Administration (SEA) on nutrition but have a nutrition aspect, as at USDA funded 43 percent of the total. The well as studies of primary nutrition. If a nar- Science and Education Administration en- row definition is used, one encompassing only compasses what were formerly known as the those studies of direct clinical applications Agricultural Research Service and the Coop- and disease prevention, the NIH nutrition erative State Research Service. Under research funding falls in the annual range of USDA's new reorganization, most human nu- $20 million. Even the higher $80 million trition research will be coordinated by SEA's figure, incidentally, amounts to less than 3 Human Nutrition Center. percent of the NIH research budget. The Science and Education Administration HEW and USDA are responsible for the Cooperative Research (SEA-CR) of USDA is majority of federally supported human nutri- unique among Federal agencies in that it links 20 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 Table 4. - Federal Expenditures for Human Nutrition Research An Approximation of FY '77 Expenditures (millions of dollars) Office of Science & Office of Management Agency Technology Policy & Budgetb Department of Health, Education, & Welfare $ 88.6 $22.0 National Institutes of Health 80.4C 22.0d Food and Drug Administration 3.9 National Center for Health Statistics 2.4 Alcohol, Drug Abuse, and Mental Health Administration 1.1 Health Services Administration 0.5* Center for Disease Control 0.3* Department of Agriculture 22.0 21.8 Agricultural Research Service 14.0 13.2 Cooperative State Research Service 7.5 8.1 Economic Research Service 0.5 0.5 Agency for International Development 2.9 0 Department of Defense 2.3* 2.2 Veterans Administration 0.5* 4.1 National Science Foundation 0.3* 0 Grand total. $116.6 $50.2 affice of Science and Technology Policy, New Directions in Federally Supported Human Nutrition Research, December 1977. Poffice of Management and Budget, Special Analyses-Budget of the U.S. Government FY 1979. This figure includes studies designed to assess the mechanisms and the consequences of food or nutrient intake in the intact organism. particularly man: investigations involving nutrient variables at the cellular or subcellular level, including metabolic studies in animals and man: research designed to elucidate the metabolic role or function of an essential nutrient in both animal models and man, as appropriate; all studies concerned with genetic-nutrient-environmental interactions; dietary studies ex- pected to produce changes in health status, including the maintenance of health and the treatment of disease in man. This figure includes biochemical, physiological, and clinical studies of nutritional needs for normal growth, development, and health: nutritional needs of patients with specific common diseases: and experimental assessments of feeding programs. *Estimates of FY 1976 expenditures provided by draft Government Accounting Office report, Human Nutrition Research- Need for a Coordinated Approach to Advance Our Knowledge, 1977. Federal and State research efforts. SEA-CR levels could be made since current estimates administers funds that Congress appropri- of Federal spending for human nutrition ates to the States for agricultural research. research are questionable. Estimates for FY This work is conducted at the State agricul- 1977 range from $50 million to $117 million tural experiment stations, land-grant colleges (table 4). The lower figure, based on agency and universities, approved schools of for- responses to a standard questionnaire, was estry, colleges of 1890, and Tuskegee In- developed by the Office of Management and stitute. In FY 1977, the States used $7.5 Budget (OMB) for the FY 1979 budget. The million of the Federal money available to higher figure came from an OSTP working them for human nutrition research. The group and appeared in the December 1977 States themselves provided $11.7 million for report "New Directions in Human Nutrition human nutrition research in 1976. Most of Research." the Federal money came from funds author- ized by the Hatch Act, as amended, and P.L. Neither is reliable. The $50 million, for ex- 89-106 (an act to amend the Agriculture Act ample, fails to include certain nutrition of 1954). The funds are accounted for under research activities within HEW, AID, and the the Hatch Act research program called Peo- National Science Foundation. The $117 mil- ple, Communities, and Institutions, which lion, on the other hand, includes $80.4 million comprised 12 percent of total Hatch Act of NIH spending-much of it of tenuous con- research funds in 1977. nection to human nutrition research. In testi- mony before the Senate Select Committee on Federal human nutrition research may be Nutrition and Human Needs on October 17, financially undernourished. However, no 1977, NIH Director Dr. Donald Fredrickson analysis of the adequacy of present funding conceded that, based on a strict definition, 21 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 his agency devoted only around $20 million to whether any of these funds are devoted to human nutrition research in FY 1977 (a fig- research on which methods are most effeo- ure reported to OMB). tive for reaching people. Another statistic which raised questions OTA concluded that most estimates of came from the Veterans Administration (VA). human nutrition research funding were ques- GAO put the VA's FY 1976 nutrition research tionable and that total funding fell con- spending at $0.5 million. In FY 1977, the VA siderably short of the reported $117 million reported sharply increased expenditures of level. Regardless of which overall figure is $4.1 million, even though nutrition research more nearly accurate, certain areas iden- was not recognized as a high priority by the tified by OTA are not now receiving sufficient agency. Federal support, the result of a lack of recognition of their importance and zero or In some cases, it was difficult to determine almost no funds. Those areas most in need of how much (if any) money was being spent for increased funding are the role of diet in the certain types of important nutrition research. prevention of chronic disease and obesity, For instance, the Federal Government is now nutrition education and consumer informa- annually spending about $70 million on nutri- tion, monitoring nutritional status, and nutri- tion education programs. It is unclear tion policy and management. ISSUE 3 - Personnel Resource Requirements Estimates of the number of scientists they are engaged in research activities. This engaged in human nutrition research also does not indicate the degree of involvement proved elusive. and, of course, neglects those outside of dietetics engaged in nutrition research. In an attempt to determine the current number of scientists engaged in human-nutri- The two Government agencies that fund tion research and the numbers of research the largest portion of nutrition research, scientists being trained, OTA contacted five HEW and USDA, do maintain figures on sci- professional societies and six Government entist-years devoted to nutrition research agencies. Of the professional societies, the and 5-year projections of personnel needs. At American Public Health Association, Insti- USDA in FY 1976, 193.5 scientist years were tute of Food Technologists, and American devoted to human nutrition research as de- Chemical Society make no attempt to distin- fined by the agency. The 5-year projection of guish between members engaged in research need for nutrition research scientists at versus other career orientations and USDA is for 260.7 scientist years, a 20-per- therefore could not supply information on the cent increase. proportion of their membership engaged in In a written response to an OTA question- human nutrition research or training of nutri- naire, NIH informed OTA that 70 scientists tion research scientists. Membership in the were employed in human nutrition research American Institute of Nutrition (AIN) is in 1977. But NIH Director Fredrickson sub- limited to those who have made significant mitted a written statement to the Senate contributions to the field of nutrition re- Select Committee on Nutrition and Human search. By definition, all of AIN's 1,730 mem- Needs that during that same time period 180 bers are nutrition research scientists. This intramural investigators in NIH were directly number seriously underestimates the total involved in human nutrition research. Of that number of scientists in the field, since junior number, 20 were defined as "classical nutri- people are not eligible for membership and tionists" when nutrition research was de- very few behavior and education researchers fined as "the study of food and nutrients." In are included. AIN does not keep any figures FY 1977, 20 lead scientists, those holding on training. Of the American Dietetic Asso- M.D., Ph.D., or D.V.M. degrees, and 50 junior ciation's 21,751 members in 1977, 764 state scientists were conducting nutrition research 22 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 at Letterman Army Institute of Research of professional nutrition training programs as the Department of Defense. well as increased training support. For grad- uate students in nutrition and food science, Before a comprehensive nutrition research program is established, consideration must such changes might include greater stress on be given to the ability of the field to sustain nutritional pharmacology, food science prin- such a program. No accurate figures exist on ciples, nutrition education, nutritional status evaluation, and nutrition-related diseases. how many scientists are currently engaged in human nutrition research. Furthermore, few Training would be further strengthened by reports on nutrition research mention this postdoctoral research work with either hu- aspect of planning. mans or experimental animals. Greater em- phasis on nutritional biochemistry and clini- Implementation of the research priority cal nutrition in undergraduate medical edu- areas identified in this report may require cation may help attract physicians to the changes of emphasis in existing graduate and field. 23 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES Accumulating the fragmented research activities of the 14 Federal agen- cies supporting human nutrition research does not, as a whole, constitute a coherent strategy for the solution of current diet-related health problems. A goód understanding of the status quo can be gained by analysis of the Food and Agriculture Act of 1977 which established research goals and priorities for the Department of Agriculture (USDA). The picture of the present situation can be completed by reviewing the research goals and priorities at the Na- tional Institutes of Health (NIH). Alternatives to the status quo can be found in the recently published reports of the Office of Science and Technology Policy (OSTP) and the General Accounting Office (GAO). These two alter- natives, plus an alternative developed by OTA, are examined here and provide Congress with several alternative strategies that may be pursued. Each of the alternatives are examined from three perspectives: Do the stated goals and priorities adequately address current U.S. health problems? Is nutrition research defined clearly to permit realistic estimation of Federal expend- itures? Is consideration given to the personnel requirements to fulfill pro- posed research priorities? THE STATUS QUO: NUTRITION RESEARCH IN THE FEDERAL GOVERNMENT Goals and Priorities The Food and Agriculture Act of 1977 rec- fants, children, adolescents, elderly men and ognized the relationship between diet and the women, and pregnant women; and that there general health of the population. The legis- is a critical need for objective data concern- lation states "that there is increasing evi- ing food safety, the potential of food enrich- dence of a relationship between diet and ment, and means to encourage better nutri- many of the leading causes of death in the tional practices." United States; that improved nutrition is an integral component of preventive health care; The legislation declares that the Secretary that there is a serious need for research on of Agriculture shall develop and implement a the chronic effects of diet on degenerative national food and human nutrition research diseases and related disorders; that nutrition program that shall include, but not be limited and health considerations are important to to, five areas: U.S. agricultural policy; that there is insuffi- cient knowledge concerning precise human 1. Research on human nutritional require- nutritional requirements, the interaction of ments. the various nutritional constituents of food, and differences in nutritional requirements 2. Research on nutrient composition of among different population groups such as in- foods and the effects of agricultural 27 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 practices, handling, food processing, "Reviewing the policies, plans, and goals and cooking on the nutrients they con- of programs within USDA involving the tain. food and agricultural sciences, and 3. Surveillance of the nutritional benefits related programs in other Federal and provided to participants in the food pro- State departments and agencies and in grams administered by USDA. the colleges and universities developed by the Secretary under this title; 4. Research on the factors affecting food preference and habits. Reviewing and ssessing the extent of agricultural research and extension be- 5. The development of techniques and ing conducted by private foundations equipment to assist consumers in the and businesses, and the relationships of home or in institutions in selecting food such research and extension to federally that supplies a nutritionally adequate supported agricultural research and ex- diet. tension; Reviewing and providing consultation to Although the legislation points up the rela- the Secretary on national policies, prior- tionship between diet and leading causes of ities, and strategies for agricultural death in the United States, the research pri- research and extension for both the ority areas spelled out do not pursue this line short and long term; of inquiry. Since the legislation pertains almost exclusively to USDA, it lays out what Assessing the overall adequacy of, and could be considered a partial strategy to making recommendations to the Secre- solve the problems of diet and chronic de- tary with regard to, the distribution of generative diseases-research on nutrient resources and the allocation of funds au- needs, on the composition of the food supply, thorized by this title; on ways to help consumers select a healthful Preparing and submitting to the diet, and surveillance of the population. Fur- Secretary, not later than October 31 of thermore, funding proposed in the FY 1979 sch year, a statement of recommenda- budget does not match the ambitious wording tions as to allocations of responsibilities of the legislation. and levels of funding among federally supported agricultural research and ex- The Food and Agriculture Act of 1977 tension programs; and designated the Secretary of Agriculture to "establish jointly with the Secretary of Not later than March 1 of each year sub- Health, Education, and Welfare procedures mitting a report on its appraisal of the for coordination with respect to nutrition President's proposed budget for the food research in areas of mutual interest." Sec- and agricultural sciences for the fiscal tion 1406 amends the National Science and year beginning in such year and the Technology Policy, Organization, and Priori- recommendations of the Secretary con- ties Act of 1976 (90 Stat. 471; 42 U.S.C. 6651 tained in the annual report.' (h)), by creating a standing subcommittee to be known as the Subcommittee on Food and As indicated earlier, the Food and Agricul- Renewable Resources. ture Act of 1977 does not clearly give USDA the lead responsibility for human nutrition The legislation also established a National research. Section 1405 declares "the Depart- Agricultural Research and Extension Users ment of Agriculture is designated as the lead Advisory Board composed of 21 members rep- agency of the Federal Government for agri- resenting a wide variety of agricultural pro- cultural research (except with respect to the ducer, consumer, marketing, and environ- biomedical aspects of human nutrition con- mental interests. Two members must be en- cerned with diagnosis or treatment of dis- gaged in human nutrition work. The Advisory easc). Human nutrition is one of the Board has the responsibilities for: areas included in the definition of "food and 28 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 agricultural sciences (section 1404). But the long-range goals of the AID nutri- Section 1409 states that "*t is the intent of tion program are: to have developing coun- Congress in enacting this title to augment, tries incorporate nutrition considerations in- coordinate, and supplement the planning, ini- to their social and economic development tiation, and conduct of agricultural research plans; to create the methodologies for assess- ing needs, determining causes, and selecting programs existing prior to the enactment of interventions: and to have available the most this title, except that it is not the intent of cost-effective interventions with information Congress in enacting this title to limit the on when they are most appropriate to apply, authority of the Secretary of Health, Educa- the cost and other requirements for imple- tion, and Welfare under any Act which the menting them, the best methods for imple- Secretary of Health, Education, and Welfare menting them, and information on expected administers." Thus a clear mandate is not results. given to USDA to be the lead agency for The AID nutrition research program is human nutrition research. designed to provide new knowledge that will Section 1423 (b) requires the Secretary of help implement programs to attain these Agriculture to "periodically consult with the goals. The AID nutrition research program administrators of the other Federal depart- attempts to assess the functional signifi- cance of improvements in nutrition; it seeks ments and agencies." As discussed earlier, to establish whether nutritional needs can be this unilateral approach to coordination satisfied with locally available foods; it relies on the goodwill of other agencies to evaluates the effectiveness of nutrition in- cooperate with USDA in the goal of research tervention; and it seeks to inform govern- coordination. ments about the potential impact of policies in food and nutrition. Research priorities at NIH are summarized in table 3. A wide range of basic and applied It is therefore apparent that the AID nutri- research are embodied in these priorities. tion research program is not and should not The major emphasis is on basic and curative- be designed to address the research needs oriented disease research rather than dis- outlined in this report. The AID program is ease prevention. This becomes more clear as designed to meet the needs of host countries. allocations of funds to the different areas are Should a research project yield results ap- studied. The Nutrition Study Section at NIH plicable to problems discussed in this report, reviewed a total of 181 grant proposals in FY it is serendipitous. There is a clear need to en- 1977, and approved 119, totaling $4.7 million. courage international research, much of Only four other study sections recommended which would be epidemiological, to identify for approval grants totaling less than $4.7 and explore dietary and lifestyle factors con- million in this period of time. Two of these tributing to the major chronic diseases. sections have been disbanded, their work be- In theory, AID's nutrition research ac- ing referred to other study sections. Since tivities undergo peer review. Research funds research in nutrition involves many different are publicized through the distribution of a disciplines and crosses traditional discipli- brochure, and information on AID's research nary lines, NIH maintains that many grant needs are circulated among professional applications with nutrition components are groups and announced at professional meet- referred to other study sections. It can there- ings. 'Projects that are awarded on the basis fore be assumed that $4.7 million is what NIH of predominant capability are very carefully clearly defined as human nutrition research, reviewed before approval. Fewer and fewer and the remainder of the $80.4 million of projects follow this latter nutrition research funded by NIH if FY 1977 was basic and disease-oriented research In practice, the system seems to have func- with nutrition components of varying degrees tioned somewhat differently. Human nutri- of relevance. ¹Irwin Hornstein, Deputy Director, Office of Nutri- The Agency for International Development tion, Agency for International Development, June 8, (AID) is the Federal agency primarily respon- 1978. sible for international nutrition research. ²Ibid. 29 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research received an estimated $2.7 mil- human nutrition research is made in the Act. lion from AID in FY 1977. Most of this re- search was conceived by agency staff who In response to these requirements, USDA requested $43 million for human nutrition then had a scientific research group develop research in its FY 1979 budget proposal. This study proposals. The proposals were is a 95-percent increase over its FY 1977 screened by AID staff members before being spending of $22 million. submitted to the Research Advisory Commit- tee for technical feasibility evaluation. The At NIH, nutrition research support has re- agency does not widely advertise requests for mained relatively constant over the last sev- proposals, and few unsolicited proposals are eral years, constituting less than 3 percent of received. Some panel participants felt that the total research budget. Estimates of actual this system reduces the scientific base of ex- dollar outlays for human nutrition research pertise on which the agency can draw and vary from $20 million to $80 million for FY leads to an inbreeding of research ideas. 1977. Definition and Funding Personnel Resource Requirements The Food and Agriculture Act of 1977 does not explicitly define the term "nutrition" nor Both the USDA and HEW support under- the scope of "nutrition research." It implies graduate, predoctoral, and postdoctoral that "nutrition research" includes research students through a variety of tuition grants, on diet and disease, certain aspects of agri- loans, fellowships, and training grants. The cultural policy, nutritional requirements, Food and Agriculture Act establishes grants food composition and nutrient interactions, and fellowships for food and agricultural food safety, food enrichment, and means of sciences education at the undergraduate encouraging better nutritional practices. through postdoctoral levels. The program is There is no reference in the legislation to in- authorized in FY 1978 for $25 million, ex- ternational nutrition research. panding to $50 million by FY 1982. The pro- Section 1423 (a) of the Food and portion of this money to be devoted to training Agriculture Act of 1977 states that the Secre- nutrition researchers is not specified. tary of Agriculture "shall increase support The Department of Health, Education, and for such research [research into food and Welfare has traditionally supported training human nutrition] to a level that provides of research scientists through training grants resources adequate to meet the policy of this and fellowships. In FY 1977 these totaled subtitle." No specific authorization for $2.3 million for human nutrition research. NEW DIRECTIONS IN FEDERALLY SUPPORTED HUMAN NUTRITION RESEARCH: THE OSTP REPORT Goals and Priorities eral nutrition research activities. Although the report focused only on domestic research, it encouraged various Federal agencies in- In December 1977, OSTP published a re- volved in such activities to assess the poten- port on Government nutrition research. The tial international benefits from current and report defined the scope of human nutrition plonned projects. research, described existing Federal pro- grams, identified research areas that need he working groups of the OSTP inter- more attention, and suggested means for en- agency senior nutrition research staff recom- hancing the coordination and quality of Fed- mended four priority research activities: 30 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 1. Effects of nutrition on human health and In HEW, the programs of the Food and performance in pregnancy, infancy and Drug Administration (FDA), the National early childhood, old age, obesity, iron Center for Health Statistics (NCHS), the deficiency, nutrient toxicity, and in- Center for Disease Control (CDC), and NIH must be coordinated in the high-priority ac- teractions; tivities identified. At NIH, it is essential 2. Food sciences (methodology for analyz- for the NIH Director and for the Nutrition ing food composition, nutrient bio-avail- Coordinating Committee under his direction ability in foods, updating national to have the authority to prioritize nutrition nutrient data bank, expanding food com- research needs. The Director of NIH, has a position measurements); relationship to the several Institutes which 3. Nutrition education research (factors permits allocation of funds for nutrition research in the absence of specific statutory determining dietary practices, identifi- authorities for reprogramming between In- cation of good nutritional practices, ad stitute appropriations. hoc <educational research committee); In USDA, it is essential that the nutrition and research activities of the Agricultural Re- 4. Diet and nutritional status surveillance search Service (ARS), the Cooperative State (food composition, survey methodology, Research Service (CSRS), the Food and Nutri- measurements of nutritional status, tion Service (FNS), and the Economic Re- analysis of the Health and Nutrition Ex- search Service (ERS) be coordinated through amination Survey (HANES) data, epi- the Secretary of Agriculture." demiological studies). Finally, the establishment of an ad hoc in- The criteria used by the working group in teragency nutrition education research com- mittee is recommended. This committee selecting research areas for greater attention were impact, substantial existing knowledge would: identify and summarize research find- ings related to nutrition education research gap. and researchability. The priority areas and summarize pertinent findings from other chosen reflect the narrowness of these cri- areas of education research, establish priori- teria. The priorities tend toward short-term ties, and develop a plan for conducting nutri- projects that lack long-term commitments tion education research. needed to identify the nutrition elements of major health problems facing adult Ameri- It is doubtful that OSTP through FCCSET cans-the chronic degenerative diseases and would be able to adequately oversee coordi- obesity. nation of nutrition research activities. The staff of the Office is small, and their respon- In the OSTP report several recommenda- sibilities large. With a budget of $50 million tions are made for coordination within and to $117 million per year, nutrition research is among the departments conducting nutrition a very small component of the FY 1977 $3.6 research. First of all, the participants in the billion research budget for health and agri- study requested OSTP "to continue to take a culture. lead role in coordinating and monitoring External reviews by teams of nonagency nutrition research activities." OSTP could scientists may improve the quality of intra- serve as a focal point for interagency plan- mural human nutrition research activities, ning through the Federal Coordinating Coun- but they cannot be expected to improve re- cil on Science, Engineering, and Technology search coordination. This recommendation (FCCSET), chaired by the Director of OSTP. calls for the external reviews to be conducted Secondly, external reviews of the intramural within 12 months of the report's publication grants process in both NIH and USDA with by an unspecified number of multidiscipli- joint participation of Federal agencies in nary teams. Scientists from agencies con- developing requests for proposals and in ducting nutrition research would also par- reviewing research in progress. ticipate. The report suggests that this would To improve coordination and communica- be expected to increase communication and tion within HEW and USDA, the report rec- understanding of Federal programs. Since ommends: the review would only be conducted once and 31 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 no provisions are made for improving bad Food consumption patterns and nutri- situations if they are found, it is doubtful that tional status of the general population it would be of any lasting use in improving in- and of special high-risk subgroups with- teragency communication or the quality of in- in the population; evaluation of the nutri- tramural research. tional impacts of various intervention The proposal that Federal agencies jointly strategies and public policies. participate in developing requests for re- The OSTP report established Federal ex- search proposals and in reviewing research penditures for nutrition research for FY 1977 in progress has merit, as does the proposal at $116.6 million. The report stated that no for an ad hoc interagency nutrition education specific funding levels would be recommend- research committee. The ideas could be fur- ther explored by USDA and HEW and pro- ed, but that the report's objectives could be met "at least in part by reallocation of posals for implementation developed. resources from existing programs to the higher priority areas identified." It is highly unlikely that this could be accomplished Definition and Funding without outside intervention. It is also ques- tionable whether such a strategy makes good The scope of human nutrition research, as sense, since the amount of human nutrition defined by the OSTP study, included in- research conducted in this country is so small vestigation of: in comparison to our $3.6 billion in health and Basic physiological and biochemical agriculture research expenditures and our mechanisms for the digestion, absorp- $160.6 billion in health costs. Furthermore: at tion, metabolism, and transport of nutri- least $60 million of the $117 million is basic ents; the role of food ingredients in research on metabolism which underlies human health and performance and in many of the biological and health sciences. A the prevention and treatment of disease; cut in this funding would severely constrain progress in basic research. Nutrient composition of foods; the ef- fects of storage, processing, and packag- ing; and the biological availability of nu- trients in the foods at the time of con- Personnel Resource Requirements sumption; Determinants of dietary practices and The OSTP report does not consider the per- methods for educating the public about sonnel resources needed to fulfill the re- dietary practices; and search priorities contained in the report. FEDERAL HUMAN NUTRITION RESEARCH NEEDS A COORDINATED APPROACH TO ADVANCE NUTRITION KNOWLEDGE: THE GAO REPORT Goals and Priorities Knowledge of dietary nutrients required to promote or maintain growth or well- The General Accounting Office was asked being at various stages and conditions of to identify research gaps and needs in the life: field of human nutrition. The scope of the Information on the composition of the report was restricted to the domestic situa- current U.S. food supply and the extent tion. Gaps identified by GAO included: that nutrients are biologically available; 32 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Evaluation of long-term health conse- Eliminate unnecessary research that quences of the modern diet; and may exist among Federal agencies. Promote Government-wide human nutri- Assessment of the Nation's current tion research planning, coordination, nutritional status in terms of dietary ex- and reporting." cesses and imbalances, as well as defi- ciencies. These recommendations are not suffi- ciently specific to be considered a strategy GAO recommended research along the for organizing nutrition research. Further- following lines to overcome these research more, in an early draft of their report, OSTP gaps: assigned lead and support agency respon- sibilities for specific nutrition research Long-term studies of human subjects areas. This approach was abandoned in the across the full range of both health and final report because of agency objections. A disease; general goal of improved research planning, coordination, and reporting is commendable, Comparative studies of populations of but without specifics probably will not be at- tained. differing geographic, cultural, and genetic backgrounds; Basic investigations of the functions and Definition and Funding interactions of dietary components; GAO identifies the third barrier to prog- Updated and expanded food composition ress in nutrition research as "instability of data; and federally funded extramural research." The report does not make specific recommenda- Improved techniques for assessing long- tions as to how to improve this situation. term toxicological risks. However, it endorses the development of fed- erally funded regional research centers in conjunction with universities and colleges. The priorities set out in the GAO report in- GAO estimates U.S. Government expend- volve the types of research that will probably itures for human nutrition research at $73 provide the most information on the role of million to $117 million annually. It makes no diet in disease. However, work is also needed attempt to define nutrition research or to on how best to convey the research findings analyze agency reports on nutrition research to the public so they can be translated into expenditures. daily life. The GAO report cites "lack of central focus and coordination" and "shortage of nu- Personnel Resource Requirements trition scientists" as two of the three prin- cipal barriers to progress in human nutrition The GAO report highlights the concern of research. To remedy the first of these, the re- the scientific community that there is a short- port recommends that the Director of OSTP age of nutrition research scientists. If this "work with the Federal agencies to further situation exists, it holds significant implica- define the subject areas comprising human tions for the ability of the research commun- nutrition research and make recommenda- ity to absorb research funds should large in- tions to the Director of OMB to: creases be made in the future. Since no accu- rate information exists on the numbers and expertise of nutrition research scientists out- Assign where practicable, each area to side Government laboratories, analysis of re- a lead Federal agency. search capabilities is impossible. 33 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 A COMPREHENSIVE NUTRITION RESEARCH STRATEGY Goals and Priorities points are outlined in table 5. The rationale for the selection of each is contained in the The focus now lacking in Federal nutrition appendix. research could be achieved by defining the Several mechanisms for coordinating Fed- scope of human nutrition research, defining eral nutrition research activities have been general goals for Federal agencies that con- suggested. These include assigning respon- duct such research, and specifying research sibilities for research areas to various agen- priority areas that are in line with the gen- cies, making one agency the lead agency, eral goals. A reorientation of Federal nutri- placing coordination responsibility under a tion research efforts should recognize the third party, assigning coordination respon- changing nature of our food supply by placing sibility to the assistant secretary level, and greater emphasis on the role of diet in concentrating all nutrition research activities preventing chronic diseases. At the same in either USDA or HEW. time, Government programs must continue The first alternative (assigning respon- striving to eliminate hunger and malnutrition sibilities for research areas to various agen- through intervention programs and research. cies) would make USDA and HEW the two lead agencies in human nutrition research. Such a reoriented research strategy re- This approach is similar to the one taken in quires an increased focus on today's complex the Food and Agriculture Act of 1977 in food supply. especially on the effects of proc- which the legitimate roles of both agencies in essed food, food additives and contaminants, nutrition research are recognized. Under and similar problems that concern consum- such a system of joint responsibility, the con- ers, food producers, and health profession- cerns of each agency would have to be de- als. Research in the food sciences would fined to minimize duplication of effort. An ef- enable us to evaluate the adequacy of the fective system of intra-agency cooperation food supply and to develop recommendations would also be necessary. However, since it for needed changes. Such changes might in- may not be possible to clearly separate the clude new processing techniques, fortifica- concerns of nutrition and disease from those tion, reformulation, or selection of alternative of "normal nutrition," some overlap would food items by consumers. probably be inevitable. Broader information and intervention ef- The second alternative assigns one agency forts outside of the health care system are main responsibility for nutrition research. also necessary. The public should know what Since USDA and HEW fund 87 percent of the scientific community has learned about Federal human nutrition research, they are the relationships among lifestyles, food con- the most likely candidates for the lead agency sumption, and health. Developing improved role. There are arguments both for and ways of conveying such knowledge would en- against giving such responsibility to one or courage the public to adopt better eating the other agency. habits and other health-promoting behavior. Currently USDA plays the major role in OTA working group participants felt that carrying out food intervention programs in neither the existing legislation nor the priori- the United States. By giving it primary re- ties suggested in the OSTP and GAO reports sponsibility for funding and coordinating provided the holistic, integrated research nutrition research efforts, the Government's strategy needed to meet current and pro- research and food intervention activities jected diet-related problems in the United might be better coordinated. At the same States. Seven elements of a comprehensive time, Federal research activities might research strategy to define the role of nutri- become more responsive to consumer views tion in the prevention of chronic disease and and needs because of USDA's major involve- to improve management of current nutrition- ment in food and nutrition education pro- related problems were discussed. The seven grams. 34 Source: https://www.industrydocuments.ucsf.edu/docs/rInf0227 Table 5.-A Seven-Point Nutrition Research Strategy The role of diet in the prevention of chronic disease and obesity Major health problems and diet-related risk factors Diet, aging, and disease Methods for preventing obesity Nutrition and mental development The role of nutrition in the treatment of disease and support of therapy Nutritional support of patients with severe disease and injury Other disease states Technology for delivery of nutrients to patients Behavioral and emotional problems Nutrition education and consumer information Factors affecting lifetime eating habits and identification of critical points for education Development and evaluation of nutrition education and communication methods Methods for simplifying consumer information utilization Requirements for essential nutrients Methods for determining nutrient needs Interactions among nutrient requirements based on functional criteria Pharmacologic and toxicologic effects of on nutritions Bioavailability of nutrients in foods Nutritional aspects of food science and food safety Food composition New food processing and handling procedures to maintain nutrient content Better methods of assuring food safety Monitoring nutritional status Methods for improving integration of food consumption and nutritional status surveillance Evaluation of the effects of food and nutrition education programs Nutrition policy and management Food-related interventions Other interventions USDA now coordinates research in the ments for giving HEW, the agency concerned area of food production with the State agri- with health, the lead responsibility for direct- culture experiment stations and other coop- ing nutrition research. However, such re- erating institutions. Some link between the search has not been a main HEW concern in nutritional concerns of consumers and the the past. Disease-prevention research has food production system seems to be essential. generally received much less support than But USDA has traditionally had little respon- specific disease-oriented or curative-oriented sibility or expertise in the area of human research. Moreover, HEW has not been con- health and disease. One of the major needs in cerned with the nutrient requirements of Federal nutrition research activities is a healthy people, food consumption patterns, or reorientation of priorities to stress the role of food composition. In addition, HEW has no nutrition in the prevention of disease. Thus nationwide programs of nutrition and health separating health-related nutrition research education comparable to those developed by from the overall direction of health research USDA. may not be wise. If health-related nutrition research fell exclusively under USDA, poten- tial conflicts might arise. The research might The report by OSTP recommended that the produce recommendations for substantial lead role in nutrition research be given to a shifts in food practices. Such findings and third party which would formulate policy and recommendations could conflict with the coordinate and monitor programs. Under this traditional interests of producer groups. arrangement, various agencies would retain their existing nutrition research respon- Many of the research priorities identified sibilities, but their activities would be over- by OTA as well as other groups involve the seen by the third party. The concept offers relationship of human health to nutritional some positive features. It would focus atten- practices. Therefore, there are strong argu- tion on nutrition while retaining the healthy 35 Source: https://www.industrydocuments.ucsf.edu/docs/rlnf0227 competition among agencies involved in nutri- A pluralistic approach to human nutrition tion research. research, with well-defined agency respon- sibilities for HEW and USDA, appears to be However, such a third-party concept also the best means of coordinating Federal raises several problems. It involves another research efforts. Such an approach could layer of Federal bureaucracy. A third-party produce the kind of creative competition that oversight body might have no real power to would likely enhance human nutrition influence budgets and allocate resources research. It would also result in some within and among agencies, especially since overlapping of efforts, which should be it would lack a political constituency. These minimized by the coordinating process. potential deficiencies would be further mag- The coordinating function might best be nified by inadequate staff and expertise. In carried out by an interagency committee with the end, such a coordinating mechanism would probably only serve as a means to ex- a rotating chairmanship. This arrangement change information, much as the nutrition would be consistent with a pluralistic ap- proach to research. At the same time, it coordinating committee does within NIH and the Current Research Information System would help ensure against any one agency (CRIS) does for USDA. building a "most-favored" relationship with the coordinating committee. Another alternative would give assistant Coordination of Federal nutrition activities secretaries in HEW and USDA responsibility extends beyond specific mechanisms for for coordinating nutrition research policy intra- and inter-agency coordination. It also within and between their respective agen- includes information storage, retrieval, and cies. Lack of high-level commitment to nutri- integration. No uniform system presently ex- tion research has been a problem in the past. ists among the various agencies involved in Placing responsibility for nutrition at the nutrition research. Computerized systems assistant secretary level might create the that permit information integration and re- visibility and commitment needed to effec- trieval need to be explored. At the very least, tively coordinate nutrition research efforts. relevant branches of HEW and USDA should Such an arrangement would require adminis- have a common indexing and data retrieval trative changes within both agencies. At pre- system for this type of information. Since sent, it is unclear if the USDA reorganization federally supported research accounts for that created a Human Nutrition Center the major share of research in the nutrition within SEA will accomplish this goal. and health maintenance areas, integration among these agencies is essential. Integration A final option would consolidate nutrition of nutrition research data is also desirable programs in one agency, either USDA or among the public, private, and voluntary sec- HEW. These activities would include re- tors. search, education, regulation, training, serv- ice delivery, monitoring and surveillance, and food and other intervention programs. Both Definition and Funding USDA and HEW have recently shown interest in this concept in papers entitled USDA's Commitment to Food and Nutrition Policy and As outlined under issue 2, OTA could not The Role of HEW in Human Nutrition: Future perform an analysis of the present Federal Directions. However, the wisdom of such a human nutrition research budget, since pres- consolidation is debatable. Although both ent expenditure estimates are so disparate. agencies currently have a number of nutri- Federal spending on human nutrition tion programs, the expertise involved is quite research should be precisely determined. By specialized. Whether this approach would eliminating the present confusion, Congress solve coordination problems probably will be better able to judge appropriate levels depends on the agency's commitment to the of funding for nutrition research. Congress field of nutrition. could request GAO to audit the human nutri- 36 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research expenditures of Federal agen- facilitate future congressional oversight cies. The GAO audit, based on a constant hearings. definition, should determine total Federal spending for human nutrition research, the number of scientist years involved, and Personnel Resource Requirements Federal expenditures in the seven priority areas set out in this report. If Congress were to choose to implement On the basis of such information, Congress the OTA comprehensive nutrition research would have several options. The first would strategy, there is a clear need to establish be to maintain the status quo in nutrition how many scientists are both presently in- research funding, with possible reallocation volved in, or training for, nutrition research. of some funds to areas not now receiving sup- This census would include a breakdown in port. As a second option, Congress could ap- terms of various research areas, such as propriate, additional funds to specific nutri- Government facilities, universities, medical tion research areas that are not getting facilities, private institutes, and industry. enough support. Finally, Congress could ear- This kind of census would identify where nu- mark a percentage of Hatch funds for human trition research personnel gaps exist and nutrition research. Such an audit, together where greater support is necessary. To fill with a uniform system for reporting human such gaps, expanded Federal support should nutrition research spending, could also be considered. 37 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONCRESSIONAL OPTIONS vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONGRESSIONAL OPTIONS OTA found that three key issues underlie the basic finding that the Fed- eral Government has failed to adjust the emphasis of its human nutrition research activities to meet the changing health problems of the American people. Alternative approaches of dealing with these issues have been ex- plored. Congress can elect to maintain the status quo, with or without minor shifts, or choose among the strategies and options offered by OTA, the General Accounting Office (GAO), and the Office of Science and Technology Policy (OSTP), (see chapter III). Either alternative has economic, institutional, and health implications. Option 1: Congress Could Choose To Maintain the Overall Status Quo Maintaining the status quo could mean itoring nutrition status, and nutrition policy refraining from any action. In a broader and management. sense, it also could involve minor im- provements in the present system-without If Congress chooses to refrain from any ac- making substantial changes. tion to await the recommendations of the President's Reorganization Project, no ad- A. Congress could refrain from any action, verse effects would be expected. awaiting the recommendations of the President's Reorganization Project. B. Congress could amend the Food and Agri- culture Act of 1977 to clarify the desig- In August of 1977, President Carter nation of lead agency for human nutrition directed the Reorganization Project staff at research. the Office of Management and Budget to thor- oughly review the organization and structure At the present time, the Department of of Federal food and nutrition programs. Food Agriculture (USDA) interprets the Food and and nutrition research is one of the seven ma- Agriculture Act of 1977 to mean that USDA is jor areas under review. A final report to the the lead agency for human nutrition re- President, expected in January of 1979, will search, an interpretation not shared by the include recommendations that may signifi- Department of Health, Education, and Wel- cantly alter the organization, and thus the fare (HEW). If Congress intended USDA to course, of nutrition research activities. have primary responsibility for this research area, the Act will require amendment. Since significant strides have been made in nutrition research, there is no reason to ex- C. Congress could develop nutrition research pect a decline in research productivity if cur- goals and priorities for HEW that comple- rent funding levels are maintained. However, ment the goals and priorities outlined for since several important areas of nutrition USDA in the Food and Agriculture Act of research receive little support at present, 1977. progress in these areas would be slow. These areas include the role of nutrition in the pre- The legislation contains strong language on vention of disease, nutrition education, mon- the relationship of diet to many of the leading 41 Source: https://lwww.industrydocuments.ucsf.edu/docs/rinf0227

The fourth image represents which nutrient?

rlnf0227

rlnf0227_p22, rlnf0227_p23, rlnf0227_p24, rlnf0227_p25, rlnf0227_p26, rlnf0227_p27, rlnf0227_p28, rlnf0227_p29, rlnf0227_p30, rlnf0227_p31, rlnf0227_p32, rlnf0227_p33, rlnf0227_p34, rlnf0227_p35, rlnf0227_p36, rlnf0227_p37, rlnf0227_p38, rlnf0227_p39, rlnf0227_p40, rlnf0227_p41, rlnf0227_p42, rlnf0227_p43

Carbohydrates, carbohydrates

lating research findings. Because of a general noted that this language is ambiguous. It does lack of accessibility, it is often extremely dif- not specify "lead," and it leaves cooperation ficult for agencies to communicate research to the goodwill of HEW. information to the public or Congress. The need for improved coordination in Of course, some overlap in interests is in- nutrition research extends beyond the execu- evitable in similar areas of research, and tive agencies to Congress. At present 14 con- duplication of research results is a necessary gressional committees and 20 subcommittees part of scientific research. But unnecessary are concerned with nutrition matters. The duplication should be avoided. Minimizing principals include the Senate Committees on duplication by developing more efficient Agriculture, Nutrition, and Forestry (Sub- means of sharing information on planned, on- committee on Nutrition); Appropriations going, and completed research is an achiev- (Subcommittees on Labor-Health, Education able goal. and Welfare, and Agriculture); the House In the same sense that some duplication is Agriculture Committee (Subcommittee on a necessary part of scientific research, Domestic Marketing, Consumer Relations, healthy competition among agencies may and Nutrition); the House Appropriations stimulate greater effort and ultimately bene- Committee (Subcommittees on Agriculture fit the public. But the proprietary stance and Labor-Health, Education, and Welfare); taken by some agencies is wasteful and in- House Interstate and Foreign Commerce hibits joint planning. Internecine struggles at Committee (Subcommittees on Oversight and higher levels of Government apparently fos- Investigations, and Health and Environment); ter such attitudes. However, career civil serv- and the House Science and Technology Com- ants and the public, as well as the overall mittee (Subcommittee on Domestic and Inter- Federal research effort, suffer as a result. national Scientific Planning, Analysis, and The turf battles that lead agencies to work at Cooperation, and the Subcommittee on Sci- cross purposes should be eliminated. Agen- ence, Research, and Technology). Since some cies involved in nutrition research should duplication of interest exists, joint sessions of demonstrate a commitment to coordination relevant congressional subcommittees to con- and the avoidance of unnecessary duplica- sider plans and hearings for oversight pur- tion. This commitment needs to be built in, not poses should be considered. only at the "political" level of the higher There is a strong relationship between echelons of Government but also in the career human nutrition research conducted abroad civil service. and research needs in the United States. The The establishment at USDA of the Human research goals identified in this report can be Nutrition Center and the Human Nutrition best achieved if international and domestic Policy Committee and at HEW of the Nutrition research activities are tuned together. Coordinating Committee are two positive Nutrition research in other countries may steps toward intra-agency coordination. They help in solving domestic nutrition problems. not only indicate a commitment to nutrition For example, epidemiological investigations research but also can serve as mechanisms of certain chronic diseases require good in- for interagency coordination and information formation about disease incidence. This may exchange. be obtained from studies of societies with The Food and Agriculture Act of 1977 lifestyles and food habits very different from specifies that the Secretary of Agriculture our own. The high incidence of malnutrition shall "periodically consult with the adminis- in some developing nations also provides an trators of other Federal departments and opportunity to investigate relationships be- agencies that have responsibility for coor- tween the nutritional status and functional dinating Federal nutrition research activ- performance of individuals in a way that ities." However without the support and in- would be impossible in the United States. It volvement of the Secretary of HEW, unilat- may be possible to extrapolate the results of eral USDA efforts to coordinate research studies of severe malnutrition abroad to may not be effective. Likewise, it should be margina! nutritional areas in this country. 16 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 The study of worldwide populations and will have a dual reward-assistance to mal- food patterns is essential to the better under- nourished peoples abroad and increased standing of some of the priority research knowledge of human nutrient needs and areas of nutrition. Thus any effort to increase health status under changing environmental international nutrition research capabilities conditions. ISSUE 2 - Definition and Funding of Human Nutrition Research If one accepts that the goals of human genetics, animal nutrition, plant nutrition, nutrition research are twofold-(1) the pro- and plant genetics comes under this classi- motion of optimum health and performance, fication. While there is need to integrate such and (2) the treatment of diseases through diet agricultural research with human nutrition therapy and the support of other medical concerns, these areas should not be consid- therapies-th definition of human nutrition ered human nutrition research. Similarly, research flows from these stated goals. If all basic research on metabolism of nutrients, if the research areas involving nutrition are not directly applicable to people, should not listed, from basic studies on the metabolism be considered human nutrition research. of nutrients to genetic studies on the develop- Basic research on metabolism should be con- ment of foods with specific nutrient charac- sidered as basic research underlying all of teristics, it is clear that some areas of the biomedical and life sciences. Human research are more closely related to these nutrition research builds upon this knowl- stated goals than others. Accordingly, the edge base, but the apparent commitment to definition of human nutrition research must and budget for human nutrition research take into account these relationships to should not be inflated by its inclusion. stated goals. Throughout this assessment, a recurrent In terms of this assessment, nutrition problem has been that of definition of human research falls into three broad categories. nutrition research. Agencies report as human Most closely related to the stated goals is nutrition research studies that appear to research into the biochemical and physiologi- have little to do with human nutrition. Ex- cal effects of food on the body in health and amples are "Catalytic Functions and Metab- disease. This category includes research on olism of Vitamin B6 in Bacteria and Fungi," nutritional management of disease, nutrient "Nutritional Imbalance and Metabolic Alter- needs and interactions, and research which ations in Fungi," or "Hepatoma Incidence in promotes optimum health and disease pre- Trout on Dietary Aflatoxin and PCB." Such vention through diet. studies are worthwhile and contribute to our understanding of basic biochemistry but are Research on food and nutrition quality not directly applicable to humans. determinants is also related to the stated The almost unanimous consensus of the goals, but less directly so than the previous category. Under this heading would be re- participants in the OTA study was that at- search into food composition, especially the tribution of these Federal expenditures to nutritive components and changes in nutrient "human nutrition research" was improper. composition that occur from point of origin to Fourteen different Federal agencies are point of consumption; food safety; social, cul- engaged in some sort of nutrition research. tural, and economic aspects of food habits; Each agency has developed its own definition feeding programs; nutrition education; con- of human nutrition research and set priorities sumer information; and nutrition surveillance on the basis of how it interprets its legislation and monitoring. mandate. The agencies and their priorities are shown in table 3. The third category of research involves basic research on sources of human food and Federal expenditures for human nutrition basic biochemistry. Research into animal research in FY 1977 (shown in table 4) were 17 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3. - Federal Government Agencies Active in Food and Nutrition Programs and Their Nutrition Research Priorities Food and nutrition Department Agency programs Research priorities Health, Edu- National National Institute of Arthritis, Metabolism, and Digestive Diseases cation, & Institutes (NIAMDD).Basic hysiological studies of nutrients; basic metabolism Welfare of Health studies; obesit, trace elements nutrition support of patients; fiber; anemias. National Institute of Child Health and Human Development (NICHHD). Nutrition and fetal development; metabolic capacities of normal, low- birthweight, and premature infants; diet modification for low-birth- weight and premature infants; optimum nutrition in developmental years; nutrition and reproductive potential; genetic variability-nuti tional interaction; prevention- - metabolic antecedents of adult disease. National Cancer Institute (NCI). Nutrition support of cancer patient; nu- trition in cancer etiology; host-tumor interactions and competition for nutrients; prevention strategies based on nutrition; diet and nutrition in the rehabilitation of cancer patients. National Heart, Lung, and Blood Institute (NHLBI). Nutrition in etiology of arteriosclerosis and hypertension; achieving and maintaining dietary change; development of food composition tables; methodology-col lecting, recording, and evaluating dietary data. National Institute of General Medical Sciences (NIGMS). Trauma- tized/burned patients and nutrition. National Institute of Environmental Health Sciences (NIEHS). Neuro- toxicity; mutagenesis; teratology; environmental contaminants in food. National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Protein-calorie malnutrition, B-vitamin deficiencies and the nervous system; genetic disorders and the nervous system; specific nutritional problems in the central nervous system; stroke. National Institute of Dental Research (NIDR). Sucrose and caries; poor nutrition and periodontal disease; poor nutrition and oral mucus mem- branes; nutrition in craniofacial malformations and oral-facial struc- tures; nutrition and salivary gland development. National Institute of Allergy and Infectious Disease (NIAID). Interrelated factors hearing on malnutrition, infection, and the immune system. National Eye Institute (NEI). Vitamins A, B-12, and other nutrients in visual processes; diseases of visual system, e.g., keratomalacia; metab- olism of visual cells; protein changes in the lens. National Institute on Aging (NIA). Nutritional status of the elderly; aspects of increase in life span including dietary manipulations; vitamin supplementation in elderly; nutrient intake as a consequence of econ- omic status in elderly; relationship among nutrition, cellular structure, and function in elderly. Division of Research Resources (DRR). Nutrient requirements for growth, gestation, lactation in primates and laboratory rodents; stand- ard diets for specific objectives; interaction of various nutrients on physiological function in laboratory animals; differences in nutrient re- quirements among strains of animals within a species. Food & Regulatory activities Nutrient efficacy and safety; nutrient interrelationships as concerned Drug related to: nutrition with disease prevention; nutrient bioavailability for food fortification Admin- labeling, ingredient purposes; nutrient quality assessment of processed foods; medical istration labeling, food for food assessment; food composition and nutrient analysis as related to special dietary use, FDA mission; and consumer studies of perceptions about food values food advertising, nutri- and nutritional quality and educational models to help correct tion quality of foods misconceptions about them. Health Re- Health and Nutrition Assessment of the nutritional status of the American people. sources Examination Survey Admin- istration 18 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3 - -continued Food and nutrition Department Agency programs Research priorities Center for Epidemiological surveillance studies in cooperation with State Disease agencies assistance to AID in similar international areas. Control Health Collaborative research and screening program for phenylketonuria. Services Admin- istration Alcohol, Effects of alcohol consumption on nutrient metabolism and nutritional Drug deficiencies; study of food additive consumption and hyperactivity Abuse, & in children. Mental 5 Health Admin- istration Agriculture Agricul- Human Requirements for Nutrients tural Re- Determine the requirements for lipid intake and identification of the search forms of these nutrients in foods that may be useful in meeting Service* these requirements. Determine the requirements for mineral intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for vitamin intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for protein and amino acid intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for carbohydrate and energy intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Food Composition and Improvement To provide accurate, up-to-date, and comprehensive information in a readily usable form on the composition of all important foods for those nutrients required by and biologically useful to man. To provide the technology for the nutritional improvement of foods when enhanced levels of certain nutrients in the diet are needed to correct possible dietary faults. Food Consumption and Use To provide accurate, up-to-date, and comprehensive information in a readily usable form on food consumption and dietary levels. To provide consultative assistance on food and nutrition problems and provide sound guidance materials on nutrition for the consumer and for nutrition educators, program leaders, and food program man- agers; to identify techniques which will assist people in selecting nu- tritionally adequate diets within different budget limitations; to iden- tify means to modify undesirable food habits; to strengthen nutri- tionally desirable food choice. To identify and develop suitable and safe procedures for food man- agement and preparation for home and institutional consumers, for best retention of both nutritional and eating qualities and to avoid food-borne illness. Coopera- Nutrient requirements; nutritional status of special population groups tive State including children, low income, and aging; metabolic function of Research nutrients in the diet and their interactions; nutrient content of foods; Service* effects of processing on nutrients; food delivery systems; food habits and use); dietary patterns. 19 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table -continued Food and nutrition Department Agency programs Research priorities Economic Economic and social research relating to domestic food programs; Research nutrition policy in LDCs; food choices (demand); nutritional programs Service' for the elderly. Defense Determination of nutritional and dietary standards for Armed Forces personnel subsisted under normal and special operating conditions; evaluation of nutritional adequacy of food as consumed; evaluation of the nutritional status of Armed Forces personnel; establishment of sanitary and food hygiene standards for all food program activities; food aspects of preventive medicine. National Nutritional control of neurotransmitters; role of dietary protein and Aeronautics specific amino acids in optimizing human performance under stress. & Space Ad- ministration Veterans Depart- Research in disease and diet: nutrition and disease or clinical nutrition, Adminis- ment of dietary therapy; effect of disease on nutrition; environmental toxicants, tration Medicine alcohol, and nutrition; nutrition and cancer; nutrition and vision re- & Surgery search; nutrition-related therapy. Metabolic effects: Investigations on or related to malabsorption syn- dromes, inborn errors of metabolism, and familial or inherited nutri- tional defects. Nutrition requirements: Studies of nutrient metabolism, malnutrition, neuroendocrine nutrient interactions, fundamental intermediary metab- olism involving the role of one or more nutrients. State Agency Development of new low-cost nutritious foods; development and for Inter- dissemination of new appropriate technologies; understanding national nutritional needs and requirements; testing and evaluation of nutrition Develop- program alternatives; research on methodologies for improving national ment nutrition planning and programing. National Basic research in the behavioral, education, and social sciences in Science areas applicable to foods and nutrition. Foundation Under USDA's recent reorganization, ARS is now called Federal Research, and is housed within the Science and Education Administration. Under USDA S recent reorganization, CRS is called Cooperative Research and is housed within the Science and Education Administration Under USDA S recent reorganization, ERS is called Economics and is housed within the Economics, Statistics. and Cooperatives Service. Under USDA recent reorganization, ES is called Extension and is housed within the Science and Education Administration estimated at between $50 million and $117 tion research. Seventy-five percent of Federal million, depending on how "nutrition re- nutrition research is conducted outside of the search' was defined. If for example, the NIH two departments through competitive grants definition is used, NIH appears to be spend- and contracts. Using the more realistic fund- ing $80 million for human nutrition research. ing figure of $50 million for FY 1977, NIH at This broad definition takes in studies of basic HEW funded 44 percent of the total, and the biochemistry, studies which are not focused Science and Education Administration (SEA) on nutrition but have a nutrition aspect, as at USDA funded 43 percent of the total. The well as studies of primary nutrition. If a nar- Science and Education Administration en- row definition is used, one encompassing only compasses what were formerly known as the those studies of direct clinical applications Agricultural Research Service and the Coop- and disease prevention, the NIH nutrition erative State Research Service. Under research funding falls in the annual range of USDA's new reorganization, most human nu- $20 million. Even the higher $80 million trition research will be coordinated by SEA's figure, incidentally, amounts to less than 3 Human Nutrition Center. percent of the NIH research budget. The Science and Education Administration HEW and USDA are responsible for the Cooperative Research (SEA-CR) of USDA is majority of federally supported human nutri- unique among Federal agencies in that it links 20 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 Table 4. - Federal Expenditures for Human Nutrition Research An Approximation of FY '77 Expenditures (millions of dollars) Office of Science & Office of Management Agency Technology Policy & Budgetb Department of Health, Education, & Welfare $ 88.6 $22.0 National Institutes of Health 80.4C 22.0d Food and Drug Administration 3.9 National Center for Health Statistics 2.4 Alcohol, Drug Abuse, and Mental Health Administration 1.1 Health Services Administration 0.5* Center for Disease Control 0.3* Department of Agriculture 22.0 21.8 Agricultural Research Service 14.0 13.2 Cooperative State Research Service 7.5 8.1 Economic Research Service 0.5 0.5 Agency for International Development 2.9 0 Department of Defense 2.3* 2.2 Veterans Administration 0.5* 4.1 National Science Foundation 0.3* 0 Grand total. $116.6 $50.2 affice of Science and Technology Policy, New Directions in Federally Supported Human Nutrition Research, December 1977. Poffice of Management and Budget, Special Analyses-Budget of the U.S. Government FY 1979. This figure includes studies designed to assess the mechanisms and the consequences of food or nutrient intake in the intact organism. particularly man: investigations involving nutrient variables at the cellular or subcellular level, including metabolic studies in animals and man: research designed to elucidate the metabolic role or function of an essential nutrient in both animal models and man, as appropriate; all studies concerned with genetic-nutrient-environmental interactions; dietary studies ex- pected to produce changes in health status, including the maintenance of health and the treatment of disease in man. This figure includes biochemical, physiological, and clinical studies of nutritional needs for normal growth, development, and health: nutritional needs of patients with specific common diseases: and experimental assessments of feeding programs. *Estimates of FY 1976 expenditures provided by draft Government Accounting Office report, Human Nutrition Research- Need for a Coordinated Approach to Advance Our Knowledge, 1977. Federal and State research efforts. SEA-CR levels could be made since current estimates administers funds that Congress appropri- of Federal spending for human nutrition ates to the States for agricultural research. research are questionable. Estimates for FY This work is conducted at the State agricul- 1977 range from $50 million to $117 million tural experiment stations, land-grant colleges (table 4). The lower figure, based on agency and universities, approved schools of for- responses to a standard questionnaire, was estry, colleges of 1890, and Tuskegee In- developed by the Office of Management and stitute. In FY 1977, the States used $7.5 Budget (OMB) for the FY 1979 budget. The million of the Federal money available to higher figure came from an OSTP working them for human nutrition research. The group and appeared in the December 1977 States themselves provided $11.7 million for report "New Directions in Human Nutrition human nutrition research in 1976. Most of Research." the Federal money came from funds author- ized by the Hatch Act, as amended, and P.L. Neither is reliable. The $50 million, for ex- 89-106 (an act to amend the Agriculture Act ample, fails to include certain nutrition of 1954). The funds are accounted for under research activities within HEW, AID, and the the Hatch Act research program called Peo- National Science Foundation. The $117 mil- ple, Communities, and Institutions, which lion, on the other hand, includes $80.4 million comprised 12 percent of total Hatch Act of NIH spending-much of it of tenuous con- research funds in 1977. nection to human nutrition research. In testi- mony before the Senate Select Committee on Federal human nutrition research may be Nutrition and Human Needs on October 17, financially undernourished. However, no 1977, NIH Director Dr. Donald Fredrickson analysis of the adequacy of present funding conceded that, based on a strict definition, 21 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 his agency devoted only around $20 million to whether any of these funds are devoted to human nutrition research in FY 1977 (a fig- research on which methods are most effeo- ure reported to OMB). tive for reaching people. Another statistic which raised questions OTA concluded that most estimates of came from the Veterans Administration (VA). human nutrition research funding were ques- GAO put the VA's FY 1976 nutrition research tionable and that total funding fell con- spending at $0.5 million. In FY 1977, the VA siderably short of the reported $117 million reported sharply increased expenditures of level. Regardless of which overall figure is $4.1 million, even though nutrition research more nearly accurate, certain areas iden- was not recognized as a high priority by the tified by OTA are not now receiving sufficient agency. Federal support, the result of a lack of recognition of their importance and zero or In some cases, it was difficult to determine almost no funds. Those areas most in need of how much (if any) money was being spent for increased funding are the role of diet in the certain types of important nutrition research. prevention of chronic disease and obesity, For instance, the Federal Government is now nutrition education and consumer informa- annually spending about $70 million on nutri- tion, monitoring nutritional status, and nutri- tion education programs. It is unclear tion policy and management. ISSUE 3 - Personnel Resource Requirements Estimates of the number of scientists they are engaged in research activities. This engaged in human nutrition research also does not indicate the degree of involvement proved elusive. and, of course, neglects those outside of dietetics engaged in nutrition research. In an attempt to determine the current number of scientists engaged in human-nutri- The two Government agencies that fund tion research and the numbers of research the largest portion of nutrition research, scientists being trained, OTA contacted five HEW and USDA, do maintain figures on sci- professional societies and six Government entist-years devoted to nutrition research agencies. Of the professional societies, the and 5-year projections of personnel needs. At American Public Health Association, Insti- USDA in FY 1976, 193.5 scientist years were tute of Food Technologists, and American devoted to human nutrition research as de- Chemical Society make no attempt to distin- fined by the agency. The 5-year projection of guish between members engaged in research need for nutrition research scientists at versus other career orientations and USDA is for 260.7 scientist years, a 20-per- therefore could not supply information on the cent increase. proportion of their membership engaged in In a written response to an OTA question- human nutrition research or training of nutri- naire, NIH informed OTA that 70 scientists tion research scientists. Membership in the were employed in human nutrition research American Institute of Nutrition (AIN) is in 1977. But NIH Director Fredrickson sub- limited to those who have made significant mitted a written statement to the Senate contributions to the field of nutrition re- Select Committee on Nutrition and Human search. By definition, all of AIN's 1,730 mem- Needs that during that same time period 180 bers are nutrition research scientists. This intramural investigators in NIH were directly number seriously underestimates the total involved in human nutrition research. Of that number of scientists in the field, since junior number, 20 were defined as "classical nutri- people are not eligible for membership and tionists" when nutrition research was de- very few behavior and education researchers fined as "the study of food and nutrients." In are included. AIN does not keep any figures FY 1977, 20 lead scientists, those holding on training. Of the American Dietetic Asso- M.D., Ph.D., or D.V.M. degrees, and 50 junior ciation's 21,751 members in 1977, 764 state scientists were conducting nutrition research 22 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 at Letterman Army Institute of Research of professional nutrition training programs as the Department of Defense. well as increased training support. For grad- uate students in nutrition and food science, Before a comprehensive nutrition research program is established, consideration must such changes might include greater stress on be given to the ability of the field to sustain nutritional pharmacology, food science prin- such a program. No accurate figures exist on ciples, nutrition education, nutritional status evaluation, and nutrition-related diseases. how many scientists are currently engaged in human nutrition research. Furthermore, few Training would be further strengthened by reports on nutrition research mention this postdoctoral research work with either hu- aspect of planning. mans or experimental animals. Greater em- phasis on nutritional biochemistry and clini- Implementation of the research priority cal nutrition in undergraduate medical edu- areas identified in this report may require cation may help attract physicians to the changes of emphasis in existing graduate and field. 23 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES Accumulating the fragmented research activities of the 14 Federal agen- cies supporting human nutrition research does not, as a whole, constitute a coherent strategy for the solution of current diet-related health problems. A goód understanding of the status quo can be gained by analysis of the Food and Agriculture Act of 1977 which established research goals and priorities for the Department of Agriculture (USDA). The picture of the present situation can be completed by reviewing the research goals and priorities at the Na- tional Institutes of Health (NIH). Alternatives to the status quo can be found in the recently published reports of the Office of Science and Technology Policy (OSTP) and the General Accounting Office (GAO). These two alter- natives, plus an alternative developed by OTA, are examined here and provide Congress with several alternative strategies that may be pursued. Each of the alternatives are examined from three perspectives: Do the stated goals and priorities adequately address current U.S. health problems? Is nutrition research defined clearly to permit realistic estimation of Federal expend- itures? Is consideration given to the personnel requirements to fulfill pro- posed research priorities? THE STATUS QUO: NUTRITION RESEARCH IN THE FEDERAL GOVERNMENT Goals and Priorities The Food and Agriculture Act of 1977 rec- fants, children, adolescents, elderly men and ognized the relationship between diet and the women, and pregnant women; and that there general health of the population. The legis- is a critical need for objective data concern- lation states "that there is increasing evi- ing food safety, the potential of food enrich- dence of a relationship between diet and ment, and means to encourage better nutri- many of the leading causes of death in the tional practices." United States; that improved nutrition is an integral component of preventive health care; The legislation declares that the Secretary that there is a serious need for research on of Agriculture shall develop and implement a the chronic effects of diet on degenerative national food and human nutrition research diseases and related disorders; that nutrition program that shall include, but not be limited and health considerations are important to to, five areas: U.S. agricultural policy; that there is insuffi- cient knowledge concerning precise human 1. Research on human nutritional require- nutritional requirements, the interaction of ments. the various nutritional constituents of food, and differences in nutritional requirements 2. Research on nutrient composition of among different population groups such as in- foods and the effects of agricultural 27 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 practices, handling, food processing, "Reviewing the policies, plans, and goals and cooking on the nutrients they con- of programs within USDA involving the tain. food and agricultural sciences, and 3. Surveillance of the nutritional benefits related programs in other Federal and provided to participants in the food pro- State departments and agencies and in grams administered by USDA. the colleges and universities developed by the Secretary under this title; 4. Research on the factors affecting food preference and habits. Reviewing and ssessing the extent of agricultural research and extension be- 5. The development of techniques and ing conducted by private foundations equipment to assist consumers in the and businesses, and the relationships of home or in institutions in selecting food such research and extension to federally that supplies a nutritionally adequate supported agricultural research and ex- diet. tension; Reviewing and providing consultation to Although the legislation points up the rela- the Secretary on national policies, prior- tionship between diet and leading causes of ities, and strategies for agricultural death in the United States, the research pri- research and extension for both the ority areas spelled out do not pursue this line short and long term; of inquiry. Since the legislation pertains almost exclusively to USDA, it lays out what Assessing the overall adequacy of, and could be considered a partial strategy to making recommendations to the Secre- solve the problems of diet and chronic de- tary with regard to, the distribution of generative diseases-research on nutrient resources and the allocation of funds au- needs, on the composition of the food supply, thorized by this title; on ways to help consumers select a healthful Preparing and submitting to the diet, and surveillance of the population. Fur- Secretary, not later than October 31 of thermore, funding proposed in the FY 1979 sch year, a statement of recommenda- budget does not match the ambitious wording tions as to allocations of responsibilities of the legislation. and levels of funding among federally supported agricultural research and ex- The Food and Agriculture Act of 1977 tension programs; and designated the Secretary of Agriculture to "establish jointly with the Secretary of Not later than March 1 of each year sub- Health, Education, and Welfare procedures mitting a report on its appraisal of the for coordination with respect to nutrition President's proposed budget for the food research in areas of mutual interest." Sec- and agricultural sciences for the fiscal tion 1406 amends the National Science and year beginning in such year and the Technology Policy, Organization, and Priori- recommendations of the Secretary con- ties Act of 1976 (90 Stat. 471; 42 U.S.C. 6651 tained in the annual report.' (h)), by creating a standing subcommittee to be known as the Subcommittee on Food and As indicated earlier, the Food and Agricul- Renewable Resources. ture Act of 1977 does not clearly give USDA the lead responsibility for human nutrition The legislation also established a National research. Section 1405 declares "the Depart- Agricultural Research and Extension Users ment of Agriculture is designated as the lead Advisory Board composed of 21 members rep- agency of the Federal Government for agri- resenting a wide variety of agricultural pro- cultural research (except with respect to the ducer, consumer, marketing, and environ- biomedical aspects of human nutrition con- mental interests. Two members must be en- cerned with diagnosis or treatment of dis- gaged in human nutrition work. The Advisory easc). Human nutrition is one of the Board has the responsibilities for: areas included in the definition of "food and 28 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 agricultural sciences (section 1404). But the long-range goals of the AID nutri- Section 1409 states that "*t is the intent of tion program are: to have developing coun- Congress in enacting this title to augment, tries incorporate nutrition considerations in- coordinate, and supplement the planning, ini- to their social and economic development tiation, and conduct of agricultural research plans; to create the methodologies for assess- ing needs, determining causes, and selecting programs existing prior to the enactment of interventions: and to have available the most this title, except that it is not the intent of cost-effective interventions with information Congress in enacting this title to limit the on when they are most appropriate to apply, authority of the Secretary of Health, Educa- the cost and other requirements for imple- tion, and Welfare under any Act which the menting them, the best methods for imple- Secretary of Health, Education, and Welfare menting them, and information on expected administers." Thus a clear mandate is not results. given to USDA to be the lead agency for The AID nutrition research program is human nutrition research. designed to provide new knowledge that will Section 1423 (b) requires the Secretary of help implement programs to attain these Agriculture to "periodically consult with the goals. The AID nutrition research program administrators of the other Federal depart- attempts to assess the functional signifi- cance of improvements in nutrition; it seeks ments and agencies." As discussed earlier, to establish whether nutritional needs can be this unilateral approach to coordination satisfied with locally available foods; it relies on the goodwill of other agencies to evaluates the effectiveness of nutrition in- cooperate with USDA in the goal of research tervention; and it seeks to inform govern- coordination. ments about the potential impact of policies in food and nutrition. Research priorities at NIH are summarized in table 3. A wide range of basic and applied It is therefore apparent that the AID nutri- research are embodied in these priorities. tion research program is not and should not The major emphasis is on basic and curative- be designed to address the research needs oriented disease research rather than dis- outlined in this report. The AID program is ease prevention. This becomes more clear as designed to meet the needs of host countries. allocations of funds to the different areas are Should a research project yield results ap- studied. The Nutrition Study Section at NIH plicable to problems discussed in this report, reviewed a total of 181 grant proposals in FY it is serendipitous. There is a clear need to en- 1977, and approved 119, totaling $4.7 million. courage international research, much of Only four other study sections recommended which would be epidemiological, to identify for approval grants totaling less than $4.7 and explore dietary and lifestyle factors con- million in this period of time. Two of these tributing to the major chronic diseases. sections have been disbanded, their work be- In theory, AID's nutrition research ac- ing referred to other study sections. Since tivities undergo peer review. Research funds research in nutrition involves many different are publicized through the distribution of a disciplines and crosses traditional discipli- brochure, and information on AID's research nary lines, NIH maintains that many grant needs are circulated among professional applications with nutrition components are groups and announced at professional meet- referred to other study sections. It can there- ings. 'Projects that are awarded on the basis fore be assumed that $4.7 million is what NIH of predominant capability are very carefully clearly defined as human nutrition research, reviewed before approval. Fewer and fewer and the remainder of the $80.4 million of projects follow this latter nutrition research funded by NIH if FY 1977 was basic and disease-oriented research In practice, the system seems to have func- with nutrition components of varying degrees tioned somewhat differently. Human nutri- of relevance. ¹Irwin Hornstein, Deputy Director, Office of Nutri- The Agency for International Development tion, Agency for International Development, June 8, (AID) is the Federal agency primarily respon- 1978. sible for international nutrition research. ²Ibid. 29 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research received an estimated $2.7 mil- human nutrition research is made in the Act. lion from AID in FY 1977. Most of this re- search was conceived by agency staff who In response to these requirements, USDA requested $43 million for human nutrition then had a scientific research group develop research in its FY 1979 budget proposal. This study proposals. The proposals were is a 95-percent increase over its FY 1977 screened by AID staff members before being spending of $22 million. submitted to the Research Advisory Commit- tee for technical feasibility evaluation. The At NIH, nutrition research support has re- agency does not widely advertise requests for mained relatively constant over the last sev- proposals, and few unsolicited proposals are eral years, constituting less than 3 percent of received. Some panel participants felt that the total research budget. Estimates of actual this system reduces the scientific base of ex- dollar outlays for human nutrition research pertise on which the agency can draw and vary from $20 million to $80 million for FY leads to an inbreeding of research ideas. 1977. Definition and Funding Personnel Resource Requirements The Food and Agriculture Act of 1977 does not explicitly define the term "nutrition" nor Both the USDA and HEW support under- the scope of "nutrition research." It implies graduate, predoctoral, and postdoctoral that "nutrition research" includes research students through a variety of tuition grants, on diet and disease, certain aspects of agri- loans, fellowships, and training grants. The cultural policy, nutritional requirements, Food and Agriculture Act establishes grants food composition and nutrient interactions, and fellowships for food and agricultural food safety, food enrichment, and means of sciences education at the undergraduate encouraging better nutritional practices. through postdoctoral levels. The program is There is no reference in the legislation to in- authorized in FY 1978 for $25 million, ex- ternational nutrition research. panding to $50 million by FY 1982. The pro- Section 1423 (a) of the Food and portion of this money to be devoted to training Agriculture Act of 1977 states that the Secre- nutrition researchers is not specified. tary of Agriculture "shall increase support The Department of Health, Education, and for such research [research into food and Welfare has traditionally supported training human nutrition] to a level that provides of research scientists through training grants resources adequate to meet the policy of this and fellowships. In FY 1977 these totaled subtitle." No specific authorization for $2.3 million for human nutrition research. NEW DIRECTIONS IN FEDERALLY SUPPORTED HUMAN NUTRITION RESEARCH: THE OSTP REPORT Goals and Priorities eral nutrition research activities. Although the report focused only on domestic research, it encouraged various Federal agencies in- In December 1977, OSTP published a re- volved in such activities to assess the poten- port on Government nutrition research. The tial international benefits from current and report defined the scope of human nutrition plonned projects. research, described existing Federal pro- grams, identified research areas that need he working groups of the OSTP inter- more attention, and suggested means for en- agency senior nutrition research staff recom- hancing the coordination and quality of Fed- mended four priority research activities: 30 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 1. Effects of nutrition on human health and In HEW, the programs of the Food and performance in pregnancy, infancy and Drug Administration (FDA), the National early childhood, old age, obesity, iron Center for Health Statistics (NCHS), the deficiency, nutrient toxicity, and in- Center for Disease Control (CDC), and NIH must be coordinated in the high-priority ac- teractions; tivities identified. At NIH, it is essential 2. Food sciences (methodology for analyz- for the NIH Director and for the Nutrition ing food composition, nutrient bio-avail- Coordinating Committee under his direction ability in foods, updating national to have the authority to prioritize nutrition nutrient data bank, expanding food com- research needs. The Director of NIH, has a position measurements); relationship to the several Institutes which 3. Nutrition education research (factors permits allocation of funds for nutrition research in the absence of specific statutory determining dietary practices, identifi- authorities for reprogramming between In- cation of good nutritional practices, ad stitute appropriations. hoc <educational research committee); In USDA, it is essential that the nutrition and research activities of the Agricultural Re- 4. Diet and nutritional status surveillance search Service (ARS), the Cooperative State (food composition, survey methodology, Research Service (CSRS), the Food and Nutri- measurements of nutritional status, tion Service (FNS), and the Economic Re- analysis of the Health and Nutrition Ex- search Service (ERS) be coordinated through amination Survey (HANES) data, epi- the Secretary of Agriculture." demiological studies). Finally, the establishment of an ad hoc in- The criteria used by the working group in teragency nutrition education research com- mittee is recommended. This committee selecting research areas for greater attention were impact, substantial existing knowledge would: identify and summarize research find- ings related to nutrition education research gap. and researchability. The priority areas and summarize pertinent findings from other chosen reflect the narrowness of these cri- areas of education research, establish priori- teria. The priorities tend toward short-term ties, and develop a plan for conducting nutri- projects that lack long-term commitments tion education research. needed to identify the nutrition elements of major health problems facing adult Ameri- It is doubtful that OSTP through FCCSET cans-the chronic degenerative diseases and would be able to adequately oversee coordi- obesity. nation of nutrition research activities. The staff of the Office is small, and their respon- In the OSTP report several recommenda- sibilities large. With a budget of $50 million tions are made for coordination within and to $117 million per year, nutrition research is among the departments conducting nutrition a very small component of the FY 1977 $3.6 research. First of all, the participants in the billion research budget for health and agri- study requested OSTP "to continue to take a culture. lead role in coordinating and monitoring External reviews by teams of nonagency nutrition research activities." OSTP could scientists may improve the quality of intra- serve as a focal point for interagency plan- mural human nutrition research activities, ning through the Federal Coordinating Coun- but they cannot be expected to improve re- cil on Science, Engineering, and Technology search coordination. This recommendation (FCCSET), chaired by the Director of OSTP. calls for the external reviews to be conducted Secondly, external reviews of the intramural within 12 months of the report's publication grants process in both NIH and USDA with by an unspecified number of multidiscipli- joint participation of Federal agencies in nary teams. Scientists from agencies con- developing requests for proposals and in ducting nutrition research would also par- reviewing research in progress. ticipate. The report suggests that this would To improve coordination and communica- be expected to increase communication and tion within HEW and USDA, the report rec- understanding of Federal programs. Since ommends: the review would only be conducted once and 31 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 no provisions are made for improving bad Food consumption patterns and nutri- situations if they are found, it is doubtful that tional status of the general population it would be of any lasting use in improving in- and of special high-risk subgroups with- teragency communication or the quality of in- in the population; evaluation of the nutri- tramural research. tional impacts of various intervention The proposal that Federal agencies jointly strategies and public policies. participate in developing requests for re- The OSTP report established Federal ex- search proposals and in reviewing research penditures for nutrition research for FY 1977 in progress has merit, as does the proposal at $116.6 million. The report stated that no for an ad hoc interagency nutrition education specific funding levels would be recommend- research committee. The ideas could be fur- ther explored by USDA and HEW and pro- ed, but that the report's objectives could be met "at least in part by reallocation of posals for implementation developed. resources from existing programs to the higher priority areas identified." It is highly unlikely that this could be accomplished Definition and Funding without outside intervention. It is also ques- tionable whether such a strategy makes good The scope of human nutrition research, as sense, since the amount of human nutrition defined by the OSTP study, included in- research conducted in this country is so small vestigation of: in comparison to our $3.6 billion in health and Basic physiological and biochemical agriculture research expenditures and our mechanisms for the digestion, absorp- $160.6 billion in health costs. Furthermore: at tion, metabolism, and transport of nutri- least $60 million of the $117 million is basic ents; the role of food ingredients in research on metabolism which underlies human health and performance and in many of the biological and health sciences. A the prevention and treatment of disease; cut in this funding would severely constrain progress in basic research. Nutrient composition of foods; the ef- fects of storage, processing, and packag- ing; and the biological availability of nu- trients in the foods at the time of con- Personnel Resource Requirements sumption; Determinants of dietary practices and The OSTP report does not consider the per- methods for educating the public about sonnel resources needed to fulfill the re- dietary practices; and search priorities contained in the report. FEDERAL HUMAN NUTRITION RESEARCH NEEDS A COORDINATED APPROACH TO ADVANCE NUTRITION KNOWLEDGE: THE GAO REPORT Goals and Priorities Knowledge of dietary nutrients required to promote or maintain growth or well- The General Accounting Office was asked being at various stages and conditions of to identify research gaps and needs in the life: field of human nutrition. The scope of the Information on the composition of the report was restricted to the domestic situa- current U.S. food supply and the extent tion. Gaps identified by GAO included: that nutrients are biologically available; 32 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Evaluation of long-term health conse- Eliminate unnecessary research that quences of the modern diet; and may exist among Federal agencies. Promote Government-wide human nutri- Assessment of the Nation's current tion research planning, coordination, nutritional status in terms of dietary ex- and reporting." cesses and imbalances, as well as defi- ciencies. These recommendations are not suffi- ciently specific to be considered a strategy GAO recommended research along the for organizing nutrition research. Further- following lines to overcome these research more, in an early draft of their report, OSTP gaps: assigned lead and support agency respon- sibilities for specific nutrition research Long-term studies of human subjects areas. This approach was abandoned in the across the full range of both health and final report because of agency objections. A disease; general goal of improved research planning, coordination, and reporting is commendable, Comparative studies of populations of but without specifics probably will not be at- tained. differing geographic, cultural, and genetic backgrounds; Basic investigations of the functions and Definition and Funding interactions of dietary components; GAO identifies the third barrier to prog- Updated and expanded food composition ress in nutrition research as "instability of data; and federally funded extramural research." The report does not make specific recommenda- Improved techniques for assessing long- tions as to how to improve this situation. term toxicological risks. However, it endorses the development of fed- erally funded regional research centers in conjunction with universities and colleges. The priorities set out in the GAO report in- GAO estimates U.S. Government expend- volve the types of research that will probably itures for human nutrition research at $73 provide the most information on the role of million to $117 million annually. It makes no diet in disease. However, work is also needed attempt to define nutrition research or to on how best to convey the research findings analyze agency reports on nutrition research to the public so they can be translated into expenditures. daily life. The GAO report cites "lack of central focus and coordination" and "shortage of nu- Personnel Resource Requirements trition scientists" as two of the three prin- cipal barriers to progress in human nutrition The GAO report highlights the concern of research. To remedy the first of these, the re- the scientific community that there is a short- port recommends that the Director of OSTP age of nutrition research scientists. If this "work with the Federal agencies to further situation exists, it holds significant implica- define the subject areas comprising human tions for the ability of the research commun- nutrition research and make recommenda- ity to absorb research funds should large in- tions to the Director of OMB to: creases be made in the future. Since no accu- rate information exists on the numbers and expertise of nutrition research scientists out- Assign where practicable, each area to side Government laboratories, analysis of re- a lead Federal agency. search capabilities is impossible. 33 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 A COMPREHENSIVE NUTRITION RESEARCH STRATEGY Goals and Priorities points are outlined in table 5. The rationale for the selection of each is contained in the The focus now lacking in Federal nutrition appendix. research could be achieved by defining the Several mechanisms for coordinating Fed- scope of human nutrition research, defining eral nutrition research activities have been general goals for Federal agencies that con- suggested. These include assigning respon- duct such research, and specifying research sibilities for research areas to various agen- priority areas that are in line with the gen- cies, making one agency the lead agency, eral goals. A reorientation of Federal nutri- placing coordination responsibility under a tion research efforts should recognize the third party, assigning coordination respon- changing nature of our food supply by placing sibility to the assistant secretary level, and greater emphasis on the role of diet in concentrating all nutrition research activities preventing chronic diseases. At the same in either USDA or HEW. time, Government programs must continue The first alternative (assigning respon- striving to eliminate hunger and malnutrition sibilities for research areas to various agen- through intervention programs and research. cies) would make USDA and HEW the two lead agencies in human nutrition research. Such a reoriented research strategy re- This approach is similar to the one taken in quires an increased focus on today's complex the Food and Agriculture Act of 1977 in food supply. especially on the effects of proc- which the legitimate roles of both agencies in essed food, food additives and contaminants, nutrition research are recognized. Under and similar problems that concern consum- such a system of joint responsibility, the con- ers, food producers, and health profession- cerns of each agency would have to be de- als. Research in the food sciences would fined to minimize duplication of effort. An ef- enable us to evaluate the adequacy of the fective system of intra-agency cooperation food supply and to develop recommendations would also be necessary. However, since it for needed changes. Such changes might in- may not be possible to clearly separate the clude new processing techniques, fortifica- concerns of nutrition and disease from those tion, reformulation, or selection of alternative of "normal nutrition," some overlap would food items by consumers. probably be inevitable. Broader information and intervention ef- The second alternative assigns one agency forts outside of the health care system are main responsibility for nutrition research. also necessary. The public should know what Since USDA and HEW fund 87 percent of the scientific community has learned about Federal human nutrition research, they are the relationships among lifestyles, food con- the most likely candidates for the lead agency sumption, and health. Developing improved role. There are arguments both for and ways of conveying such knowledge would en- against giving such responsibility to one or courage the public to adopt better eating the other agency. habits and other health-promoting behavior. Currently USDA plays the major role in OTA working group participants felt that carrying out food intervention programs in neither the existing legislation nor the priori- the United States. By giving it primary re- ties suggested in the OSTP and GAO reports sponsibility for funding and coordinating provided the holistic, integrated research nutrition research efforts, the Government's strategy needed to meet current and pro- research and food intervention activities jected diet-related problems in the United might be better coordinated. At the same States. Seven elements of a comprehensive time, Federal research activities might research strategy to define the role of nutri- become more responsive to consumer views tion in the prevention of chronic disease and and needs because of USDA's major involve- to improve management of current nutrition- ment in food and nutrition education pro- related problems were discussed. The seven grams. 34 Source: https://www.industrydocuments.ucsf.edu/docs/rInf0227 Table 5.-A Seven-Point Nutrition Research Strategy The role of diet in the prevention of chronic disease and obesity Major health problems and diet-related risk factors Diet, aging, and disease Methods for preventing obesity Nutrition and mental development The role of nutrition in the treatment of disease and support of therapy Nutritional support of patients with severe disease and injury Other disease states Technology for delivery of nutrients to patients Behavioral and emotional problems Nutrition education and consumer information Factors affecting lifetime eating habits and identification of critical points for education Development and evaluation of nutrition education and communication methods Methods for simplifying consumer information utilization Requirements for essential nutrients Methods for determining nutrient needs Interactions among nutrient requirements based on functional criteria Pharmacologic and toxicologic effects of on nutritions Bioavailability of nutrients in foods Nutritional aspects of food science and food safety Food composition New food processing and handling procedures to maintain nutrient content Better methods of assuring food safety Monitoring nutritional status Methods for improving integration of food consumption and nutritional status surveillance Evaluation of the effects of food and nutrition education programs Nutrition policy and management Food-related interventions Other interventions USDA now coordinates research in the ments for giving HEW, the agency concerned area of food production with the State agri- with health, the lead responsibility for direct- culture experiment stations and other coop- ing nutrition research. However, such re- erating institutions. Some link between the search has not been a main HEW concern in nutritional concerns of consumers and the the past. Disease-prevention research has food production system seems to be essential. generally received much less support than But USDA has traditionally had little respon- specific disease-oriented or curative-oriented sibility or expertise in the area of human research. Moreover, HEW has not been con- health and disease. One of the major needs in cerned with the nutrient requirements of Federal nutrition research activities is a healthy people, food consumption patterns, or reorientation of priorities to stress the role of food composition. In addition, HEW has no nutrition in the prevention of disease. Thus nationwide programs of nutrition and health separating health-related nutrition research education comparable to those developed by from the overall direction of health research USDA. may not be wise. If health-related nutrition research fell exclusively under USDA, poten- tial conflicts might arise. The research might The report by OSTP recommended that the produce recommendations for substantial lead role in nutrition research be given to a shifts in food practices. Such findings and third party which would formulate policy and recommendations could conflict with the coordinate and monitor programs. Under this traditional interests of producer groups. arrangement, various agencies would retain their existing nutrition research respon- Many of the research priorities identified sibilities, but their activities would be over- by OTA as well as other groups involve the seen by the third party. The concept offers relationship of human health to nutritional some positive features. It would focus atten- practices. Therefore, there are strong argu- tion on nutrition while retaining the healthy 35 Source: https://www.industrydocuments.ucsf.edu/docs/rlnf0227 competition among agencies involved in nutri- A pluralistic approach to human nutrition tion research. research, with well-defined agency respon- sibilities for HEW and USDA, appears to be However, such a third-party concept also the best means of coordinating Federal raises several problems. It involves another research efforts. Such an approach could layer of Federal bureaucracy. A third-party produce the kind of creative competition that oversight body might have no real power to would likely enhance human nutrition influence budgets and allocate resources research. It would also result in some within and among agencies, especially since overlapping of efforts, which should be it would lack a political constituency. These minimized by the coordinating process. potential deficiencies would be further mag- The coordinating function might best be nified by inadequate staff and expertise. In carried out by an interagency committee with the end, such a coordinating mechanism would probably only serve as a means to ex- a rotating chairmanship. This arrangement change information, much as the nutrition would be consistent with a pluralistic ap- proach to research. At the same time, it coordinating committee does within NIH and the Current Research Information System would help ensure against any one agency (CRIS) does for USDA. building a "most-favored" relationship with the coordinating committee. Another alternative would give assistant Coordination of Federal nutrition activities secretaries in HEW and USDA responsibility extends beyond specific mechanisms for for coordinating nutrition research policy intra- and inter-agency coordination. It also within and between their respective agen- includes information storage, retrieval, and cies. Lack of high-level commitment to nutri- integration. No uniform system presently ex- tion research has been a problem in the past. ists among the various agencies involved in Placing responsibility for nutrition at the nutrition research. Computerized systems assistant secretary level might create the that permit information integration and re- visibility and commitment needed to effec- trieval need to be explored. At the very least, tively coordinate nutrition research efforts. relevant branches of HEW and USDA should Such an arrangement would require adminis- have a common indexing and data retrieval trative changes within both agencies. At pre- system for this type of information. Since sent, it is unclear if the USDA reorganization federally supported research accounts for that created a Human Nutrition Center the major share of research in the nutrition within SEA will accomplish this goal. and health maintenance areas, integration among these agencies is essential. Integration A final option would consolidate nutrition of nutrition research data is also desirable programs in one agency, either USDA or among the public, private, and voluntary sec- HEW. These activities would include re- tors. search, education, regulation, training, serv- ice delivery, monitoring and surveillance, and food and other intervention programs. Both Definition and Funding USDA and HEW have recently shown interest in this concept in papers entitled USDA's Commitment to Food and Nutrition Policy and As outlined under issue 2, OTA could not The Role of HEW in Human Nutrition: Future perform an analysis of the present Federal Directions. However, the wisdom of such a human nutrition research budget, since pres- consolidation is debatable. Although both ent expenditure estimates are so disparate. agencies currently have a number of nutri- Federal spending on human nutrition tion programs, the expertise involved is quite research should be precisely determined. By specialized. Whether this approach would eliminating the present confusion, Congress solve coordination problems probably will be better able to judge appropriate levels depends on the agency's commitment to the of funding for nutrition research. Congress field of nutrition. could request GAO to audit the human nutri- 36 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research expenditures of Federal agen- facilitate future congressional oversight cies. The GAO audit, based on a constant hearings. definition, should determine total Federal spending for human nutrition research, the number of scientist years involved, and Personnel Resource Requirements Federal expenditures in the seven priority areas set out in this report. If Congress were to choose to implement On the basis of such information, Congress the OTA comprehensive nutrition research would have several options. The first would strategy, there is a clear need to establish be to maintain the status quo in nutrition how many scientists are both presently in- research funding, with possible reallocation volved in, or training for, nutrition research. of some funds to areas not now receiving sup- This census would include a breakdown in port. As a second option, Congress could ap- terms of various research areas, such as propriate, additional funds to specific nutri- Government facilities, universities, medical tion research areas that are not getting facilities, private institutes, and industry. enough support. Finally, Congress could ear- This kind of census would identify where nu- mark a percentage of Hatch funds for human trition research personnel gaps exist and nutrition research. Such an audit, together where greater support is necessary. To fill with a uniform system for reporting human such gaps, expanded Federal support should nutrition research spending, could also be considered. 37 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONCRESSIONAL OPTIONS vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONGRESSIONAL OPTIONS OTA found that three key issues underlie the basic finding that the Fed- eral Government has failed to adjust the emphasis of its human nutrition research activities to meet the changing health problems of the American people. Alternative approaches of dealing with these issues have been ex- plored. Congress can elect to maintain the status quo, with or without minor shifts, or choose among the strategies and options offered by OTA, the General Accounting Office (GAO), and the Office of Science and Technology Policy (OSTP), (see chapter III). Either alternative has economic, institutional, and health implications. Option 1: Congress Could Choose To Maintain the Overall Status Quo Maintaining the status quo could mean itoring nutrition status, and nutrition policy refraining from any action. In a broader and management. sense, it also could involve minor im- provements in the present system-without If Congress chooses to refrain from any ac- making substantial changes. tion to await the recommendations of the President's Reorganization Project, no ad- A. Congress could refrain from any action, verse effects would be expected. awaiting the recommendations of the President's Reorganization Project. B. Congress could amend the Food and Agri- culture Act of 1977 to clarify the desig- In August of 1977, President Carter nation of lead agency for human nutrition directed the Reorganization Project staff at research. the Office of Management and Budget to thor- oughly review the organization and structure At the present time, the Department of of Federal food and nutrition programs. Food Agriculture (USDA) interprets the Food and and nutrition research is one of the seven ma- Agriculture Act of 1977 to mean that USDA is jor areas under review. A final report to the the lead agency for human nutrition re- President, expected in January of 1979, will search, an interpretation not shared by the include recommendations that may signifi- Department of Health, Education, and Wel- cantly alter the organization, and thus the fare (HEW). If Congress intended USDA to course, of nutrition research activities. have primary responsibility for this research area, the Act will require amendment. Since significant strides have been made in nutrition research, there is no reason to ex- C. Congress could develop nutrition research pect a decline in research productivity if cur- goals and priorities for HEW that comple- rent funding levels are maintained. However, ment the goals and priorities outlined for since several important areas of nutrition USDA in the Food and Agriculture Act of research receive little support at present, 1977. progress in these areas would be slow. These areas include the role of nutrition in the pre- The legislation contains strong language on vention of disease, nutrition education, mon- the relationship of diet to many of the leading 41 Source: https://lwww.industrydocuments.ucsf.edu/docs/rinf0227

The fifth image represents which nutrient?

rlnf0227

rlnf0227_p22, rlnf0227_p23, rlnf0227_p24, rlnf0227_p25, rlnf0227_p26, rlnf0227_p27, rlnf0227_p28, rlnf0227_p29, rlnf0227_p30, rlnf0227_p31, rlnf0227_p32, rlnf0227_p33, rlnf0227_p34, rlnf0227_p35, rlnf0227_p36, rlnf0227_p37, rlnf0227_p38, rlnf0227_p39, rlnf0227_p40, rlnf0227_p41, rlnf0227_p42, rlnf0227_p43

proteins, Proteins

lating research findings. Because of a general noted that this language is ambiguous. It does lack of accessibility, it is often extremely dif- not specify "lead," and it leaves cooperation ficult for agencies to communicate research to the goodwill of HEW. information to the public or Congress. The need for improved coordination in Of course, some overlap in interests is in- nutrition research extends beyond the execu- evitable in similar areas of research, and tive agencies to Congress. At present 14 con- duplication of research results is a necessary gressional committees and 20 subcommittees part of scientific research. But unnecessary are concerned with nutrition matters. The duplication should be avoided. Minimizing principals include the Senate Committees on duplication by developing more efficient Agriculture, Nutrition, and Forestry (Sub- means of sharing information on planned, on- committee on Nutrition); Appropriations going, and completed research is an achiev- (Subcommittees on Labor-Health, Education able goal. and Welfare, and Agriculture); the House In the same sense that some duplication is Agriculture Committee (Subcommittee on a necessary part of scientific research, Domestic Marketing, Consumer Relations, healthy competition among agencies may and Nutrition); the House Appropriations stimulate greater effort and ultimately bene- Committee (Subcommittees on Agriculture fit the public. But the proprietary stance and Labor-Health, Education, and Welfare); taken by some agencies is wasteful and in- House Interstate and Foreign Commerce hibits joint planning. Internecine struggles at Committee (Subcommittees on Oversight and higher levels of Government apparently fos- Investigations, and Health and Environment); ter such attitudes. However, career civil serv- and the House Science and Technology Com- ants and the public, as well as the overall mittee (Subcommittee on Domestic and Inter- Federal research effort, suffer as a result. national Scientific Planning, Analysis, and The turf battles that lead agencies to work at Cooperation, and the Subcommittee on Sci- cross purposes should be eliminated. Agen- ence, Research, and Technology). Since some cies involved in nutrition research should duplication of interest exists, joint sessions of demonstrate a commitment to coordination relevant congressional subcommittees to con- and the avoidance of unnecessary duplica- sider plans and hearings for oversight pur- tion. This commitment needs to be built in, not poses should be considered. only at the "political" level of the higher There is a strong relationship between echelons of Government but also in the career human nutrition research conducted abroad civil service. and research needs in the United States. The The establishment at USDA of the Human research goals identified in this report can be Nutrition Center and the Human Nutrition best achieved if international and domestic Policy Committee and at HEW of the Nutrition research activities are tuned together. Coordinating Committee are two positive Nutrition research in other countries may steps toward intra-agency coordination. They help in solving domestic nutrition problems. not only indicate a commitment to nutrition For example, epidemiological investigations research but also can serve as mechanisms of certain chronic diseases require good in- for interagency coordination and information formation about disease incidence. This may exchange. be obtained from studies of societies with The Food and Agriculture Act of 1977 lifestyles and food habits very different from specifies that the Secretary of Agriculture our own. The high incidence of malnutrition shall "periodically consult with the adminis- in some developing nations also provides an trators of other Federal departments and opportunity to investigate relationships be- agencies that have responsibility for coor- tween the nutritional status and functional dinating Federal nutrition research activ- performance of individuals in a way that ities." However without the support and in- would be impossible in the United States. It volvement of the Secretary of HEW, unilat- may be possible to extrapolate the results of eral USDA efforts to coordinate research studies of severe malnutrition abroad to may not be effective. Likewise, it should be margina! nutritional areas in this country. 16 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 The study of worldwide populations and will have a dual reward-assistance to mal- food patterns is essential to the better under- nourished peoples abroad and increased standing of some of the priority research knowledge of human nutrient needs and areas of nutrition. Thus any effort to increase health status under changing environmental international nutrition research capabilities conditions. ISSUE 2 - Definition and Funding of Human Nutrition Research If one accepts that the goals of human genetics, animal nutrition, plant nutrition, nutrition research are twofold-(1) the pro- and plant genetics comes under this classi- motion of optimum health and performance, fication. While there is need to integrate such and (2) the treatment of diseases through diet agricultural research with human nutrition therapy and the support of other medical concerns, these areas should not be consid- therapies-th definition of human nutrition ered human nutrition research. Similarly, research flows from these stated goals. If all basic research on metabolism of nutrients, if the research areas involving nutrition are not directly applicable to people, should not listed, from basic studies on the metabolism be considered human nutrition research. of nutrients to genetic studies on the develop- Basic research on metabolism should be con- ment of foods with specific nutrient charac- sidered as basic research underlying all of teristics, it is clear that some areas of the biomedical and life sciences. Human research are more closely related to these nutrition research builds upon this knowl- stated goals than others. Accordingly, the edge base, but the apparent commitment to definition of human nutrition research must and budget for human nutrition research take into account these relationships to should not be inflated by its inclusion. stated goals. Throughout this assessment, a recurrent In terms of this assessment, nutrition problem has been that of definition of human research falls into three broad categories. nutrition research. Agencies report as human Most closely related to the stated goals is nutrition research studies that appear to research into the biochemical and physiologi- have little to do with human nutrition. Ex- cal effects of food on the body in health and amples are "Catalytic Functions and Metab- disease. This category includes research on olism of Vitamin B6 in Bacteria and Fungi," nutritional management of disease, nutrient "Nutritional Imbalance and Metabolic Alter- needs and interactions, and research which ations in Fungi," or "Hepatoma Incidence in promotes optimum health and disease pre- Trout on Dietary Aflatoxin and PCB." Such vention through diet. studies are worthwhile and contribute to our understanding of basic biochemistry but are Research on food and nutrition quality not directly applicable to humans. determinants is also related to the stated The almost unanimous consensus of the goals, but less directly so than the previous category. Under this heading would be re- participants in the OTA study was that at- search into food composition, especially the tribution of these Federal expenditures to nutritive components and changes in nutrient "human nutrition research" was improper. composition that occur from point of origin to Fourteen different Federal agencies are point of consumption; food safety; social, cul- engaged in some sort of nutrition research. tural, and economic aspects of food habits; Each agency has developed its own definition feeding programs; nutrition education; con- of human nutrition research and set priorities sumer information; and nutrition surveillance on the basis of how it interprets its legislation and monitoring. mandate. The agencies and their priorities are shown in table 3. The third category of research involves basic research on sources of human food and Federal expenditures for human nutrition basic biochemistry. Research into animal research in FY 1977 (shown in table 4) were 17 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3. - Federal Government Agencies Active in Food and Nutrition Programs and Their Nutrition Research Priorities Food and nutrition Department Agency programs Research priorities Health, Edu- National National Institute of Arthritis, Metabolism, and Digestive Diseases cation, & Institutes (NIAMDD).Basic hysiological studies of nutrients; basic metabolism Welfare of Health studies; obesit, trace elements nutrition support of patients; fiber; anemias. National Institute of Child Health and Human Development (NICHHD). Nutrition and fetal development; metabolic capacities of normal, low- birthweight, and premature infants; diet modification for low-birth- weight and premature infants; optimum nutrition in developmental years; nutrition and reproductive potential; genetic variability-nuti tional interaction; prevention- - metabolic antecedents of adult disease. National Cancer Institute (NCI). Nutrition support of cancer patient; nu- trition in cancer etiology; host-tumor interactions and competition for nutrients; prevention strategies based on nutrition; diet and nutrition in the rehabilitation of cancer patients. National Heart, Lung, and Blood Institute (NHLBI). Nutrition in etiology of arteriosclerosis and hypertension; achieving and maintaining dietary change; development of food composition tables; methodology-col lecting, recording, and evaluating dietary data. National Institute of General Medical Sciences (NIGMS). Trauma- tized/burned patients and nutrition. National Institute of Environmental Health Sciences (NIEHS). Neuro- toxicity; mutagenesis; teratology; environmental contaminants in food. National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Protein-calorie malnutrition, B-vitamin deficiencies and the nervous system; genetic disorders and the nervous system; specific nutritional problems in the central nervous system; stroke. National Institute of Dental Research (NIDR). Sucrose and caries; poor nutrition and periodontal disease; poor nutrition and oral mucus mem- branes; nutrition in craniofacial malformations and oral-facial struc- tures; nutrition and salivary gland development. National Institute of Allergy and Infectious Disease (NIAID). Interrelated factors hearing on malnutrition, infection, and the immune system. National Eye Institute (NEI). Vitamins A, B-12, and other nutrients in visual processes; diseases of visual system, e.g., keratomalacia; metab- olism of visual cells; protein changes in the lens. National Institute on Aging (NIA). Nutritional status of the elderly; aspects of increase in life span including dietary manipulations; vitamin supplementation in elderly; nutrient intake as a consequence of econ- omic status in elderly; relationship among nutrition, cellular structure, and function in elderly. Division of Research Resources (DRR). Nutrient requirements for growth, gestation, lactation in primates and laboratory rodents; stand- ard diets for specific objectives; interaction of various nutrients on physiological function in laboratory animals; differences in nutrient re- quirements among strains of animals within a species. Food & Regulatory activities Nutrient efficacy and safety; nutrient interrelationships as concerned Drug related to: nutrition with disease prevention; nutrient bioavailability for food fortification Admin- labeling, ingredient purposes; nutrient quality assessment of processed foods; medical istration labeling, food for food assessment; food composition and nutrient analysis as related to special dietary use, FDA mission; and consumer studies of perceptions about food values food advertising, nutri- and nutritional quality and educational models to help correct tion quality of foods misconceptions about them. Health Re- Health and Nutrition Assessment of the nutritional status of the American people. sources Examination Survey Admin- istration 18 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table 3 - -continued Food and nutrition Department Agency programs Research priorities Center for Epidemiological surveillance studies in cooperation with State Disease agencies assistance to AID in similar international areas. Control Health Collaborative research and screening program for phenylketonuria. Services Admin- istration Alcohol, Effects of alcohol consumption on nutrient metabolism and nutritional Drug deficiencies; study of food additive consumption and hyperactivity Abuse, & in children. Mental 5 Health Admin- istration Agriculture Agricul- Human Requirements for Nutrients tural Re- Determine the requirements for lipid intake and identification of the search forms of these nutrients in foods that may be useful in meeting Service* these requirements. Determine the requirements for mineral intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for vitamin intake by humans and identi- fication of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for protein and amino acid intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Determine the requirements for carbohydrate and energy intake by humans and identification of the forms of these nutrients in foods that may be useful in meeting these requirements. Food Composition and Improvement To provide accurate, up-to-date, and comprehensive information in a readily usable form on the composition of all important foods for those nutrients required by and biologically useful to man. To provide the technology for the nutritional improvement of foods when enhanced levels of certain nutrients in the diet are needed to correct possible dietary faults. Food Consumption and Use To provide accurate, up-to-date, and comprehensive information in a readily usable form on food consumption and dietary levels. To provide consultative assistance on food and nutrition problems and provide sound guidance materials on nutrition for the consumer and for nutrition educators, program leaders, and food program man- agers; to identify techniques which will assist people in selecting nu- tritionally adequate diets within different budget limitations; to iden- tify means to modify undesirable food habits; to strengthen nutri- tionally desirable food choice. To identify and develop suitable and safe procedures for food man- agement and preparation for home and institutional consumers, for best retention of both nutritional and eating qualities and to avoid food-borne illness. Coopera- Nutrient requirements; nutritional status of special population groups tive State including children, low income, and aging; metabolic function of Research nutrients in the diet and their interactions; nutrient content of foods; Service* effects of processing on nutrients; food delivery systems; food habits and use); dietary patterns. 19 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Table -continued Food and nutrition Department Agency programs Research priorities Economic Economic and social research relating to domestic food programs; Research nutrition policy in LDCs; food choices (demand); nutritional programs Service' for the elderly. Defense Determination of nutritional and dietary standards for Armed Forces personnel subsisted under normal and special operating conditions; evaluation of nutritional adequacy of food as consumed; evaluation of the nutritional status of Armed Forces personnel; establishment of sanitary and food hygiene standards for all food program activities; food aspects of preventive medicine. National Nutritional control of neurotransmitters; role of dietary protein and Aeronautics specific amino acids in optimizing human performance under stress. & Space Ad- ministration Veterans Depart- Research in disease and diet: nutrition and disease or clinical nutrition, Adminis- ment of dietary therapy; effect of disease on nutrition; environmental toxicants, tration Medicine alcohol, and nutrition; nutrition and cancer; nutrition and vision re- & Surgery search; nutrition-related therapy. Metabolic effects: Investigations on or related to malabsorption syn- dromes, inborn errors of metabolism, and familial or inherited nutri- tional defects. Nutrition requirements: Studies of nutrient metabolism, malnutrition, neuroendocrine nutrient interactions, fundamental intermediary metab- olism involving the role of one or more nutrients. State Agency Development of new low-cost nutritious foods; development and for Inter- dissemination of new appropriate technologies; understanding national nutritional needs and requirements; testing and evaluation of nutrition Develop- program alternatives; research on methodologies for improving national ment nutrition planning and programing. National Basic research in the behavioral, education, and social sciences in Science areas applicable to foods and nutrition. Foundation Under USDA's recent reorganization, ARS is now called Federal Research, and is housed within the Science and Education Administration. Under USDA S recent reorganization, CRS is called Cooperative Research and is housed within the Science and Education Administration Under USDA S recent reorganization, ERS is called Economics and is housed within the Economics, Statistics. and Cooperatives Service. Under USDA recent reorganization, ES is called Extension and is housed within the Science and Education Administration estimated at between $50 million and $117 tion research. Seventy-five percent of Federal million, depending on how "nutrition re- nutrition research is conducted outside of the search' was defined. If for example, the NIH two departments through competitive grants definition is used, NIH appears to be spend- and contracts. Using the more realistic fund- ing $80 million for human nutrition research. ing figure of $50 million for FY 1977, NIH at This broad definition takes in studies of basic HEW funded 44 percent of the total, and the biochemistry, studies which are not focused Science and Education Administration (SEA) on nutrition but have a nutrition aspect, as at USDA funded 43 percent of the total. The well as studies of primary nutrition. If a nar- Science and Education Administration en- row definition is used, one encompassing only compasses what were formerly known as the those studies of direct clinical applications Agricultural Research Service and the Coop- and disease prevention, the NIH nutrition erative State Research Service. Under research funding falls in the annual range of USDA's new reorganization, most human nu- $20 million. Even the higher $80 million trition research will be coordinated by SEA's figure, incidentally, amounts to less than 3 Human Nutrition Center. percent of the NIH research budget. The Science and Education Administration HEW and USDA are responsible for the Cooperative Research (SEA-CR) of USDA is majority of federally supported human nutri- unique among Federal agencies in that it links 20 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 Table 4. - Federal Expenditures for Human Nutrition Research An Approximation of FY '77 Expenditures (millions of dollars) Office of Science & Office of Management Agency Technology Policy & Budgetb Department of Health, Education, & Welfare $ 88.6 $22.0 National Institutes of Health 80.4C 22.0d Food and Drug Administration 3.9 National Center for Health Statistics 2.4 Alcohol, Drug Abuse, and Mental Health Administration 1.1 Health Services Administration 0.5* Center for Disease Control 0.3* Department of Agriculture 22.0 21.8 Agricultural Research Service 14.0 13.2 Cooperative State Research Service 7.5 8.1 Economic Research Service 0.5 0.5 Agency for International Development 2.9 0 Department of Defense 2.3* 2.2 Veterans Administration 0.5* 4.1 National Science Foundation 0.3* 0 Grand total. $116.6 $50.2 affice of Science and Technology Policy, New Directions in Federally Supported Human Nutrition Research, December 1977. Poffice of Management and Budget, Special Analyses-Budget of the U.S. Government FY 1979. This figure includes studies designed to assess the mechanisms and the consequences of food or nutrient intake in the intact organism. particularly man: investigations involving nutrient variables at the cellular or subcellular level, including metabolic studies in animals and man: research designed to elucidate the metabolic role or function of an essential nutrient in both animal models and man, as appropriate; all studies concerned with genetic-nutrient-environmental interactions; dietary studies ex- pected to produce changes in health status, including the maintenance of health and the treatment of disease in man. This figure includes biochemical, physiological, and clinical studies of nutritional needs for normal growth, development, and health: nutritional needs of patients with specific common diseases: and experimental assessments of feeding programs. *Estimates of FY 1976 expenditures provided by draft Government Accounting Office report, Human Nutrition Research- Need for a Coordinated Approach to Advance Our Knowledge, 1977. Federal and State research efforts. SEA-CR levels could be made since current estimates administers funds that Congress appropri- of Federal spending for human nutrition ates to the States for agricultural research. research are questionable. Estimates for FY This work is conducted at the State agricul- 1977 range from $50 million to $117 million tural experiment stations, land-grant colleges (table 4). The lower figure, based on agency and universities, approved schools of for- responses to a standard questionnaire, was estry, colleges of 1890, and Tuskegee In- developed by the Office of Management and stitute. In FY 1977, the States used $7.5 Budget (OMB) for the FY 1979 budget. The million of the Federal money available to higher figure came from an OSTP working them for human nutrition research. The group and appeared in the December 1977 States themselves provided $11.7 million for report "New Directions in Human Nutrition human nutrition research in 1976. Most of Research." the Federal money came from funds author- ized by the Hatch Act, as amended, and P.L. Neither is reliable. The $50 million, for ex- 89-106 (an act to amend the Agriculture Act ample, fails to include certain nutrition of 1954). The funds are accounted for under research activities within HEW, AID, and the the Hatch Act research program called Peo- National Science Foundation. The $117 mil- ple, Communities, and Institutions, which lion, on the other hand, includes $80.4 million comprised 12 percent of total Hatch Act of NIH spending-much of it of tenuous con- research funds in 1977. nection to human nutrition research. In testi- mony before the Senate Select Committee on Federal human nutrition research may be Nutrition and Human Needs on October 17, financially undernourished. However, no 1977, NIH Director Dr. Donald Fredrickson analysis of the adequacy of present funding conceded that, based on a strict definition, 21 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 his agency devoted only around $20 million to whether any of these funds are devoted to human nutrition research in FY 1977 (a fig- research on which methods are most effeo- ure reported to OMB). tive for reaching people. Another statistic which raised questions OTA concluded that most estimates of came from the Veterans Administration (VA). human nutrition research funding were ques- GAO put the VA's FY 1976 nutrition research tionable and that total funding fell con- spending at $0.5 million. In FY 1977, the VA siderably short of the reported $117 million reported sharply increased expenditures of level. Regardless of which overall figure is $4.1 million, even though nutrition research more nearly accurate, certain areas iden- was not recognized as a high priority by the tified by OTA are not now receiving sufficient agency. Federal support, the result of a lack of recognition of their importance and zero or In some cases, it was difficult to determine almost no funds. Those areas most in need of how much (if any) money was being spent for increased funding are the role of diet in the certain types of important nutrition research. prevention of chronic disease and obesity, For instance, the Federal Government is now nutrition education and consumer informa- annually spending about $70 million on nutri- tion, monitoring nutritional status, and nutri- tion education programs. It is unclear tion policy and management. ISSUE 3 - Personnel Resource Requirements Estimates of the number of scientists they are engaged in research activities. This engaged in human nutrition research also does not indicate the degree of involvement proved elusive. and, of course, neglects those outside of dietetics engaged in nutrition research. In an attempt to determine the current number of scientists engaged in human-nutri- The two Government agencies that fund tion research and the numbers of research the largest portion of nutrition research, scientists being trained, OTA contacted five HEW and USDA, do maintain figures on sci- professional societies and six Government entist-years devoted to nutrition research agencies. Of the professional societies, the and 5-year projections of personnel needs. At American Public Health Association, Insti- USDA in FY 1976, 193.5 scientist years were tute of Food Technologists, and American devoted to human nutrition research as de- Chemical Society make no attempt to distin- fined by the agency. The 5-year projection of guish between members engaged in research need for nutrition research scientists at versus other career orientations and USDA is for 260.7 scientist years, a 20-per- therefore could not supply information on the cent increase. proportion of their membership engaged in In a written response to an OTA question- human nutrition research or training of nutri- naire, NIH informed OTA that 70 scientists tion research scientists. Membership in the were employed in human nutrition research American Institute of Nutrition (AIN) is in 1977. But NIH Director Fredrickson sub- limited to those who have made significant mitted a written statement to the Senate contributions to the field of nutrition re- Select Committee on Nutrition and Human search. By definition, all of AIN's 1,730 mem- Needs that during that same time period 180 bers are nutrition research scientists. This intramural investigators in NIH were directly number seriously underestimates the total involved in human nutrition research. Of that number of scientists in the field, since junior number, 20 were defined as "classical nutri- people are not eligible for membership and tionists" when nutrition research was de- very few behavior and education researchers fined as "the study of food and nutrients." In are included. AIN does not keep any figures FY 1977, 20 lead scientists, those holding on training. Of the American Dietetic Asso- M.D., Ph.D., or D.V.M. degrees, and 50 junior ciation's 21,751 members in 1977, 764 state scientists were conducting nutrition research 22 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 at Letterman Army Institute of Research of professional nutrition training programs as the Department of Defense. well as increased training support. For grad- uate students in nutrition and food science, Before a comprehensive nutrition research program is established, consideration must such changes might include greater stress on be given to the ability of the field to sustain nutritional pharmacology, food science prin- such a program. No accurate figures exist on ciples, nutrition education, nutritional status evaluation, and nutrition-related diseases. how many scientists are currently engaged in human nutrition research. Furthermore, few Training would be further strengthened by reports on nutrition research mention this postdoctoral research work with either hu- aspect of planning. mans or experimental animals. Greater em- phasis on nutritional biochemistry and clini- Implementation of the research priority cal nutrition in undergraduate medical edu- areas identified in this report may require cation may help attract physicians to the changes of emphasis in existing graduate and field. 23 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter III NUTRITION RESEARCH STRATEGIES Accumulating the fragmented research activities of the 14 Federal agen- cies supporting human nutrition research does not, as a whole, constitute a coherent strategy for the solution of current diet-related health problems. A goód understanding of the status quo can be gained by analysis of the Food and Agriculture Act of 1977 which established research goals and priorities for the Department of Agriculture (USDA). The picture of the present situation can be completed by reviewing the research goals and priorities at the Na- tional Institutes of Health (NIH). Alternatives to the status quo can be found in the recently published reports of the Office of Science and Technology Policy (OSTP) and the General Accounting Office (GAO). These two alter- natives, plus an alternative developed by OTA, are examined here and provide Congress with several alternative strategies that may be pursued. Each of the alternatives are examined from three perspectives: Do the stated goals and priorities adequately address current U.S. health problems? Is nutrition research defined clearly to permit realistic estimation of Federal expend- itures? Is consideration given to the personnel requirements to fulfill pro- posed research priorities? THE STATUS QUO: NUTRITION RESEARCH IN THE FEDERAL GOVERNMENT Goals and Priorities The Food and Agriculture Act of 1977 rec- fants, children, adolescents, elderly men and ognized the relationship between diet and the women, and pregnant women; and that there general health of the population. The legis- is a critical need for objective data concern- lation states "that there is increasing evi- ing food safety, the potential of food enrich- dence of a relationship between diet and ment, and means to encourage better nutri- many of the leading causes of death in the tional practices." United States; that improved nutrition is an integral component of preventive health care; The legislation declares that the Secretary that there is a serious need for research on of Agriculture shall develop and implement a the chronic effects of diet on degenerative national food and human nutrition research diseases and related disorders; that nutrition program that shall include, but not be limited and health considerations are important to to, five areas: U.S. agricultural policy; that there is insuffi- cient knowledge concerning precise human 1. Research on human nutritional require- nutritional requirements, the interaction of ments. the various nutritional constituents of food, and differences in nutritional requirements 2. Research on nutrient composition of among different population groups such as in- foods and the effects of agricultural 27 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 practices, handling, food processing, "Reviewing the policies, plans, and goals and cooking on the nutrients they con- of programs within USDA involving the tain. food and agricultural sciences, and 3. Surveillance of the nutritional benefits related programs in other Federal and provided to participants in the food pro- State departments and agencies and in grams administered by USDA. the colleges and universities developed by the Secretary under this title; 4. Research on the factors affecting food preference and habits. Reviewing and ssessing the extent of agricultural research and extension be- 5. The development of techniques and ing conducted by private foundations equipment to assist consumers in the and businesses, and the relationships of home or in institutions in selecting food such research and extension to federally that supplies a nutritionally adequate supported agricultural research and ex- diet. tension; Reviewing and providing consultation to Although the legislation points up the rela- the Secretary on national policies, prior- tionship between diet and leading causes of ities, and strategies for agricultural death in the United States, the research pri- research and extension for both the ority areas spelled out do not pursue this line short and long term; of inquiry. Since the legislation pertains almost exclusively to USDA, it lays out what Assessing the overall adequacy of, and could be considered a partial strategy to making recommendations to the Secre- solve the problems of diet and chronic de- tary with regard to, the distribution of generative diseases-research on nutrient resources and the allocation of funds au- needs, on the composition of the food supply, thorized by this title; on ways to help consumers select a healthful Preparing and submitting to the diet, and surveillance of the population. Fur- Secretary, not later than October 31 of thermore, funding proposed in the FY 1979 sch year, a statement of recommenda- budget does not match the ambitious wording tions as to allocations of responsibilities of the legislation. and levels of funding among federally supported agricultural research and ex- The Food and Agriculture Act of 1977 tension programs; and designated the Secretary of Agriculture to "establish jointly with the Secretary of Not later than March 1 of each year sub- Health, Education, and Welfare procedures mitting a report on its appraisal of the for coordination with respect to nutrition President's proposed budget for the food research in areas of mutual interest." Sec- and agricultural sciences for the fiscal tion 1406 amends the National Science and year beginning in such year and the Technology Policy, Organization, and Priori- recommendations of the Secretary con- ties Act of 1976 (90 Stat. 471; 42 U.S.C. 6651 tained in the annual report.' (h)), by creating a standing subcommittee to be known as the Subcommittee on Food and As indicated earlier, the Food and Agricul- Renewable Resources. ture Act of 1977 does not clearly give USDA the lead responsibility for human nutrition The legislation also established a National research. Section 1405 declares "the Depart- Agricultural Research and Extension Users ment of Agriculture is designated as the lead Advisory Board composed of 21 members rep- agency of the Federal Government for agri- resenting a wide variety of agricultural pro- cultural research (except with respect to the ducer, consumer, marketing, and environ- biomedical aspects of human nutrition con- mental interests. Two members must be en- cerned with diagnosis or treatment of dis- gaged in human nutrition work. The Advisory easc). Human nutrition is one of the Board has the responsibilities for: areas included in the definition of "food and 28 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 agricultural sciences (section 1404). But the long-range goals of the AID nutri- Section 1409 states that "*t is the intent of tion program are: to have developing coun- Congress in enacting this title to augment, tries incorporate nutrition considerations in- coordinate, and supplement the planning, ini- to their social and economic development tiation, and conduct of agricultural research plans; to create the methodologies for assess- ing needs, determining causes, and selecting programs existing prior to the enactment of interventions: and to have available the most this title, except that it is not the intent of cost-effective interventions with information Congress in enacting this title to limit the on when they are most appropriate to apply, authority of the Secretary of Health, Educa- the cost and other requirements for imple- tion, and Welfare under any Act which the menting them, the best methods for imple- Secretary of Health, Education, and Welfare menting them, and information on expected administers." Thus a clear mandate is not results. given to USDA to be the lead agency for The AID nutrition research program is human nutrition research. designed to provide new knowledge that will Section 1423 (b) requires the Secretary of help implement programs to attain these Agriculture to "periodically consult with the goals. The AID nutrition research program administrators of the other Federal depart- attempts to assess the functional signifi- cance of improvements in nutrition; it seeks ments and agencies." As discussed earlier, to establish whether nutritional needs can be this unilateral approach to coordination satisfied with locally available foods; it relies on the goodwill of other agencies to evaluates the effectiveness of nutrition in- cooperate with USDA in the goal of research tervention; and it seeks to inform govern- coordination. ments about the potential impact of policies in food and nutrition. Research priorities at NIH are summarized in table 3. A wide range of basic and applied It is therefore apparent that the AID nutri- research are embodied in these priorities. tion research program is not and should not The major emphasis is on basic and curative- be designed to address the research needs oriented disease research rather than dis- outlined in this report. The AID program is ease prevention. This becomes more clear as designed to meet the needs of host countries. allocations of funds to the different areas are Should a research project yield results ap- studied. The Nutrition Study Section at NIH plicable to problems discussed in this report, reviewed a total of 181 grant proposals in FY it is serendipitous. There is a clear need to en- 1977, and approved 119, totaling $4.7 million. courage international research, much of Only four other study sections recommended which would be epidemiological, to identify for approval grants totaling less than $4.7 and explore dietary and lifestyle factors con- million in this period of time. Two of these tributing to the major chronic diseases. sections have been disbanded, their work be- In theory, AID's nutrition research ac- ing referred to other study sections. Since tivities undergo peer review. Research funds research in nutrition involves many different are publicized through the distribution of a disciplines and crosses traditional discipli- brochure, and information on AID's research nary lines, NIH maintains that many grant needs are circulated among professional applications with nutrition components are groups and announced at professional meet- referred to other study sections. It can there- ings. 'Projects that are awarded on the basis fore be assumed that $4.7 million is what NIH of predominant capability are very carefully clearly defined as human nutrition research, reviewed before approval. Fewer and fewer and the remainder of the $80.4 million of projects follow this latter nutrition research funded by NIH if FY 1977 was basic and disease-oriented research In practice, the system seems to have func- with nutrition components of varying degrees tioned somewhat differently. Human nutri- of relevance. ¹Irwin Hornstein, Deputy Director, Office of Nutri- The Agency for International Development tion, Agency for International Development, June 8, (AID) is the Federal agency primarily respon- 1978. sible for international nutrition research. ²Ibid. 29 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research received an estimated $2.7 mil- human nutrition research is made in the Act. lion from AID in FY 1977. Most of this re- search was conceived by agency staff who In response to these requirements, USDA requested $43 million for human nutrition then had a scientific research group develop research in its FY 1979 budget proposal. This study proposals. The proposals were is a 95-percent increase over its FY 1977 screened by AID staff members before being spending of $22 million. submitted to the Research Advisory Commit- tee for technical feasibility evaluation. The At NIH, nutrition research support has re- agency does not widely advertise requests for mained relatively constant over the last sev- proposals, and few unsolicited proposals are eral years, constituting less than 3 percent of received. Some panel participants felt that the total research budget. Estimates of actual this system reduces the scientific base of ex- dollar outlays for human nutrition research pertise on which the agency can draw and vary from $20 million to $80 million for FY leads to an inbreeding of research ideas. 1977. Definition and Funding Personnel Resource Requirements The Food and Agriculture Act of 1977 does not explicitly define the term "nutrition" nor Both the USDA and HEW support under- the scope of "nutrition research." It implies graduate, predoctoral, and postdoctoral that "nutrition research" includes research students through a variety of tuition grants, on diet and disease, certain aspects of agri- loans, fellowships, and training grants. The cultural policy, nutritional requirements, Food and Agriculture Act establishes grants food composition and nutrient interactions, and fellowships for food and agricultural food safety, food enrichment, and means of sciences education at the undergraduate encouraging better nutritional practices. through postdoctoral levels. The program is There is no reference in the legislation to in- authorized in FY 1978 for $25 million, ex- ternational nutrition research. panding to $50 million by FY 1982. The pro- Section 1423 (a) of the Food and portion of this money to be devoted to training Agriculture Act of 1977 states that the Secre- nutrition researchers is not specified. tary of Agriculture "shall increase support The Department of Health, Education, and for such research [research into food and Welfare has traditionally supported training human nutrition] to a level that provides of research scientists through training grants resources adequate to meet the policy of this and fellowships. In FY 1977 these totaled subtitle." No specific authorization for $2.3 million for human nutrition research. NEW DIRECTIONS IN FEDERALLY SUPPORTED HUMAN NUTRITION RESEARCH: THE OSTP REPORT Goals and Priorities eral nutrition research activities. Although the report focused only on domestic research, it encouraged various Federal agencies in- In December 1977, OSTP published a re- volved in such activities to assess the poten- port on Government nutrition research. The tial international benefits from current and report defined the scope of human nutrition plonned projects. research, described existing Federal pro- grams, identified research areas that need he working groups of the OSTP inter- more attention, and suggested means for en- agency senior nutrition research staff recom- hancing the coordination and quality of Fed- mended four priority research activities: 30 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 1. Effects of nutrition on human health and In HEW, the programs of the Food and performance in pregnancy, infancy and Drug Administration (FDA), the National early childhood, old age, obesity, iron Center for Health Statistics (NCHS), the deficiency, nutrient toxicity, and in- Center for Disease Control (CDC), and NIH must be coordinated in the high-priority ac- teractions; tivities identified. At NIH, it is essential 2. Food sciences (methodology for analyz- for the NIH Director and for the Nutrition ing food composition, nutrient bio-avail- Coordinating Committee under his direction ability in foods, updating national to have the authority to prioritize nutrition nutrient data bank, expanding food com- research needs. The Director of NIH, has a position measurements); relationship to the several Institutes which 3. Nutrition education research (factors permits allocation of funds for nutrition research in the absence of specific statutory determining dietary practices, identifi- authorities for reprogramming between In- cation of good nutritional practices, ad stitute appropriations. hoc <educational research committee); In USDA, it is essential that the nutrition and research activities of the Agricultural Re- 4. Diet and nutritional status surveillance search Service (ARS), the Cooperative State (food composition, survey methodology, Research Service (CSRS), the Food and Nutri- measurements of nutritional status, tion Service (FNS), and the Economic Re- analysis of the Health and Nutrition Ex- search Service (ERS) be coordinated through amination Survey (HANES) data, epi- the Secretary of Agriculture." demiological studies). Finally, the establishment of an ad hoc in- The criteria used by the working group in teragency nutrition education research com- mittee is recommended. This committee selecting research areas for greater attention were impact, substantial existing knowledge would: identify and summarize research find- ings related to nutrition education research gap. and researchability. The priority areas and summarize pertinent findings from other chosen reflect the narrowness of these cri- areas of education research, establish priori- teria. The priorities tend toward short-term ties, and develop a plan for conducting nutri- projects that lack long-term commitments tion education research. needed to identify the nutrition elements of major health problems facing adult Ameri- It is doubtful that OSTP through FCCSET cans-the chronic degenerative diseases and would be able to adequately oversee coordi- obesity. nation of nutrition research activities. The staff of the Office is small, and their respon- In the OSTP report several recommenda- sibilities large. With a budget of $50 million tions are made for coordination within and to $117 million per year, nutrition research is among the departments conducting nutrition a very small component of the FY 1977 $3.6 research. First of all, the participants in the billion research budget for health and agri- study requested OSTP "to continue to take a culture. lead role in coordinating and monitoring External reviews by teams of nonagency nutrition research activities." OSTP could scientists may improve the quality of intra- serve as a focal point for interagency plan- mural human nutrition research activities, ning through the Federal Coordinating Coun- but they cannot be expected to improve re- cil on Science, Engineering, and Technology search coordination. This recommendation (FCCSET), chaired by the Director of OSTP. calls for the external reviews to be conducted Secondly, external reviews of the intramural within 12 months of the report's publication grants process in both NIH and USDA with by an unspecified number of multidiscipli- joint participation of Federal agencies in nary teams. Scientists from agencies con- developing requests for proposals and in ducting nutrition research would also par- reviewing research in progress. ticipate. The report suggests that this would To improve coordination and communica- be expected to increase communication and tion within HEW and USDA, the report rec- understanding of Federal programs. Since ommends: the review would only be conducted once and 31 Source: https:/lwww.industrydocuments.ucsf.edu/docs/rinf0227 no provisions are made for improving bad Food consumption patterns and nutri- situations if they are found, it is doubtful that tional status of the general population it would be of any lasting use in improving in- and of special high-risk subgroups with- teragency communication or the quality of in- in the population; evaluation of the nutri- tramural research. tional impacts of various intervention The proposal that Federal agencies jointly strategies and public policies. participate in developing requests for re- The OSTP report established Federal ex- search proposals and in reviewing research penditures for nutrition research for FY 1977 in progress has merit, as does the proposal at $116.6 million. The report stated that no for an ad hoc interagency nutrition education specific funding levels would be recommend- research committee. The ideas could be fur- ther explored by USDA and HEW and pro- ed, but that the report's objectives could be met "at least in part by reallocation of posals for implementation developed. resources from existing programs to the higher priority areas identified." It is highly unlikely that this could be accomplished Definition and Funding without outside intervention. It is also ques- tionable whether such a strategy makes good The scope of human nutrition research, as sense, since the amount of human nutrition defined by the OSTP study, included in- research conducted in this country is so small vestigation of: in comparison to our $3.6 billion in health and Basic physiological and biochemical agriculture research expenditures and our mechanisms for the digestion, absorp- $160.6 billion in health costs. Furthermore: at tion, metabolism, and transport of nutri- least $60 million of the $117 million is basic ents; the role of food ingredients in research on metabolism which underlies human health and performance and in many of the biological and health sciences. A the prevention and treatment of disease; cut in this funding would severely constrain progress in basic research. Nutrient composition of foods; the ef- fects of storage, processing, and packag- ing; and the biological availability of nu- trients in the foods at the time of con- Personnel Resource Requirements sumption; Determinants of dietary practices and The OSTP report does not consider the per- methods for educating the public about sonnel resources needed to fulfill the re- dietary practices; and search priorities contained in the report. FEDERAL HUMAN NUTRITION RESEARCH NEEDS A COORDINATED APPROACH TO ADVANCE NUTRITION KNOWLEDGE: THE GAO REPORT Goals and Priorities Knowledge of dietary nutrients required to promote or maintain growth or well- The General Accounting Office was asked being at various stages and conditions of to identify research gaps and needs in the life: field of human nutrition. The scope of the Information on the composition of the report was restricted to the domestic situa- current U.S. food supply and the extent tion. Gaps identified by GAO included: that nutrients are biologically available; 32 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Evaluation of long-term health conse- Eliminate unnecessary research that quences of the modern diet; and may exist among Federal agencies. Promote Government-wide human nutri- Assessment of the Nation's current tion research planning, coordination, nutritional status in terms of dietary ex- and reporting." cesses and imbalances, as well as defi- ciencies. These recommendations are not suffi- ciently specific to be considered a strategy GAO recommended research along the for organizing nutrition research. Further- following lines to overcome these research more, in an early draft of their report, OSTP gaps: assigned lead and support agency respon- sibilities for specific nutrition research Long-term studies of human subjects areas. This approach was abandoned in the across the full range of both health and final report because of agency objections. A disease; general goal of improved research planning, coordination, and reporting is commendable, Comparative studies of populations of but without specifics probably will not be at- tained. differing geographic, cultural, and genetic backgrounds; Basic investigations of the functions and Definition and Funding interactions of dietary components; GAO identifies the third barrier to prog- Updated and expanded food composition ress in nutrition research as "instability of data; and federally funded extramural research." The report does not make specific recommenda- Improved techniques for assessing long- tions as to how to improve this situation. term toxicological risks. However, it endorses the development of fed- erally funded regional research centers in conjunction with universities and colleges. The priorities set out in the GAO report in- GAO estimates U.S. Government expend- volve the types of research that will probably itures for human nutrition research at $73 provide the most information on the role of million to $117 million annually. It makes no diet in disease. However, work is also needed attempt to define nutrition research or to on how best to convey the research findings analyze agency reports on nutrition research to the public so they can be translated into expenditures. daily life. The GAO report cites "lack of central focus and coordination" and "shortage of nu- Personnel Resource Requirements trition scientists" as two of the three prin- cipal barriers to progress in human nutrition The GAO report highlights the concern of research. To remedy the first of these, the re- the scientific community that there is a short- port recommends that the Director of OSTP age of nutrition research scientists. If this "work with the Federal agencies to further situation exists, it holds significant implica- define the subject areas comprising human tions for the ability of the research commun- nutrition research and make recommenda- ity to absorb research funds should large in- tions to the Director of OMB to: creases be made in the future. Since no accu- rate information exists on the numbers and expertise of nutrition research scientists out- Assign where practicable, each area to side Government laboratories, analysis of re- a lead Federal agency. search capabilities is impossible. 33 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 A COMPREHENSIVE NUTRITION RESEARCH STRATEGY Goals and Priorities points are outlined in table 5. The rationale for the selection of each is contained in the The focus now lacking in Federal nutrition appendix. research could be achieved by defining the Several mechanisms for coordinating Fed- scope of human nutrition research, defining eral nutrition research activities have been general goals for Federal agencies that con- suggested. These include assigning respon- duct such research, and specifying research sibilities for research areas to various agen- priority areas that are in line with the gen- cies, making one agency the lead agency, eral goals. A reorientation of Federal nutri- placing coordination responsibility under a tion research efforts should recognize the third party, assigning coordination respon- changing nature of our food supply by placing sibility to the assistant secretary level, and greater emphasis on the role of diet in concentrating all nutrition research activities preventing chronic diseases. At the same in either USDA or HEW. time, Government programs must continue The first alternative (assigning respon- striving to eliminate hunger and malnutrition sibilities for research areas to various agen- through intervention programs and research. cies) would make USDA and HEW the two lead agencies in human nutrition research. Such a reoriented research strategy re- This approach is similar to the one taken in quires an increased focus on today's complex the Food and Agriculture Act of 1977 in food supply. especially on the effects of proc- which the legitimate roles of both agencies in essed food, food additives and contaminants, nutrition research are recognized. Under and similar problems that concern consum- such a system of joint responsibility, the con- ers, food producers, and health profession- cerns of each agency would have to be de- als. Research in the food sciences would fined to minimize duplication of effort. An ef- enable us to evaluate the adequacy of the fective system of intra-agency cooperation food supply and to develop recommendations would also be necessary. However, since it for needed changes. Such changes might in- may not be possible to clearly separate the clude new processing techniques, fortifica- concerns of nutrition and disease from those tion, reformulation, or selection of alternative of "normal nutrition," some overlap would food items by consumers. probably be inevitable. Broader information and intervention ef- The second alternative assigns one agency forts outside of the health care system are main responsibility for nutrition research. also necessary. The public should know what Since USDA and HEW fund 87 percent of the scientific community has learned about Federal human nutrition research, they are the relationships among lifestyles, food con- the most likely candidates for the lead agency sumption, and health. Developing improved role. There are arguments both for and ways of conveying such knowledge would en- against giving such responsibility to one or courage the public to adopt better eating the other agency. habits and other health-promoting behavior. Currently USDA plays the major role in OTA working group participants felt that carrying out food intervention programs in neither the existing legislation nor the priori- the United States. By giving it primary re- ties suggested in the OSTP and GAO reports sponsibility for funding and coordinating provided the holistic, integrated research nutrition research efforts, the Government's strategy needed to meet current and pro- research and food intervention activities jected diet-related problems in the United might be better coordinated. At the same States. Seven elements of a comprehensive time, Federal research activities might research strategy to define the role of nutri- become more responsive to consumer views tion in the prevention of chronic disease and and needs because of USDA's major involve- to improve management of current nutrition- ment in food and nutrition education pro- related problems were discussed. The seven grams. 34 Source: https://www.industrydocuments.ucsf.edu/docs/rInf0227 Table 5.-A Seven-Point Nutrition Research Strategy The role of diet in the prevention of chronic disease and obesity Major health problems and diet-related risk factors Diet, aging, and disease Methods for preventing obesity Nutrition and mental development The role of nutrition in the treatment of disease and support of therapy Nutritional support of patients with severe disease and injury Other disease states Technology for delivery of nutrients to patients Behavioral and emotional problems Nutrition education and consumer information Factors affecting lifetime eating habits and identification of critical points for education Development and evaluation of nutrition education and communication methods Methods for simplifying consumer information utilization Requirements for essential nutrients Methods for determining nutrient needs Interactions among nutrient requirements based on functional criteria Pharmacologic and toxicologic effects of on nutritions Bioavailability of nutrients in foods Nutritional aspects of food science and food safety Food composition New food processing and handling procedures to maintain nutrient content Better methods of assuring food safety Monitoring nutritional status Methods for improving integration of food consumption and nutritional status surveillance Evaluation of the effects of food and nutrition education programs Nutrition policy and management Food-related interventions Other interventions USDA now coordinates research in the ments for giving HEW, the agency concerned area of food production with the State agri- with health, the lead responsibility for direct- culture experiment stations and other coop- ing nutrition research. However, such re- erating institutions. Some link between the search has not been a main HEW concern in nutritional concerns of consumers and the the past. Disease-prevention research has food production system seems to be essential. generally received much less support than But USDA has traditionally had little respon- specific disease-oriented or curative-oriented sibility or expertise in the area of human research. Moreover, HEW has not been con- health and disease. One of the major needs in cerned with the nutrient requirements of Federal nutrition research activities is a healthy people, food consumption patterns, or reorientation of priorities to stress the role of food composition. In addition, HEW has no nutrition in the prevention of disease. Thus nationwide programs of nutrition and health separating health-related nutrition research education comparable to those developed by from the overall direction of health research USDA. may not be wise. If health-related nutrition research fell exclusively under USDA, poten- tial conflicts might arise. The research might The report by OSTP recommended that the produce recommendations for substantial lead role in nutrition research be given to a shifts in food practices. Such findings and third party which would formulate policy and recommendations could conflict with the coordinate and monitor programs. Under this traditional interests of producer groups. arrangement, various agencies would retain their existing nutrition research respon- Many of the research priorities identified sibilities, but their activities would be over- by OTA as well as other groups involve the seen by the third party. The concept offers relationship of human health to nutritional some positive features. It would focus atten- practices. Therefore, there are strong argu- tion on nutrition while retaining the healthy 35 Source: https://www.industrydocuments.ucsf.edu/docs/rlnf0227 competition among agencies involved in nutri- A pluralistic approach to human nutrition tion research. research, with well-defined agency respon- sibilities for HEW and USDA, appears to be However, such a third-party concept also the best means of coordinating Federal raises several problems. It involves another research efforts. Such an approach could layer of Federal bureaucracy. A third-party produce the kind of creative competition that oversight body might have no real power to would likely enhance human nutrition influence budgets and allocate resources research. It would also result in some within and among agencies, especially since overlapping of efforts, which should be it would lack a political constituency. These minimized by the coordinating process. potential deficiencies would be further mag- The coordinating function might best be nified by inadequate staff and expertise. In carried out by an interagency committee with the end, such a coordinating mechanism would probably only serve as a means to ex- a rotating chairmanship. This arrangement change information, much as the nutrition would be consistent with a pluralistic ap- proach to research. At the same time, it coordinating committee does within NIH and the Current Research Information System would help ensure against any one agency (CRIS) does for USDA. building a "most-favored" relationship with the coordinating committee. Another alternative would give assistant Coordination of Federal nutrition activities secretaries in HEW and USDA responsibility extends beyond specific mechanisms for for coordinating nutrition research policy intra- and inter-agency coordination. It also within and between their respective agen- includes information storage, retrieval, and cies. Lack of high-level commitment to nutri- integration. No uniform system presently ex- tion research has been a problem in the past. ists among the various agencies involved in Placing responsibility for nutrition at the nutrition research. Computerized systems assistant secretary level might create the that permit information integration and re- visibility and commitment needed to effec- trieval need to be explored. At the very least, tively coordinate nutrition research efforts. relevant branches of HEW and USDA should Such an arrangement would require adminis- have a common indexing and data retrieval trative changes within both agencies. At pre- system for this type of information. Since sent, it is unclear if the USDA reorganization federally supported research accounts for that created a Human Nutrition Center the major share of research in the nutrition within SEA will accomplish this goal. and health maintenance areas, integration among these agencies is essential. Integration A final option would consolidate nutrition of nutrition research data is also desirable programs in one agency, either USDA or among the public, private, and voluntary sec- HEW. These activities would include re- tors. search, education, regulation, training, serv- ice delivery, monitoring and surveillance, and food and other intervention programs. Both Definition and Funding USDA and HEW have recently shown interest in this concept in papers entitled USDA's Commitment to Food and Nutrition Policy and As outlined under issue 2, OTA could not The Role of HEW in Human Nutrition: Future perform an analysis of the present Federal Directions. However, the wisdom of such a human nutrition research budget, since pres- consolidation is debatable. Although both ent expenditure estimates are so disparate. agencies currently have a number of nutri- Federal spending on human nutrition tion programs, the expertise involved is quite research should be precisely determined. By specialized. Whether this approach would eliminating the present confusion, Congress solve coordination problems probably will be better able to judge appropriate levels depends on the agency's commitment to the of funding for nutrition research. Congress field of nutrition. could request GAO to audit the human nutri- 36 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 tion research expenditures of Federal agen- facilitate future congressional oversight cies. The GAO audit, based on a constant hearings. definition, should determine total Federal spending for human nutrition research, the number of scientist years involved, and Personnel Resource Requirements Federal expenditures in the seven priority areas set out in this report. If Congress were to choose to implement On the basis of such information, Congress the OTA comprehensive nutrition research would have several options. The first would strategy, there is a clear need to establish be to maintain the status quo in nutrition how many scientists are both presently in- research funding, with possible reallocation volved in, or training for, nutrition research. of some funds to areas not now receiving sup- This census would include a breakdown in port. As a second option, Congress could ap- terms of various research areas, such as propriate, additional funds to specific nutri- Government facilities, universities, medical tion research areas that are not getting facilities, private institutes, and industry. enough support. Finally, Congress could ear- This kind of census would identify where nu- mark a percentage of Hatch funds for human trition research personnel gaps exist and nutrition research. Such an audit, together where greater support is necessary. To fill with a uniform system for reporting human such gaps, expanded Federal support should nutrition research spending, could also be considered. 37 Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONCRESSIONAL OPTIONS vitamins fats minerals carbohydrates proteins Source: https://www.industrydocuments.ucsf.edu/docs/rinf0227 Chapter IV CONGRESSIONAL OPTIONS OTA found that three key issues underlie the basic finding that the Fed- eral Government has failed to adjust the emphasis of its human nutrition research activities to meet the changing health problems of the American people. Alternative approaches of dealing with these issues have been ex- plored. Congress can elect to maintain the status quo, with or without minor shifts, or choose among the strategies and options offered by OTA, the General Accounting Office (GAO), and the Office of Science and Technology Policy (OSTP), (see chapter III). Either alternative has economic, institutional, and health implications. Option 1: Congress Could Choose To Maintain the Overall Status Quo Maintaining the status quo could mean itoring nutrition status, and nutrition policy refraining from any action. In a broader and management. sense, it also could involve minor im- provements in the present system-without If Congress chooses to refrain from any ac- making substantial changes. tion to await the recommendations of the President's Reorganization Project, no ad- A. Congress could refrain from any action, verse effects would be expected. awaiting the recommendations of the President's Reorganization Project. B. Congress could amend the Food and Agri- culture Act of 1977 to clarify the desig- In August of 1977, President Carter nation of lead agency for human nutrition directed the Reorganization Project staff at research. the Office of Management and Budget to thor- oughly review the organization and structure At the present time, the Department of of Federal food and nutrition programs. Food Agriculture (USDA) interprets the Food and and nutrition research is one of the seven ma- Agriculture Act of 1977 to mean that USDA is jor areas under review. A final report to the the lead agency for human nutrition re- President, expected in January of 1979, will search, an interpretation not shared by the include recommendations that may signifi- Department of Health, Education, and Wel- cantly alter the organization, and thus the fare (HEW). If Congress intended USDA to course, of nutrition research activities. have primary responsibility for this research area, the Act will require amendment. Since significant strides have been made in nutrition research, there is no reason to ex- C. Congress could develop nutrition research pect a decline in research productivity if cur- goals and priorities for HEW that comple- rent funding levels are maintained. However, ment the goals and priorities outlined for since several important areas of nutrition USDA in the Food and Agriculture Act of research receive little support at present, 1977. progress in these areas would be slow. These areas include the role of nutrition in the pre- The legislation contains strong language on vention of disease, nutrition education, mon- the relationship of diet to many of the leading 41 Source: https://lwww.industrydocuments.ucsf.edu/docs/rinf0227

What is the page number?

xtpg0227

xtpg0227_p0, xtpg0227_p1, xtpg0227_p2

Page 2, 2

SODIUM AND POTASSIUM Dietary allowances have not been established for sodium and potassium since deficiencies of these nutrients are rarely encountered under usual conditions. Sodium occurs in many foods and is often added to food to improve palatability or for the preservation of foods. In the United States the customary intake has been estimated to be from 3 to 7 gms per person per day. Salt depletion in industrial works, "miners cramps, " was recorded in 1923 (1). The basis of this deficiency, characterized by nausea, vomiting, vertigo, mental apathy, exhaustion, cramps and respiratory failure, is failure to replace the salt losses during excessive sweating while the water losses are replaced. Workers in hot environments should have free access to water. If more than 4 liters of water is consumed, extra salt should be provided, approximately 1 gm per liter of water (2-4). In addition to the losses in sweat, significant sodium depletion may be caused by vomiting or diarrhea or by urinary losses in patients with chronic renal disease. Salt depletion also occurs in adenocortical failure -and some types of central nervous system disease (5). Diets restricted in sodium have been used in a number of conditions, particularly those in which edema formation is a significant problem (5). Since prolonged feeding of high salt diets to experimental animals produces hypertension (6,7), the possibility that sodium intakes may be of etiologic significance in hypertensive disease and atherosclerosis in man is of considerable current interest (8,9). A compilation of the sodium content of foods has been prepared (10). Potassium deficiency is a well defined syndrome occuring as a complication of many pathologic states (11). The symptoms associated with hypokalemia are Source: https://www.industrydocuments.ucsf.edu/docsixtpg0227 SODIUM & POTASSIUM Page 2 over-all muscle weakness poor intestinal tone with distension, cardiac weakness, weakness of the respiratory muscles and their eventual failure (12, 13). Darrow (14) has emphasized the importance of the potassium deficiency syndromes associated with infectious diarrhea in infants and its treatment. Particular care must be used to ensure adequate provision of potassium during prolonged intravenous feeding or when limited food can be taken and artificial preparations must be used. Only limited data upon the potassium requirement of man is available (15). An intake of 0.8 to 1.3 gms per day has been estimated to be near the minimal Usual diets potassium need. A mixed diet in the United States will contain from 2.5 to 4.5 gms of potassium per 3000 calories. A well chosen diet of 1500 calories may contain 2.5 gm but poorly selected low calorie diets might provide 1.5 gms or less. LITERATURE CITED 1. Moss, K. N. Proc. Roy. Soc. London B95, 181, 1923-24. 2. Johnson, R. E. Gastroenterology 1, 832, 1943. 3. Hastings A. B. and Guest Bull. Food and Nutrition Board, NRC, 4, 167, 1944. 4. Council of Pharmacy and Chem. J. A. M. A. 129, 131, 1945. 5. Forbes, G. B. in Mineral Metabolism, vol. 2, Part B, Academic Press, New York 1962, p. 2 6. Soperstein, L. A., W. L. Brandt and D. R. Drury. Proc. Soc. Exp. Biol. & Med. 73, 82, 1950. 7. Meneeley, G. R., C. 0. T. Ball and J. B. Youmans. Ann. Int. Med. 47, 263, 1957. 8. Dahl, L. K. New Eng. J. Med. 258, 1152 and 1205, 1958. 9. Dahl, L. K. J. Exp. Med. 112, 635, 1960. Source: https://www.industrydocuments.ucsf.edu/docs/xtpg0227 SODIUM & POTASSIUM Page 3 10. National Acad. of Sciences. National Res. Council Publication #325, Washington, 1954. 11. Wilde, W. S. in Mineral Metabolism, vol. 2, Part B, (c. L. Comar and F. Bronner, eds. ) Academic Press, New York, 1962. 12. Elkington, J. R. and Danowski, T. S. The Body Fluids, Williams and Wilkens, Baltimore, 1955. 13. Moore, F. D. and M. R. Ball The Metabolic Response to Surgery, C. C. Thomas Springfield, Illinois, 1952. 14. Darrow, D. C., et al, Pediatrics 3, 129, 1949. 15. Bean, W. B. and R. Hodges. Proc. Central Soc. Clin. Res. 30, 9, 1957. 6/21/63 Source: https://www.industrydocuments.ucsf.edu/docs/xtpg0227

What is the table number?

xtkg0227

xtkg0227_p0, xtkg0227_p1, xtkg0227_p2, xtkg0227_p3, xtkg0227_p4, xtkg0227_p5, xtkg0227_p6, xtkg0227_p7, xtkg0227_p8, xtkg0227_p9

1, Table 1

Department of the Army Office of the Surgeon General Contract No. DA-49-007-MD 544 ON THE NUTRITIVE VALUE OF THE MAJOR NUTRIENTS OF IRRADIATED FOODS and APPRAISAL OF THE TOXICITY OF IRRADIATED FOODS V. Chalam Metta M. S. Mameesh P. B. Rama Rao Connor Johnson Division of Animal Nutrition University of Illinois Urbana, Illinois Progress Report No. 18 for period March 16, 1960-Sept. 1, 1960 This is not a final report. Conclusions stated are subject to change on the basis of additional evidence. Information contained herein is not to be reprinted or published without written permission from Research and Development Division, Office of the Surgeon General, Department of the Army, Washington 25, D. C. J-1 Source: https://www.industrydocuments.ucsf.edu/docsixtkg0227 -2- Table of Contents Page Summary 3 Effect of feeding vitamin K-deficient diets to female rats. 4 Reproduction in the irradiated beef-fed female rats 4 Synthetic diets and vitamin K nutrition of the female rats. 4 Reproduction by the female rat on synthetic vitamin K-low diet. 4 Relationship of the female sex hormone and vitamin K in the rat 5 Vitamin K deficiency in the male and female chick 5 Vitamin K content of casein chick assay 6 Effect of different diets on the plasma prothrombin time of rats. 6 Studies on solvent-extracted beef (irradiated and non-irradiated) 6 Studies in progress 7 Papers published and personnel. 7 Tables. 8 J-2 Source: https://www.industrydocuments.ucsf.edu/docsixtkg0227 -3- Summary 1. Feeding of irradiated beef or vitamin K-low synthetic diets results in hypoprothrombinemia and hemorrhagic deaths of growing male rats. The female rat is markedly resistant to K deficiency. The possibility of estrogen involvement in the role of K in some unknown manner is worthy of further study. 2. Normal reproduction was obtained in female rats maintained on synthetic K-low diets or irradiated beef diets and mated with normal males. The survival of the pups was, however, poor. None of them died of hemorrhage, and good survival has been obtained on rats fed irradiated beef diets with supplements of K only when they are maintained in an isolated room free from respiratory disease. 3. Although it was found that the female rat is markedly resistant to vitamin K deficiency, our work with chicks suggests that both male and female chicks are equally succeptible to vitamin K deficiency. 4. Bioassay of the chick for vitamin K indicated that there is a difference in content of vitamin K between Labco casein (approximately 30 Y K/100 gm) and Nutritional Biochemicals Corporation casein (less than 15 / 1/100 gm). Rats main- tained on Labco casein showed normal prothrombin times, whereas those on NBC showed elevated prothrombin times. 5. When beef (irradiated and non-irradiated), after extraction by alcohol and ether, is fed to male rats, hypoprothrombinemia results. The primary cause of hemorrhagic syndrome in the male rat fed irradiated beef is the destruction of K in beef by irradiation. J-3 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 -4- Effect of feeding vitamin K-deficient diets to female rats. The resistance of the female rat, as compared to the male rat, to vitamin K deficiency on irradiated beef and synthetic K-free diets has been repeatedly demonstrated in our laboratory. Several hypotheses have been suggested to explain this difference. One is that the female rat may practice coprophagy to a greater extent and thus obtain more K from the feces. It may also be that the male rat, because of his greater food intake and growth, may develop the deficiency more rapidly than the female. The third possibility is that there is an actual sex difference under hormonal control. In report 17, data have been presented (table 2 of same report) to show that the greater food intake, and hence greater rate of body weight gain of the male rat, does not result in this specific difference with respect to K deficiency of the female rat. This was demonstrated by suitable paired-feeding of the irradiated beef. Also, prevention of coprophagy did not result in hypoprothrombinemia of the female rats over a 36-day period. Reproduction in the irradiated-beef-fed female Three female rats which had been housed in tubular cages to prevent coprophagy were continued on the irradiated beef diet (ad libitum) for 80 days. Then they were transferred to regular screen-bottom cages and mated with normal male rats. They conceived and gave birth to 11, 10 and 8 pups, respectively. Although 15 of these pups died within 15 days, there was no evidence of hemorrhage in them. The fact that essentially normal reproduction occurred in female rats fed a diet on which all males had died of vitamin K deficiency further emphasizes the marked resistance of the female to this vitamin deficiency. Synthetic diets and vitamin K nutrition of the female rat An experiment was conducted to study the vitamin K requirement of the growing female rat. The basal synthetic diet containing 25% NBC casein (report 17) was used with and without supplementation of 1% sulphathalidine, Data presented in the earlier report (table 2, report 17) show that 2 out of 7 female rats prevented from practicing coprophagy, and consuming ad libitum this K-low synthetic diet, died of hemorrhage after 60 days. When coprophagy was not prevented they main- tained normal prothrombin levels. Addition of sulphathalidine at a 1% level in the diet resulted in elevated plasma prothrombin time (mean value for 7 female rats, 33.5 seconds) even when coprophagy was allowed, presumably due to the effect of sulphathalidine on the availability of intestinally synthesized vitamin K. Thus the marked resistance of the female rat to K deficiency, in comparison to the susceptibility of the male rat, is not affected by the prevention of coprophagy, nor due to food intake or slower rate of growth, but is apparently due to a sex difference presumably under hormonal control. Reproduction by the female rat on synthetic K-low diet. In continuation of the above experiment, 5 female rats maintained on the K-low diet in tubular cages for 94 days to prevent coprophagy were transferred to regular cages and mated with control male rats which had been raised on Purina chow to study again the effect of dietary K deficiency on reproduction. All females conceived and gave birth to live pups. Most of them died within 5 days, although none showed any hemorrhagic symptoms. This poor survival of the pups was also obtained when female rats had been maintained in tubular cages on irradiated beef diets. J-4 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 -5- In our earlier studies on longevity and reproduction performance of female rats maintained on irradiated beef diets (Metta et al., $59) supplemented with 0.1 Y K3 (menadione) per gram dry diet, there was practically no survival of pups following the first mating and about 35% survival following the second mating with stock male rats. However, when the rats were maintained in an isolation room free from respiratory disease, 66-74% survival of the pups was obtained. Relationship of the female sex hormone and vitamin K in the rat The very low vitamin K needs of the female rat for growth and reproduction suggested that estrogens may be involved in some unknown manner in vitamin K function and metabolism in the body. Since a well-known function of K is in the production of prothrombin from the polygonal cells of the liver, a pre- liminary study was made to determine if estrogen was involved in the production of prothrombin. Six male weanling rats of the Sprague-Dawley strain were housed in tubular cages and fed ad libitum a K-free diet of the following percentage composition: sucrose, 66.5; Drackett soya protein, 20; DL methionine, 0.5; vitaminized cerelose (without K), 5; glycerol, 2; methyl linoleate (60% potency) 2; œ-tocopheryl succinate, 0.012; vitamin A, 1000 I.U.: vitamin Da, 100 units; and minerals 446, 4. On the 16th day of feeding one rat showed symptoms of subcutaneous bleeding. On the 18th day the rats were taken off the experiment. One rat was injected intramuscularly with 20 Y° of K3 in corn oil; 3 rats were injected with 1 mg each of estrodiol in 1/2 ml corn oil; and 2 other rats served as controls. After 24 hours, plasma prothrombin times were determined according to Quick (1938)¹ Results as follows: Intramuscular No. of rats Plasma prothrombin injection time, seconds 20 Y K3 injected 1 17 1 mg estrodiol 3 15,14,60+ None 2 17, 27 This preliminary trial indicates only the necessity of repeating this experiment with at least 8-10 rats in each group, since the deficiency is not uniformly produced in all rats. Vitamin K deficiency in the male and female chick We have routinely used female chicks for the bioassay of vitamin K. Since a marked resistance to K deficiency is shown by the female rat, a similar possibility needed to be investigated in the chick. Fifty male and 50 female one-day-old chicks were fed a vitamin K-free diet for 15 days. At 5, 10 and 15 days, respectively, 15 chicks of each group were sacrificed and the plasma prothrombin times determined. The clotting time increased progressively, but no significant differences were obtained with respect to the prothrombin times between the male and the female chicks at any of the specified intervals. 1 Quick, A. J. 1938 The nature of the bleeding in jaundice. J. Am. Med. Assoc. 110: 1658. U-5 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 -6- Vitamin K content of casein as determined by chick assay. Dietary need for vitamin K by the rat was not considered essential for a long time. Reports by Barnes and Fiala (1959)2 and by Mameesh and Johnson (1959) have demonstrated the need for dietary K on certain purified diets. We have routinely used the Drackett soya protein diet for producing K deficiency in the rat as well as in the chick. Also, casein (Nutritional Biochemicals Corporation) has been successfully used in place of the soya protein. When the SO=called "vitamin-free" casein (Labco) was incorporated into the rat diet, it did not result in K deficiency. The purpose of this experiment was to determine the vitamin K activity in these two different brands of casein by the chick assay. Fifty one-day-old female chicks were maintained on the K-free soya protein diet (report 17) for 19 days. They were then divided into five groups. One of these groups was fed a diet containing 35% NBC casein; a second, 35% Labco casein; and the remaining three groups, a basal soya protein diet with graded supplements of vitamin K (table 1). The plasma prothrombin times were then determined. Data in table 1 show that a supplementation of 0.1 r/gm diet to the basal soya protein diet is necessary to maintain normal prothrombin time (25 seconds) in the chick. The mean prothrombin time of chicks on the Labco casein is 33 seconds, and the difference is significant at about 3% level. Calculation shows that 100 gms of Labco casein has about 30 Y of K. The mean prothrombin time of chicks on the NBC casein diet is 46 seconds and significantly higher than that on the basal soya diet supplemented with .1 Y° K/gm diet (25 seconds P < . 01). NBC casein provides less than half as much vitamin K as Labco casein. Effect of different diets on the plasma prothrombin time of rats For a period of 4 weeks, 50 male rats were fed beef, Drackett soya protein and Labco casein diets ad libitum, as detailed in table 2. At the end of the experiment the plasma prothrombin times were determined. Results in table 2 show that an oral supplement of 2 Y K3/rat/day is needed to maintain normal pro- thrombin times in rats fed the soya protein diet. The prothrombin times of rats fed Labco casein and non-irradiated beef diets were in the normal range (13=35). Hypothrombinemie was noted in rats on the irradiated beef (prothrombin time 49-72 seconds) and oral supplementation of 2 Y K3/rat/day maintained the prothrombin time in the range 19-38 seconds. These findings corroborate the results obtained on the K content of casein by the chick assay. Studies on solvent-extracted beef (irradiated and non-irradiated) Bioassay of irradiated and non-irradiated beef using the chick has shown that irradiation destroys, or renders unavailable, vitamin K in the beef (report 17). The purpose of this experiment was to determine the effect of feeding rats irradiated and non-irradiated beef (after exhaustive extraction with alcohol and ether to remove the lipid material) on the plasma prothrombin levels. The basal composition of the diet used is given in table 3. In table 4 data are given on the prothrombin time of rats fed these diets with and without K supplementation. It is clearly seen that even non-irradiated beef (Bos lipid-free) is a poor source of vitamin K 2 Barnes, Richard Ho, and Grace Fiala 1959 Effects of the prevention of coprophagy in the rat. VI. Vitamin K. J. Nutrition, 68, 603. J-6 Source: https://wwww.industrydocuments.ucsf.edu/docs/xtkg0227 -1- High prothrombin times within the range 76-120 are obtained. Oral supplementation of 2 Y K1/rat/day maintains the prothrombin times in the range 15-30 on both irradiated and non-irradiated beef diets. This confirms our earlier observation that the principal cause of the hemorrhagic syndrome obtained on irradiated beef diets is the destruction of vitamin K in beef by irradiation and indicates the absence of any vitamin K antagonist produced in beef by irradiation. Studies in progress Further studies are in progress on: 1) the very marked sex difference with respect to vitamin K deficiency, 2) development of a sensitive chemical assay for vitamin K1 and analogues; and 3) absorption of dietary and intestinally synthesized vitamin K. Papers published Johnson, B. Connor, M. S. Mameesh, V. C. Metta, and P. B. Rama Rao. Vitamin K nutrition and irradiation sterilization. Fed. Proceedings (in press). Mameesh, M. S., and B. Connor Johnson. The absence of hemorrhagic compounds in irradiated beef. J. Nutrition, 71, 122, 1960. Metta, V. C., and B. Connor Johnson. Effect of feeding vitamin K-deficient diets to female rats. J. Nutrition (in press). Rama Rao, P. B., V. C. Metta, and B. Connor Johnson. The amino acid composition and nutritive value of proteins. II. Amino acid mixtures as a dietary source of nitrogen for growth. Jo Nutrition, 71, 327, 1960. Rama Rao, P. V. C. Metta, H. W. Norton, and B. Connor Johnson. The amino acid composition and nutritive value of proteins. III. The total protein and the non- essential amino nitrogen requirement. J. Nutrition, 71, 361, 1960. Mameesh, M. S., and V. C. Metta. Irradiation sterilization in vitamin K nutrition. Fifth International Congress on Nutrition, Sept. g 1960. Paper No. 260, p. 57. Rama Rao, P. Bo, H. W. Norton, and B. Connor Johnson. The amino acid composition and nutritive value of proteins. IV. Methionine, cystine, phenylalanine and tyrosine requirements. J. Nutrition (in press). Personnel Chief Investigator: Dr. B. Connor Johnson Personnel working on the project during the period of this report: Dr. V. Chalam Metta, Research Assistant Professor Dr. M. S. Mameesh, Research Associate Dr. P. B. Rama Rao, Research Associate Mr. James Bergan, (Half-time) Junior Laboratory Attendant Mr. Louis Nash, Junior Laboratory Attendant Plus student help. TCM:MSM:PBR:BCJ:rmd J-7 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 Table 1 Effect of menadione and casein diets on the prothrombin time of K-deficient chicks1 Diet Supplement Prothrombin time2 sec. Soya protein - 200 + Soya protein 0.01 K33 T/gm diet 146 + 3.35 Soya protein 0.1 K3 r/gm diet 25 1.7 Casein (Labco) 4 - 33 2.9 Casein (NBC) - 46 + 4.0 1 Chicks were maintained on the soya protein (K-deficient) diet for 19 days. They were then grouped and fed the diets indicated for 4 days and the plasma prothrombin time of chicks determined. 2 Average of 6 chicks/group. 3 2-methyl-1,4-naphthoquinone. The protein level in all the diets was 35% (N X 6.25). Mean standard deviation of the mean. J-8 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 Table 2 Hemorrhagic deaths and plasma prothrombin times of rats fed irradiated beef, Drackett soya protein and vitamin-free casein diets 1 Oral Plasma pro- No. of Diet supplement thrombin hemorrhagic time, seconds deaths Drackett soya protein - 120 + 4 " " " 1 Y K3²/rat/day 75 (33-120) 1 11 " " 2 Y K3/rat/day 21 (17-30) - Labco (vit.-free casein) - 21 (14-35) - Beef O - 15 (13-19) - Beef 6 - 54 (49-72) 1 Beef 6 1 Y K3/rat/day 38 (21-65) 1 Beef 6 2 Y K3/rat/day 28 (19-38) - 1 6 male rats per group. 2 2-methyl-1,4-naphthoquinone. Rats fed these diets for 4 weeks. J-9 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 Table 3 Ingredient gm Beef¹ 15 Vitaminized glucose² 15 Sucrose 10 Triolein 5 Cod-liver oil 1.5 Wheat-germ oil 0.5 Mineral mix 446 4.0 Starch 49.0 1 Beef (irradiated 5.58 megarad, or non- irradiated) was freeze-dried and extracted for 24 hours with alcohol and for 24 hours with ether. 2 Without K. d-10 Source: https://www.industrydocuments.ucsf.edu/docsixtkg0227

What is the title of the first column of the table?

xtkg0227

xtkg0227_p0, xtkg0227_p1, xtkg0227_p2, xtkg0227_p3, xtkg0227_p4, xtkg0227_p5, xtkg0227_p6, xtkg0227_p7, xtkg0227_p8, xtkg0227_p9

Diet

Department of the Army Office of the Surgeon General Contract No. DA-49-007-MD 544 ON THE NUTRITIVE VALUE OF THE MAJOR NUTRIENTS OF IRRADIATED FOODS and APPRAISAL OF THE TOXICITY OF IRRADIATED FOODS V. Chalam Metta M. S. Mameesh P. B. Rama Rao Connor Johnson Division of Animal Nutrition University of Illinois Urbana, Illinois Progress Report No. 18 for period March 16, 1960-Sept. 1, 1960 This is not a final report. Conclusions stated are subject to change on the basis of additional evidence. Information contained herein is not to be reprinted or published without written permission from Research and Development Division, Office of the Surgeon General, Department of the Army, Washington 25, D. C. J-1 Source: https://www.industrydocuments.ucsf.edu/docsixtkg0227 -2- Table of Contents Page Summary 3 Effect of feeding vitamin K-deficient diets to female rats. 4 Reproduction in the irradiated beef-fed female rats 4 Synthetic diets and vitamin K nutrition of the female rats. 4 Reproduction by the female rat on synthetic vitamin K-low diet. 4 Relationship of the female sex hormone and vitamin K in the rat 5 Vitamin K deficiency in the male and female chick 5 Vitamin K content of casein chick assay 6 Effect of different diets on the plasma prothrombin time of rats. 6 Studies on solvent-extracted beef (irradiated and non-irradiated) 6 Studies in progress 7 Papers published and personnel. 7 Tables. 8 J-2 Source: https://www.industrydocuments.ucsf.edu/docsixtkg0227 -3- Summary 1. Feeding of irradiated beef or vitamin K-low synthetic diets results in hypoprothrombinemia and hemorrhagic deaths of growing male rats. The female rat is markedly resistant to K deficiency. The possibility of estrogen involvement in the role of K in some unknown manner is worthy of further study. 2. Normal reproduction was obtained in female rats maintained on synthetic K-low diets or irradiated beef diets and mated with normal males. The survival of the pups was, however, poor. None of them died of hemorrhage, and good survival has been obtained on rats fed irradiated beef diets with supplements of K only when they are maintained in an isolated room free from respiratory disease. 3. Although it was found that the female rat is markedly resistant to vitamin K deficiency, our work with chicks suggests that both male and female chicks are equally succeptible to vitamin K deficiency. 4. Bioassay of the chick for vitamin K indicated that there is a difference in content of vitamin K between Labco casein (approximately 30 Y K/100 gm) and Nutritional Biochemicals Corporation casein (less than 15 / 1/100 gm). Rats main- tained on Labco casein showed normal prothrombin times, whereas those on NBC showed elevated prothrombin times. 5. When beef (irradiated and non-irradiated), after extraction by alcohol and ether, is fed to male rats, hypoprothrombinemia results. The primary cause of hemorrhagic syndrome in the male rat fed irradiated beef is the destruction of K in beef by irradiation. J-3 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 -4- Effect of feeding vitamin K-deficient diets to female rats. The resistance of the female rat, as compared to the male rat, to vitamin K deficiency on irradiated beef and synthetic K-free diets has been repeatedly demonstrated in our laboratory. Several hypotheses have been suggested to explain this difference. One is that the female rat may practice coprophagy to a greater extent and thus obtain more K from the feces. It may also be that the male rat, because of his greater food intake and growth, may develop the deficiency more rapidly than the female. The third possibility is that there is an actual sex difference under hormonal control. In report 17, data have been presented (table 2 of same report) to show that the greater food intake, and hence greater rate of body weight gain of the male rat, does not result in this specific difference with respect to K deficiency of the female rat. This was demonstrated by suitable paired-feeding of the irradiated beef. Also, prevention of coprophagy did not result in hypoprothrombinemia of the female rats over a 36-day period. Reproduction in the irradiated-beef-fed female Three female rats which had been housed in tubular cages to prevent coprophagy were continued on the irradiated beef diet (ad libitum) for 80 days. Then they were transferred to regular screen-bottom cages and mated with normal male rats. They conceived and gave birth to 11, 10 and 8 pups, respectively. Although 15 of these pups died within 15 days, there was no evidence of hemorrhage in them. The fact that essentially normal reproduction occurred in female rats fed a diet on which all males had died of vitamin K deficiency further emphasizes the marked resistance of the female to this vitamin deficiency. Synthetic diets and vitamin K nutrition of the female rat An experiment was conducted to study the vitamin K requirement of the growing female rat. The basal synthetic diet containing 25% NBC casein (report 17) was used with and without supplementation of 1% sulphathalidine, Data presented in the earlier report (table 2, report 17) show that 2 out of 7 female rats prevented from practicing coprophagy, and consuming ad libitum this K-low synthetic diet, died of hemorrhage after 60 days. When coprophagy was not prevented they main- tained normal prothrombin levels. Addition of sulphathalidine at a 1% level in the diet resulted in elevated plasma prothrombin time (mean value for 7 female rats, 33.5 seconds) even when coprophagy was allowed, presumably due to the effect of sulphathalidine on the availability of intestinally synthesized vitamin K. Thus the marked resistance of the female rat to K deficiency, in comparison to the susceptibility of the male rat, is not affected by the prevention of coprophagy, nor due to food intake or slower rate of growth, but is apparently due to a sex difference presumably under hormonal control. Reproduction by the female rat on synthetic K-low diet. In continuation of the above experiment, 5 female rats maintained on the K-low diet in tubular cages for 94 days to prevent coprophagy were transferred to regular cages and mated with control male rats which had been raised on Purina chow to study again the effect of dietary K deficiency on reproduction. All females conceived and gave birth to live pups. Most of them died within 5 days, although none showed any hemorrhagic symptoms. This poor survival of the pups was also obtained when female rats had been maintained in tubular cages on irradiated beef diets. J-4 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 -5- In our earlier studies on longevity and reproduction performance of female rats maintained on irradiated beef diets (Metta et al., $59) supplemented with 0.1 Y K3 (menadione) per gram dry diet, there was practically no survival of pups following the first mating and about 35% survival following the second mating with stock male rats. However, when the rats were maintained in an isolation room free from respiratory disease, 66-74% survival of the pups was obtained. Relationship of the female sex hormone and vitamin K in the rat The very low vitamin K needs of the female rat for growth and reproduction suggested that estrogens may be involved in some unknown manner in vitamin K function and metabolism in the body. Since a well-known function of K is in the production of prothrombin from the polygonal cells of the liver, a pre- liminary study was made to determine if estrogen was involved in the production of prothrombin. Six male weanling rats of the Sprague-Dawley strain were housed in tubular cages and fed ad libitum a K-free diet of the following percentage composition: sucrose, 66.5; Drackett soya protein, 20; DL methionine, 0.5; vitaminized cerelose (without K), 5; glycerol, 2; methyl linoleate (60% potency) 2; œ-tocopheryl succinate, 0.012; vitamin A, 1000 I.U.: vitamin Da, 100 units; and minerals 446, 4. On the 16th day of feeding one rat showed symptoms of subcutaneous bleeding. On the 18th day the rats were taken off the experiment. One rat was injected intramuscularly with 20 Y° of K3 in corn oil; 3 rats were injected with 1 mg each of estrodiol in 1/2 ml corn oil; and 2 other rats served as controls. After 24 hours, plasma prothrombin times were determined according to Quick (1938)¹ Results as follows: Intramuscular No. of rats Plasma prothrombin injection time, seconds 20 Y K3 injected 1 17 1 mg estrodiol 3 15,14,60+ None 2 17, 27 This preliminary trial indicates only the necessity of repeating this experiment with at least 8-10 rats in each group, since the deficiency is not uniformly produced in all rats. Vitamin K deficiency in the male and female chick We have routinely used female chicks for the bioassay of vitamin K. Since a marked resistance to K deficiency is shown by the female rat, a similar possibility needed to be investigated in the chick. Fifty male and 50 female one-day-old chicks were fed a vitamin K-free diet for 15 days. At 5, 10 and 15 days, respectively, 15 chicks of each group were sacrificed and the plasma prothrombin times determined. The clotting time increased progressively, but no significant differences were obtained with respect to the prothrombin times between the male and the female chicks at any of the specified intervals. 1 Quick, A. J. 1938 The nature of the bleeding in jaundice. J. Am. Med. Assoc. 110: 1658. U-5 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 -6- Vitamin K content of casein as determined by chick assay. Dietary need for vitamin K by the rat was not considered essential for a long time. Reports by Barnes and Fiala (1959)2 and by Mameesh and Johnson (1959) have demonstrated the need for dietary K on certain purified diets. We have routinely used the Drackett soya protein diet for producing K deficiency in the rat as well as in the chick. Also, casein (Nutritional Biochemicals Corporation) has been successfully used in place of the soya protein. When the SO=called "vitamin-free" casein (Labco) was incorporated into the rat diet, it did not result in K deficiency. The purpose of this experiment was to determine the vitamin K activity in these two different brands of casein by the chick assay. Fifty one-day-old female chicks were maintained on the K-free soya protein diet (report 17) for 19 days. They were then divided into five groups. One of these groups was fed a diet containing 35% NBC casein; a second, 35% Labco casein; and the remaining three groups, a basal soya protein diet with graded supplements of vitamin K (table 1). The plasma prothrombin times were then determined. Data in table 1 show that a supplementation of 0.1 r/gm diet to the basal soya protein diet is necessary to maintain normal prothrombin time (25 seconds) in the chick. The mean prothrombin time of chicks on the Labco casein is 33 seconds, and the difference is significant at about 3% level. Calculation shows that 100 gms of Labco casein has about 30 Y of K. The mean prothrombin time of chicks on the NBC casein diet is 46 seconds and significantly higher than that on the basal soya diet supplemented with .1 Y° K/gm diet (25 seconds P < . 01). NBC casein provides less than half as much vitamin K as Labco casein. Effect of different diets on the plasma prothrombin time of rats For a period of 4 weeks, 50 male rats were fed beef, Drackett soya protein and Labco casein diets ad libitum, as detailed in table 2. At the end of the experiment the plasma prothrombin times were determined. Results in table 2 show that an oral supplement of 2 Y K3/rat/day is needed to maintain normal pro- thrombin times in rats fed the soya protein diet. The prothrombin times of rats fed Labco casein and non-irradiated beef diets were in the normal range (13=35). Hypothrombinemie was noted in rats on the irradiated beef (prothrombin time 49-72 seconds) and oral supplementation of 2 Y K3/rat/day maintained the prothrombin time in the range 19-38 seconds. These findings corroborate the results obtained on the K content of casein by the chick assay. Studies on solvent-extracted beef (irradiated and non-irradiated) Bioassay of irradiated and non-irradiated beef using the chick has shown that irradiation destroys, or renders unavailable, vitamin K in the beef (report 17). The purpose of this experiment was to determine the effect of feeding rats irradiated and non-irradiated beef (after exhaustive extraction with alcohol and ether to remove the lipid material) on the plasma prothrombin levels. The basal composition of the diet used is given in table 3. In table 4 data are given on the prothrombin time of rats fed these diets with and without K supplementation. It is clearly seen that even non-irradiated beef (Bos lipid-free) is a poor source of vitamin K 2 Barnes, Richard Ho, and Grace Fiala 1959 Effects of the prevention of coprophagy in the rat. VI. Vitamin K. J. Nutrition, 68, 603. J-6 Source: https://wwww.industrydocuments.ucsf.edu/docs/xtkg0227 -1- High prothrombin times within the range 76-120 are obtained. Oral supplementation of 2 Y K1/rat/day maintains the prothrombin times in the range 15-30 on both irradiated and non-irradiated beef diets. This confirms our earlier observation that the principal cause of the hemorrhagic syndrome obtained on irradiated beef diets is the destruction of vitamin K in beef by irradiation and indicates the absence of any vitamin K antagonist produced in beef by irradiation. Studies in progress Further studies are in progress on: 1) the very marked sex difference with respect to vitamin K deficiency, 2) development of a sensitive chemical assay for vitamin K1 and analogues; and 3) absorption of dietary and intestinally synthesized vitamin K. Papers published Johnson, B. Connor, M. S. Mameesh, V. C. Metta, and P. B. Rama Rao. Vitamin K nutrition and irradiation sterilization. Fed. Proceedings (in press). Mameesh, M. S., and B. Connor Johnson. The absence of hemorrhagic compounds in irradiated beef. J. Nutrition, 71, 122, 1960. Metta, V. C., and B. Connor Johnson. Effect of feeding vitamin K-deficient diets to female rats. J. Nutrition (in press). Rama Rao, P. B., V. C. Metta, and B. Connor Johnson. The amino acid composition and nutritive value of proteins. II. Amino acid mixtures as a dietary source of nitrogen for growth. Jo Nutrition, 71, 327, 1960. Rama Rao, P. V. C. Metta, H. W. Norton, and B. Connor Johnson. The amino acid composition and nutritive value of proteins. III. The total protein and the non- essential amino nitrogen requirement. J. Nutrition, 71, 361, 1960. Mameesh, M. S., and V. C. Metta. Irradiation sterilization in vitamin K nutrition. Fifth International Congress on Nutrition, Sept. g 1960. Paper No. 260, p. 57. Rama Rao, P. Bo, H. W. Norton, and B. Connor Johnson. The amino acid composition and nutritive value of proteins. IV. Methionine, cystine, phenylalanine and tyrosine requirements. J. Nutrition (in press). Personnel Chief Investigator: Dr. B. Connor Johnson Personnel working on the project during the period of this report: Dr. V. Chalam Metta, Research Assistant Professor Dr. M. S. Mameesh, Research Associate Dr. P. B. Rama Rao, Research Associate Mr. James Bergan, (Half-time) Junior Laboratory Attendant Mr. Louis Nash, Junior Laboratory Attendant Plus student help. TCM:MSM:PBR:BCJ:rmd J-7 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 Table 1 Effect of menadione and casein diets on the prothrombin time of K-deficient chicks1 Diet Supplement Prothrombin time2 sec. Soya protein - 200 + Soya protein 0.01 K33 T/gm diet 146 + 3.35 Soya protein 0.1 K3 r/gm diet 25 1.7 Casein (Labco) 4 - 33 2.9 Casein (NBC) - 46 + 4.0 1 Chicks were maintained on the soya protein (K-deficient) diet for 19 days. They were then grouped and fed the diets indicated for 4 days and the plasma prothrombin time of chicks determined. 2 Average of 6 chicks/group. 3 2-methyl-1,4-naphthoquinone. The protein level in all the diets was 35% (N X 6.25). Mean standard deviation of the mean. J-8 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 Table 2 Hemorrhagic deaths and plasma prothrombin times of rats fed irradiated beef, Drackett soya protein and vitamin-free casein diets 1 Oral Plasma pro- No. of Diet supplement thrombin hemorrhagic time, seconds deaths Drackett soya protein - 120 + 4 " " " 1 Y K3²/rat/day 75 (33-120) 1 11 " " 2 Y K3/rat/day 21 (17-30) - Labco (vit.-free casein) - 21 (14-35) - Beef O - 15 (13-19) - Beef 6 - 54 (49-72) 1 Beef 6 1 Y K3/rat/day 38 (21-65) 1 Beef 6 2 Y K3/rat/day 28 (19-38) - 1 6 male rats per group. 2 2-methyl-1,4-naphthoquinone. Rats fed these diets for 4 weeks. J-9 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 Table 3 Ingredient gm Beef¹ 15 Vitaminized glucose² 15 Sucrose 10 Triolein 5 Cod-liver oil 1.5 Wheat-germ oil 0.5 Mineral mix 446 4.0 Starch 49.0 1 Beef (irradiated 5.58 megarad, or non- irradiated) was freeze-dried and extracted for 24 hours with alcohol and for 24 hours with ether. 2 Without K. d-10 Source: https://www.industrydocuments.ucsf.edu/docsixtkg0227

What is the title of the second column of the table?

xtkg0227

xtkg0227_p0, xtkg0227_p1, xtkg0227_p2, xtkg0227_p3, xtkg0227_p4, xtkg0227_p5, xtkg0227_p6, xtkg0227_p7, xtkg0227_p8, xtkg0227_p9

Supplement

Department of the Army Office of the Surgeon General Contract No. DA-49-007-MD 544 ON THE NUTRITIVE VALUE OF THE MAJOR NUTRIENTS OF IRRADIATED FOODS and APPRAISAL OF THE TOXICITY OF IRRADIATED FOODS V. Chalam Metta M. S. Mameesh P. B. Rama Rao Connor Johnson Division of Animal Nutrition University of Illinois Urbana, Illinois Progress Report No. 18 for period March 16, 1960-Sept. 1, 1960 This is not a final report. Conclusions stated are subject to change on the basis of additional evidence. Information contained herein is not to be reprinted or published without written permission from Research and Development Division, Office of the Surgeon General, Department of the Army, Washington 25, D. C. J-1 Source: https://www.industrydocuments.ucsf.edu/docsixtkg0227 -2- Table of Contents Page Summary 3 Effect of feeding vitamin K-deficient diets to female rats. 4 Reproduction in the irradiated beef-fed female rats 4 Synthetic diets and vitamin K nutrition of the female rats. 4 Reproduction by the female rat on synthetic vitamin K-low diet. 4 Relationship of the female sex hormone and vitamin K in the rat 5 Vitamin K deficiency in the male and female chick 5 Vitamin K content of casein chick assay 6 Effect of different diets on the plasma prothrombin time of rats. 6 Studies on solvent-extracted beef (irradiated and non-irradiated) 6 Studies in progress 7 Papers published and personnel. 7 Tables. 8 J-2 Source: https://www.industrydocuments.ucsf.edu/docsixtkg0227 -3- Summary 1. Feeding of irradiated beef or vitamin K-low synthetic diets results in hypoprothrombinemia and hemorrhagic deaths of growing male rats. The female rat is markedly resistant to K deficiency. The possibility of estrogen involvement in the role of K in some unknown manner is worthy of further study. 2. Normal reproduction was obtained in female rats maintained on synthetic K-low diets or irradiated beef diets and mated with normal males. The survival of the pups was, however, poor. None of them died of hemorrhage, and good survival has been obtained on rats fed irradiated beef diets with supplements of K only when they are maintained in an isolated room free from respiratory disease. 3. Although it was found that the female rat is markedly resistant to vitamin K deficiency, our work with chicks suggests that both male and female chicks are equally succeptible to vitamin K deficiency. 4. Bioassay of the chick for vitamin K indicated that there is a difference in content of vitamin K between Labco casein (approximately 30 Y K/100 gm) and Nutritional Biochemicals Corporation casein (less than 15 / 1/100 gm). Rats main- tained on Labco casein showed normal prothrombin times, whereas those on NBC showed elevated prothrombin times. 5. When beef (irradiated and non-irradiated), after extraction by alcohol and ether, is fed to male rats, hypoprothrombinemia results. The primary cause of hemorrhagic syndrome in the male rat fed irradiated beef is the destruction of K in beef by irradiation. J-3 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 -4- Effect of feeding vitamin K-deficient diets to female rats. The resistance of the female rat, as compared to the male rat, to vitamin K deficiency on irradiated beef and synthetic K-free diets has been repeatedly demonstrated in our laboratory. Several hypotheses have been suggested to explain this difference. One is that the female rat may practice coprophagy to a greater extent and thus obtain more K from the feces. It may also be that the male rat, because of his greater food intake and growth, may develop the deficiency more rapidly than the female. The third possibility is that there is an actual sex difference under hormonal control. In report 17, data have been presented (table 2 of same report) to show that the greater food intake, and hence greater rate of body weight gain of the male rat, does not result in this specific difference with respect to K deficiency of the female rat. This was demonstrated by suitable paired-feeding of the irradiated beef. Also, prevention of coprophagy did not result in hypoprothrombinemia of the female rats over a 36-day period. Reproduction in the irradiated-beef-fed female Three female rats which had been housed in tubular cages to prevent coprophagy were continued on the irradiated beef diet (ad libitum) for 80 days. Then they were transferred to regular screen-bottom cages and mated with normal male rats. They conceived and gave birth to 11, 10 and 8 pups, respectively. Although 15 of these pups died within 15 days, there was no evidence of hemorrhage in them. The fact that essentially normal reproduction occurred in female rats fed a diet on which all males had died of vitamin K deficiency further emphasizes the marked resistance of the female to this vitamin deficiency. Synthetic diets and vitamin K nutrition of the female rat An experiment was conducted to study the vitamin K requirement of the growing female rat. The basal synthetic diet containing 25% NBC casein (report 17) was used with and without supplementation of 1% sulphathalidine, Data presented in the earlier report (table 2, report 17) show that 2 out of 7 female rats prevented from practicing coprophagy, and consuming ad libitum this K-low synthetic diet, died of hemorrhage after 60 days. When coprophagy was not prevented they main- tained normal prothrombin levels. Addition of sulphathalidine at a 1% level in the diet resulted in elevated plasma prothrombin time (mean value for 7 female rats, 33.5 seconds) even when coprophagy was allowed, presumably due to the effect of sulphathalidine on the availability of intestinally synthesized vitamin K. Thus the marked resistance of the female rat to K deficiency, in comparison to the susceptibility of the male rat, is not affected by the prevention of coprophagy, nor due to food intake or slower rate of growth, but is apparently due to a sex difference presumably under hormonal control. Reproduction by the female rat on synthetic K-low diet. In continuation of the above experiment, 5 female rats maintained on the K-low diet in tubular cages for 94 days to prevent coprophagy were transferred to regular cages and mated with control male rats which had been raised on Purina chow to study again the effect of dietary K deficiency on reproduction. All females conceived and gave birth to live pups. Most of them died within 5 days, although none showed any hemorrhagic symptoms. This poor survival of the pups was also obtained when female rats had been maintained in tubular cages on irradiated beef diets. J-4 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 -5- In our earlier studies on longevity and reproduction performance of female rats maintained on irradiated beef diets (Metta et al., $59) supplemented with 0.1 Y K3 (menadione) per gram dry diet, there was practically no survival of pups following the first mating and about 35% survival following the second mating with stock male rats. However, when the rats were maintained in an isolation room free from respiratory disease, 66-74% survival of the pups was obtained. Relationship of the female sex hormone and vitamin K in the rat The very low vitamin K needs of the female rat for growth and reproduction suggested that estrogens may be involved in some unknown manner in vitamin K function and metabolism in the body. Since a well-known function of K is in the production of prothrombin from the polygonal cells of the liver, a pre- liminary study was made to determine if estrogen was involved in the production of prothrombin. Six male weanling rats of the Sprague-Dawley strain were housed in tubular cages and fed ad libitum a K-free diet of the following percentage composition: sucrose, 66.5; Drackett soya protein, 20; DL methionine, 0.5; vitaminized cerelose (without K), 5; glycerol, 2; methyl linoleate (60% potency) 2; œ-tocopheryl succinate, 0.012; vitamin A, 1000 I.U.: vitamin Da, 100 units; and minerals 446, 4. On the 16th day of feeding one rat showed symptoms of subcutaneous bleeding. On the 18th day the rats were taken off the experiment. One rat was injected intramuscularly with 20 Y° of K3 in corn oil; 3 rats were injected with 1 mg each of estrodiol in 1/2 ml corn oil; and 2 other rats served as controls. After 24 hours, plasma prothrombin times were determined according to Quick (1938)¹ Results as follows: Intramuscular No. of rats Plasma prothrombin injection time, seconds 20 Y K3 injected 1 17 1 mg estrodiol 3 15,14,60+ None 2 17, 27 This preliminary trial indicates only the necessity of repeating this experiment with at least 8-10 rats in each group, since the deficiency is not uniformly produced in all rats. Vitamin K deficiency in the male and female chick We have routinely used female chicks for the bioassay of vitamin K. Since a marked resistance to K deficiency is shown by the female rat, a similar possibility needed to be investigated in the chick. Fifty male and 50 female one-day-old chicks were fed a vitamin K-free diet for 15 days. At 5, 10 and 15 days, respectively, 15 chicks of each group were sacrificed and the plasma prothrombin times determined. The clotting time increased progressively, but no significant differences were obtained with respect to the prothrombin times between the male and the female chicks at any of the specified intervals. 1 Quick, A. J. 1938 The nature of the bleeding in jaundice. J. Am. Med. Assoc. 110: 1658. U-5 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 -6- Vitamin K content of casein as determined by chick assay. Dietary need for vitamin K by the rat was not considered essential for a long time. Reports by Barnes and Fiala (1959)2 and by Mameesh and Johnson (1959) have demonstrated the need for dietary K on certain purified diets. We have routinely used the Drackett soya protein diet for producing K deficiency in the rat as well as in the chick. Also, casein (Nutritional Biochemicals Corporation) has been successfully used in place of the soya protein. When the SO=called "vitamin-free" casein (Labco) was incorporated into the rat diet, it did not result in K deficiency. The purpose of this experiment was to determine the vitamin K activity in these two different brands of casein by the chick assay. Fifty one-day-old female chicks were maintained on the K-free soya protein diet (report 17) for 19 days. They were then divided into five groups. One of these groups was fed a diet containing 35% NBC casein; a second, 35% Labco casein; and the remaining three groups, a basal soya protein diet with graded supplements of vitamin K (table 1). The plasma prothrombin times were then determined. Data in table 1 show that a supplementation of 0.1 r/gm diet to the basal soya protein diet is necessary to maintain normal prothrombin time (25 seconds) in the chick. The mean prothrombin time of chicks on the Labco casein is 33 seconds, and the difference is significant at about 3% level. Calculation shows that 100 gms of Labco casein has about 30 Y of K. The mean prothrombin time of chicks on the NBC casein diet is 46 seconds and significantly higher than that on the basal soya diet supplemented with .1 Y° K/gm diet (25 seconds P < . 01). NBC casein provides less than half as much vitamin K as Labco casein. Effect of different diets on the plasma prothrombin time of rats For a period of 4 weeks, 50 male rats were fed beef, Drackett soya protein and Labco casein diets ad libitum, as detailed in table 2. At the end of the experiment the plasma prothrombin times were determined. Results in table 2 show that an oral supplement of 2 Y K3/rat/day is needed to maintain normal pro- thrombin times in rats fed the soya protein diet. The prothrombin times of rats fed Labco casein and non-irradiated beef diets were in the normal range (13=35). Hypothrombinemie was noted in rats on the irradiated beef (prothrombin time 49-72 seconds) and oral supplementation of 2 Y K3/rat/day maintained the prothrombin time in the range 19-38 seconds. These findings corroborate the results obtained on the K content of casein by the chick assay. Studies on solvent-extracted beef (irradiated and non-irradiated) Bioassay of irradiated and non-irradiated beef using the chick has shown that irradiation destroys, or renders unavailable, vitamin K in the beef (report 17). The purpose of this experiment was to determine the effect of feeding rats irradiated and non-irradiated beef (after exhaustive extraction with alcohol and ether to remove the lipid material) on the plasma prothrombin levels. The basal composition of the diet used is given in table 3. In table 4 data are given on the prothrombin time of rats fed these diets with and without K supplementation. It is clearly seen that even non-irradiated beef (Bos lipid-free) is a poor source of vitamin K 2 Barnes, Richard Ho, and Grace Fiala 1959 Effects of the prevention of coprophagy in the rat. VI. Vitamin K. J. Nutrition, 68, 603. J-6 Source: https://wwww.industrydocuments.ucsf.edu/docs/xtkg0227 -1- High prothrombin times within the range 76-120 are obtained. Oral supplementation of 2 Y K1/rat/day maintains the prothrombin times in the range 15-30 on both irradiated and non-irradiated beef diets. This confirms our earlier observation that the principal cause of the hemorrhagic syndrome obtained on irradiated beef diets is the destruction of vitamin K in beef by irradiation and indicates the absence of any vitamin K antagonist produced in beef by irradiation. Studies in progress Further studies are in progress on: 1) the very marked sex difference with respect to vitamin K deficiency, 2) development of a sensitive chemical assay for vitamin K1 and analogues; and 3) absorption of dietary and intestinally synthesized vitamin K. Papers published Johnson, B. Connor, M. S. Mameesh, V. C. Metta, and P. B. Rama Rao. Vitamin K nutrition and irradiation sterilization. Fed. Proceedings (in press). Mameesh, M. S., and B. Connor Johnson. The absence of hemorrhagic compounds in irradiated beef. J. Nutrition, 71, 122, 1960. Metta, V. C., and B. Connor Johnson. Effect of feeding vitamin K-deficient diets to female rats. J. Nutrition (in press). Rama Rao, P. B., V. C. Metta, and B. Connor Johnson. The amino acid composition and nutritive value of proteins. II. Amino acid mixtures as a dietary source of nitrogen for growth. Jo Nutrition, 71, 327, 1960. Rama Rao, P. V. C. Metta, H. W. Norton, and B. Connor Johnson. The amino acid composition and nutritive value of proteins. III. The total protein and the non- essential amino nitrogen requirement. J. Nutrition, 71, 361, 1960. Mameesh, M. S., and V. C. Metta. Irradiation sterilization in vitamin K nutrition. Fifth International Congress on Nutrition, Sept. g 1960. Paper No. 260, p. 57. Rama Rao, P. Bo, H. W. Norton, and B. Connor Johnson. The amino acid composition and nutritive value of proteins. IV. Methionine, cystine, phenylalanine and tyrosine requirements. J. Nutrition (in press). Personnel Chief Investigator: Dr. B. Connor Johnson Personnel working on the project during the period of this report: Dr. V. Chalam Metta, Research Assistant Professor Dr. M. S. Mameesh, Research Associate Dr. P. B. Rama Rao, Research Associate Mr. James Bergan, (Half-time) Junior Laboratory Attendant Mr. Louis Nash, Junior Laboratory Attendant Plus student help. TCM:MSM:PBR:BCJ:rmd J-7 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 Table 1 Effect of menadione and casein diets on the prothrombin time of K-deficient chicks1 Diet Supplement Prothrombin time2 sec. Soya protein - 200 + Soya protein 0.01 K33 T/gm diet 146 + 3.35 Soya protein 0.1 K3 r/gm diet 25 1.7 Casein (Labco) 4 - 33 2.9 Casein (NBC) - 46 + 4.0 1 Chicks were maintained on the soya protein (K-deficient) diet for 19 days. They were then grouped and fed the diets indicated for 4 days and the plasma prothrombin time of chicks determined. 2 Average of 6 chicks/group. 3 2-methyl-1,4-naphthoquinone. The protein level in all the diets was 35% (N X 6.25). Mean standard deviation of the mean. J-8 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 Table 2 Hemorrhagic deaths and plasma prothrombin times of rats fed irradiated beef, Drackett soya protein and vitamin-free casein diets 1 Oral Plasma pro- No. of Diet supplement thrombin hemorrhagic time, seconds deaths Drackett soya protein - 120 + 4 " " " 1 Y K3²/rat/day 75 (33-120) 1 11 " " 2 Y K3/rat/day 21 (17-30) - Labco (vit.-free casein) - 21 (14-35) - Beef O - 15 (13-19) - Beef 6 - 54 (49-72) 1 Beef 6 1 Y K3/rat/day 38 (21-65) 1 Beef 6 2 Y K3/rat/day 28 (19-38) - 1 6 male rats per group. 2 2-methyl-1,4-naphthoquinone. Rats fed these diets for 4 weeks. J-9 Source: https://www.industrydocuments.ucsf.edu/docs/xtkg0227 Table 3 Ingredient gm Beef¹ 15 Vitaminized glucose² 15 Sucrose 10 Triolein 5 Cod-liver oil 1.5 Wheat-germ oil 0.5 Mineral mix 446 4.0 Starch 49.0 1 Beef (irradiated 5.58 megarad, or non- irradiated) was freeze-dried and extracted for 24 hours with alcohol and for 24 hours with ether. 2 Without K. d-10 Source: https://www.industrydocuments.ucsf.edu/docsixtkg0227

Who is the account executive?

qzmd0217

qzmd0217_p0

Clare Cheng

com cune July 16, 1996 CONFIDENTIAL Dr. Michael Merren 8042 Wurzbach, #640 San Antonio, TX 78229 Dear Dr. Merren, Thank you for agreeing to speak at the Epilepsy Advisory Meeting to be held in Atlanta from August 2 to August 4, 1996. A revised agenda for the scientific portion of the meeting is attached. The details for your presentation are as follow: Date: Saturday, August 3, 1996 Time: 1:30 - 5:00 p.m. Location: Monte Carlo Room A Topic: "Emerging AED Uses/Physician's Role" Title: "Overview of Non-Epilepsy AED Uses and Neurontin in Non- Epilepsy Uses" Length: Approximately 30 minutes Thank you in advance for your assistance. If you have any questions, please do not hesitate to contact me at (212) 907-4343. Sincerely, Clare Cheng VILLY Account Executive V043199 Source:

What is the name of the location?

qzmd0217

qzmd0217_p0

Monte Carlo room A, Monte Carlo Room A

com cune July 16, 1996 CONFIDENTIAL Dr. Michael Merren 8042 Wurzbach, #640 San Antonio, TX 78229 Dear Dr. Merren, Thank you for agreeing to speak at the Epilepsy Advisory Meeting to be held in Atlanta from August 2 to August 4, 1996. A revised agenda for the scientific portion of the meeting is attached. The details for your presentation are as follow: Date: Saturday, August 3, 1996 Time: 1:30 - 5:00 p.m. Location: Monte Carlo Room A Topic: "Emerging AED Uses/Physician's Role" Title: "Overview of Non-Epilepsy AED Uses and Neurontin in Non- Epilepsy Uses" Length: Approximately 30 minutes Thank you in advance for your assistance. If you have any questions, please do not hesitate to contact me at (212) 907-4343. Sincerely, Clare Cheng VILLY Account Executive V043199 Source:

What is the length?

qzmd0217

qzmd0217_p0

Approximately 30 minutes

com cune July 16, 1996 CONFIDENTIAL Dr. Michael Merren 8042 Wurzbach, #640 San Antonio, TX 78229 Dear Dr. Merren, Thank you for agreeing to speak at the Epilepsy Advisory Meeting to be held in Atlanta from August 2 to August 4, 1996. A revised agenda for the scientific portion of the meeting is attached. The details for your presentation are as follow: Date: Saturday, August 3, 1996 Time: 1:30 - 5:00 p.m. Location: Monte Carlo Room A Topic: "Emerging AED Uses/Physician's Role" Title: "Overview of Non-Epilepsy AED Uses and Neurontin in Non- Epilepsy Uses" Length: Approximately 30 minutes Thank you in advance for your assistance. If you have any questions, please do not hesitate to contact me at (212) 907-4343. Sincerely, Clare Cheng VILLY Account Executive V043199 Source:

Mention item "c" which may be included in making salads?

mswg0227

mswg0227_p4

head lettuce with dressing, Head lettuce with dressing.

9. Salads may include the following: 2. Grapefruit slices (unswoetened) on lettuce leaves with dressing. b. Tossed solad of lettuce, tomatoes, carrots, radishes, green peppers. C. Hoad lettuce with dressing. d. Sliced tomatoes on lettuce. e. Cabbage slaw. f. Jellied vegetable solod (unflavored gelatine with chopped vegetables) g. Tomato aspic h. Relish plate of carrot and celory sticks and radishes. A little cheese may be added to the salad dressing if desired. These salads may be substituted for one vegetable at a meal. 10. If desired, any of the following desserts moy be added without altering the diet substantially. When cream or milk is called for a corresponding amount may be subtracted from the daily total in- take. A. LEMON JELLY (Six Servings) 1 envelope unsweetened gelatine 1 4, cup cold water 12 cups boiling water Grated rind of one lemon 4 tbl. lemon juice 1 gr. saccharin Boil lemon rind and water for two minutes. Softon gelatine in cold water. Add to hot liquid and stir until dissolved. Add lomon juice and saccharin. Strain into molds and chill until set. B. LEMON SNOW (Six Servings) Make up recipe for lemon jelly 2 egg whites When lemon jelly is noarly sot, beat until frothy. Beat egg whites until stiff, and fold into gelatine mixture. Pour into molds and chill until firm. C. LEMON BAVARIAN (Six Servings) Make up recipe for lemon jelly 1/2 cup cream (whipped) When jelly is nearly set, beat until frothy, fold in whipped cream, mold and chill until set. 2/49 DH-236.5 Source: https://www.industrydocuments.ucsf.edu/docs/mswg0227

Mention item "e" which may be included in making salads?

mswg0227

mswg0227_p4

Cabbage slaw., cabbage slaw

9. Salads may include the following: 2. Grapefruit slices (unswoetened) on lettuce leaves with dressing. b. Tossed solad of lettuce, tomatoes, carrots, radishes, green peppers. C. Hoad lettuce with dressing. d. Sliced tomatoes on lettuce. e. Cabbage slaw. f. Jellied vegetable solod (unflavored gelatine with chopped vegetables) g. Tomato aspic h. Relish plate of carrot and celory sticks and radishes. A little cheese may be added to the salad dressing if desired. These salads may be substituted for one vegetable at a meal. 10. If desired, any of the following desserts moy be added without altering the diet substantially. When cream or milk is called for a corresponding amount may be subtracted from the daily total in- take. A. LEMON JELLY (Six Servings) 1 envelope unsweetened gelatine 1 4, cup cold water 12 cups boiling water Grated rind of one lemon 4 tbl. lemon juice 1 gr. saccharin Boil lemon rind and water for two minutes. Softon gelatine in cold water. Add to hot liquid and stir until dissolved. Add lomon juice and saccharin. Strain into molds and chill until set. B. LEMON SNOW (Six Servings) Make up recipe for lemon jelly 2 egg whites When lemon jelly is noarly sot, beat until frothy. Beat egg whites until stiff, and fold into gelatine mixture. Pour into molds and chill until firm. C. LEMON BAVARIAN (Six Servings) Make up recipe for lemon jelly 1/2 cup cream (whipped) When jelly is nearly set, beat until frothy, fold in whipped cream, mold and chill until set. 2/49 DH-236.5 Source: https://www.industrydocuments.ucsf.edu/docs/mswg0227

Mention item "d" which may be included in making salads?

mswg0227

mswg0227_p4

sliced tomatoes on lettuce, Sliced tomatoes on lettuce

9. Salads may include the following: 2. Grapefruit slices (unswoetened) on lettuce leaves with dressing. b. Tossed solad of lettuce, tomatoes, carrots, radishes, green peppers. C. Hoad lettuce with dressing. d. Sliced tomatoes on lettuce. e. Cabbage slaw. f. Jellied vegetable solod (unflavored gelatine with chopped vegetables) g. Tomato aspic h. Relish plate of carrot and celory sticks and radishes. A little cheese may be added to the salad dressing if desired. These salads may be substituted for one vegetable at a meal. 10. If desired, any of the following desserts moy be added without altering the diet substantially. When cream or milk is called for a corresponding amount may be subtracted from the daily total in- take. A. LEMON JELLY (Six Servings) 1 envelope unsweetened gelatine 1 4, cup cold water 12 cups boiling water Grated rind of one lemon 4 tbl. lemon juice 1 gr. saccharin Boil lemon rind and water for two minutes. Softon gelatine in cold water. Add to hot liquid and stir until dissolved. Add lomon juice and saccharin. Strain into molds and chill until set. B. LEMON SNOW (Six Servings) Make up recipe for lemon jelly 2 egg whites When lemon jelly is noarly sot, beat until frothy. Beat egg whites until stiff, and fold into gelatine mixture. Pour into molds and chill until firm. C. LEMON BAVARIAN (Six Servings) Make up recipe for lemon jelly 1/2 cup cream (whipped) When jelly is nearly set, beat until frothy, fold in whipped cream, mold and chill until set. 2/49 DH-236.5 Source: https://www.industrydocuments.ucsf.edu/docs/mswg0227

Mention item "g" which may be included in making salads?

mswg0227

mswg0227_p4

Tomato aspic, tomato aspic

9. Salads may include the following: 2. Grapefruit slices (unswoetened) on lettuce leaves with dressing. b. Tossed solad of lettuce, tomatoes, carrots, radishes, green peppers. C. Hoad lettuce with dressing. d. Sliced tomatoes on lettuce. e. Cabbage slaw. f. Jellied vegetable solod (unflavored gelatine with chopped vegetables) g. Tomato aspic h. Relish plate of carrot and celory sticks and radishes. A little cheese may be added to the salad dressing if desired. These salads may be substituted for one vegetable at a meal. 10. If desired, any of the following desserts moy be added without altering the diet substantially. When cream or milk is called for a corresponding amount may be subtracted from the daily total in- take. A. LEMON JELLY (Six Servings) 1 envelope unsweetened gelatine 1 4, cup cold water 12 cups boiling water Grated rind of one lemon 4 tbl. lemon juice 1 gr. saccharin Boil lemon rind and water for two minutes. Softon gelatine in cold water. Add to hot liquid and stir until dissolved. Add lomon juice and saccharin. Strain into molds and chill until set. B. LEMON SNOW (Six Servings) Make up recipe for lemon jelly 2 egg whites When lemon jelly is noarly sot, beat until frothy. Beat egg whites until stiff, and fold into gelatine mixture. Pour into molds and chill until firm. C. LEMON BAVARIAN (Six Servings) Make up recipe for lemon jelly 1/2 cup cream (whipped) When jelly is nearly set, beat until frothy, fold in whipped cream, mold and chill until set. 2/49 DH-236.5 Source: https://www.industrydocuments.ucsf.edu/docs/mswg0227

"These salads must be substituted for" what "at a meal"?

mswg0227

mswg0227_p4

one vegetable, one vegetable

9. Salads may include the following: 2. Grapefruit slices (unswoetened) on lettuce leaves with dressing. b. Tossed solad of lettuce, tomatoes, carrots, radishes, green peppers. C. Hoad lettuce with dressing. d. Sliced tomatoes on lettuce. e. Cabbage slaw. f. Jellied vegetable solod (unflavored gelatine with chopped vegetables) g. Tomato aspic h. Relish plate of carrot and celory sticks and radishes. A little cheese may be added to the salad dressing if desired. These salads may be substituted for one vegetable at a meal. 10. If desired, any of the following desserts moy be added without altering the diet substantially. When cream or milk is called for a corresponding amount may be subtracted from the daily total in- take. A. LEMON JELLY (Six Servings) 1 envelope unsweetened gelatine 1 4, cup cold water 12 cups boiling water Grated rind of one lemon 4 tbl. lemon juice 1 gr. saccharin Boil lemon rind and water for two minutes. Softon gelatine in cold water. Add to hot liquid and stir until dissolved. Add lomon juice and saccharin. Strain into molds and chill until set. B. LEMON SNOW (Six Servings) Make up recipe for lemon jelly 2 egg whites When lemon jelly is noarly sot, beat until frothy. Beat egg whites until stiff, and fold into gelatine mixture. Pour into molds and chill until firm. C. LEMON BAVARIAN (Six Servings) Make up recipe for lemon jelly 1/2 cup cream (whipped) When jelly is nearly set, beat until frothy, fold in whipped cream, mold and chill until set. 2/49 DH-236.5 Source: https://www.industrydocuments.ucsf.edu/docs/mswg0227

Which dessert name is given as "A" under "10"?

mswg0227

mswg0227_p4

lemon jelly, LEMON JELLY

9. Salads may include the following: 2. Grapefruit slices (unswoetened) on lettuce leaves with dressing. b. Tossed solad of lettuce, tomatoes, carrots, radishes, green peppers. C. Hoad lettuce with dressing. d. Sliced tomatoes on lettuce. e. Cabbage slaw. f. Jellied vegetable solod (unflavored gelatine with chopped vegetables) g. Tomato aspic h. Relish plate of carrot and celory sticks and radishes. A little cheese may be added to the salad dressing if desired. These salads may be substituted for one vegetable at a meal. 10. If desired, any of the following desserts moy be added without altering the diet substantially. When cream or milk is called for a corresponding amount may be subtracted from the daily total in- take. A. LEMON JELLY (Six Servings) 1 envelope unsweetened gelatine 1 4, cup cold water 12 cups boiling water Grated rind of one lemon 4 tbl. lemon juice 1 gr. saccharin Boil lemon rind and water for two minutes. Softon gelatine in cold water. Add to hot liquid and stir until dissolved. Add lomon juice and saccharin. Strain into molds and chill until set. B. LEMON SNOW (Six Servings) Make up recipe for lemon jelly 2 egg whites When lemon jelly is noarly sot, beat until frothy. Beat egg whites until stiff, and fold into gelatine mixture. Pour into molds and chill until firm. C. LEMON BAVARIAN (Six Servings) Make up recipe for lemon jelly 1/2 cup cream (whipped) When jelly is nearly set, beat until frothy, fold in whipped cream, mold and chill until set. 2/49 DH-236.5 Source: https://www.industrydocuments.ucsf.edu/docs/mswg0227

Which dessert name is given as "B" under "10"?

mswg0227

mswg0227_p4

LEMON SNOW, lemon snow

9. Salads may include the following: 2. Grapefruit slices (unswoetened) on lettuce leaves with dressing. b. Tossed solad of lettuce, tomatoes, carrots, radishes, green peppers. C. Hoad lettuce with dressing. d. Sliced tomatoes on lettuce. e. Cabbage slaw. f. Jellied vegetable solod (unflavored gelatine with chopped vegetables) g. Tomato aspic h. Relish plate of carrot and celory sticks and radishes. A little cheese may be added to the salad dressing if desired. These salads may be substituted for one vegetable at a meal. 10. If desired, any of the following desserts moy be added without altering the diet substantially. When cream or milk is called for a corresponding amount may be subtracted from the daily total in- take. A. LEMON JELLY (Six Servings) 1 envelope unsweetened gelatine 1 4, cup cold water 12 cups boiling water Grated rind of one lemon 4 tbl. lemon juice 1 gr. saccharin Boil lemon rind and water for two minutes. Softon gelatine in cold water. Add to hot liquid and stir until dissolved. Add lomon juice and saccharin. Strain into molds and chill until set. B. LEMON SNOW (Six Servings) Make up recipe for lemon jelly 2 egg whites When lemon jelly is noarly sot, beat until frothy. Beat egg whites until stiff, and fold into gelatine mixture. Pour into molds and chill until firm. C. LEMON BAVARIAN (Six Servings) Make up recipe for lemon jelly 1/2 cup cream (whipped) When jelly is nearly set, beat until frothy, fold in whipped cream, mold and chill until set. 2/49 DH-236.5 Source: https://www.industrydocuments.ucsf.edu/docs/mswg0227

Provide the reference number given at right bottom corner of the page?

mswg0227

mswg0227_p4

2/49 DH-236.5, DH-236.5, 2/49 DH-236.5

9. Salads may include the following: 2. Grapefruit slices (unswoetened) on lettuce leaves with dressing. b. Tossed solad of lettuce, tomatoes, carrots, radishes, green peppers. C. Hoad lettuce with dressing. d. Sliced tomatoes on lettuce. e. Cabbage slaw. f. Jellied vegetable solod (unflavored gelatine with chopped vegetables) g. Tomato aspic h. Relish plate of carrot and celory sticks and radishes. A little cheese may be added to the salad dressing if desired. These salads may be substituted for one vegetable at a meal. 10. If desired, any of the following desserts moy be added without altering the diet substantially. When cream or milk is called for a corresponding amount may be subtracted from the daily total in- take. A. LEMON JELLY (Six Servings) 1 envelope unsweetened gelatine 1 4, cup cold water 12 cups boiling water Grated rind of one lemon 4 tbl. lemon juice 1 gr. saccharin Boil lemon rind and water for two minutes. Softon gelatine in cold water. Add to hot liquid and stir until dissolved. Add lomon juice and saccharin. Strain into molds and chill until set. B. LEMON SNOW (Six Servings) Make up recipe for lemon jelly 2 egg whites When lemon jelly is noarly sot, beat until frothy. Beat egg whites until stiff, and fold into gelatine mixture. Pour into molds and chill until firm. C. LEMON BAVARIAN (Six Servings) Make up recipe for lemon jelly 1/2 cup cream (whipped) When jelly is nearly set, beat until frothy, fold in whipped cream, mold and chill until set. 2/49 DH-236.5 Source: https://www.industrydocuments.ucsf.edu/docs/mswg0227

Dessert recipe for how many servings is given?

mswg0227

mswg0227_p4

SIX SERVINGS, Six, Six servings

9. Salads may include the following: 2. Grapefruit slices (unswoetened) on lettuce leaves with dressing. b. Tossed solad of lettuce, tomatoes, carrots, radishes, green peppers. C. Hoad lettuce with dressing. d. Sliced tomatoes on lettuce. e. Cabbage slaw. f. Jellied vegetable solod (unflavored gelatine with chopped vegetables) g. Tomato aspic h. Relish plate of carrot and celory sticks and radishes. A little cheese may be added to the salad dressing if desired. These salads may be substituted for one vegetable at a meal. 10. If desired, any of the following desserts moy be added without altering the diet substantially. When cream or milk is called for a corresponding amount may be subtracted from the daily total in- take. A. LEMON JELLY (Six Servings) 1 envelope unsweetened gelatine 1 4, cup cold water 12 cups boiling water Grated rind of one lemon 4 tbl. lemon juice 1 gr. saccharin Boil lemon rind and water for two minutes. Softon gelatine in cold water. Add to hot liquid and stir until dissolved. Add lomon juice and saccharin. Strain into molds and chill until set. B. LEMON SNOW (Six Servings) Make up recipe for lemon jelly 2 egg whites When lemon jelly is noarly sot, beat until frothy. Beat egg whites until stiff, and fold into gelatine mixture. Pour into molds and chill until firm. C. LEMON BAVARIAN (Six Servings) Make up recipe for lemon jelly 1/2 cup cream (whipped) When jelly is nearly set, beat until frothy, fold in whipped cream, mold and chill until set. 2/49 DH-236.5 Source: https://www.industrydocuments.ucsf.edu/docs/mswg0227

What type of profiles is shown in the table ?

jnjm0223

jnjm0223_p107, jnjm0223_p108, jnjm0223_p109, jnjm0223_p110, jnjm0223_p111, jnjm0223_p112, jnjm0223_p113

Nerontin Critical Congress Profiles, Critical Congress Profiles

Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site American Academy of Family AAFP Yes Yes Yes Family Physicians 100 North America 99 14,886 4,500 www.aafp.org Physicians. Annual Scientific Rest of World 1 Assembly. American College of Physicians- ACP-ASIM No Yes Yes Internists 95 United States 93 10,000 7,000 www.acponline.org American Society of Internal Medicine Other 5 Rest of World 7 Annual Session. International Society of Internal ICIM Yes Yes Yes Internists 95 Japan 70 7,000 5,000 www.acponline.org/isin Medicine. Biennial Congress. Other 5 North America 10 Europe 10 Rest of World 10 Primary Medicine Today East. Pri-Med East No Yes Yes Primary Care 55 United States 100 8,000 6,991 www.pri-med.com Annual Meeting. Pediatricians 9 Other 36 Primary Medicine Today MidWest. Pri-Med No Yes Yes Primary Care 61 United States 100 5,216 5,112 www.pri-med.com Annual Meeting. MidWest Pediatricians 10 Primary Care Other 29 Primary Medicine Today South. Pri-Med South No Yes Yes Primary Care 56 United States 100 5,000 4,512 www.pri-med.com Annual Meeting. Pediatricians 8 Other 36 Primary Medicine Today West. Annual Pri-Med West No Yes Yes Primary Care 65 United States 100 9,000 8,369 www.pri-med.com Meeting. Pediatricians 10 Other 25 Society of General Internal Medicine. SGIM Yes No No Primary Care N/A North America 90 1,700 1,700 www.sgim.org Annual Meeting. Rest of World 10 WONCA Asia Pacific Regional WONCA-Asia A/R A/R A/R Primary Care N/A A/R A/R 1,000 800 www.wonca.org Conference. Annual. WONCA Europe. Annual Conference. WONCA-Europe Yes Yes Yes Primary Care N/A Europe 50 3,000 3,000 ww.wonca.org Other Rest of World 50 WONCA World Congress of Family WONCA-World Yes Yes No Family Physicians 100 North America 10 5,000 4,000 www.wonca.org Doctors. Triennial. Rest of World 90 American Academy of Child and AACAP Yes No Yes Psychiatrists 90 North America 60 3,000 3,000 www.aacap.org Adolescent Psychiatry. Annual Other 10 Europe 15 Meeting. Asia 15 Other 10 American Psychiatric Association. APA Yes Yes Yes Psychrists 90 N/A N/A 19,000 19,000 www.psych.org Annual Meeting. Other 10 Psychiatry Anxiety Disorders Association of ADAA Yes Yes Yes Physicians N/A United States 100 600 600 www.adaa.org America National Conference. Annual. Medical Students N/A Association of European Psychiatrists. AEP Yes Yes Yes Researchers N/A Europe 87 2,600 2,575 www.aep.lu Biennial Congress. Other N/A North America 4 Asia 5 Rest of World 4 A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 107 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026113 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Collegium Internationale Neuro- CINP Yes Yes Yes Psychiatrists N/A North America N/A 5,000 5,000 www.cinp.org Psychopharmacologicum. Biennial Other N/A United Kingdom N/A Congress. European College of ECNP Yes Yes Yes N/A N/A N/A N/A 5,000 5,000 www.encp.nl Neuropsychopharmacology. Annual Congress. Institute on Psychiatric Services. IPS Yes Yes Yes Psychiatrists N/A North America 95 2,000 2,000 www.psych.org Annual Meeting. Psychologists N/A Rest of World 5 Other N/A International Conference on Bipolar ICBD Yes No Yes Psychiatrists N/A United States N/A 859 700 ww.wpic.pitt.edu Disorder. Biennial. Psychologists N/A Rest of World N/A Social Workers N/A Medical Students N/A International Congress of ICN A/R A/R A/R Psychiatrists N/A International N/A A/R A/R www.kenes.com Neuropsychiatry. Biennial. Psychiatry (cont.) International Forum on Mood and IFMAD Yes Yes Yes Psychiatrists 100 United States N/A 650 600 www.aisc.it Anxiety Disorders. Annual Meeting. Europe N/A Rest of World N/A New Clinical Drug Evaluation Unit. NCDEU Yes No No Government N/A N/A N/A 1,200 1,200 www.nimh.nih.gov Annual Meeting. Industry N/A Stress and Anxiety Research Society. STAR Yes No No Psychologists 100 Europe 52 200 200 www.star-society.org Annual International Conference. Asia 22 North America 11 Africa 7 Rest of World 8 US Psychiatric and Mental Health USPMHC Yes Yes Yes Psychiatrists 63 Europe N/A 3,000 3,000 www.cmeinc.com Congress. Annual. Psychologists 9 United States N/A Nurses 17 Social Workers 4 Other 7 World Congress of Psychiatry. WCP Yes Yes Yes Psychiatrists N/A N/A N/A 10,000 10,000 www.wpanet.org Triennial. Government N/A Other N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 108 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026114 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Associated Professional Sleep APSS Yes Yes Yes Researchers 33 North America 88 4,000 3,200 www.apss.org Societies. Annual Meeting. Pulmonologists 21 Rest of World 12 Neurologists 16 Psychologists 8 Neuroscientists 8 Psychiatrists 8 Other 6 Sleep European Sleep Research Society. ESRS Yes Yes Yes Physicians N/A International N/A 950 N/A www.esrs.org Biennial Congress. Neurologists N/A Biologists N/A Psychologists N/A World Conference Sleep Odyssey. WCSO Yes Yes Yes Researchers N/A Unied States N/A A/R A/R www.wfsrs.org Quadrennial. Physicians N/A Europe N/A Rest of World N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 109 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026115 DATE 29-Oct-01 REF Neurontin PSC Meeting CLIENT Pfizer MTG DATE 19-Sep-01 VENUE Pfizer PRESENT Pfizer: L Tive, E Mutisya, S Brigandi, MEDICAL ACTION S Piron, M Garcia, J Kaplan, M COMMUNICATIONS Rowbotham, L Knapp, A Fannon, A Crespo, D Probert, J Marino, C Blanckmeister, C Banta MAC: M Vinegra, S Valerio, S Steen, A Masonis, J Mierop, S Tyler COPIED TO E Shapiro, K Kennon, R Glanzman, M Ulrey, K Taylor, M Balkenhol, H Duda Racki, T Hylan, T Hsu, L Collins ACTION REPORT SUBJECT Neurontin PSC Meeting 1.0 Introduction The following action report summarizes the decisions, issues and action items discussed during the Neurontin Publications Subcommittee (PSC) meeting held on September 19. During the meeting the following topics were covered: 2002 congress presentations Issues regarding specific manuscripts Future meeting between NYHQ and Ann Arbor Key message development update Journal and congress profiling update Bibliography development update 2.0 2002 Congress Presentations Joan Kaplan (JK) initiated the discussion by informing the team that the 2001 International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP) has been cancelled. However, the 2 posters scheduled to be presented at that meeting should be included in future presentation plans. The team developed the following plan for poster presentations in 2002: 2.1 American Academy of Neurology (AAN) Dosing response/exposure response (Neuropathic Pain) QOL data from the 5 pivotal trials (Neuropathic Pain) - Steve Piron SP (SP) mentioned that Brett Stacey had expressed an interest in this the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 fizer_LKnapp_0026116 type of subanalysis. SP will contact Stacey to further explore his interest. 2.2 American Pain Society (APS) Efficacy data from the 5 pivotal trials - This poster was originally targeted for ICMTNP. Both the abstract and poster have been completed. MAC will provide reformatting and production support MAC as needed. 2.3 International Association for the Study of Pain (IASP) Practical dosing and titration POPP (tentative, pending subanalysis results) 2.4 American Academy of Family Practioners (AAFP) Screening tool - Stephen Valerio (SV) and Amy Masonis (AEM) of MAC both advised the team that this is a very difficult meeting in terms of acceptance of presentations. The academy has rigorous rules regarding both representation of data and pharmaceutical company funding of accepted presentations. 2.5 American Diabetes Association (ADA) Latin America diabetic neuropathy study Pooled results from the 2 diabetic neuropathy trials MAC will determine the abstract deadlines and meeting dates for ADA MAC and forward these to the team. 2.6 Other Possible Presentations In addition to the above; the following presentations will be added to the list for 2002, pending the following actions: Sleep study - MAC will contact Dr. Erhenberg to find out whether he has previously presented these data at a congress, and if not, MAC whether he would be interested in doing so. MAC will also solicit his preference as to which meeting he would like to present the data. HIV-neuropathy study - This poster was originally to be presented at ICMTNP. Elizabeth Mutisya (EM) will ask Prof. Rowbotham if he EM would prefer to present these data at American Academy of Neurology (AAN), American Pain Society (APS), or International Association for the Study of Pain (IASP). In addition, MAC will MAC follow-up with the International AIDS Conference (IAIDSC) regarding its rules for re-presentation. The team strongly felt that it would be advantageous to have these data presented at this meeting as well. Action Report: 19-Sep-01 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026117 Philippine post-marketing surveillance EM will review these data to determine whether there is any EM potential for presentation material. CRPS placebo cross-over Michael Rowbotham (MR) will follow-up with Prof. Hill to find out MR whether he has any presentation plans for these data. 3.0 Manuscript Issues 3.1 Latin America Diabetic Neuropathy EM informed the team that the preliminary data have just come in and further analysis needs to be done. While the manuscript is currently targeted for the JAMA special issue, the December 31 deadline may be tight. After the data have been reviewed; MAC will distribute a MAC journal query form so that a list of potential back-up journals can be developed. Leslie Tive (LT) was identified as the lead reviewer. EM, Lloyd Knapp (LK), SP, Angela Crespo (AC) and Lingshi Tan (LT) were identified as reviewers. John Marino (JM) recommended that a Brazilian and Mexican be selected as authors. LT also suggested Klaus as an author, even though he no longer is a Pfizer employee. 3.2 Treatment of Diabetic Neuropathy Review for JAMA The team agreed that Larry Blonde and Roy Freeman should co-author this paper, with Bruce Nicholson to provide the viewpoints of an endocrinologist, an anesthesiologist, and a neurologist respectively. LK will be the lead reviewer; MR and EM will also review the manuscript. MR pointed out that the focus of the review should be to convince diabetologists that the treatment of the neuropathic pain associated with diabetes should consist of more than the underlying condition; therapy should be directed toward relieving the symptom itself. 3.3 Gabapentin Review SV reminded the team that the journal Expert Opinion on Pharmacotherapy had solicited a review from Dr. Nicholson, who then asked for Pfizer's help. It was decided that since this was an industry- focused journal, this manuscript was not a priority for the team. It was MAC decided that MAC would look into using a previous review by Nicholson as the backbone for this review and would add some new data to update it. 3.4 Dosing Manuscripts SV informed the team that he had spoken with Dr. McLean, who suggested that the 2 dosing manuscripts be combined since the fundamental issue underlying the manuscripts is the same, namely, intrasubject variability. AC and the team disagreed, arguing that the the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pizer_LKnapp_0026118 clinical issues associated with the 2 conditions were quite different. SV MAC suggested that he would get back to Dr. McLean and mention that Pfizer would first like to write 2 clinically focused reviews and then follow-up with a more detailed, kinetically based review next year. The team agreed to this plan. [Post-meeting note: SV has left a message for Dr. McLean and is awaiting a response.] 3.5 POPP Study The team decided that this manuscript would be placed on hold until the subanalysis is completed. The team selected The Journal of Pain and Symptom Management as the target journal with Pain Medicine as a backup. 3.6 European Journal of Pain Supplement The team was updated regarding the status of the supplement. MAC has received reviewer comments. These will be sent to Stephen MAC Brigandi (SB) who will forward them to Embryon. [Post-meeting note: SB both of these actions have been completed.] The final version will be sent to LT for final approval next week. 4.0 Meeting with NYHQ and Ann Arbor The meeting to discuss the transfer of study data and to determine whether there are studies that have not been published has been confirmed for the afternoon of October 3. The meeting to discuss the subanalyses will be arranged independently. 5.0 Key Messages Update Most of the key message meetings have taken place, and the approved list is undergoing final revisions. Corporate messages will be reviewed by a small committee via e-mail or teleconference. The entire list will be reviewed by a single committee in order to finalize it; however, the list will be revisited in the future. 6.0 Profile and Bibliography Update MAC presented the latest journal and congress profiles and reminded the team that profiling is continuing. MAC also presented the latest screen shots from the bibliography. LT requested a special meeting to discuss the bibliography, independent of other publication issues. In addition; MAC was actioned to provide a small working model to be MAC tested at the meeting. Stephen Valerio Medical Projects Director the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026119

What is the first Column heading given?

jnjm0223

jnjm0223_p107, jnjm0223_p108, jnjm0223_p109, jnjm0223_p110, jnjm0223_p111, jnjm0223_p112, jnjm0223_p113

Specialty

Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site American Academy of Family AAFP Yes Yes Yes Family Physicians 100 North America 99 14,886 4,500 www.aafp.org Physicians. Annual Scientific Rest of World 1 Assembly. American College of Physicians- ACP-ASIM No Yes Yes Internists 95 United States 93 10,000 7,000 www.acponline.org American Society of Internal Medicine Other 5 Rest of World 7 Annual Session. International Society of Internal ICIM Yes Yes Yes Internists 95 Japan 70 7,000 5,000 www.acponline.org/isin Medicine. Biennial Congress. Other 5 North America 10 Europe 10 Rest of World 10 Primary Medicine Today East. Pri-Med East No Yes Yes Primary Care 55 United States 100 8,000 6,991 www.pri-med.com Annual Meeting. Pediatricians 9 Other 36 Primary Medicine Today MidWest. Pri-Med No Yes Yes Primary Care 61 United States 100 5,216 5,112 www.pri-med.com Annual Meeting. MidWest Pediatricians 10 Primary Care Other 29 Primary Medicine Today South. Pri-Med South No Yes Yes Primary Care 56 United States 100 5,000 4,512 www.pri-med.com Annual Meeting. Pediatricians 8 Other 36 Primary Medicine Today West. Annual Pri-Med West No Yes Yes Primary Care 65 United States 100 9,000 8,369 www.pri-med.com Meeting. Pediatricians 10 Other 25 Society of General Internal Medicine. SGIM Yes No No Primary Care N/A North America 90 1,700 1,700 www.sgim.org Annual Meeting. Rest of World 10 WONCA Asia Pacific Regional WONCA-Asia A/R A/R A/R Primary Care N/A A/R A/R 1,000 800 www.wonca.org Conference. Annual. WONCA Europe. Annual Conference. WONCA-Europe Yes Yes Yes Primary Care N/A Europe 50 3,000 3,000 ww.wonca.org Other Rest of World 50 WONCA World Congress of Family WONCA-World Yes Yes No Family Physicians 100 North America 10 5,000 4,000 www.wonca.org Doctors. Triennial. Rest of World 90 American Academy of Child and AACAP Yes No Yes Psychiatrists 90 North America 60 3,000 3,000 www.aacap.org Adolescent Psychiatry. Annual Other 10 Europe 15 Meeting. Asia 15 Other 10 American Psychiatric Association. APA Yes Yes Yes Psychrists 90 N/A N/A 19,000 19,000 www.psych.org Annual Meeting. Other 10 Psychiatry Anxiety Disorders Association of ADAA Yes Yes Yes Physicians N/A United States 100 600 600 www.adaa.org America National Conference. Annual. Medical Students N/A Association of European Psychiatrists. AEP Yes Yes Yes Researchers N/A Europe 87 2,600 2,575 www.aep.lu Biennial Congress. Other N/A North America 4 Asia 5 Rest of World 4 A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 107 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026113 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Collegium Internationale Neuro- CINP Yes Yes Yes Psychiatrists N/A North America N/A 5,000 5,000 www.cinp.org Psychopharmacologicum. Biennial Other N/A United Kingdom N/A Congress. European College of ECNP Yes Yes Yes N/A N/A N/A N/A 5,000 5,000 www.encp.nl Neuropsychopharmacology. Annual Congress. Institute on Psychiatric Services. IPS Yes Yes Yes Psychiatrists N/A North America 95 2,000 2,000 www.psych.org Annual Meeting. Psychologists N/A Rest of World 5 Other N/A International Conference on Bipolar ICBD Yes No Yes Psychiatrists N/A United States N/A 859 700 ww.wpic.pitt.edu Disorder. Biennial. Psychologists N/A Rest of World N/A Social Workers N/A Medical Students N/A International Congress of ICN A/R A/R A/R Psychiatrists N/A International N/A A/R A/R www.kenes.com Neuropsychiatry. Biennial. Psychiatry (cont.) International Forum on Mood and IFMAD Yes Yes Yes Psychiatrists 100 United States N/A 650 600 www.aisc.it Anxiety Disorders. Annual Meeting. Europe N/A Rest of World N/A New Clinical Drug Evaluation Unit. NCDEU Yes No No Government N/A N/A N/A 1,200 1,200 www.nimh.nih.gov Annual Meeting. Industry N/A Stress and Anxiety Research Society. STAR Yes No No Psychologists 100 Europe 52 200 200 www.star-society.org Annual International Conference. Asia 22 North America 11 Africa 7 Rest of World 8 US Psychiatric and Mental Health USPMHC Yes Yes Yes Psychiatrists 63 Europe N/A 3,000 3,000 www.cmeinc.com Congress. Annual. Psychologists 9 United States N/A Nurses 17 Social Workers 4 Other 7 World Congress of Psychiatry. WCP Yes Yes Yes Psychiatrists N/A N/A N/A 10,000 10,000 www.wpanet.org Triennial. Government N/A Other N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 108 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026114 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Associated Professional Sleep APSS Yes Yes Yes Researchers 33 North America 88 4,000 3,200 www.apss.org Societies. Annual Meeting. Pulmonologists 21 Rest of World 12 Neurologists 16 Psychologists 8 Neuroscientists 8 Psychiatrists 8 Other 6 Sleep European Sleep Research Society. ESRS Yes Yes Yes Physicians N/A International N/A 950 N/A www.esrs.org Biennial Congress. Neurologists N/A Biologists N/A Psychologists N/A World Conference Sleep Odyssey. WCSO Yes Yes Yes Researchers N/A Unied States N/A A/R A/R www.wfsrs.org Quadrennial. Physicians N/A Europe N/A Rest of World N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 109 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026115 DATE 29-Oct-01 REF Neurontin PSC Meeting CLIENT Pfizer MTG DATE 19-Sep-01 VENUE Pfizer PRESENT Pfizer: L Tive, E Mutisya, S Brigandi, MEDICAL ACTION S Piron, M Garcia, J Kaplan, M COMMUNICATIONS Rowbotham, L Knapp, A Fannon, A Crespo, D Probert, J Marino, C Blanckmeister, C Banta MAC: M Vinegra, S Valerio, S Steen, A Masonis, J Mierop, S Tyler COPIED TO E Shapiro, K Kennon, R Glanzman, M Ulrey, K Taylor, M Balkenhol, H Duda Racki, T Hylan, T Hsu, L Collins ACTION REPORT SUBJECT Neurontin PSC Meeting 1.0 Introduction The following action report summarizes the decisions, issues and action items discussed during the Neurontin Publications Subcommittee (PSC) meeting held on September 19. During the meeting the following topics were covered: 2002 congress presentations Issues regarding specific manuscripts Future meeting between NYHQ and Ann Arbor Key message development update Journal and congress profiling update Bibliography development update 2.0 2002 Congress Presentations Joan Kaplan (JK) initiated the discussion by informing the team that the 2001 International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP) has been cancelled. However, the 2 posters scheduled to be presented at that meeting should be included in future presentation plans. The team developed the following plan for poster presentations in 2002: 2.1 American Academy of Neurology (AAN) Dosing response/exposure response (Neuropathic Pain) QOL data from the 5 pivotal trials (Neuropathic Pain) - Steve Piron SP (SP) mentioned that Brett Stacey had expressed an interest in this the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 fizer_LKnapp_0026116 type of subanalysis. SP will contact Stacey to further explore his interest. 2.2 American Pain Society (APS) Efficacy data from the 5 pivotal trials - This poster was originally targeted for ICMTNP. Both the abstract and poster have been completed. MAC will provide reformatting and production support MAC as needed. 2.3 International Association for the Study of Pain (IASP) Practical dosing and titration POPP (tentative, pending subanalysis results) 2.4 American Academy of Family Practioners (AAFP) Screening tool - Stephen Valerio (SV) and Amy Masonis (AEM) of MAC both advised the team that this is a very difficult meeting in terms of acceptance of presentations. The academy has rigorous rules regarding both representation of data and pharmaceutical company funding of accepted presentations. 2.5 American Diabetes Association (ADA) Latin America diabetic neuropathy study Pooled results from the 2 diabetic neuropathy trials MAC will determine the abstract deadlines and meeting dates for ADA MAC and forward these to the team. 2.6 Other Possible Presentations In addition to the above; the following presentations will be added to the list for 2002, pending the following actions: Sleep study - MAC will contact Dr. Erhenberg to find out whether he has previously presented these data at a congress, and if not, MAC whether he would be interested in doing so. MAC will also solicit his preference as to which meeting he would like to present the data. HIV-neuropathy study - This poster was originally to be presented at ICMTNP. Elizabeth Mutisya (EM) will ask Prof. Rowbotham if he EM would prefer to present these data at American Academy of Neurology (AAN), American Pain Society (APS), or International Association for the Study of Pain (IASP). In addition, MAC will MAC follow-up with the International AIDS Conference (IAIDSC) regarding its rules for re-presentation. The team strongly felt that it would be advantageous to have these data presented at this meeting as well. Action Report: 19-Sep-01 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026117 Philippine post-marketing surveillance EM will review these data to determine whether there is any EM potential for presentation material. CRPS placebo cross-over Michael Rowbotham (MR) will follow-up with Prof. Hill to find out MR whether he has any presentation plans for these data. 3.0 Manuscript Issues 3.1 Latin America Diabetic Neuropathy EM informed the team that the preliminary data have just come in and further analysis needs to be done. While the manuscript is currently targeted for the JAMA special issue, the December 31 deadline may be tight. After the data have been reviewed; MAC will distribute a MAC journal query form so that a list of potential back-up journals can be developed. Leslie Tive (LT) was identified as the lead reviewer. EM, Lloyd Knapp (LK), SP, Angela Crespo (AC) and Lingshi Tan (LT) were identified as reviewers. John Marino (JM) recommended that a Brazilian and Mexican be selected as authors. LT also suggested Klaus as an author, even though he no longer is a Pfizer employee. 3.2 Treatment of Diabetic Neuropathy Review for JAMA The team agreed that Larry Blonde and Roy Freeman should co-author this paper, with Bruce Nicholson to provide the viewpoints of an endocrinologist, an anesthesiologist, and a neurologist respectively. LK will be the lead reviewer; MR and EM will also review the manuscript. MR pointed out that the focus of the review should be to convince diabetologists that the treatment of the neuropathic pain associated with diabetes should consist of more than the underlying condition; therapy should be directed toward relieving the symptom itself. 3.3 Gabapentin Review SV reminded the team that the journal Expert Opinion on Pharmacotherapy had solicited a review from Dr. Nicholson, who then asked for Pfizer's help. It was decided that since this was an industry- focused journal, this manuscript was not a priority for the team. It was MAC decided that MAC would look into using a previous review by Nicholson as the backbone for this review and would add some new data to update it. 3.4 Dosing Manuscripts SV informed the team that he had spoken with Dr. McLean, who suggested that the 2 dosing manuscripts be combined since the fundamental issue underlying the manuscripts is the same, namely, intrasubject variability. AC and the team disagreed, arguing that the the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pizer_LKnapp_0026118 clinical issues associated with the 2 conditions were quite different. SV MAC suggested that he would get back to Dr. McLean and mention that Pfizer would first like to write 2 clinically focused reviews and then follow-up with a more detailed, kinetically based review next year. The team agreed to this plan. [Post-meeting note: SV has left a message for Dr. McLean and is awaiting a response.] 3.5 POPP Study The team decided that this manuscript would be placed on hold until the subanalysis is completed. The team selected The Journal of Pain and Symptom Management as the target journal with Pain Medicine as a backup. 3.6 European Journal of Pain Supplement The team was updated regarding the status of the supplement. MAC has received reviewer comments. These will be sent to Stephen MAC Brigandi (SB) who will forward them to Embryon. [Post-meeting note: SB both of these actions have been completed.] The final version will be sent to LT for final approval next week. 4.0 Meeting with NYHQ and Ann Arbor The meeting to discuss the transfer of study data and to determine whether there are studies that have not been published has been confirmed for the afternoon of October 3. The meeting to discuss the subanalyses will be arranged independently. 5.0 Key Messages Update Most of the key message meetings have taken place, and the approved list is undergoing final revisions. Corporate messages will be reviewed by a small committee via e-mail or teleconference. The entire list will be reviewed by a single committee in order to finalize it; however, the list will be revisited in the future. 6.0 Profile and Bibliography Update MAC presented the latest journal and congress profiles and reminded the team that profiling is continuing. MAC also presented the latest screen shots from the bibliography. LT requested a special meeting to discuss the bibliography, independent of other publication issues. In addition; MAC was actioned to provide a small working model to be MAC tested at the meeting. Stephen Valerio Medical Projects Director the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026119

Whose responsibility is to provide the correct information?

fmjm0223

fmjm0223_p46, fmjm0223_p47, fmjm0223_p48, fmjm0223_p49

Author, "authors", "It is the authors responsibility", "Authors"

Blackwell Science Copyright Assignment Form By signing this form you certify that your contribution is your original work, has not been published before and is not being considered for publication elsewhere; that you have obtained permission for and acknowledged the source of any excerpts from other copyright works; that to the best of your knowledge your paper contains no statements which are libelous, unfawful or in any way actionable and that you have informed any co-authors of the terms of this agreement and are signing on their behalf. Then print out the form and complete parts 1 and 2. If you do not own the copyright to your article, please complete part 1 and get the copyright holder to complete and sign part 3. Return the form to the address below and keep a duplicate for your records. 1 To be completed in all cases Name: Dr. Beate Roder Address: Pfizer GmbH International Medical Research Mooswaldallee 1 79090 Freiburg, Germany Journal Title: Diabetic Medicine - Journal of Diabetes UK Article Title: Gabapentin in painful diabetic neuropathy : a randomised, double-blind, placebo-controlled study 2 To be filled in if the copyright belongs to you In consideration of the publication of my contribution in the above journal, I hereby warrant: (a) that in the case of joint authorship I have been authorised by all co-authors to sign this agreement on their behalf, and references to the singular shall include the plural as appropriate; (b) that this article is the author(s)' original work, has not been previously published elsewhere either in printed or electronic form (including World Wide Web home pages, discussion groups and other electronic bulletin boards), and is not under consideration for publication elsewhere; (c) that this article contains 'no violation of any existing copyright or other third party right or any material of an obscene, libellous or otherwise unlawful nature, and that I will indemnify and keep indemnified the Editor and Blackwell Science Ltd against all claims and expenses (including legal costs and expenses) arising from any breach of this warranty and the other warranties on my behalf in this agreement; (d) that 1 have obtained permission for and acknowledged the source of any illustrations, diagrams or other material included in the article of which I am not the copyright owner. In consideration of the publication of my contribution in the above journal, I hereby assign to Blackwell Science Ltd (acting as agent for the owner of copyright in the journal where different) the present and/or future copyright throughout the world in any form and in any language (including without limitation on optical disk, transmission over the internet and other communications networks, and in any other electronic form) Signed: Beak Roder Date: 15-Teb-2002 (to be signed by corresponding or senior author on behalf of all authors) CONFIDENTIAL Source: ttps://www.industrydocuments.ucsf.edu/docs/fmjm22ger LeslieTive 0020887. 3 To be filled in if the copyright does not belong to you Please provide the complete and full title of the copyright holder. This will be printed on the copyright line on each page of the article. It is the author's responsibility to provide the correct information. (a) Name and address of copyright holder (if not the author) : (b) The copyright holder hereby grants Blackwell Science Ltd non-exclusive rights to deal with requests from third parties in the manner specified in paragraphs 4 and 6 of the notes. Signed: Date: PLEASE RETURN ONE SIGNED COPY OF THIS FORM AND KEEP A DUPLICATE the inument CONFIDENTIAL Source: 0020888 Notes on the Assignment of Copyright 1 The journal's policy is to acquire copyright for all contributions. There are two reasons for this: (a) ownership of copyright by one central organisation tends to ensure maximum international protection against infringement; (b) it also ensures that requests by third parties to reprint a contribution, or part of it, are handled efficiently and in accordance with a general policy which is sensible both to any relevant changes in international copyright legislation and to the general desirability of encouraging the dissemination of knowledge. 2 The author retains his or her moral rights in the article including the right to be identified as the author whenever and wherever the article is published, under the terms of the UK Copyright Designs and Patents Act 1988. 3 In assigning your copyright you are not forfeiting your rights to use your contribution elsewhere. This you may do after obtaining our permission (only withheld in exceptional circumstances) provided that the journal is acknowledged as the original source. 4 All requests to reprint your contribution, or a substantial part of it, or figures, tables or illustrations from it in another publication (including publications of Blackwell Science) will be subject to your approval (which we will assume is given if we have not heard from you within thirty days of your approval being sought). 5 The journal is registered with the Copyright Licensing Agency (London) and the Copyright Clearance Center (New York), non-profit making organizations which offer centralized licensing arrangements for photocopying. Any income. received through these arrangements will be used to further the interests of the journal. 6 It is understood that in some cases copyright will be held by the contributor's employer (for instance the Britéh or US Government). If so, the journal requires non-exclusive permission to deal with requests from third parties, on the understanding that any requests it receives from third parties will be handled in accordance with. paragraph 4 above (i.e. you and your employer will be asked to approve the proposed use). If you are or were a UK Crown servant and the contribution is made in that capacity, the article must be submitted for clearance by- the Permanent Head of the Department concerned. If you are or were a US Government employee and the contribution is made in that capacity, assignment applies only to the extent allowable by US law. In all cases, the Publishers must be informed as soon as the article is accepted for publication so that the appropriate arrangements can be made with the contributor's employer. 7 In addition to reproduction in conventional printed form your article may be stored electronically and then printed out (e.g. from CD-ROM under the ADONIS document delivery scheme) to meet individual requests. Your assignment of copyright signifies your agreement to the journal making arrangements to include your paper in such document delivery services and electronic journal databases. 8 By signing this form you certify that your .contribution is your original work, has not been published before and is not being considered for publication elsewhere; that you have obtained permission for and acknowledged the source of any excerpts from other copyright works; that to the best of your knowledge your paper contains no statements which are libelous, unlawful or in any way actionable and that you have informed any co-authors of the terms of this agreement and are signing on their behalf. Pfizer LeslieTive 0020889: CONFIDENTIAL Source: https://wwww.industrydocuments.ucsf.edu/docs/fmjm0223 Gabapentin in painful diabetic neuropathy: a randomised, double-blind, placebo- controlled study J Reckless on behalf of the Gabapentin Diabetic Neuropathic Pain Study Group², B Roder³, P Maisonobe4 The Wolfson Centre, Royal United Hospital, Combe Park, Bath BA1 3NG, UK ²France: N Attal, o Blin, F Boureau, G Chazot, P Denise, D Kong-A-Siou, M Lantéri- Minet, J Latarjet, B Laurent, G Mick, C Minello, L Rambaud, G Said, P Tajfel. Germany: M Anders, E Austenat, F Best, J Beyer, U Böckmann, W Hüning, M Huptas, C Jaursch- Hancke, V-F Lindner, C Metzger, M Plum, LA Röhrig, T Scholten, R Wörz. Italy: S Caronna, M Farinelli, R Giórgino, G Masotti, C Messina, F Rasi, M Trovati, P Zagnoni. South Africa: LA Distiller, LI Robertson. Spain: J de Andrés Ibáñez, ML Franco Gay, JL Madrid, MA Quesada García, MV Ribera Canudas, G Roca Amatria, J Serra i Catafau. United Kingdom: MS Chong, RJC Guy, AB Johnson, RW Johnson, D Kerr, JP O'Hare, V Patel, JPD Reckless, DD Sandeman, HCR Simpson. GmbH, Mooswaldallee 1, 79090-Freiburg, Germany 4Pfizer GRD, 3-9 rue de la Loge, 94265 Fresites Cedex, France Correspondence to: Dr Beate Roder, Pfizer GmbH, Mooswaldallee 1, 79090 Freiburg, Germany. Telephone ++49 761 518 2146, fax ++49 761 518 3072, [email protected] Running title: Gabapentin for painful diabetic neuropathy 1 Source: https://www.industrydocuments.ucsf.edu/docs/fmjm02E3er LeslieTive 0020890 CONFIDENTIAL

Who grants Blackwell Science Ltd non-exclusive rights to deal with requests from third parties?

fmjm0223

fmjm0223_p46, fmjm0223_p47, fmjm0223_p48, fmjm0223_p49

The copyright holder, copyright holder

Blackwell Science Copyright Assignment Form By signing this form you certify that your contribution is your original work, has not been published before and is not being considered for publication elsewhere; that you have obtained permission for and acknowledged the source of any excerpts from other copyright works; that to the best of your knowledge your paper contains no statements which are libelous, unfawful or in any way actionable and that you have informed any co-authors of the terms of this agreement and are signing on their behalf. Then print out the form and complete parts 1 and 2. If you do not own the copyright to your article, please complete part 1 and get the copyright holder to complete and sign part 3. Return the form to the address below and keep a duplicate for your records. 1 To be completed in all cases Name: Dr. Beate Roder Address: Pfizer GmbH International Medical Research Mooswaldallee 1 79090 Freiburg, Germany Journal Title: Diabetic Medicine - Journal of Diabetes UK Article Title: Gabapentin in painful diabetic neuropathy : a randomised, double-blind, placebo-controlled study 2 To be filled in if the copyright belongs to you In consideration of the publication of my contribution in the above journal, I hereby warrant: (a) that in the case of joint authorship I have been authorised by all co-authors to sign this agreement on their behalf, and references to the singular shall include the plural as appropriate; (b) that this article is the author(s)' original work, has not been previously published elsewhere either in printed or electronic form (including World Wide Web home pages, discussion groups and other electronic bulletin boards), and is not under consideration for publication elsewhere; (c) that this article contains 'no violation of any existing copyright or other third party right or any material of an obscene, libellous or otherwise unlawful nature, and that I will indemnify and keep indemnified the Editor and Blackwell Science Ltd against all claims and expenses (including legal costs and expenses) arising from any breach of this warranty and the other warranties on my behalf in this agreement; (d) that 1 have obtained permission for and acknowledged the source of any illustrations, diagrams or other material included in the article of which I am not the copyright owner. In consideration of the publication of my contribution in the above journal, I hereby assign to Blackwell Science Ltd (acting as agent for the owner of copyright in the journal where different) the present and/or future copyright throughout the world in any form and in any language (including without limitation on optical disk, transmission over the internet and other communications networks, and in any other electronic form) Signed: Beak Roder Date: 15-Teb-2002 (to be signed by corresponding or senior author on behalf of all authors) CONFIDENTIAL Source: ttps://www.industrydocuments.ucsf.edu/docs/fmjm22ger LeslieTive 0020887. 3 To be filled in if the copyright does not belong to you Please provide the complete and full title of the copyright holder. This will be printed on the copyright line on each page of the article. It is the author's responsibility to provide the correct information. (a) Name and address of copyright holder (if not the author) : (b) The copyright holder hereby grants Blackwell Science Ltd non-exclusive rights to deal with requests from third parties in the manner specified in paragraphs 4 and 6 of the notes. Signed: Date: PLEASE RETURN ONE SIGNED COPY OF THIS FORM AND KEEP A DUPLICATE the inument CONFIDENTIAL Source: 0020888 Notes on the Assignment of Copyright 1 The journal's policy is to acquire copyright for all contributions. There are two reasons for this: (a) ownership of copyright by one central organisation tends to ensure maximum international protection against infringement; (b) it also ensures that requests by third parties to reprint a contribution, or part of it, are handled efficiently and in accordance with a general policy which is sensible both to any relevant changes in international copyright legislation and to the general desirability of encouraging the dissemination of knowledge. 2 The author retains his or her moral rights in the article including the right to be identified as the author whenever and wherever the article is published, under the terms of the UK Copyright Designs and Patents Act 1988. 3 In assigning your copyright you are not forfeiting your rights to use your contribution elsewhere. This you may do after obtaining our permission (only withheld in exceptional circumstances) provided that the journal is acknowledged as the original source. 4 All requests to reprint your contribution, or a substantial part of it, or figures, tables or illustrations from it in another publication (including publications of Blackwell Science) will be subject to your approval (which we will assume is given if we have not heard from you within thirty days of your approval being sought). 5 The journal is registered with the Copyright Licensing Agency (London) and the Copyright Clearance Center (New York), non-profit making organizations which offer centralized licensing arrangements for photocopying. Any income. received through these arrangements will be used to further the interests of the journal. 6 It is understood that in some cases copyright will be held by the contributor's employer (for instance the Britéh or US Government). If so, the journal requires non-exclusive permission to deal with requests from third parties, on the understanding that any requests it receives from third parties will be handled in accordance with. paragraph 4 above (i.e. you and your employer will be asked to approve the proposed use). If you are or were a UK Crown servant and the contribution is made in that capacity, the article must be submitted for clearance by- the Permanent Head of the Department concerned. If you are or were a US Government employee and the contribution is made in that capacity, assignment applies only to the extent allowable by US law. In all cases, the Publishers must be informed as soon as the article is accepted for publication so that the appropriate arrangements can be made with the contributor's employer. 7 In addition to reproduction in conventional printed form your article may be stored electronically and then printed out (e.g. from CD-ROM under the ADONIS document delivery scheme) to meet individual requests. Your assignment of copyright signifies your agreement to the journal making arrangements to include your paper in such document delivery services and electronic journal databases. 8 By signing this form you certify that your .contribution is your original work, has not been published before and is not being considered for publication elsewhere; that you have obtained permission for and acknowledged the source of any excerpts from other copyright works; that to the best of your knowledge your paper contains no statements which are libelous, unlawful or in any way actionable and that you have informed any co-authors of the terms of this agreement and are signing on their behalf. Pfizer LeslieTive 0020889: CONFIDENTIAL Source: https://wwww.industrydocuments.ucsf.edu/docs/fmjm0223 Gabapentin in painful diabetic neuropathy: a randomised, double-blind, placebo- controlled study J Reckless on behalf of the Gabapentin Diabetic Neuropathic Pain Study Group², B Roder³, P Maisonobe4 The Wolfson Centre, Royal United Hospital, Combe Park, Bath BA1 3NG, UK ²France: N Attal, o Blin, F Boureau, G Chazot, P Denise, D Kong-A-Siou, M Lantéri- Minet, J Latarjet, B Laurent, G Mick, C Minello, L Rambaud, G Said, P Tajfel. Germany: M Anders, E Austenat, F Best, J Beyer, U Böckmann, W Hüning, M Huptas, C Jaursch- Hancke, V-F Lindner, C Metzger, M Plum, LA Röhrig, T Scholten, R Wörz. Italy: S Caronna, M Farinelli, R Giórgino, G Masotti, C Messina, F Rasi, M Trovati, P Zagnoni. South Africa: LA Distiller, LI Robertson. Spain: J de Andrés Ibáñez, ML Franco Gay, JL Madrid, MA Quesada García, MV Ribera Canudas, G Roca Amatria, J Serra i Catafau. United Kingdom: MS Chong, RJC Guy, AB Johnson, RW Johnson, D Kerr, JP O'Hare, V Patel, JPD Reckless, DD Sandeman, HCR Simpson. GmbH, Mooswaldallee 1, 79090-Freiburg, Germany 4Pfizer GRD, 3-9 rue de la Loge, 94265 Fresites Cedex, France Correspondence to: Dr Beate Roder, Pfizer GmbH, Mooswaldallee 1, 79090 Freiburg, Germany. Telephone ++49 761 518 2146, fax ++49 761 518 3072, [email protected] Running title: Gabapentin for painful diabetic neuropathy 1 Source: https://www.industrydocuments.ucsf.edu/docs/fmjm02E3er LeslieTive 0020890 CONFIDENTIAL

The Invitation Was Made By A?

rjmd0217

rjmd0217_p0, rjmd0217_p1, rjmd0217_p2

Firm other than Pharmaceutical Company

G EVENT 1:" Page'smits (+), 601964 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether OT not you attended. Was A Pharmaceutical Company Associated With The Event? City/State: Yes Company Name: Parke Davis 192 Event Date (Month/Day/Year): 2 / 109 / 98 No The Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm Firm other Name: than Pharmaceutical medical Company research Associatin up What Type Of Honorarlum Was Offerod? (Chock AL That Apply) Meals University/Medical Institution (eg., Vanderbilt University) Name: Charitable Contribution Cash/Check Clinical/Professional Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Other: (please specify) Gift Certificate (please specify for what): medical Suppler Textbooks (please specify): Tho Evont Was Sponsored By: (Check All That Apply) Pharmaccutical Company: Parke navi 192 Other: None University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES Because Of: (Check All That Managed Care Company: Interest In The Topic Other: (please specify) Type Of Honoraria Offered Tho Announcod Topic Was: (Check All Tha Appy) Topic Reputation Of Speakers General Therapeutic Area 48. CME Credits Offered (e.g., hypertension, heart failure, diabetes): It of Epilepsy Convenient Location A Therapeutic Class of Drugs Other (please specify): (e.g., ACE Inhibitors, diuretics): NO, Because Of: (Check All That Apply) A Specific Product Manufactured by The Pharnuceutical Company: 12233 Neurontin Lack Of Interest In The Topic Disease Management Program Scheduling Conflict (professional or personal) (treatment guldellnes, protocols, care maps, etc.): Type Of Honoraria Offered Other: No CME Credits Offered Evont Location: (Ploase Chock Appropriale Box And Record Spocific Namo On Uno Bolow): Inconvenient Location/Distance Hotel Restaurant Convention Mkt. Res. Facility Other (please specify): Home Office Other (Specify Name): Telephone Conference If You Attended, Please Continue With The Questions On The Following Pages. Pleaso Continuo With Tho Quostions To The Right S-L09819 Please Continue With The Questions For Event 1 On The Next Page. 15 CE 4 EVENT 1: Page 2 of 3 601964 PRODUCT INFORMATION Yes (Please complete the boxes in this section.) How many times Wore Specific Products Discussed? have you been No (Please go to the "General Theme" detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 1 Product Name: Neurontin Not Detailed Nonprescriber Nonprescriber THEME(S): (Piease Be As Specific As Possible) 12233 ply 1 Detail Low Low 2 Details Moderate Modorato Advance in tx of Epilepsy 3 Details High High >3 Details 2 Product Name: 2/98 Not Detailod Nonprescribor Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderato Moderate 3 Details High High >3 Details 3 p'oduct Name: Not Detailod Nonprescriber Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderato Moderato 3 Details High High >3 Details GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topics Discussed (Advanco in tx of opilepsy. - Focu in Neworks) S-L09818 15 Source:

was a pharmaceutical company associated with the event?

qlmd0217

qlmd0217_p0, qlmd0217_p1, qlmd0217_p2

Yes, yes

EVENT 1: Page 1 of 3 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether or nol you attended. Was A Pharmacoutical Company Associated With The Event? Yes Company Name: Saussen 125 City/State: SF Ca 602484 Event Date (Month/Day/Yoer): 78112898 No Tho Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical CMC, Company Ive (99) What Type Of Honorarlum Was Offered? (Chock As That Apply) Firm Name: Meals University/Medical Institution (c.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Professlonal Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Gift Certificate (please specify for what): Other: (please specify) Textbooks (please specify): Tho Evont Was Sponsored By: (Chock Alf, That Janasen Appy) 125 Other: Pharmaceutical Company: Nonc University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES, Because Of: (Check All Thut Managed Care Company: Interest In The Topic D Other: (please specl(y) CME, 245 Type Of Honoraria Offered Tho Announced Tople Was: (Chock AI That Appy) Toplc Reputation Of Speakers General Therapeutic Area 74 CME Credits Offered (e.g, hypertension, heart fallure, diabetes): Progress in Pay chosis Convenient Location A Therapeutic Class of Drugs Other (please specily): (e.g., ACE Inhibitors, dluretics): NO, Because Of: (Check All Thet Apply) A Specific Product Manufactured by The Pharmaccutical Company: Lack Of Interest In The Topic Discase Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honorarla Offered No CME Credits Offered Other: Inconvenient Location/Distance Event Locallon: (Ploase Crock Appropriase Dour And Necord Spoditic Name On Line Bolow): Other (please specify): Hotel Restaurant Convention Mkt. Res. Facility Home Office Other (Specify Name): airport marristt : If You Attended, Please Continue With The Questions On The Following Pages. : Ploaso Continuo With The Questions To The Right Please Continue With The Questions For Event 1 On The Next Page. 18 S-L09960 Source: https://www.industrydocuments.ucsf.edu/docs/qlmd0217 EVENT 1: Page 2 of 3 PRODUCT INTORMATION Woro Spocific Products Discussod? Yes (Please complete the boxes in this section.) How many times No (Please go to the "General Theme" have you been detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 2 Product Name: neurouten THEME(S): Not Dotailed Nopproscriber Nonprescribor (Please Be As Specific As l'ossible) 1 Detail Low Low helps impulsivity in 2 Dotails Moderato Modorato 3 Dotails High High >3 Dotails REDACTED GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topic Discussed cognitive impairment prior to 1st Belizaphieine break 250 S-L09961 Please Continue With The Questions For Event 1 On The Next Page. ISF Source: https://www.industrydocuments.ucsf.edu/docs/gimd0217

what is the hotel name?

qlmd0217

qlmd0217_p0, qlmd0217_p1, qlmd0217_p2

Airport Marriott, airport marriott

EVENT 1: Page 1 of 3 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether or nol you attended. Was A Pharmacoutical Company Associated With The Event? Yes Company Name: Saussen 125 City/State: SF Ca 602484 Event Date (Month/Day/Yoer): 78112898 No Tho Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical CMC, Company Ive (99) What Type Of Honorarlum Was Offered? (Chock As That Apply) Firm Name: Meals University/Medical Institution (c.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Professlonal Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Gift Certificate (please specify for what): Other: (please specify) Textbooks (please specify): Tho Evont Was Sponsored By: (Chock Alf, That Janasen Appy) 125 Other: Pharmaceutical Company: Nonc University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES, Because Of: (Check All Thut Managed Care Company: Interest In The Topic D Other: (please specl(y) CME, 245 Type Of Honoraria Offered Tho Announced Tople Was: (Chock AI That Appy) Toplc Reputation Of Speakers General Therapeutic Area 74 CME Credits Offered (e.g, hypertension, heart fallure, diabetes): Progress in Pay chosis Convenient Location A Therapeutic Class of Drugs Other (please specily): (e.g., ACE Inhibitors, dluretics): NO, Because Of: (Check All Thet Apply) A Specific Product Manufactured by The Pharmaccutical Company: Lack Of Interest In The Topic Discase Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honorarla Offered No CME Credits Offered Other: Inconvenient Location/Distance Event Locallon: (Ploase Crock Appropriase Dour And Necord Spoditic Name On Line Bolow): Other (please specify): Hotel Restaurant Convention Mkt. Res. Facility Home Office Other (Specify Name): airport marristt : If You Attended, Please Continue With The Questions On The Following Pages. : Ploaso Continuo With The Questions To The Right Please Continue With The Questions For Event 1 On The Next Page. 18 S-L09960 Source: https://www.industrydocuments.ucsf.edu/docs/qlmd0217 EVENT 1: Page 2 of 3 PRODUCT INTORMATION Woro Spocific Products Discussod? Yes (Please complete the boxes in this section.) How many times No (Please go to the "General Theme" have you been detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 2 Product Name: neurouten THEME(S): Not Dotailed Nopproscriber Nonprescribor (Please Be As Specific As l'ossible) 1 Detail Low Low helps impulsivity in 2 Dotails Moderato Modorato 3 Dotails High High >3 Dotails REDACTED GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topic Discussed cognitive impairment prior to 1st Belizaphieine break 250 S-L09961 Please Continue With The Questions For Event 1 On The Next Page. ISF Source: https://www.industrydocuments.ucsf.edu/docs/gimd0217

what is the city/state?

qlmd0217

qlmd0217_p0, qlmd0217_p1, qlmd0217_p2

SF, Ca, SF, CA

EVENT 1: Page 1 of 3 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether or nol you attended. Was A Pharmacoutical Company Associated With The Event? Yes Company Name: Saussen 125 City/State: SF Ca 602484 Event Date (Month/Day/Yoer): 78112898 No Tho Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical CMC, Company Ive (99) What Type Of Honorarlum Was Offered? (Chock As That Apply) Firm Name: Meals University/Medical Institution (c.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Professlonal Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Gift Certificate (please specify for what): Other: (please specify) Textbooks (please specify): Tho Evont Was Sponsored By: (Chock Alf, That Janasen Appy) 125 Other: Pharmaceutical Company: Nonc University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES, Because Of: (Check All Thut Managed Care Company: Interest In The Topic D Other: (please specl(y) CME, 245 Type Of Honoraria Offered Tho Announced Tople Was: (Chock AI That Appy) Toplc Reputation Of Speakers General Therapeutic Area 74 CME Credits Offered (e.g, hypertension, heart fallure, diabetes): Progress in Pay chosis Convenient Location A Therapeutic Class of Drugs Other (please specily): (e.g., ACE Inhibitors, dluretics): NO, Because Of: (Check All Thet Apply) A Specific Product Manufactured by The Pharmaccutical Company: Lack Of Interest In The Topic Discase Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honorarla Offered No CME Credits Offered Other: Inconvenient Location/Distance Event Locallon: (Ploase Crock Appropriase Dour And Necord Spoditic Name On Line Bolow): Other (please specify): Hotel Restaurant Convention Mkt. Res. Facility Home Office Other (Specify Name): airport marristt : If You Attended, Please Continue With The Questions On The Following Pages. : Ploaso Continuo With The Questions To The Right Please Continue With The Questions For Event 1 On The Next Page. 18 S-L09960 Source: https://www.industrydocuments.ucsf.edu/docs/qlmd0217 EVENT 1: Page 2 of 3 PRODUCT INTORMATION Woro Spocific Products Discussod? Yes (Please complete the boxes in this section.) How many times No (Please go to the "General Theme" have you been detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 2 Product Name: neurouten THEME(S): Not Dotailed Nopproscriber Nonprescribor (Please Be As Specific As l'ossible) 1 Detail Low Low helps impulsivity in 2 Dotails Moderato Modorato 3 Dotails High High >3 Dotails REDACTED GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topic Discussed cognitive impairment prior to 1st Belizaphieine break 250 S-L09961 Please Continue With The Questions For Event 1 On The Next Page. ISF Source: https://www.industrydocuments.ucsf.edu/docs/gimd0217

were CME credits offered?

qlmd0217

qlmd0217_p0, qlmd0217_p1, qlmd0217_p2

Yes, yes

EVENT 1: Page 1 of 3 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether or nol you attended. Was A Pharmacoutical Company Associated With The Event? Yes Company Name: Saussen 125 City/State: SF Ca 602484 Event Date (Month/Day/Yoer): 78112898 No Tho Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical CMC, Company Ive (99) What Type Of Honorarlum Was Offered? (Chock As That Apply) Firm Name: Meals University/Medical Institution (c.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Professlonal Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Gift Certificate (please specify for what): Other: (please specify) Textbooks (please specify): Tho Evont Was Sponsored By: (Chock Alf, That Janasen Appy) 125 Other: Pharmaceutical Company: Nonc University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES, Because Of: (Check All Thut Managed Care Company: Interest In The Topic D Other: (please specl(y) CME, 245 Type Of Honoraria Offered Tho Announced Tople Was: (Chock AI That Appy) Toplc Reputation Of Speakers General Therapeutic Area 74 CME Credits Offered (e.g, hypertension, heart fallure, diabetes): Progress in Pay chosis Convenient Location A Therapeutic Class of Drugs Other (please specily): (e.g., ACE Inhibitors, dluretics): NO, Because Of: (Check All Thet Apply) A Specific Product Manufactured by The Pharmaccutical Company: Lack Of Interest In The Topic Discase Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honorarla Offered No CME Credits Offered Other: Inconvenient Location/Distance Event Locallon: (Ploase Crock Appropriase Dour And Necord Spoditic Name On Line Bolow): Other (please specify): Hotel Restaurant Convention Mkt. Res. Facility Home Office Other (Specify Name): airport marristt : If You Attended, Please Continue With The Questions On The Following Pages. : Ploaso Continuo With The Questions To The Right Please Continue With The Questions For Event 1 On The Next Page. 18 S-L09960 Source: https://www.industrydocuments.ucsf.edu/docs/qlmd0217 EVENT 1: Page 2 of 3 PRODUCT INTORMATION Woro Spocific Products Discussod? Yes (Please complete the boxes in this section.) How many times No (Please go to the "General Theme" have you been detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 2 Product Name: neurouten THEME(S): Not Dotailed Nopproscriber Nonprescribor (Please Be As Specific As l'ossible) 1 Detail Low Low helps impulsivity in 2 Dotails Moderato Modorato 3 Dotails High High >3 Dotails REDACTED GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topic Discussed cognitive impairment prior to 1st Belizaphieine break 250 S-L09961 Please Continue With The Questions For Event 1 On The Next Page. ISF Source: https://www.industrydocuments.ucsf.edu/docs/gimd0217

what type of Honorarlum was offered?

qlmd0217

qlmd0217_p0, qlmd0217_p1, qlmd0217_p2

Meals, meals

EVENT 1: Page 1 of 3 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether or nol you attended. Was A Pharmacoutical Company Associated With The Event? Yes Company Name: Saussen 125 City/State: SF Ca 602484 Event Date (Month/Day/Yoer): 78112898 No Tho Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical CMC, Company Ive (99) What Type Of Honorarlum Was Offered? (Chock As That Apply) Firm Name: Meals University/Medical Institution (c.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Professlonal Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Gift Certificate (please specify for what): Other: (please specify) Textbooks (please specify): Tho Evont Was Sponsored By: (Chock Alf, That Janasen Appy) 125 Other: Pharmaceutical Company: Nonc University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES, Because Of: (Check All Thut Managed Care Company: Interest In The Topic D Other: (please specl(y) CME, 245 Type Of Honoraria Offered Tho Announced Tople Was: (Chock AI That Appy) Toplc Reputation Of Speakers General Therapeutic Area 74 CME Credits Offered (e.g, hypertension, heart fallure, diabetes): Progress in Pay chosis Convenient Location A Therapeutic Class of Drugs Other (please specily): (e.g., ACE Inhibitors, dluretics): NO, Because Of: (Check All Thet Apply) A Specific Product Manufactured by The Pharmaccutical Company: Lack Of Interest In The Topic Discase Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honorarla Offered No CME Credits Offered Other: Inconvenient Location/Distance Event Locallon: (Ploase Crock Appropriase Dour And Necord Spoditic Name On Line Bolow): Other (please specify): Hotel Restaurant Convention Mkt. Res. Facility Home Office Other (Specify Name): airport marristt : If You Attended, Please Continue With The Questions On The Following Pages. : Ploaso Continuo With The Questions To The Right Please Continue With The Questions For Event 1 On The Next Page. 18 S-L09960 Source: https://www.industrydocuments.ucsf.edu/docs/qlmd0217 EVENT 1: Page 2 of 3 PRODUCT INTORMATION Woro Spocific Products Discussod? Yes (Please complete the boxes in this section.) How many times No (Please go to the "General Theme" have you been detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 2 Product Name: neurouten THEME(S): Not Dotailed Nopproscriber Nonprescribor (Please Be As Specific As l'ossible) 1 Detail Low Low helps impulsivity in 2 Dotails Moderato Modorato 3 Dotails High High >3 Dotails REDACTED GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topic Discussed cognitive impairment prior to 1st Belizaphieine break 250 S-L09961 Please Continue With The Questions For Event 1 On The Next Page. ISF Source: https://www.industrydocuments.ucsf.edu/docs/gimd0217

what is the event number?

qlmd0217

qlmd0217_p0, qlmd0217_p1, qlmd0217_p2

1, Event 1

EVENT 1: Page 1 of 3 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether or nol you attended. Was A Pharmacoutical Company Associated With The Event? Yes Company Name: Saussen 125 City/State: SF Ca 602484 Event Date (Month/Day/Yoer): 78112898 No Tho Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical CMC, Company Ive (99) What Type Of Honorarlum Was Offered? (Chock As That Apply) Firm Name: Meals University/Medical Institution (c.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Professlonal Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Gift Certificate (please specify for what): Other: (please specify) Textbooks (please specify): Tho Evont Was Sponsored By: (Chock Alf, That Janasen Appy) 125 Other: Pharmaceutical Company: Nonc University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES, Because Of: (Check All Thut Managed Care Company: Interest In The Topic D Other: (please specl(y) CME, 245 Type Of Honoraria Offered Tho Announced Tople Was: (Chock AI That Appy) Toplc Reputation Of Speakers General Therapeutic Area 74 CME Credits Offered (e.g, hypertension, heart fallure, diabetes): Progress in Pay chosis Convenient Location A Therapeutic Class of Drugs Other (please specily): (e.g., ACE Inhibitors, dluretics): NO, Because Of: (Check All Thet Apply) A Specific Product Manufactured by The Pharmaccutical Company: Lack Of Interest In The Topic Discase Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honorarla Offered No CME Credits Offered Other: Inconvenient Location/Distance Event Locallon: (Ploase Crock Appropriase Dour And Necord Spoditic Name On Line Bolow): Other (please specify): Hotel Restaurant Convention Mkt. Res. Facility Home Office Other (Specify Name): airport marristt : If You Attended, Please Continue With The Questions On The Following Pages. : Ploaso Continuo With The Questions To The Right Please Continue With The Questions For Event 1 On The Next Page. 18 S-L09960 Source: https://www.industrydocuments.ucsf.edu/docs/qlmd0217 EVENT 1: Page 2 of 3 PRODUCT INTORMATION Woro Spocific Products Discussod? Yes (Please complete the boxes in this section.) How many times No (Please go to the "General Theme" have you been detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 2 Product Name: neurouten THEME(S): Not Dotailed Nopproscriber Nonprescribor (Please Be As Specific As l'ossible) 1 Detail Low Low helps impulsivity in 2 Dotails Moderato Modorato 3 Dotails High High >3 Dotails REDACTED GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topic Discussed cognitive impairment prior to 1st Belizaphieine break 250 S-L09961 Please Continue With The Questions For Event 1 On The Next Page. ISF Source: https://www.industrydocuments.ucsf.edu/docs/gimd0217

what is the page number mentioned?

qlmd0217

qlmd0217_p0, qlmd0217_p1, qlmd0217_p2

Page 1 of 3, page 1 of 3

EVENT 1: Page 1 of 3 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether or nol you attended. Was A Pharmacoutical Company Associated With The Event? Yes Company Name: Saussen 125 City/State: SF Ca 602484 Event Date (Month/Day/Yoer): 78112898 No Tho Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical CMC, Company Ive (99) What Type Of Honorarlum Was Offered? (Chock As That Apply) Firm Name: Meals University/Medical Institution (c.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Professlonal Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Gift Certificate (please specify for what): Other: (please specify) Textbooks (please specify): Tho Evont Was Sponsored By: (Chock Alf, That Janasen Appy) 125 Other: Pharmaceutical Company: Nonc University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES, Because Of: (Check All Thut Managed Care Company: Interest In The Topic D Other: (please specl(y) CME, 245 Type Of Honoraria Offered Tho Announced Tople Was: (Chock AI That Appy) Toplc Reputation Of Speakers General Therapeutic Area 74 CME Credits Offered (e.g, hypertension, heart fallure, diabetes): Progress in Pay chosis Convenient Location A Therapeutic Class of Drugs Other (please specily): (e.g., ACE Inhibitors, dluretics): NO, Because Of: (Check All Thet Apply) A Specific Product Manufactured by The Pharmaccutical Company: Lack Of Interest In The Topic Discase Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honorarla Offered No CME Credits Offered Other: Inconvenient Location/Distance Event Locallon: (Ploase Crock Appropriase Dour And Necord Spoditic Name On Line Bolow): Other (please specify): Hotel Restaurant Convention Mkt. Res. Facility Home Office Other (Specify Name): airport marristt : If You Attended, Please Continue With The Questions On The Following Pages. : Ploaso Continuo With The Questions To The Right Please Continue With The Questions For Event 1 On The Next Page. 18 S-L09960 Source: https://www.industrydocuments.ucsf.edu/docs/qlmd0217 EVENT 1: Page 2 of 3 PRODUCT INTORMATION Woro Spocific Products Discussod? Yes (Please complete the boxes in this section.) How many times No (Please go to the "General Theme" have you been detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 2 Product Name: neurouten THEME(S): Not Dotailed Nopproscriber Nonprescribor (Please Be As Specific As l'ossible) 1 Detail Low Low helps impulsivity in 2 Dotails Moderato Modorato 3 Dotails High High >3 Dotails REDACTED GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topic Discussed cognitive impairment prior to 1st Belizaphieine break 250 S-L09961 Please Continue With The Questions For Event 1 On The Next Page. ISF Source: https://www.industrydocuments.ucsf.edu/docs/gimd0217

what is the status of study # 945-420-010?

jnjm0223

jnjm0223_p32, jnjm0223_p33, jnjm0223_p34, jnjm0223_p35, jnjm0223_p36, jnjm0223_p37, jnjm0223_p38, jnjm0223_p39, jnjm0223_p40, jnjm0223_p41, jnjm0223_p42, jnjm0223_p43, jnjm0223_p44, jnjm0223_p45, jnjm0223_p46, jnjm0223_p47, jnjm0223_p48, jnjm0223_p49, jnjm0223_p50, jnjm0223_p51, jnjm0223_p52, jnjm0223_p53, jnjm0223_p54, jnjm0223_p55, jnjm0223_p56, jnjm0223_p57, jnjm0223_p58, jnjm0223_p59, jnjm0223_p60, jnjm0223_p61, jnjm0223_p62, jnjm0223_p63, jnjm0223_p64, jnjm0223_p65, jnjm0223_p66, jnjm0223_p67, jnjm0223_p68, jnjm0223_p69, jnjm0223_p70, jnjm0223_p71

In progress, in progress

Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Gabapentin for the treatment of Rowbotham MC 2 In development. Pain or Neurology AIDS/HIV painful HIV polyneuropathy Neuropathic Pain: HIV neuropathic pain study 2 In development. AIDS/HIV Neuropathic Pain: Treatment of diabetic neuropathy Nicholson B Knapp L 1 In development. JAMA 31-Dec-01 01-May-02 Diabetic Blonde L, Freeman R Rowbotham M, Mutisya E Neuropathy Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 32 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026038 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Gabapentin in painful diabetic Reckless J 2 In development. Diabetic Medicine Diabetic neuropathy: a randomized, Roder B, Maisonobe P Neuropathy double-blind, placebo controlled study (224) Neuropathic Pain: Phantom limb pain (UK) Critchley 1 In development. Phantom Limb Neuropathic Pain: Restless leg syndrome (Spain) 4-high Proposed. Restless Leg Syndrome Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 33 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026039 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Sleep quality and patient-reported Ehrenberg BL Glanzman R 2 Complete CONSORT Neurology 01-Aug-01 01-Nov-01 01-Mar-02 Sleep health status in periodic limb Wagner AK, Chang H, Piron S, Hsu T requirements. movement disorder treated with Corbett KR, Rogers WH gabapentin: a double-blind, randomized, placebo-controlled, cross-over study Psychiatric Gabapentin in the treatment of Marcotte D 2 In development. Primary Psychiatry 01-Oct-01 01-Dec-01 01-Apr-02 Disorders dementia and behavioral disturbance Psychiatric Psychiatric applications of Pande AC 3-high On hold. Disorders gabapentin Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 34 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026040 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Psychiatric Gabapentin and methylphenidate Hamrin V 2 In development. Disorders: Bipolar treatment of a preadolescent with Disorder ADHD and bipolar disorder Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 35 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026041 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Myrick H, Henderson S, Brady KT, Malcolm R. Gabapentin in the treatment of Jan-01 cocaine dependence: a case series. J Clin Psychiatry. 2001;62:19-23. Crawford P, Brown S, Kerr M, Parke Davis Clinical Trials Group. A randomized Mar-01 open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy. Seizure. 2001;10:107-115. Appleton R, Fichtner K, LaMoreaux L, et al. Gabapentin as add-on therapy in Apr-01 children with refractory partial seizures: a 24-week, multicentre, open-label study. Dev Med Child Neurol. 2001;43:267-273. Lado FA, Sperber EF, Moshe SL. Anticonvulsant efficacy of gabapentin on Apr-01 kindling in the immature brain. Epilepsia. 2001;42:458-463. Kwan P, Sills GJ, Brodie MJ. The mechanisms of action of commonly used Apr-01 antiepileptic drugs. Pharmacol Ther. 2001;90:21-34. Medical Action Communications 31-Oct-01 36 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026042 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Haig GM, Bockbrader HN, Wesche DL, Boellner SW, Ouellet D, Brown RR, May-01 Randinitis EJ, Posvar EL. Single-dose gabapentin pharmacokinetics and safety in healthy infants and children. J Clin Pharmacol. 2001;41:507-514. Bridges D, Thompson SWN, Rice ASC. Mechanisms of neuropathic pain. Br J Jul-01 Anaesth. 2001;87:12-26. Schmidt D, Stefan H, Elger CE. Gabapentin-monotherapy in 503 patients with Aug-01 partial epilepsy dissatisfied with initial standard antiepileptic drug therapy. Nervenheilkunde. 2001;20:321-325. Maneuf YP, Hughes J, McKnight AT. Gabapentin inhibits the substance Aug-01 P-facilitated K(+) -evoked release of. Pain. 2001;93(2):191-196. Beran R. Australian study of titration to effect profile of safety (AUS-STEPS): Oct-01 high-dose gabapentin (Neurontin) in partial seizures. Epilepsia. In Press. Medical Action Communications 31-Oct-01 37 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pizer_LKnapp_0026043 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Rice ASC, Maton S, Postherpetic Neuralgia Study Group. Gabapentin in Nov-01 postherpetic neuralgia: a randomised, double blind, placebo controlled study. Pain. In Press. Medical Action Communications 31-Oct-01 38 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026044 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-195 Double-blind, Meador K Data Lock randomized, two-period crossover comparison and behavioral effects of Interim gabapentin and carbamazepine in healthy Data Analysis volunteers FSR Completion Epilespy (BID/TID study) Data Lock Interim Data Analysis FSR Completion 945-421-002 GBP vs Valproate Spain Data Lock (add-on with CBZ, then remove CBZ and drop to monotherapy) Interim Data Analysis FSR Completion Phase III double-blind, Miller, R Data Lock 200,000. 16-Dec-96 placebo-controlled study 00-based assessing the efficacy of on 100 gabapentin in patients Interim patients with amotrophic lateral out of sclerosis (ALS) Data Analysis 200 required for study FSR Completion An open, matched control Magnus-Mi Holmes, L US Data Lock 433,943 01-Nov-95 23-Dec-99 study comparing the ller, L Harvey E, Keither cognitive abilities of D, Khoshbin S, children born to epileptic Adams J, Ryan L Interim mothers who received antiepileptic drug Data Analysis treatment to children born to non-epileptic mothers FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 39 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026045 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 073-170 An open, matched control Magnus-Mi Holmes, L US Data Lock study comparing the ller, L cognitive abilities of children exposed in utero Interim to anti epileptic monotherapy to children Data Analysis born to non-epileptic mothers FSR Completion 945-419-277 Complex/simple partial Accepted Greece Data Lock Information from seizures vs. CBZ London meeting (monotherapy), 13-Aug-01 attended by double-blind, 36 wks. Interim SBS, AEM: initiation delayed due to Data Analysis integration of research budgets. FSR Completion 945-92 Epilepsy Monotherapy vs Complete 14 Countries Data Lock Information from CBZ (290 pts) London meeting 13-Aug-01 attended by Interim SBS, AEM: poster presented from Data Analysis mid-term analysis of 100pts--study now complete-research FSR Completion report written 945-952-236 Neurontin for neurogenic Completed Herbert J Apr-96 Dec-98 Data Lock 78,500 pain in multiple sclerosis Interim Data Analysis FSR Completion 945-954-241 Neurontin in Essential Completed Uitti R Jul-98 Feb-99 Data Lock 48,000 temor Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 40 Source:https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026046 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-250 Gabapentin adjunctive Completed Ketter T Apr-98 Dec-99 Data Lock 90,691 treatment in patients with bipolar disorder Interim Data Analysis FSR Completion 945-954-252 In vivo determination of Completed Kuzniecky R Dec-96 Nov-97 Data Lock 216,610 human brain gaba Gilliam F concentrations in volunteers receiving Interim gabapentin:an escalating dose response study Data Analysis FSR Completion 945-400-281 VA COOP STUDY #428 Completed Ramsay E Jan-99 Dec-99 Data Lock 50,000 Interim Data Analysis FSR Completion 945-952-282 Gabapentin Completed Gidal B, Jul-95 Aug-00 Data Lock 87,993.1 pharmacology: Effects of Weissman J 5 GABA on human cerebral GABA concentrations Interim studies with NMR spectroscopy Data Analysis FSR Completion 945-400-WW2 SALINSKY BUDGET Completed Salinsky M Dec-96 Oct-98 Data Lock 159,364 TRF FR WE Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 41 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026047 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-090 Dose Intitiaition: Titration Completed Multicenter Jan-94 Dec-98 Data Lock 2,801,75 vs. Non-Titration 6 Interim Data Analysis FSR Completion 945-400-193 Neurontin STEPS (Study Completed Multicenter Jan-95 May-98 Data Lock 4,269,90 and of titration to 0 945-400-200 effectiveness and profile of safety) Interim Data Analysis FSR Completion 945-400-211 A Double-blind, Completed Carr D, Jan-96 Jan-99 Data Lock 1,967,40 randomized, placebo Rosenberg J, 0 controlled, parallel group, Dunteman E, multicenter trial to Harden N, Interim determine the efficacy Kreitzer J, Mann and safety of Neurontin JD, Obbens E, Data Analysis in subjects with peripheral Rowbotham M, neuropathy (Post-herpetic Ross E, Yokiel Neuralgia) J, Schell D, FSR Completion Singer E, Stewart RM, 945-400-217 MIGRAINE BID Completed Jan-97 Dec-99 Data Lock 1,849,73 0.03 Interim Data Analysis FSR Completion 945-400-220 MIGRAINE TID Completed Sep-96 Sep-98 Data Lock 699,598. 81 Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 42 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026048 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-953-231 Evaluation of the efficacy Completed Duntley Dec-96 Mar-99 Data Lock 46,650 of neurontin in the treatment of restless leg syndome and periodic Interim limb movement Data Analysis FSR Completion 945-952-233 Neurontin in the treatment Completed Feinberg Oct-96 Mar-99 Data Lock 35,000 of agitation in patients with demetia Interim Data Analysis FSR Completion 945-953-243 Double-blind, Completed Klapper JA Apr-98 Dec-98 Data Lock 1,100 randomized, placebo-controlled, parallel group trial to Interim determine the efficacy and safety of neurontin Data Analysis (gabapentin) in subjects with trigeminal neuralgia FSR Completion 945-954-244 Quantitative assessments Completed Longmire D Jul-96 Dec-96 Data Lock 15,000 of sympathetic pseudomotor changes induced by gabapentin in Interim patients with neuropathic pain Data Analysis FSR Completion 945-954-246 Adjunctive treatment for Completed Aug-98 Oct-99 Data Lock 0.01 bipolar disorder Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 43 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026049 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-954-247 A retrospective study of Completed Nuckolls J Nov-97 Jan-98 Data Lock 4,375 the effectiveness of gabapentin in the treatment of mood Interim disorders Data Analysis FSR Completion 945-954-249 A blinded randomized trial Completed Hines R Jul-99 Oct-99 Data Lock 2,000 to evaluate the efficacy of gabapentin versus ibuprofen in patients with Interim chronic pelvic pain Data Analysis FSR Completion 945-954-253 Category analysis of the Completed Longmire D Aug-97 Jun-98 Data Lock 15,000 effects of gabapentin on neuropathic pain: an open-label community Interim based outcomes study of over six hundred patient Data Analysis records FSR Completion 945-954-254 A double-blind, Completed Lyketsos Aug-98 Mar-99 Data Lock 0.01 placebo-controlled, parallel clinical trial using gabapentin to treat the Interim behavioral disturbances of out-patients with Data Analysis dementia FSR Completion 945-954-256 Gabapentin in the Completed Myrick H Jun-98 Dec-99 Data Lock 31,000 treatment of cocaine dependence Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 44 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026050 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-953-257 Evaluation of the efficacy Completed Ondo W Nov-96 Mar-99 Data Lock 63,000 of gabapentin for essential tremor Interim Data Analysis FSR Completion 945-952-261 Gabapentin therapy Completed Holmes May 97 Mar-99 Data Lock 22,740 following status epilepticus Interim Data Analysis FSR Completion 945-951-270 Open-label, Completed Gidal B May-98 Dec-99 Data Lock 7,214 non-randomized, pilot study to determine whether chronic neurontin Interim administration results in significant changes in Data Analysis various sex hormones FSR Completion 945-951-417 LEPPIK/SUDEP Completed Leppik I Oct-99 Dec-99 Data Lock 15,000 Interim Data Analysis FSR Completion 945-400-AA1 GABAPENTIN/CYT P450 Completed Dec-97 Feb-99 Data Lock 26,425 REOPENED Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 45 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026051 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-AAA GBP COMBINATION Completed Hammond Jan-98 Nov-98 Data Lock 35,219.1 STUDY FR. 1 0 Interim Data Analysis FSR Completion 945-400-EXT PUBLICATIONS Completed Holmes Jan-97 Apr-98 Data Lock 52,300.0 STARTED 1/9 1 Interim Data Analysis FSR Completion 945-951-NC1 BEYDOUN MONEY FR Completed Beydoun A Aug-96 Dec-96 Data Lock 13,915 X02E00 PE Interim Data Analysis FSR Completion 945-952-NE1 GORSIN WAS Completed Gorson K Dec-95 Apr-97 Data Lock 23,333.3 1YYE00-DIABET 4 Interim Data Analysis FSR Completion 945-954-PUB PUBLICATION-NEURON Completed Holmes L Jan-96 Oct-97 Data Lock 85,962.8 TIN INC T Marcotte D 9 Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 46 Source:https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026052 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-QQQ EXTERNAL STUDIES Completed Yaksh T Jul-96 Dec-96 Data Lock 48,000 BUD.TRANS Interim Data Analysis FSR Completion 945-954-SE3 EPILEPSY AND Completed May-97 Jun-97 Data Lock 34,856.5 WOMENS INFECTI 0 Interim Data Analysis FSR Completion 945-954-SE5 RYBACK BUDGET TRSF Completed Ryback R Aug-97 Jun-98 Data Lock 18,000 FR S Interim Data Analysis FSR Completion 945-954-SE8 CLOSED 4/00-NEUR IN Completed Nov-97 Oct-98 Data Lock 0 COCAINE Interim Data Analysis FSR Completion 945-954-SEA QUANTITATIVE Completed May-98 Dec-98 Data Lock 0 ASSESMENT OF S Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 47 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026053 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-X02 NEUR-COST BENEFIT Completed Arthur D. Little, Jun-94 Sep-96 Data Lock 300,000 Inc. Interim Data Analysis FSR Completion 945-400-X03 STEPS-MISC Completed Sep-94 Aug-95 Data Lock 299,000 NEURONTIN Interim Data Analysis FSR Completion 945-400-X04 USUAL CARE Completed Morris, III G Jan-94 Oct-99 Data Lock 65,319.1 Park K 2 Interim Data Analysis FSR Completion 945-400-X05 PREGNANCY REG Completed General Jan-95 Dec-95 Data Lock 100,049. Hospital Corp. 42 Interim Data Analysis FSR Completion 945-400-X07 WALS (MILLER) 200.0 Completed Miller R Jan-97 Dec-97 Data Lock 200,000 FROM Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 48 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026054 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-XXX PUBLICATION Completed Jan-95 Dec-95 Data Lock 100,000 SUPPORT Interim Data Analysis FSR Completion 945-224 GBP in Diabetic Completed Multicenter Data Lock Information from Neuropathy (pcbo study out of London meeting controlled-open-label Germany 13-Aug-01 attended by extension for 4 mos) Interim SBS, AEM: not to be published until Data Analysis PHN--very good data for sleep and QoL FSR Completion 945-025 Post-herpetic neuralgia Completed Rice, Maton UK Data Lock To be published in Nov-01 issue of Pain Interim Data Analysis FSR Completion 945-026 Mixed-symptoms study Completed Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: key target for publication-oovarall Data Analysis results not overwhelming but very positive for subset of FSR Completion pts with NeP Neuropathic pain vs. Completed Data Lock Information from plac., DB, crossover 6 London meeting wks. Disability Services 13-Aug-01 attended by Clinic Interim SBS, AEM: 17 pts. randomized;13 Data Analysis completed both 6-week arms. FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 49 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026055 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-262 Placebo-controlled trial of Completed Magnus-Mi Miller, R US, Canada Jun-99 Dec-99 Data Lock 15,000 gabapentin in spinal ller, L Bradley W, muscular atrophy Brooke M, Bryan W, Barohn R, Interim lannaccone S, Leshner R, Data Analysis Mendell J, Kissel J, Russman B, Samaha F, Smith FSR Completion S 945-955-250 Gabapentin adjunctive Completed Magnus-Mi Ketter, T US Apr-98 Dec-99 Data Lock 90,691 02-Jun-98 treatment in patients with ller, L Winsberg M. bipolar depression DeGolia S, Dunai M, O'Meara C, Interim Tate D, Strong C Data Analysis FSR Completion 945-954-237 Pregnancy and epilepsy Completed Montouris, G US Dec-98 Dec-00 Data Lock 45,000 20-Jul-98 15-Feb-99 in the treatment of seizures in women of childbearing age Interim Data Analysis FSR Completion 945-954-264 Reproductive hormones, Completed Magnus-Mi Pennell, P US Feb-99 Dec-99 Data Lock 68,000 01-Apr-99 antiepileptic drug levels ller, L Henry T, Litt B, and seizure occurance in Epstein C women with catamenial Interim epilepsy Data Analysis FSR Completion 945-952-232 A randomized controlled Completed Ehrenberg, B US Dec-95 Aug-00 Data Lock 75,000 09-Mar-98 pilot study of gabapentin (neurontin) in patients with restless leg Interim syndrome/periodic limb movement disorder Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 50 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026056 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-245 Randomized, Completed Magnus-Mi Rowbotham, R US Apr-99 Jun-00 Data Lock 275,000 double-blind study ller, L Sacks G, Young assessing "low dose" S versus "high dose" Interim gabapentin for the treatment of painful HIV Data Analysis neuropathy FSR Completion 945-951-304 Oral absorption of Completed Magnus-Mi Gidal, B US Oct-99 Jun-00 Data Lock 36,200 10-Sep-99 03-Dec-99 gabapentin solution: ller, L Sheth R pharmacokinetic impact of mixing with milk juice Interim or enteral supplements Data Analysis FSR Completion 945-954-242 Gabapentin for the Completed Magnus-Mi Hansen, H US Jun-99 Apr-00 Data Lock 35,000 08-Feb-99 01-Mar-99 treatment of fibromyalgia ller, L Wodecki R Interim Data Analysis FSR Completion 945-954-255 Retrospective study of the Completed Magnus-Mi Marcotte, D US Jun-99 Dec-99 Data Lock 20,000 15-Oct-99 15-Dec-00 effectiveness of ller, L gabapentin with dementia with behavioral Interim disturbance Data Analysis FSR Completion 945-953-228 Effect of gabapentin on Completed Diaz-Arrastia, R US Apr-99 Dec-99 Data Lock 20,000 13-Apr-99 12-Feb-01 plasma homocystine and Agostini M, folate levels Kokkinakis D Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 51 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026057 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-420-010 Neuropathic pain cancer In Progress Italy Data Lock Information from pts. (refractory to opiates, London meeting vs. placebo, 10 days, 13-Aug-01 attended by 600-1800 mg titr., add-on) Interim SBS, AEM: potential for final data end Q4/01 Data Analysis FSR Completion Efficacy and safety of In Progress Gudez-Santos M Philippines Data Lock gabapentin in comparison Hernandez M, with carbamazepine in Poblete A the management of pain Interim secondary to trigeminal neuralgia Data Analysis FSR Completion 945-278 Trigeminal neuralgia Cancelled Drug only Cunliffe UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: early termination-accrual Data Analysis problems (32 pts.); rept in prep. FSR Completion 945-241 Vulvadynia Cancelled Drug only Smith UK Data Lock Interim Data Analysis FSR Completion 945-279 Phantom limb pain Completed Drug only Critchley UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: presented this year-Michael Data Analysis Rowbotham has this data. Poster presented at EFIC (17 pts.). FSR Completion Publication in prep. Bold = Lead Investigator Medical Action Communications 31-Oct-01 52 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026058 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-425 CRPS vs. placebo In Progress Drug only Hill D UK Data Lock Information from crossover London meeting 13-Aug-01 attended by Interim SBS, AEM: all 10 pts. enrolled; completion Data Analysis anticipated next yr FSR Completion 945-285 Refl. Symp. Dys. In Progress Drug only Souter UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: ongoing--need to locate Data Analysis protocol-13 of 15 pts. enrolled; target compl. Feb. 2001 FSR Completion 945-410 Back pain-surgically In Progress Drug only Hester UK Data Lock Information from refractory London meeting 13-Aug-01 attended by Interim SBS, AEM: 15 to 20 Data Analysis patients currently recruited-10 of 27 pts. enrolled; target FSR Completion 945-420 HIV neuropathy In Progress Drug only Manji UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: recruitment complete but study still Data Analysis ongoing-completion Sept. 2001 FSR Completion 945-293 Essential tremor Planned Drug only Wills, Naashef UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: not yet started 40 pts. Data Analysis targeted FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 53 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026059 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Bipolar disorder Grant Walden Germany Data Lock (retrospective analysis) Interim Data Analysis FSR Completion 945-418-428 Add-on treatment children Grant Lagae Belgium Data Lock Interim Data Analysis FSR Completion 945-418-432 Perineal pain-open study Grant Herbaut Belgium Data Lock Interim Data Analysis FSR Completion A9451010 Gabapentin in Approved Grant Spain Data Lock Information from neuropathic pain London meeting (open-label study) 13-Aug-01 attended by Interim SBS, AEM: anticipated start in Sept Data Analysis FSR Completion Effects of GBP on NeP Cancelled Grant Spain Data Lock and sleep symptoms (double-blind) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 54 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026060 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-275-273 Epilepsy-elderly add-on Cancelled Grant Australia Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: terminated - low enrollment Data Analysis FSR Completion Cancer pain Completed Grant Kloke Germany Data Lock Information from (retrospective analysis) London Meeting 13-Aug-01 attended by Interim SBS, AEM: report received-in review to Data Analysis determine how strongly publication should be pursued FSR Completion 945-400-281 Treatment of seizures in Completed Grant Magnus-Mi Veteran affairs US Jan-98 Jan-01 Data Lock 125,000= 06-Dec-00 the elderly population ller, L cooperative 25,000/yr studies program for 5 Balish M, Towne Interim years + A, Salinsky M, 50,000 Felicetta J, Data Analysis additional Rodgers-Neame for N, McLean M. central Rutecki P, FSR Completion laborator Mamdani M, y Uthman B, Spitz 945-954-258 Use of gabapentin for Completed Grant Magnus-Mi Pellock, J US Nov-99 Oct-00 Data Lock 7,000 15-Dec-00 symptom control in ller, L Fusun Alehan, children with attention MD-Medical deficit hyperactivity College of Interim disorder-a pilot study Virginia, Richmond, VA Data Analysis FSR Completion 945-952-263 Reproductive function in Completed Grant Magnus-Mi Morell, M US Nov-99 Oct-00 Data Lock 171,587 11-Oct-99 AED treated women with ller, L Sauer M, Giudice epilepsy L Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 55 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026061 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments HIV polyneuropathy In Progress Grant Schielke Germany Data Lock Information from London Meeting 13-Aug-01 attended by Interim SBS, AEM: patient accrual slow--currently Data Analysis only 30 pts FSR Completion Tension headaches In Progress Grant Arnold Germany Data Lock Information from London Meeting 13-Aug-01 attended by Interim SBS, AEM: slow enrollment Data Analysis FSR Completion 945-475-433 Carpal Tunnel Syndrome- In Progress Grant Australia Data Lock Information from neuropath. pain prophyl. London meeting (vs. placebo, DB 13-Aug-01 attended by crossover, Interim SBS, AEM: started at 8 wks., titr. to 4800 mg, end of '98 20 pts., 1 center) Data Analysis FSR Completion 945-475-433 Carpal Tunnel Syndrome- In Progress Grant Australia Data Lock Information from neuropath. pain prophyl. London meeting (vs. placebo, DB 13-Aug-01 attended by crossover, Interim SBS, AEM: started at 8 wks., titr. to 4800 mg, end of '98 20 pts., 1 center) Data Analysis FSR Completion Post-marketing In Progress Grant Korea (Jeil Data Lock surveillance Pharmaceuti cals) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 56 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026062 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments PMS In Progress Grant Phillipines Data Lock Interim Data Analysis FSR Completion A945-10. Evaluation of gabapentin Planned Grant Italy Data Lock Information from effect in the prevention of London meeting oxaliplatin induced 13-Aug-01 attended by neurotoxicity in Interim SBS, AEM: very gabapentin treated or expensive study--Italy untreated population Data Analysis cannnot support this study at all. Looking to see whether NYHQ will FSR Completion be able to fund the entire study. A945-1002 A double-blind Planned Grant Italy Data Lock Information from randomised trial London meeting comparing gabapentin 13-Aug-01 attended by versus placebo in the Interim SBS, AEM: from same prophylaxis and treatment Data Analysis protocol as #11--this of acute oxaliplatin half may not be induced neurotoxicity pursued. FSR Completion GBP vs CBZ in epilepsy Planned Grant Spain Data Lock Information from (double-blind study) London meeting 13-Aug-01 attended by Interim SBS, AEM: still no response on whether Data Analysis this has been approved. FSR Completion Insomnia (preference for Planned Grant Spain Data Lock GBP over BZD in insonmia) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 57 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026063 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Insomnia (preference for Planned Grant Spain Data Lock GBP over BZD in insonmia) Interim Data Analysis FSR Completion Participation of the Planned Grant Venezuela Data Lock endogenous pain modulatory system in experimentally induced Interim neuropathic pain. New perspectives on the Data Analysis mechanism of action of gabapentin FSR Completion Functional Proposed Grant Spain Data Lock Information from characterization of the London meeting GABA-mediated actions 13-Aug-01 attended by induced by gabapentin Interim SBS, AEM: awaiting (MOA study) response from Data Analysis NYHQ--submitted in July FSR Completion Post-hernia repair Proposed Grant UK Data Lock Information from (inguinaldynia) London meeting 13-Aug-01 attended by Interim SBS, AEM: good protocol, local grant Data Analysis study FSR Completion Amytriptyline comparator Proposed Grant UK Data Lock in Cancer Pain-full spectrum of cancer pain Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 58 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026064 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments AWB-monotherapy Completed Marketing Schmidt D Germany Data Lock Information from (400-500 London meeting pts--post-surveillance 13-Aug-01 attended by clincal experience trial) Interim SBS, AEM: framework provided, sales force Data Analysis data gathering FSR Completion 945-212 Partial/gen. epilepsy vs. Sponsored Australia Data Lock lamotrigine Internat. ICD study Interim Data Analysis FSR Completion 945-430 Migraine prophylaxis Cancelled Sponsored Spain Data Lock Interim Data Analysis FSR Completion 945-475-206 Australia Steps Complete Sponsored Australia Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: based on same protocol on Data Analysis US-blood levels awaited FSR Completion 945-418-308 Belsteps Complete Sponsored Belgium Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: like-Australian Data Analysis steps--open-label-data entry ongoing-stat. report end-2000 FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 59 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026065 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-420-007 Epilepsy (Add-on followed Completed Sponsored Italy Data Lock by lead cmpd withdrawal) Interim Data Analysis FSR Completion 945-437-466 Postoperative/post-traum Completed Sponsored Sweden, Data Lock Information from atic pain ('POP' Finland, London meeting study--120 pts enrolled, Norway, 13-Aug-01 attended by 90-100 evaluable) Denmark Interim SBS, AEM: code broken last Data Analysis week-results available in Sept. Results to be released at Sept FSR Completion investigators meeting. 945-01/11-001 Migraine-children, adoles. Completed Sponsored Spain Data Lock Information from 9 (open-label) London meeting 13-Aug-01 attended by Interim SBS, AEM: Very Data Analysis positive results; completed approx 1-2 mos ago FSR Completion 945-475-283 Headache-chronic, daily Completed Sponsored Australia Data Lock Information from (tension Headache) London meeting 13-Aug-01 attended by Interim SBS, AEM: data management Data Analysis ongoing-possibly completed-must check FSR Completion 945-411 Diabetes-neuropathic Completed Sponsored Mexico, Data Lock Information from pain, Venez. London meeting (fixed dose vs. titration, Equador, 13-Aug-01 attended by double-blind, 7 wks.) Columb, Interim SBS, AEM: 508 Chile, Peru, patients targeted: 304 Braz Data Analysis enrolled, 188 completed. Need full info on data from CRO. FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 60 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026066 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-405-401 Pediatric study Completed Sponsored South Africa Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: part of Shapiro study similar to Data Analysis Mexican pediatric study above FSR Completion 945-420-275 Post-herpetic neuralgia Completed Sponsored Italy Data Lock Interim Data Analysis FSR Completion 945-187/87 Epilepsy-refract.-long Completed Sponsored Mexico Data Lock Information from term London meeting OC safety in children 13-Aug-01 attended by (open-label safety) Interim SBS, AEM: Publ. Devel. Med. and Child Data Analysis Neuro. FSR Completion Sub-study of allodynia In Progress Sponsored Sweden, Data Lock Information from based on POP study (20 Finland, London meeting pts.) Norway, 13-Aug-01 attended by Denmark Interim SBS, AEM: recruitment complete by Data Analysis Nov--anticipated study results by Q2/02 FSR Completion 945-222 Spasticity In Progress Sponsored Spain Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: finalized Q1/01 Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 61 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026067 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-431 Restless Leg Syndrome In Progress Sponsored Spain Data Lock Information from (including sleep London meeting architecture) 13-Aug-01 attended by Interim SBS, AEM: finishing in Sept, results in Oct/Nov Data Analysis FSR Completion 945-424 Parkinson's Disease In Progress Sponsored Spain Data Lock Information from (L-dopa related London meeting dyskinesia) 13-Aug-01 attended by Interim SBS, AEM: delayed due to PI Data Analysis pregnancy--possibly to be complete Q1/02 FSR Completion 945-276 Cancer pain (Italian In Progress Sponsored Spain Data Lock Information from study) London meeting 13-Aug-01 attended by Interim SBS, AEM: March 2002 Data Analysis final patient accrual anticipated. FSR Completion 945-436-288 Epilepsy-monotherapy In Progress Sponsored France Data Lock Information from (open-label switch, not London meeting stringently 13-Aug-01 attended by controlled-experience Interim SBS, AEM: Auralie is trial) the contact Data Analysis FSR Completion 945-445-435 Dutch Steps In Progress Sponsored Netherlands Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: contact for Netherlands--Marnix Data Analysis Artz FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 62 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026068 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-468-429 Diabetes-neuropathic In Progress Sponsored Taiwan Data Lock Information from pain London meeting 13-Aug-01 attended by Interim SBS, AEM: 9/00 12/01-Need to find out Data Analysis if this has completed FSR Completion 945-420-276 Neuropathic Pain (Cancer In Progress Sponsored Spain/Italy 8 Data Lock Information from Pain) sites London meeting 13-Aug-01 attended by Interim SBS, AEM: ongoing 10/98-6/01 Data Analysis FSR Completion 945-445-280 Refl. Symp. Dystr. pain In Progress Sponsored Netherlands Data Lock Interim Data Analysis FSR Completion 945-291 Bipolar Disorder (1 year Ongoing Sponsored Spain/Italy 3 Data Lock Information from Tx) sites London meeting 13-Aug-01 attended by Interim SBS, AEM: patient accrual currently 35 but Data Analysis need 80 total Accrual problems due to Janssen blocking FSR Completion recruitment. Issue may have been somewhat resolved. Definitely Neuropathic pain Planned Sponsored Germany Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: initiated in May, CRFs Due Oct / Data Analysis Nov, anticpated results in Jan FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 63 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026069 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-301 Refractory Planned Sponsored Canada Data Lock Information from epilepsy-children aged 1 London meeting month to 4 yrs-open 13-Aug-01 attended by Interim SBS, AEM: submission-contact Data Analysis Tibor Kapussy of Canada for info. FSR Completion 945-401 Pediatric (contributed to Planned Sponsored Mexico Data Lock Information from US FDA submission) London meeting 13-Aug-01 attended by Interim SBS, AEM: submission Data Analysis FSR Completion Peripheral neuropathic Planned Sponsored Netherlands Data Lock Information from pain London meeting open study 13-Aug-01 attended by Interim SBS, AEM: unknown whether this has started Data Analysis FSR Completion 945-437-466 Neuropathic pain Planned Sponsored Phillipines Data Lock Interim Data Analysis FSR Completion Diabetes-neuropathic Planned Sponsored Thailand Data Lock pain Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 64 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026070 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Spasticity (60 pts Rejected Sponsored Nelles Germany Data Lock Information from proposed--early London meeting intervention in stroke pts 13-Aug-01 attended by to prevent spasticity and Interim SBS, AEM: LT to pain) re-review request for Data Analysis funding FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 65 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026071 Neurontin AIDS/HIV Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % AIDS Yes Primary 30 1.5 3 4.5 BIOSIS 8.018 3,207 Infectious Disease Specialists47 North America 59 Letters Chemical Abstracts Public Health Specialists 15 Europe 32 Current Contents Pathologists 15 Far East 3 EMBASE Immunologists 8 Rest of World 6 Index Medicus Oncologists 15 MEDLINE Science Citation Index AIDS and Behavior Yes Primary 50 6 6 12 CINAHL N/A N/A N/A N/A N/A N/A Reviews EMBASE Letters AIDS Care Yes Primary N/A 6 6 12 Biological Abstracts N/A 650 Psychologists N/A United States 50 Brief Reports CINAHL Social Scientists N/A United Kingdom 25 Current Contents Nurses N/A Rest of World 25 EMBASE Other N/A Index Medicus MEDLINE Science Citation Index AIDS Patient Care Yes Primary 50 2-3 2-3 4 - 6 CINAHL N/A 5,628 Primary Care Physicians 90 N/A N/A and STDs Letters EMBASE Researchers 10 Case Reports MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 66 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026072 Neurontin AIDS/HIV Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % AIDS Reader Yes Primary 70 1 3 4 EMBASE N/A 34,576 Family Physicians 31 United States 99 Reviews MEDLINE Internists 28 Rest of World 1 Letters Hematologists 11 Oncologists 10 Other 20 International Journal Yes Primary 45 1 3 4 Current Contents 1.019 1,050 N/A N/A United Kingdom 53 of STD and AIDS Letters EMBASE Europe 17 Case Reports Index Medicus North America 14 MEDLINE Rest of World 16 SciSearch Journal of Acquired Yes Primary 60 1 2 6 7-8 BIOSIS 3.046 2,931 Infectious Disease SpecialistsN/A United States 23 Immune Deficiency Reviews Current Contents Pathologists N/A Rest of World 77 Syndromes Letters EMBASE Biologists N/A Case Reports Index Medicus Epidemiologists N/A MEDLINE Virologists N/A Science Citation Index Researchers N/A SciSearch A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 67 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026073 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Diabetes Yes Primary 25 1 1.25 3 4 4.25 Biological Abstracts 7.715 7,500 Researchers N/A North America N/A Chemical Abstracts Physicians N/A Rest of World N/A Current Contents Other N/A EMBASE Index Medicus MEDLINE Science Citation Index Diabetes and Yes Reviews 60 6 6 12 Biological Abstracts N/A 1,500 Diabetologists N/A France 60 Metabolism Primary Chemical Abstracts Endocrinologists N/A Rest of World 40 Letters Current Contents Editorials EMBASE Index Medicus MEDLINE Science Citation Index Diabetes Care Yes Primary 25 1 1.25 3 4 4.25 Biological Abstracts 4.992 13,500 Physicians N/A North America N/A Letters Chemical Abstracts Researchers N/A Europe N/A Case Reports Current Contents Nurse Practitioners N/A EMBASE Index Medicus MEDLINE Science Citation Index Diabetes Research Yes Primary 45 4 3 7 Biological Abstracts 0.982 325 Diabetologists N/A N/A N/A and Clinical Practice Reviews BIOSIS Endocrinologists N/A Letters Chemical Abstracts Brief Reports Current Contents EMBASE Index Medicus MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 68 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026074 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Diabetic Medicine Yes Primary 17 2.5 3 - 4 5.5 6.5 Current Contents 2.732 2,100 N/A N/A United Kingdom 58 Reviews EMBASE Europe 19 Letters Index Medicus North America 10 Brief Reports MEDLINE Rest of World 13 Case Reports Science Citation Index Diabetologia Yes Primary 20 6 1.5 7.5 Biological Abstracts 5.721 7,300 Endocrinologists N/A Europe 69 Letters Chemical Abstracts Internists N/A North America 16 EMBASE Researchers N/A Asia 11 Index Medicus Rest of World 4 MEDLINE Endocrine Reviews Yes N/P N/P N/P N/P Biological Abstracts 19.524 4,711 Endocrinologists 100 North America 60 BIOSIS Rest of World 40 Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE Endocrinology Yes Primary 30 1 2.5 3.5 Biological Abstracts 4.790 4,872 Endocrinologists 100 North America 68 BIOSIS Rest of World 32 Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 69 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026075 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Journal of Clinical Yes Primary 33 1 3 4 Biological Abstracts 5.447 10,158 Endocrinologists 100 United States 67 Endocrinology and Letters BIOSIS Rest of World 33 Metabolism Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE Journal of Diabetes Yes Primary 85 1 2-3 3 - 4 BIOSIS 0.851 900 Diabetologists N/A United States 40 and its Reviews Current Contents Endocrinologists N/A Europe 35 Complications Letters EMBASE Nephrologists N/A Asia 16 Editorials Index Medicus Urologists N/A Rest of World 9 Case Reports MEDLINE Primary Care Physicians N/A SciSearch A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 70 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026076 Neurontin Epilepsy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Epilepsia Yes Primary N/A 1 4 2-6 3-10 Biological Abstracts 3.787 5,220 Neurologists 94 United States 85 Letters BIOSIS Psychologists 5 Rest of World 15 Case Reports Chemical Abstracts Other 1 Current Contents EMBASE Index Medicus MEDLINE Science Citation Index SciSearch Epilepsies Yes Primary 60 2 4 6 EMBASE N/A 1,000 Neurologists N/A Europe N/A Reviews Epileptologists N/A Rest of World N/A Brief Reports Other N/A Epilepsy and Yes Primary N/A N/A N/A N/A N/A N/A 1,500 Neurologists 40 N/A N/A Behavior Letters Neuropsychiatrists 30 Editorials Radiologists 10 Brief Reports Other 20 Case Reports Epilepsy Research Yes Primary 45 2 3 5 Biological Abstracts 2.866 520 Epileptologists N/A Europe 41 Reviews BIOSIS Neurologists N/A North America 34 Letters Chemical Abstracts Pharmacologists N/A Asia 18 Editorials Current Contents Psychiatrists N/A Rest of World 7 Brief Reports EMBASE Index Medicus MEDLINE Science Citation Index A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 71 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026077

when was the london meeting held?

jnjm0223

jnjm0223_p32, jnjm0223_p33, jnjm0223_p34, jnjm0223_p35, jnjm0223_p36, jnjm0223_p37, jnjm0223_p38, jnjm0223_p39, jnjm0223_p40, jnjm0223_p41, jnjm0223_p42, jnjm0223_p43, jnjm0223_p44, jnjm0223_p45, jnjm0223_p46, jnjm0223_p47, jnjm0223_p48, jnjm0223_p49, jnjm0223_p50, jnjm0223_p51, jnjm0223_p52, jnjm0223_p53, jnjm0223_p54, jnjm0223_p55, jnjm0223_p56, jnjm0223_p57, jnjm0223_p58, jnjm0223_p59, jnjm0223_p60, jnjm0223_p61, jnjm0223_p62, jnjm0223_p63, jnjm0223_p64, jnjm0223_p65, jnjm0223_p66, jnjm0223_p67, jnjm0223_p68, jnjm0223_p69, jnjm0223_p70, jnjm0223_p71

13-Aug-01, 13-aug-01

Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Gabapentin for the treatment of Rowbotham MC 2 In development. Pain or Neurology AIDS/HIV painful HIV polyneuropathy Neuropathic Pain: HIV neuropathic pain study 2 In development. AIDS/HIV Neuropathic Pain: Treatment of diabetic neuropathy Nicholson B Knapp L 1 In development. JAMA 31-Dec-01 01-May-02 Diabetic Blonde L, Freeman R Rowbotham M, Mutisya E Neuropathy Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 32 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026038 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Gabapentin in painful diabetic Reckless J 2 In development. Diabetic Medicine Diabetic neuropathy: a randomized, Roder B, Maisonobe P Neuropathy double-blind, placebo controlled study (224) Neuropathic Pain: Phantom limb pain (UK) Critchley 1 In development. Phantom Limb Neuropathic Pain: Restless leg syndrome (Spain) 4-high Proposed. Restless Leg Syndrome Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 33 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026039 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Sleep quality and patient-reported Ehrenberg BL Glanzman R 2 Complete CONSORT Neurology 01-Aug-01 01-Nov-01 01-Mar-02 Sleep health status in periodic limb Wagner AK, Chang H, Piron S, Hsu T requirements. movement disorder treated with Corbett KR, Rogers WH gabapentin: a double-blind, randomized, placebo-controlled, cross-over study Psychiatric Gabapentin in the treatment of Marcotte D 2 In development. Primary Psychiatry 01-Oct-01 01-Dec-01 01-Apr-02 Disorders dementia and behavioral disturbance Psychiatric Psychiatric applications of Pande AC 3-high On hold. Disorders gabapentin Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 34 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026040 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Psychiatric Gabapentin and methylphenidate Hamrin V 2 In development. Disorders: Bipolar treatment of a preadolescent with Disorder ADHD and bipolar disorder Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 35 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026041 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Myrick H, Henderson S, Brady KT, Malcolm R. Gabapentin in the treatment of Jan-01 cocaine dependence: a case series. J Clin Psychiatry. 2001;62:19-23. Crawford P, Brown S, Kerr M, Parke Davis Clinical Trials Group. A randomized Mar-01 open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy. Seizure. 2001;10:107-115. Appleton R, Fichtner K, LaMoreaux L, et al. Gabapentin as add-on therapy in Apr-01 children with refractory partial seizures: a 24-week, multicentre, open-label study. Dev Med Child Neurol. 2001;43:267-273. Lado FA, Sperber EF, Moshe SL. Anticonvulsant efficacy of gabapentin on Apr-01 kindling in the immature brain. Epilepsia. 2001;42:458-463. Kwan P, Sills GJ, Brodie MJ. The mechanisms of action of commonly used Apr-01 antiepileptic drugs. Pharmacol Ther. 2001;90:21-34. Medical Action Communications 31-Oct-01 36 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026042 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Haig GM, Bockbrader HN, Wesche DL, Boellner SW, Ouellet D, Brown RR, May-01 Randinitis EJ, Posvar EL. Single-dose gabapentin pharmacokinetics and safety in healthy infants and children. J Clin Pharmacol. 2001;41:507-514. Bridges D, Thompson SWN, Rice ASC. Mechanisms of neuropathic pain. Br J Jul-01 Anaesth. 2001;87:12-26. Schmidt D, Stefan H, Elger CE. Gabapentin-monotherapy in 503 patients with Aug-01 partial epilepsy dissatisfied with initial standard antiepileptic drug therapy. Nervenheilkunde. 2001;20:321-325. Maneuf YP, Hughes J, McKnight AT. Gabapentin inhibits the substance Aug-01 P-facilitated K(+) -evoked release of. Pain. 2001;93(2):191-196. Beran R. Australian study of titration to effect profile of safety (AUS-STEPS): Oct-01 high-dose gabapentin (Neurontin) in partial seizures. Epilepsia. In Press. Medical Action Communications 31-Oct-01 37 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pizer_LKnapp_0026043 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Rice ASC, Maton S, Postherpetic Neuralgia Study Group. Gabapentin in Nov-01 postherpetic neuralgia: a randomised, double blind, placebo controlled study. Pain. In Press. Medical Action Communications 31-Oct-01 38 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026044 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-195 Double-blind, Meador K Data Lock randomized, two-period crossover comparison and behavioral effects of Interim gabapentin and carbamazepine in healthy Data Analysis volunteers FSR Completion Epilespy (BID/TID study) Data Lock Interim Data Analysis FSR Completion 945-421-002 GBP vs Valproate Spain Data Lock (add-on with CBZ, then remove CBZ and drop to monotherapy) Interim Data Analysis FSR Completion Phase III double-blind, Miller, R Data Lock 200,000. 16-Dec-96 placebo-controlled study 00-based assessing the efficacy of on 100 gabapentin in patients Interim patients with amotrophic lateral out of sclerosis (ALS) Data Analysis 200 required for study FSR Completion An open, matched control Magnus-Mi Holmes, L US Data Lock 433,943 01-Nov-95 23-Dec-99 study comparing the ller, L Harvey E, Keither cognitive abilities of D, Khoshbin S, children born to epileptic Adams J, Ryan L Interim mothers who received antiepileptic drug Data Analysis treatment to children born to non-epileptic mothers FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 39 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026045 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 073-170 An open, matched control Magnus-Mi Holmes, L US Data Lock study comparing the ller, L cognitive abilities of children exposed in utero Interim to anti epileptic monotherapy to children Data Analysis born to non-epileptic mothers FSR Completion 945-419-277 Complex/simple partial Accepted Greece Data Lock Information from seizures vs. CBZ London meeting (monotherapy), 13-Aug-01 attended by double-blind, 36 wks. Interim SBS, AEM: initiation delayed due to Data Analysis integration of research budgets. FSR Completion 945-92 Epilepsy Monotherapy vs Complete 14 Countries Data Lock Information from CBZ (290 pts) London meeting 13-Aug-01 attended by Interim SBS, AEM: poster presented from Data Analysis mid-term analysis of 100pts--study now complete-research FSR Completion report written 945-952-236 Neurontin for neurogenic Completed Herbert J Apr-96 Dec-98 Data Lock 78,500 pain in multiple sclerosis Interim Data Analysis FSR Completion 945-954-241 Neurontin in Essential Completed Uitti R Jul-98 Feb-99 Data Lock 48,000 temor Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 40 Source:https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026046 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-250 Gabapentin adjunctive Completed Ketter T Apr-98 Dec-99 Data Lock 90,691 treatment in patients with bipolar disorder Interim Data Analysis FSR Completion 945-954-252 In vivo determination of Completed Kuzniecky R Dec-96 Nov-97 Data Lock 216,610 human brain gaba Gilliam F concentrations in volunteers receiving Interim gabapentin:an escalating dose response study Data Analysis FSR Completion 945-400-281 VA COOP STUDY #428 Completed Ramsay E Jan-99 Dec-99 Data Lock 50,000 Interim Data Analysis FSR Completion 945-952-282 Gabapentin Completed Gidal B, Jul-95 Aug-00 Data Lock 87,993.1 pharmacology: Effects of Weissman J 5 GABA on human cerebral GABA concentrations Interim studies with NMR spectroscopy Data Analysis FSR Completion 945-400-WW2 SALINSKY BUDGET Completed Salinsky M Dec-96 Oct-98 Data Lock 159,364 TRF FR WE Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 41 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026047 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-090 Dose Intitiaition: Titration Completed Multicenter Jan-94 Dec-98 Data Lock 2,801,75 vs. Non-Titration 6 Interim Data Analysis FSR Completion 945-400-193 Neurontin STEPS (Study Completed Multicenter Jan-95 May-98 Data Lock 4,269,90 and of titration to 0 945-400-200 effectiveness and profile of safety) Interim Data Analysis FSR Completion 945-400-211 A Double-blind, Completed Carr D, Jan-96 Jan-99 Data Lock 1,967,40 randomized, placebo Rosenberg J, 0 controlled, parallel group, Dunteman E, multicenter trial to Harden N, Interim determine the efficacy Kreitzer J, Mann and safety of Neurontin JD, Obbens E, Data Analysis in subjects with peripheral Rowbotham M, neuropathy (Post-herpetic Ross E, Yokiel Neuralgia) J, Schell D, FSR Completion Singer E, Stewart RM, 945-400-217 MIGRAINE BID Completed Jan-97 Dec-99 Data Lock 1,849,73 0.03 Interim Data Analysis FSR Completion 945-400-220 MIGRAINE TID Completed Sep-96 Sep-98 Data Lock 699,598. 81 Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 42 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026048 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-953-231 Evaluation of the efficacy Completed Duntley Dec-96 Mar-99 Data Lock 46,650 of neurontin in the treatment of restless leg syndome and periodic Interim limb movement Data Analysis FSR Completion 945-952-233 Neurontin in the treatment Completed Feinberg Oct-96 Mar-99 Data Lock 35,000 of agitation in patients with demetia Interim Data Analysis FSR Completion 945-953-243 Double-blind, Completed Klapper JA Apr-98 Dec-98 Data Lock 1,100 randomized, placebo-controlled, parallel group trial to Interim determine the efficacy and safety of neurontin Data Analysis (gabapentin) in subjects with trigeminal neuralgia FSR Completion 945-954-244 Quantitative assessments Completed Longmire D Jul-96 Dec-96 Data Lock 15,000 of sympathetic pseudomotor changes induced by gabapentin in Interim patients with neuropathic pain Data Analysis FSR Completion 945-954-246 Adjunctive treatment for Completed Aug-98 Oct-99 Data Lock 0.01 bipolar disorder Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 43 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026049 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-954-247 A retrospective study of Completed Nuckolls J Nov-97 Jan-98 Data Lock 4,375 the effectiveness of gabapentin in the treatment of mood Interim disorders Data Analysis FSR Completion 945-954-249 A blinded randomized trial Completed Hines R Jul-99 Oct-99 Data Lock 2,000 to evaluate the efficacy of gabapentin versus ibuprofen in patients with Interim chronic pelvic pain Data Analysis FSR Completion 945-954-253 Category analysis of the Completed Longmire D Aug-97 Jun-98 Data Lock 15,000 effects of gabapentin on neuropathic pain: an open-label community Interim based outcomes study of over six hundred patient Data Analysis records FSR Completion 945-954-254 A double-blind, Completed Lyketsos Aug-98 Mar-99 Data Lock 0.01 placebo-controlled, parallel clinical trial using gabapentin to treat the Interim behavioral disturbances of out-patients with Data Analysis dementia FSR Completion 945-954-256 Gabapentin in the Completed Myrick H Jun-98 Dec-99 Data Lock 31,000 treatment of cocaine dependence Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 44 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026050 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-953-257 Evaluation of the efficacy Completed Ondo W Nov-96 Mar-99 Data Lock 63,000 of gabapentin for essential tremor Interim Data Analysis FSR Completion 945-952-261 Gabapentin therapy Completed Holmes May 97 Mar-99 Data Lock 22,740 following status epilepticus Interim Data Analysis FSR Completion 945-951-270 Open-label, Completed Gidal B May-98 Dec-99 Data Lock 7,214 non-randomized, pilot study to determine whether chronic neurontin Interim administration results in significant changes in Data Analysis various sex hormones FSR Completion 945-951-417 LEPPIK/SUDEP Completed Leppik I Oct-99 Dec-99 Data Lock 15,000 Interim Data Analysis FSR Completion 945-400-AA1 GABAPENTIN/CYT P450 Completed Dec-97 Feb-99 Data Lock 26,425 REOPENED Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 45 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026051 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-AAA GBP COMBINATION Completed Hammond Jan-98 Nov-98 Data Lock 35,219.1 STUDY FR. 1 0 Interim Data Analysis FSR Completion 945-400-EXT PUBLICATIONS Completed Holmes Jan-97 Apr-98 Data Lock 52,300.0 STARTED 1/9 1 Interim Data Analysis FSR Completion 945-951-NC1 BEYDOUN MONEY FR Completed Beydoun A Aug-96 Dec-96 Data Lock 13,915 X02E00 PE Interim Data Analysis FSR Completion 945-952-NE1 GORSIN WAS Completed Gorson K Dec-95 Apr-97 Data Lock 23,333.3 1YYE00-DIABET 4 Interim Data Analysis FSR Completion 945-954-PUB PUBLICATION-NEURON Completed Holmes L Jan-96 Oct-97 Data Lock 85,962.8 TIN INC T Marcotte D 9 Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 46 Source:https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026052 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-QQQ EXTERNAL STUDIES Completed Yaksh T Jul-96 Dec-96 Data Lock 48,000 BUD.TRANS Interim Data Analysis FSR Completion 945-954-SE3 EPILEPSY AND Completed May-97 Jun-97 Data Lock 34,856.5 WOMENS INFECTI 0 Interim Data Analysis FSR Completion 945-954-SE5 RYBACK BUDGET TRSF Completed Ryback R Aug-97 Jun-98 Data Lock 18,000 FR S Interim Data Analysis FSR Completion 945-954-SE8 CLOSED 4/00-NEUR IN Completed Nov-97 Oct-98 Data Lock 0 COCAINE Interim Data Analysis FSR Completion 945-954-SEA QUANTITATIVE Completed May-98 Dec-98 Data Lock 0 ASSESMENT OF S Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 47 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026053 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-X02 NEUR-COST BENEFIT Completed Arthur D. Little, Jun-94 Sep-96 Data Lock 300,000 Inc. Interim Data Analysis FSR Completion 945-400-X03 STEPS-MISC Completed Sep-94 Aug-95 Data Lock 299,000 NEURONTIN Interim Data Analysis FSR Completion 945-400-X04 USUAL CARE Completed Morris, III G Jan-94 Oct-99 Data Lock 65,319.1 Park K 2 Interim Data Analysis FSR Completion 945-400-X05 PREGNANCY REG Completed General Jan-95 Dec-95 Data Lock 100,049. Hospital Corp. 42 Interim Data Analysis FSR Completion 945-400-X07 WALS (MILLER) 200.0 Completed Miller R Jan-97 Dec-97 Data Lock 200,000 FROM Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 48 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026054 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-XXX PUBLICATION Completed Jan-95 Dec-95 Data Lock 100,000 SUPPORT Interim Data Analysis FSR Completion 945-224 GBP in Diabetic Completed Multicenter Data Lock Information from Neuropathy (pcbo study out of London meeting controlled-open-label Germany 13-Aug-01 attended by extension for 4 mos) Interim SBS, AEM: not to be published until Data Analysis PHN--very good data for sleep and QoL FSR Completion 945-025 Post-herpetic neuralgia Completed Rice, Maton UK Data Lock To be published in Nov-01 issue of Pain Interim Data Analysis FSR Completion 945-026 Mixed-symptoms study Completed Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: key target for publication-oovarall Data Analysis results not overwhelming but very positive for subset of FSR Completion pts with NeP Neuropathic pain vs. Completed Data Lock Information from plac., DB, crossover 6 London meeting wks. Disability Services 13-Aug-01 attended by Clinic Interim SBS, AEM: 17 pts. randomized;13 Data Analysis completed both 6-week arms. FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 49 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026055 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-262 Placebo-controlled trial of Completed Magnus-Mi Miller, R US, Canada Jun-99 Dec-99 Data Lock 15,000 gabapentin in spinal ller, L Bradley W, muscular atrophy Brooke M, Bryan W, Barohn R, Interim lannaccone S, Leshner R, Data Analysis Mendell J, Kissel J, Russman B, Samaha F, Smith FSR Completion S 945-955-250 Gabapentin adjunctive Completed Magnus-Mi Ketter, T US Apr-98 Dec-99 Data Lock 90,691 02-Jun-98 treatment in patients with ller, L Winsberg M. bipolar depression DeGolia S, Dunai M, O'Meara C, Interim Tate D, Strong C Data Analysis FSR Completion 945-954-237 Pregnancy and epilepsy Completed Montouris, G US Dec-98 Dec-00 Data Lock 45,000 20-Jul-98 15-Feb-99 in the treatment of seizures in women of childbearing age Interim Data Analysis FSR Completion 945-954-264 Reproductive hormones, Completed Magnus-Mi Pennell, P US Feb-99 Dec-99 Data Lock 68,000 01-Apr-99 antiepileptic drug levels ller, L Henry T, Litt B, and seizure occurance in Epstein C women with catamenial Interim epilepsy Data Analysis FSR Completion 945-952-232 A randomized controlled Completed Ehrenberg, B US Dec-95 Aug-00 Data Lock 75,000 09-Mar-98 pilot study of gabapentin (neurontin) in patients with restless leg Interim syndrome/periodic limb movement disorder Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 50 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026056 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-245 Randomized, Completed Magnus-Mi Rowbotham, R US Apr-99 Jun-00 Data Lock 275,000 double-blind study ller, L Sacks G, Young assessing "low dose" S versus "high dose" Interim gabapentin for the treatment of painful HIV Data Analysis neuropathy FSR Completion 945-951-304 Oral absorption of Completed Magnus-Mi Gidal, B US Oct-99 Jun-00 Data Lock 36,200 10-Sep-99 03-Dec-99 gabapentin solution: ller, L Sheth R pharmacokinetic impact of mixing with milk juice Interim or enteral supplements Data Analysis FSR Completion 945-954-242 Gabapentin for the Completed Magnus-Mi Hansen, H US Jun-99 Apr-00 Data Lock 35,000 08-Feb-99 01-Mar-99 treatment of fibromyalgia ller, L Wodecki R Interim Data Analysis FSR Completion 945-954-255 Retrospective study of the Completed Magnus-Mi Marcotte, D US Jun-99 Dec-99 Data Lock 20,000 15-Oct-99 15-Dec-00 effectiveness of ller, L gabapentin with dementia with behavioral Interim disturbance Data Analysis FSR Completion 945-953-228 Effect of gabapentin on Completed Diaz-Arrastia, R US Apr-99 Dec-99 Data Lock 20,000 13-Apr-99 12-Feb-01 plasma homocystine and Agostini M, folate levels Kokkinakis D Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 51 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026057 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-420-010 Neuropathic pain cancer In Progress Italy Data Lock Information from pts. (refractory to opiates, London meeting vs. placebo, 10 days, 13-Aug-01 attended by 600-1800 mg titr., add-on) Interim SBS, AEM: potential for final data end Q4/01 Data Analysis FSR Completion Efficacy and safety of In Progress Gudez-Santos M Philippines Data Lock gabapentin in comparison Hernandez M, with carbamazepine in Poblete A the management of pain Interim secondary to trigeminal neuralgia Data Analysis FSR Completion 945-278 Trigeminal neuralgia Cancelled Drug only Cunliffe UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: early termination-accrual Data Analysis problems (32 pts.); rept in prep. FSR Completion 945-241 Vulvadynia Cancelled Drug only Smith UK Data Lock Interim Data Analysis FSR Completion 945-279 Phantom limb pain Completed Drug only Critchley UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: presented this year-Michael Data Analysis Rowbotham has this data. Poster presented at EFIC (17 pts.). FSR Completion Publication in prep. Bold = Lead Investigator Medical Action Communications 31-Oct-01 52 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026058 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-425 CRPS vs. placebo In Progress Drug only Hill D UK Data Lock Information from crossover London meeting 13-Aug-01 attended by Interim SBS, AEM: all 10 pts. enrolled; completion Data Analysis anticipated next yr FSR Completion 945-285 Refl. Symp. Dys. In Progress Drug only Souter UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: ongoing--need to locate Data Analysis protocol-13 of 15 pts. enrolled; target compl. Feb. 2001 FSR Completion 945-410 Back pain-surgically In Progress Drug only Hester UK Data Lock Information from refractory London meeting 13-Aug-01 attended by Interim SBS, AEM: 15 to 20 Data Analysis patients currently recruited-10 of 27 pts. enrolled; target FSR Completion 945-420 HIV neuropathy In Progress Drug only Manji UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: recruitment complete but study still Data Analysis ongoing-completion Sept. 2001 FSR Completion 945-293 Essential tremor Planned Drug only Wills, Naashef UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: not yet started 40 pts. Data Analysis targeted FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 53 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026059 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Bipolar disorder Grant Walden Germany Data Lock (retrospective analysis) Interim Data Analysis FSR Completion 945-418-428 Add-on treatment children Grant Lagae Belgium Data Lock Interim Data Analysis FSR Completion 945-418-432 Perineal pain-open study Grant Herbaut Belgium Data Lock Interim Data Analysis FSR Completion A9451010 Gabapentin in Approved Grant Spain Data Lock Information from neuropathic pain London meeting (open-label study) 13-Aug-01 attended by Interim SBS, AEM: anticipated start in Sept Data Analysis FSR Completion Effects of GBP on NeP Cancelled Grant Spain Data Lock and sleep symptoms (double-blind) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 54 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026060 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-275-273 Epilepsy-elderly add-on Cancelled Grant Australia Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: terminated - low enrollment Data Analysis FSR Completion Cancer pain Completed Grant Kloke Germany Data Lock Information from (retrospective analysis) London Meeting 13-Aug-01 attended by Interim SBS, AEM: report received-in review to Data Analysis determine how strongly publication should be pursued FSR Completion 945-400-281 Treatment of seizures in Completed Grant Magnus-Mi Veteran affairs US Jan-98 Jan-01 Data Lock 125,000= 06-Dec-00 the elderly population ller, L cooperative 25,000/yr studies program for 5 Balish M, Towne Interim years + A, Salinsky M, 50,000 Felicetta J, Data Analysis additional Rodgers-Neame for N, McLean M. central Rutecki P, FSR Completion laborator Mamdani M, y Uthman B, Spitz 945-954-258 Use of gabapentin for Completed Grant Magnus-Mi Pellock, J US Nov-99 Oct-00 Data Lock 7,000 15-Dec-00 symptom control in ller, L Fusun Alehan, children with attention MD-Medical deficit hyperactivity College of Interim disorder-a pilot study Virginia, Richmond, VA Data Analysis FSR Completion 945-952-263 Reproductive function in Completed Grant Magnus-Mi Morell, M US Nov-99 Oct-00 Data Lock 171,587 11-Oct-99 AED treated women with ller, L Sauer M, Giudice epilepsy L Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 55 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026061 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments HIV polyneuropathy In Progress Grant Schielke Germany Data Lock Information from London Meeting 13-Aug-01 attended by Interim SBS, AEM: patient accrual slow--currently Data Analysis only 30 pts FSR Completion Tension headaches In Progress Grant Arnold Germany Data Lock Information from London Meeting 13-Aug-01 attended by Interim SBS, AEM: slow enrollment Data Analysis FSR Completion 945-475-433 Carpal Tunnel Syndrome- In Progress Grant Australia Data Lock Information from neuropath. pain prophyl. London meeting (vs. placebo, DB 13-Aug-01 attended by crossover, Interim SBS, AEM: started at 8 wks., titr. to 4800 mg, end of '98 20 pts., 1 center) Data Analysis FSR Completion 945-475-433 Carpal Tunnel Syndrome- In Progress Grant Australia Data Lock Information from neuropath. pain prophyl. London meeting (vs. placebo, DB 13-Aug-01 attended by crossover, Interim SBS, AEM: started at 8 wks., titr. to 4800 mg, end of '98 20 pts., 1 center) Data Analysis FSR Completion Post-marketing In Progress Grant Korea (Jeil Data Lock surveillance Pharmaceuti cals) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 56 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026062 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments PMS In Progress Grant Phillipines Data Lock Interim Data Analysis FSR Completion A945-10. Evaluation of gabapentin Planned Grant Italy Data Lock Information from effect in the prevention of London meeting oxaliplatin induced 13-Aug-01 attended by neurotoxicity in Interim SBS, AEM: very gabapentin treated or expensive study--Italy untreated population Data Analysis cannnot support this study at all. Looking to see whether NYHQ will FSR Completion be able to fund the entire study. A945-1002 A double-blind Planned Grant Italy Data Lock Information from randomised trial London meeting comparing gabapentin 13-Aug-01 attended by versus placebo in the Interim SBS, AEM: from same prophylaxis and treatment Data Analysis protocol as #11--this of acute oxaliplatin half may not be induced neurotoxicity pursued. FSR Completion GBP vs CBZ in epilepsy Planned Grant Spain Data Lock Information from (double-blind study) London meeting 13-Aug-01 attended by Interim SBS, AEM: still no response on whether Data Analysis this has been approved. FSR Completion Insomnia (preference for Planned Grant Spain Data Lock GBP over BZD in insonmia) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 57 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026063 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Insomnia (preference for Planned Grant Spain Data Lock GBP over BZD in insonmia) Interim Data Analysis FSR Completion Participation of the Planned Grant Venezuela Data Lock endogenous pain modulatory system in experimentally induced Interim neuropathic pain. New perspectives on the Data Analysis mechanism of action of gabapentin FSR Completion Functional Proposed Grant Spain Data Lock Information from characterization of the London meeting GABA-mediated actions 13-Aug-01 attended by induced by gabapentin Interim SBS, AEM: awaiting (MOA study) response from Data Analysis NYHQ--submitted in July FSR Completion Post-hernia repair Proposed Grant UK Data Lock Information from (inguinaldynia) London meeting 13-Aug-01 attended by Interim SBS, AEM: good protocol, local grant Data Analysis study FSR Completion Amytriptyline comparator Proposed Grant UK Data Lock in Cancer Pain-full spectrum of cancer pain Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 58 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026064 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments AWB-monotherapy Completed Marketing Schmidt D Germany Data Lock Information from (400-500 London meeting pts--post-surveillance 13-Aug-01 attended by clincal experience trial) Interim SBS, AEM: framework provided, sales force Data Analysis data gathering FSR Completion 945-212 Partial/gen. epilepsy vs. Sponsored Australia Data Lock lamotrigine Internat. ICD study Interim Data Analysis FSR Completion 945-430 Migraine prophylaxis Cancelled Sponsored Spain Data Lock Interim Data Analysis FSR Completion 945-475-206 Australia Steps Complete Sponsored Australia Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: based on same protocol on Data Analysis US-blood levels awaited FSR Completion 945-418-308 Belsteps Complete Sponsored Belgium Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: like-Australian Data Analysis steps--open-label-data entry ongoing-stat. report end-2000 FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 59 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026065 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-420-007 Epilepsy (Add-on followed Completed Sponsored Italy Data Lock by lead cmpd withdrawal) Interim Data Analysis FSR Completion 945-437-466 Postoperative/post-traum Completed Sponsored Sweden, Data Lock Information from atic pain ('POP' Finland, London meeting study--120 pts enrolled, Norway, 13-Aug-01 attended by 90-100 evaluable) Denmark Interim SBS, AEM: code broken last Data Analysis week-results available in Sept. Results to be released at Sept FSR Completion investigators meeting. 945-01/11-001 Migraine-children, adoles. Completed Sponsored Spain Data Lock Information from 9 (open-label) London meeting 13-Aug-01 attended by Interim SBS, AEM: Very Data Analysis positive results; completed approx 1-2 mos ago FSR Completion 945-475-283 Headache-chronic, daily Completed Sponsored Australia Data Lock Information from (tension Headache) London meeting 13-Aug-01 attended by Interim SBS, AEM: data management Data Analysis ongoing-possibly completed-must check FSR Completion 945-411 Diabetes-neuropathic Completed Sponsored Mexico, Data Lock Information from pain, Venez. London meeting (fixed dose vs. titration, Equador, 13-Aug-01 attended by double-blind, 7 wks.) Columb, Interim SBS, AEM: 508 Chile, Peru, patients targeted: 304 Braz Data Analysis enrolled, 188 completed. Need full info on data from CRO. FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 60 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026066 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-405-401 Pediatric study Completed Sponsored South Africa Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: part of Shapiro study similar to Data Analysis Mexican pediatric study above FSR Completion 945-420-275 Post-herpetic neuralgia Completed Sponsored Italy Data Lock Interim Data Analysis FSR Completion 945-187/87 Epilepsy-refract.-long Completed Sponsored Mexico Data Lock Information from term London meeting OC safety in children 13-Aug-01 attended by (open-label safety) Interim SBS, AEM: Publ. Devel. Med. and Child Data Analysis Neuro. FSR Completion Sub-study of allodynia In Progress Sponsored Sweden, Data Lock Information from based on POP study (20 Finland, London meeting pts.) Norway, 13-Aug-01 attended by Denmark Interim SBS, AEM: recruitment complete by Data Analysis Nov--anticipated study results by Q2/02 FSR Completion 945-222 Spasticity In Progress Sponsored Spain Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: finalized Q1/01 Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 61 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026067 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-431 Restless Leg Syndrome In Progress Sponsored Spain Data Lock Information from (including sleep London meeting architecture) 13-Aug-01 attended by Interim SBS, AEM: finishing in Sept, results in Oct/Nov Data Analysis FSR Completion 945-424 Parkinson's Disease In Progress Sponsored Spain Data Lock Information from (L-dopa related London meeting dyskinesia) 13-Aug-01 attended by Interim SBS, AEM: delayed due to PI Data Analysis pregnancy--possibly to be complete Q1/02 FSR Completion 945-276 Cancer pain (Italian In Progress Sponsored Spain Data Lock Information from study) London meeting 13-Aug-01 attended by Interim SBS, AEM: March 2002 Data Analysis final patient accrual anticipated. FSR Completion 945-436-288 Epilepsy-monotherapy In Progress Sponsored France Data Lock Information from (open-label switch, not London meeting stringently 13-Aug-01 attended by controlled-experience Interim SBS, AEM: Auralie is trial) the contact Data Analysis FSR Completion 945-445-435 Dutch Steps In Progress Sponsored Netherlands Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: contact for Netherlands--Marnix Data Analysis Artz FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 62 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026068 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-468-429 Diabetes-neuropathic In Progress Sponsored Taiwan Data Lock Information from pain London meeting 13-Aug-01 attended by Interim SBS, AEM: 9/00 12/01-Need to find out Data Analysis if this has completed FSR Completion 945-420-276 Neuropathic Pain (Cancer In Progress Sponsored Spain/Italy 8 Data Lock Information from Pain) sites London meeting 13-Aug-01 attended by Interim SBS, AEM: ongoing 10/98-6/01 Data Analysis FSR Completion 945-445-280 Refl. Symp. Dystr. pain In Progress Sponsored Netherlands Data Lock Interim Data Analysis FSR Completion 945-291 Bipolar Disorder (1 year Ongoing Sponsored Spain/Italy 3 Data Lock Information from Tx) sites London meeting 13-Aug-01 attended by Interim SBS, AEM: patient accrual currently 35 but Data Analysis need 80 total Accrual problems due to Janssen blocking FSR Completion recruitment. Issue may have been somewhat resolved. Definitely Neuropathic pain Planned Sponsored Germany Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: initiated in May, CRFs Due Oct / Data Analysis Nov, anticpated results in Jan FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 63 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026069 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-301 Refractory Planned Sponsored Canada Data Lock Information from epilepsy-children aged 1 London meeting month to 4 yrs-open 13-Aug-01 attended by Interim SBS, AEM: submission-contact Data Analysis Tibor Kapussy of Canada for info. FSR Completion 945-401 Pediatric (contributed to Planned Sponsored Mexico Data Lock Information from US FDA submission) London meeting 13-Aug-01 attended by Interim SBS, AEM: submission Data Analysis FSR Completion Peripheral neuropathic Planned Sponsored Netherlands Data Lock Information from pain London meeting open study 13-Aug-01 attended by Interim SBS, AEM: unknown whether this has started Data Analysis FSR Completion 945-437-466 Neuropathic pain Planned Sponsored Phillipines Data Lock Interim Data Analysis FSR Completion Diabetes-neuropathic Planned Sponsored Thailand Data Lock pain Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 64 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026070 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Spasticity (60 pts Rejected Sponsored Nelles Germany Data Lock Information from proposed--early London meeting intervention in stroke pts 13-Aug-01 attended by to prevent spasticity and Interim SBS, AEM: LT to pain) re-review request for Data Analysis funding FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 65 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026071 Neurontin AIDS/HIV Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % AIDS Yes Primary 30 1.5 3 4.5 BIOSIS 8.018 3,207 Infectious Disease Specialists47 North America 59 Letters Chemical Abstracts Public Health Specialists 15 Europe 32 Current Contents Pathologists 15 Far East 3 EMBASE Immunologists 8 Rest of World 6 Index Medicus Oncologists 15 MEDLINE Science Citation Index AIDS and Behavior Yes Primary 50 6 6 12 CINAHL N/A N/A N/A N/A N/A N/A Reviews EMBASE Letters AIDS Care Yes Primary N/A 6 6 12 Biological Abstracts N/A 650 Psychologists N/A United States 50 Brief Reports CINAHL Social Scientists N/A United Kingdom 25 Current Contents Nurses N/A Rest of World 25 EMBASE Other N/A Index Medicus MEDLINE Science Citation Index AIDS Patient Care Yes Primary 50 2-3 2-3 4 - 6 CINAHL N/A 5,628 Primary Care Physicians 90 N/A N/A and STDs Letters EMBASE Researchers 10 Case Reports MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 66 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026072 Neurontin AIDS/HIV Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % AIDS Reader Yes Primary 70 1 3 4 EMBASE N/A 34,576 Family Physicians 31 United States 99 Reviews MEDLINE Internists 28 Rest of World 1 Letters Hematologists 11 Oncologists 10 Other 20 International Journal Yes Primary 45 1 3 4 Current Contents 1.019 1,050 N/A N/A United Kingdom 53 of STD and AIDS Letters EMBASE Europe 17 Case Reports Index Medicus North America 14 MEDLINE Rest of World 16 SciSearch Journal of Acquired Yes Primary 60 1 2 6 7-8 BIOSIS 3.046 2,931 Infectious Disease SpecialistsN/A United States 23 Immune Deficiency Reviews Current Contents Pathologists N/A Rest of World 77 Syndromes Letters EMBASE Biologists N/A Case Reports Index Medicus Epidemiologists N/A MEDLINE Virologists N/A Science Citation Index Researchers N/A SciSearch A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 67 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026073 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Diabetes Yes Primary 25 1 1.25 3 4 4.25 Biological Abstracts 7.715 7,500 Researchers N/A North America N/A Chemical Abstracts Physicians N/A Rest of World N/A Current Contents Other N/A EMBASE Index Medicus MEDLINE Science Citation Index Diabetes and Yes Reviews 60 6 6 12 Biological Abstracts N/A 1,500 Diabetologists N/A France 60 Metabolism Primary Chemical Abstracts Endocrinologists N/A Rest of World 40 Letters Current Contents Editorials EMBASE Index Medicus MEDLINE Science Citation Index Diabetes Care Yes Primary 25 1 1.25 3 4 4.25 Biological Abstracts 4.992 13,500 Physicians N/A North America N/A Letters Chemical Abstracts Researchers N/A Europe N/A Case Reports Current Contents Nurse Practitioners N/A EMBASE Index Medicus MEDLINE Science Citation Index Diabetes Research Yes Primary 45 4 3 7 Biological Abstracts 0.982 325 Diabetologists N/A N/A N/A and Clinical Practice Reviews BIOSIS Endocrinologists N/A Letters Chemical Abstracts Brief Reports Current Contents EMBASE Index Medicus MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 68 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026074 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Diabetic Medicine Yes Primary 17 2.5 3 - 4 5.5 6.5 Current Contents 2.732 2,100 N/A N/A United Kingdom 58 Reviews EMBASE Europe 19 Letters Index Medicus North America 10 Brief Reports MEDLINE Rest of World 13 Case Reports Science Citation Index Diabetologia Yes Primary 20 6 1.5 7.5 Biological Abstracts 5.721 7,300 Endocrinologists N/A Europe 69 Letters Chemical Abstracts Internists N/A North America 16 EMBASE Researchers N/A Asia 11 Index Medicus Rest of World 4 MEDLINE Endocrine Reviews Yes N/P N/P N/P N/P Biological Abstracts 19.524 4,711 Endocrinologists 100 North America 60 BIOSIS Rest of World 40 Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE Endocrinology Yes Primary 30 1 2.5 3.5 Biological Abstracts 4.790 4,872 Endocrinologists 100 North America 68 BIOSIS Rest of World 32 Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 69 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026075 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Journal of Clinical Yes Primary 33 1 3 4 Biological Abstracts 5.447 10,158 Endocrinologists 100 United States 67 Endocrinology and Letters BIOSIS Rest of World 33 Metabolism Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE Journal of Diabetes Yes Primary 85 1 2-3 3 - 4 BIOSIS 0.851 900 Diabetologists N/A United States 40 and its Reviews Current Contents Endocrinologists N/A Europe 35 Complications Letters EMBASE Nephrologists N/A Asia 16 Editorials Index Medicus Urologists N/A Rest of World 9 Case Reports MEDLINE Primary Care Physicians N/A SciSearch A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 70 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026076 Neurontin Epilepsy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Epilepsia Yes Primary N/A 1 4 2-6 3-10 Biological Abstracts 3.787 5,220 Neurologists 94 United States 85 Letters BIOSIS Psychologists 5 Rest of World 15 Case Reports Chemical Abstracts Other 1 Current Contents EMBASE Index Medicus MEDLINE Science Citation Index SciSearch Epilepsies Yes Primary 60 2 4 6 EMBASE N/A 1,000 Neurologists N/A Europe N/A Reviews Epileptologists N/A Rest of World N/A Brief Reports Other N/A Epilepsy and Yes Primary N/A N/A N/A N/A N/A N/A 1,500 Neurologists 40 N/A N/A Behavior Letters Neuropsychiatrists 30 Editorials Radiologists 10 Brief Reports Other 20 Case Reports Epilepsy Research Yes Primary 45 2 3 5 Biological Abstracts 2.866 520 Epileptologists N/A Europe 41 Reviews BIOSIS Neurologists N/A North America 34 Letters Chemical Abstracts Pharmacologists N/A Asia 18 Editorials Current Contents Psychiatrists N/A Rest of World 7 Brief Reports EMBASE Index Medicus MEDLINE Science Citation Index A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 71 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026077

What is the Event Date?

rjmd0217

rjmd0217_p0, rjmd0217_p1, rjmd0217_p2

02/09/98, 02 109198

G EVENT 1:" Page'smits (+), 601964 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether OT not you attended. Was A Pharmaceutical Company Associated With The Event? City/State: Yes Company Name: Parke Davis 192 Event Date (Month/Day/Year): 2 / 109 / 98 No The Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm Firm other Name: than Pharmaceutical medical Company research Associatin up What Type Of Honorarlum Was Offerod? (Chock AL That Apply) Meals University/Medical Institution (eg., Vanderbilt University) Name: Charitable Contribution Cash/Check Clinical/Professional Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Other: (please specify) Gift Certificate (please specify for what): medical Suppler Textbooks (please specify): Tho Evont Was Sponsored By: (Check All That Apply) Pharmaccutical Company: Parke navi 192 Other: None University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES Because Of: (Check All That Managed Care Company: Interest In The Topic Other: (please specify) Type Of Honoraria Offered Tho Announcod Topic Was: (Check All Tha Appy) Topic Reputation Of Speakers General Therapeutic Area 48. CME Credits Offered (e.g., hypertension, heart failure, diabetes): It of Epilepsy Convenient Location A Therapeutic Class of Drugs Other (please specify): (e.g., ACE Inhibitors, diuretics): NO, Because Of: (Check All That Apply) A Specific Product Manufactured by The Pharnuceutical Company: 12233 Neurontin Lack Of Interest In The Topic Disease Management Program Scheduling Conflict (professional or personal) (treatment guldellnes, protocols, care maps, etc.): Type Of Honoraria Offered Other: No CME Credits Offered Evont Location: (Ploase Chock Appropriale Box And Record Spocific Namo On Uno Bolow): Inconvenient Location/Distance Hotel Restaurant Convention Mkt. Res. Facility Other (please specify): Home Office Other (Specify Name): Telephone Conference If You Attended, Please Continue With The Questions On The Following Pages. Pleaso Continuo With Tho Quostions To The Right S-L09819 Please Continue With The Questions For Event 1 On The Next Page. 15 CE 4 EVENT 1: Page 2 of 3 601964 PRODUCT INFORMATION Yes (Please complete the boxes in this section.) How many times Wore Specific Products Discussed? have you been No (Please go to the "General Theme" detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 1 Product Name: Neurontin Not Detailed Nonprescriber Nonprescriber THEME(S): (Piease Be As Specific As Possible) 12233 ply 1 Detail Low Low 2 Details Moderate Modorato Advance in tx of Epilepsy 3 Details High High >3 Details 2 Product Name: 2/98 Not Detailod Nonprescribor Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderato Moderate 3 Details High High >3 Details 3 p'oduct Name: Not Detailod Nonprescriber Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderato Moderato 3 Details High High >3 Details GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topics Discussed (Advanco in tx of opilepsy. - Focu in Neworks) S-L09818 15 Source:

what is the type/funder for study # 945-278?

jnjm0223

jnjm0223_p32, jnjm0223_p33, jnjm0223_p34, jnjm0223_p35, jnjm0223_p36, jnjm0223_p37, jnjm0223_p38, jnjm0223_p39, jnjm0223_p40, jnjm0223_p41, jnjm0223_p42, jnjm0223_p43, jnjm0223_p44, jnjm0223_p45, jnjm0223_p46, jnjm0223_p47, jnjm0223_p48, jnjm0223_p49, jnjm0223_p50, jnjm0223_p51, jnjm0223_p52, jnjm0223_p53, jnjm0223_p54, jnjm0223_p55, jnjm0223_p56, jnjm0223_p57, jnjm0223_p58, jnjm0223_p59, jnjm0223_p60, jnjm0223_p61, jnjm0223_p62, jnjm0223_p63, jnjm0223_p64, jnjm0223_p65, jnjm0223_p66, jnjm0223_p67, jnjm0223_p68, jnjm0223_p69, jnjm0223_p70, jnjm0223_p71

Drug only, drug only

Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Gabapentin for the treatment of Rowbotham MC 2 In development. Pain or Neurology AIDS/HIV painful HIV polyneuropathy Neuropathic Pain: HIV neuropathic pain study 2 In development. AIDS/HIV Neuropathic Pain: Treatment of diabetic neuropathy Nicholson B Knapp L 1 In development. JAMA 31-Dec-01 01-May-02 Diabetic Blonde L, Freeman R Rowbotham M, Mutisya E Neuropathy Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 32 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026038 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Gabapentin in painful diabetic Reckless J 2 In development. Diabetic Medicine Diabetic neuropathy: a randomized, Roder B, Maisonobe P Neuropathy double-blind, placebo controlled study (224) Neuropathic Pain: Phantom limb pain (UK) Critchley 1 In development. Phantom Limb Neuropathic Pain: Restless leg syndrome (Spain) 4-high Proposed. Restless Leg Syndrome Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 33 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026039 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Sleep quality and patient-reported Ehrenberg BL Glanzman R 2 Complete CONSORT Neurology 01-Aug-01 01-Nov-01 01-Mar-02 Sleep health status in periodic limb Wagner AK, Chang H, Piron S, Hsu T requirements. movement disorder treated with Corbett KR, Rogers WH gabapentin: a double-blind, randomized, placebo-controlled, cross-over study Psychiatric Gabapentin in the treatment of Marcotte D 2 In development. Primary Psychiatry 01-Oct-01 01-Dec-01 01-Apr-02 Disorders dementia and behavioral disturbance Psychiatric Psychiatric applications of Pande AC 3-high On hold. Disorders gabapentin Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 34 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026040 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Psychiatric Gabapentin and methylphenidate Hamrin V 2 In development. Disorders: Bipolar treatment of a preadolescent with Disorder ADHD and bipolar disorder Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 35 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026041 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Myrick H, Henderson S, Brady KT, Malcolm R. Gabapentin in the treatment of Jan-01 cocaine dependence: a case series. J Clin Psychiatry. 2001;62:19-23. Crawford P, Brown S, Kerr M, Parke Davis Clinical Trials Group. A randomized Mar-01 open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy. Seizure. 2001;10:107-115. Appleton R, Fichtner K, LaMoreaux L, et al. Gabapentin as add-on therapy in Apr-01 children with refractory partial seizures: a 24-week, multicentre, open-label study. Dev Med Child Neurol. 2001;43:267-273. Lado FA, Sperber EF, Moshe SL. Anticonvulsant efficacy of gabapentin on Apr-01 kindling in the immature brain. Epilepsia. 2001;42:458-463. Kwan P, Sills GJ, Brodie MJ. The mechanisms of action of commonly used Apr-01 antiepileptic drugs. Pharmacol Ther. 2001;90:21-34. Medical Action Communications 31-Oct-01 36 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026042 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Haig GM, Bockbrader HN, Wesche DL, Boellner SW, Ouellet D, Brown RR, May-01 Randinitis EJ, Posvar EL. Single-dose gabapentin pharmacokinetics and safety in healthy infants and children. J Clin Pharmacol. 2001;41:507-514. Bridges D, Thompson SWN, Rice ASC. Mechanisms of neuropathic pain. Br J Jul-01 Anaesth. 2001;87:12-26. Schmidt D, Stefan H, Elger CE. Gabapentin-monotherapy in 503 patients with Aug-01 partial epilepsy dissatisfied with initial standard antiepileptic drug therapy. Nervenheilkunde. 2001;20:321-325. Maneuf YP, Hughes J, McKnight AT. Gabapentin inhibits the substance Aug-01 P-facilitated K(+) -evoked release of. Pain. 2001;93(2):191-196. Beran R. Australian study of titration to effect profile of safety (AUS-STEPS): Oct-01 high-dose gabapentin (Neurontin) in partial seizures. Epilepsia. In Press. Medical Action Communications 31-Oct-01 37 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pizer_LKnapp_0026043 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Rice ASC, Maton S, Postherpetic Neuralgia Study Group. Gabapentin in Nov-01 postherpetic neuralgia: a randomised, double blind, placebo controlled study. Pain. In Press. Medical Action Communications 31-Oct-01 38 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026044 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-195 Double-blind, Meador K Data Lock randomized, two-period crossover comparison and behavioral effects of Interim gabapentin and carbamazepine in healthy Data Analysis volunteers FSR Completion Epilespy (BID/TID study) Data Lock Interim Data Analysis FSR Completion 945-421-002 GBP vs Valproate Spain Data Lock (add-on with CBZ, then remove CBZ and drop to monotherapy) Interim Data Analysis FSR Completion Phase III double-blind, Miller, R Data Lock 200,000. 16-Dec-96 placebo-controlled study 00-based assessing the efficacy of on 100 gabapentin in patients Interim patients with amotrophic lateral out of sclerosis (ALS) Data Analysis 200 required for study FSR Completion An open, matched control Magnus-Mi Holmes, L US Data Lock 433,943 01-Nov-95 23-Dec-99 study comparing the ller, L Harvey E, Keither cognitive abilities of D, Khoshbin S, children born to epileptic Adams J, Ryan L Interim mothers who received antiepileptic drug Data Analysis treatment to children born to non-epileptic mothers FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 39 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026045 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 073-170 An open, matched control Magnus-Mi Holmes, L US Data Lock study comparing the ller, L cognitive abilities of children exposed in utero Interim to anti epileptic monotherapy to children Data Analysis born to non-epileptic mothers FSR Completion 945-419-277 Complex/simple partial Accepted Greece Data Lock Information from seizures vs. CBZ London meeting (monotherapy), 13-Aug-01 attended by double-blind, 36 wks. Interim SBS, AEM: initiation delayed due to Data Analysis integration of research budgets. FSR Completion 945-92 Epilepsy Monotherapy vs Complete 14 Countries Data Lock Information from CBZ (290 pts) London meeting 13-Aug-01 attended by Interim SBS, AEM: poster presented from Data Analysis mid-term analysis of 100pts--study now complete-research FSR Completion report written 945-952-236 Neurontin for neurogenic Completed Herbert J Apr-96 Dec-98 Data Lock 78,500 pain in multiple sclerosis Interim Data Analysis FSR Completion 945-954-241 Neurontin in Essential Completed Uitti R Jul-98 Feb-99 Data Lock 48,000 temor Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 40 Source:https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026046 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-250 Gabapentin adjunctive Completed Ketter T Apr-98 Dec-99 Data Lock 90,691 treatment in patients with bipolar disorder Interim Data Analysis FSR Completion 945-954-252 In vivo determination of Completed Kuzniecky R Dec-96 Nov-97 Data Lock 216,610 human brain gaba Gilliam F concentrations in volunteers receiving Interim gabapentin:an escalating dose response study Data Analysis FSR Completion 945-400-281 VA COOP STUDY #428 Completed Ramsay E Jan-99 Dec-99 Data Lock 50,000 Interim Data Analysis FSR Completion 945-952-282 Gabapentin Completed Gidal B, Jul-95 Aug-00 Data Lock 87,993.1 pharmacology: Effects of Weissman J 5 GABA on human cerebral GABA concentrations Interim studies with NMR spectroscopy Data Analysis FSR Completion 945-400-WW2 SALINSKY BUDGET Completed Salinsky M Dec-96 Oct-98 Data Lock 159,364 TRF FR WE Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 41 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026047 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-090 Dose Intitiaition: Titration Completed Multicenter Jan-94 Dec-98 Data Lock 2,801,75 vs. Non-Titration 6 Interim Data Analysis FSR Completion 945-400-193 Neurontin STEPS (Study Completed Multicenter Jan-95 May-98 Data Lock 4,269,90 and of titration to 0 945-400-200 effectiveness and profile of safety) Interim Data Analysis FSR Completion 945-400-211 A Double-blind, Completed Carr D, Jan-96 Jan-99 Data Lock 1,967,40 randomized, placebo Rosenberg J, 0 controlled, parallel group, Dunteman E, multicenter trial to Harden N, Interim determine the efficacy Kreitzer J, Mann and safety of Neurontin JD, Obbens E, Data Analysis in subjects with peripheral Rowbotham M, neuropathy (Post-herpetic Ross E, Yokiel Neuralgia) J, Schell D, FSR Completion Singer E, Stewart RM, 945-400-217 MIGRAINE BID Completed Jan-97 Dec-99 Data Lock 1,849,73 0.03 Interim Data Analysis FSR Completion 945-400-220 MIGRAINE TID Completed Sep-96 Sep-98 Data Lock 699,598. 81 Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 42 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026048 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-953-231 Evaluation of the efficacy Completed Duntley Dec-96 Mar-99 Data Lock 46,650 of neurontin in the treatment of restless leg syndome and periodic Interim limb movement Data Analysis FSR Completion 945-952-233 Neurontin in the treatment Completed Feinberg Oct-96 Mar-99 Data Lock 35,000 of agitation in patients with demetia Interim Data Analysis FSR Completion 945-953-243 Double-blind, Completed Klapper JA Apr-98 Dec-98 Data Lock 1,100 randomized, placebo-controlled, parallel group trial to Interim determine the efficacy and safety of neurontin Data Analysis (gabapentin) in subjects with trigeminal neuralgia FSR Completion 945-954-244 Quantitative assessments Completed Longmire D Jul-96 Dec-96 Data Lock 15,000 of sympathetic pseudomotor changes induced by gabapentin in Interim patients with neuropathic pain Data Analysis FSR Completion 945-954-246 Adjunctive treatment for Completed Aug-98 Oct-99 Data Lock 0.01 bipolar disorder Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 43 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026049 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-954-247 A retrospective study of Completed Nuckolls J Nov-97 Jan-98 Data Lock 4,375 the effectiveness of gabapentin in the treatment of mood Interim disorders Data Analysis FSR Completion 945-954-249 A blinded randomized trial Completed Hines R Jul-99 Oct-99 Data Lock 2,000 to evaluate the efficacy of gabapentin versus ibuprofen in patients with Interim chronic pelvic pain Data Analysis FSR Completion 945-954-253 Category analysis of the Completed Longmire D Aug-97 Jun-98 Data Lock 15,000 effects of gabapentin on neuropathic pain: an open-label community Interim based outcomes study of over six hundred patient Data Analysis records FSR Completion 945-954-254 A double-blind, Completed Lyketsos Aug-98 Mar-99 Data Lock 0.01 placebo-controlled, parallel clinical trial using gabapentin to treat the Interim behavioral disturbances of out-patients with Data Analysis dementia FSR Completion 945-954-256 Gabapentin in the Completed Myrick H Jun-98 Dec-99 Data Lock 31,000 treatment of cocaine dependence Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 44 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026050 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-953-257 Evaluation of the efficacy Completed Ondo W Nov-96 Mar-99 Data Lock 63,000 of gabapentin for essential tremor Interim Data Analysis FSR Completion 945-952-261 Gabapentin therapy Completed Holmes May 97 Mar-99 Data Lock 22,740 following status epilepticus Interim Data Analysis FSR Completion 945-951-270 Open-label, Completed Gidal B May-98 Dec-99 Data Lock 7,214 non-randomized, pilot study to determine whether chronic neurontin Interim administration results in significant changes in Data Analysis various sex hormones FSR Completion 945-951-417 LEPPIK/SUDEP Completed Leppik I Oct-99 Dec-99 Data Lock 15,000 Interim Data Analysis FSR Completion 945-400-AA1 GABAPENTIN/CYT P450 Completed Dec-97 Feb-99 Data Lock 26,425 REOPENED Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 45 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026051 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-AAA GBP COMBINATION Completed Hammond Jan-98 Nov-98 Data Lock 35,219.1 STUDY FR. 1 0 Interim Data Analysis FSR Completion 945-400-EXT PUBLICATIONS Completed Holmes Jan-97 Apr-98 Data Lock 52,300.0 STARTED 1/9 1 Interim Data Analysis FSR Completion 945-951-NC1 BEYDOUN MONEY FR Completed Beydoun A Aug-96 Dec-96 Data Lock 13,915 X02E00 PE Interim Data Analysis FSR Completion 945-952-NE1 GORSIN WAS Completed Gorson K Dec-95 Apr-97 Data Lock 23,333.3 1YYE00-DIABET 4 Interim Data Analysis FSR Completion 945-954-PUB PUBLICATION-NEURON Completed Holmes L Jan-96 Oct-97 Data Lock 85,962.8 TIN INC T Marcotte D 9 Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 46 Source:https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026052 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-QQQ EXTERNAL STUDIES Completed Yaksh T Jul-96 Dec-96 Data Lock 48,000 BUD.TRANS Interim Data Analysis FSR Completion 945-954-SE3 EPILEPSY AND Completed May-97 Jun-97 Data Lock 34,856.5 WOMENS INFECTI 0 Interim Data Analysis FSR Completion 945-954-SE5 RYBACK BUDGET TRSF Completed Ryback R Aug-97 Jun-98 Data Lock 18,000 FR S Interim Data Analysis FSR Completion 945-954-SE8 CLOSED 4/00-NEUR IN Completed Nov-97 Oct-98 Data Lock 0 COCAINE Interim Data Analysis FSR Completion 945-954-SEA QUANTITATIVE Completed May-98 Dec-98 Data Lock 0 ASSESMENT OF S Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 47 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026053 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-X02 NEUR-COST BENEFIT Completed Arthur D. Little, Jun-94 Sep-96 Data Lock 300,000 Inc. Interim Data Analysis FSR Completion 945-400-X03 STEPS-MISC Completed Sep-94 Aug-95 Data Lock 299,000 NEURONTIN Interim Data Analysis FSR Completion 945-400-X04 USUAL CARE Completed Morris, III G Jan-94 Oct-99 Data Lock 65,319.1 Park K 2 Interim Data Analysis FSR Completion 945-400-X05 PREGNANCY REG Completed General Jan-95 Dec-95 Data Lock 100,049. Hospital Corp. 42 Interim Data Analysis FSR Completion 945-400-X07 WALS (MILLER) 200.0 Completed Miller R Jan-97 Dec-97 Data Lock 200,000 FROM Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 48 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026054 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-XXX PUBLICATION Completed Jan-95 Dec-95 Data Lock 100,000 SUPPORT Interim Data Analysis FSR Completion 945-224 GBP in Diabetic Completed Multicenter Data Lock Information from Neuropathy (pcbo study out of London meeting controlled-open-label Germany 13-Aug-01 attended by extension for 4 mos) Interim SBS, AEM: not to be published until Data Analysis PHN--very good data for sleep and QoL FSR Completion 945-025 Post-herpetic neuralgia Completed Rice, Maton UK Data Lock To be published in Nov-01 issue of Pain Interim Data Analysis FSR Completion 945-026 Mixed-symptoms study Completed Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: key target for publication-oovarall Data Analysis results not overwhelming but very positive for subset of FSR Completion pts with NeP Neuropathic pain vs. Completed Data Lock Information from plac., DB, crossover 6 London meeting wks. Disability Services 13-Aug-01 attended by Clinic Interim SBS, AEM: 17 pts. randomized;13 Data Analysis completed both 6-week arms. FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 49 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026055 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-262 Placebo-controlled trial of Completed Magnus-Mi Miller, R US, Canada Jun-99 Dec-99 Data Lock 15,000 gabapentin in spinal ller, L Bradley W, muscular atrophy Brooke M, Bryan W, Barohn R, Interim lannaccone S, Leshner R, Data Analysis Mendell J, Kissel J, Russman B, Samaha F, Smith FSR Completion S 945-955-250 Gabapentin adjunctive Completed Magnus-Mi Ketter, T US Apr-98 Dec-99 Data Lock 90,691 02-Jun-98 treatment in patients with ller, L Winsberg M. bipolar depression DeGolia S, Dunai M, O'Meara C, Interim Tate D, Strong C Data Analysis FSR Completion 945-954-237 Pregnancy and epilepsy Completed Montouris, G US Dec-98 Dec-00 Data Lock 45,000 20-Jul-98 15-Feb-99 in the treatment of seizures in women of childbearing age Interim Data Analysis FSR Completion 945-954-264 Reproductive hormones, Completed Magnus-Mi Pennell, P US Feb-99 Dec-99 Data Lock 68,000 01-Apr-99 antiepileptic drug levels ller, L Henry T, Litt B, and seizure occurance in Epstein C women with catamenial Interim epilepsy Data Analysis FSR Completion 945-952-232 A randomized controlled Completed Ehrenberg, B US Dec-95 Aug-00 Data Lock 75,000 09-Mar-98 pilot study of gabapentin (neurontin) in patients with restless leg Interim syndrome/periodic limb movement disorder Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 50 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026056 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-245 Randomized, Completed Magnus-Mi Rowbotham, R US Apr-99 Jun-00 Data Lock 275,000 double-blind study ller, L Sacks G, Young assessing "low dose" S versus "high dose" Interim gabapentin for the treatment of painful HIV Data Analysis neuropathy FSR Completion 945-951-304 Oral absorption of Completed Magnus-Mi Gidal, B US Oct-99 Jun-00 Data Lock 36,200 10-Sep-99 03-Dec-99 gabapentin solution: ller, L Sheth R pharmacokinetic impact of mixing with milk juice Interim or enteral supplements Data Analysis FSR Completion 945-954-242 Gabapentin for the Completed Magnus-Mi Hansen, H US Jun-99 Apr-00 Data Lock 35,000 08-Feb-99 01-Mar-99 treatment of fibromyalgia ller, L Wodecki R Interim Data Analysis FSR Completion 945-954-255 Retrospective study of the Completed Magnus-Mi Marcotte, D US Jun-99 Dec-99 Data Lock 20,000 15-Oct-99 15-Dec-00 effectiveness of ller, L gabapentin with dementia with behavioral Interim disturbance Data Analysis FSR Completion 945-953-228 Effect of gabapentin on Completed Diaz-Arrastia, R US Apr-99 Dec-99 Data Lock 20,000 13-Apr-99 12-Feb-01 plasma homocystine and Agostini M, folate levels Kokkinakis D Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 51 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026057 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-420-010 Neuropathic pain cancer In Progress Italy Data Lock Information from pts. (refractory to opiates, London meeting vs. placebo, 10 days, 13-Aug-01 attended by 600-1800 mg titr., add-on) Interim SBS, AEM: potential for final data end Q4/01 Data Analysis FSR Completion Efficacy and safety of In Progress Gudez-Santos M Philippines Data Lock gabapentin in comparison Hernandez M, with carbamazepine in Poblete A the management of pain Interim secondary to trigeminal neuralgia Data Analysis FSR Completion 945-278 Trigeminal neuralgia Cancelled Drug only Cunliffe UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: early termination-accrual Data Analysis problems (32 pts.); rept in prep. FSR Completion 945-241 Vulvadynia Cancelled Drug only Smith UK Data Lock Interim Data Analysis FSR Completion 945-279 Phantom limb pain Completed Drug only Critchley UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: presented this year-Michael Data Analysis Rowbotham has this data. Poster presented at EFIC (17 pts.). FSR Completion Publication in prep. Bold = Lead Investigator Medical Action Communications 31-Oct-01 52 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026058 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-425 CRPS vs. placebo In Progress Drug only Hill D UK Data Lock Information from crossover London meeting 13-Aug-01 attended by Interim SBS, AEM: all 10 pts. enrolled; completion Data Analysis anticipated next yr FSR Completion 945-285 Refl. Symp. Dys. In Progress Drug only Souter UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: ongoing--need to locate Data Analysis protocol-13 of 15 pts. enrolled; target compl. Feb. 2001 FSR Completion 945-410 Back pain-surgically In Progress Drug only Hester UK Data Lock Information from refractory London meeting 13-Aug-01 attended by Interim SBS, AEM: 15 to 20 Data Analysis patients currently recruited-10 of 27 pts. enrolled; target FSR Completion 945-420 HIV neuropathy In Progress Drug only Manji UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: recruitment complete but study still Data Analysis ongoing-completion Sept. 2001 FSR Completion 945-293 Essential tremor Planned Drug only Wills, Naashef UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: not yet started 40 pts. Data Analysis targeted FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 53 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026059 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Bipolar disorder Grant Walden Germany Data Lock (retrospective analysis) Interim Data Analysis FSR Completion 945-418-428 Add-on treatment children Grant Lagae Belgium Data Lock Interim Data Analysis FSR Completion 945-418-432 Perineal pain-open study Grant Herbaut Belgium Data Lock Interim Data Analysis FSR Completion A9451010 Gabapentin in Approved Grant Spain Data Lock Information from neuropathic pain London meeting (open-label study) 13-Aug-01 attended by Interim SBS, AEM: anticipated start in Sept Data Analysis FSR Completion Effects of GBP on NeP Cancelled Grant Spain Data Lock and sleep symptoms (double-blind) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 54 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026060 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-275-273 Epilepsy-elderly add-on Cancelled Grant Australia Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: terminated - low enrollment Data Analysis FSR Completion Cancer pain Completed Grant Kloke Germany Data Lock Information from (retrospective analysis) London Meeting 13-Aug-01 attended by Interim SBS, AEM: report received-in review to Data Analysis determine how strongly publication should be pursued FSR Completion 945-400-281 Treatment of seizures in Completed Grant Magnus-Mi Veteran affairs US Jan-98 Jan-01 Data Lock 125,000= 06-Dec-00 the elderly population ller, L cooperative 25,000/yr studies program for 5 Balish M, Towne Interim years + A, Salinsky M, 50,000 Felicetta J, Data Analysis additional Rodgers-Neame for N, McLean M. central Rutecki P, FSR Completion laborator Mamdani M, y Uthman B, Spitz 945-954-258 Use of gabapentin for Completed Grant Magnus-Mi Pellock, J US Nov-99 Oct-00 Data Lock 7,000 15-Dec-00 symptom control in ller, L Fusun Alehan, children with attention MD-Medical deficit hyperactivity College of Interim disorder-a pilot study Virginia, Richmond, VA Data Analysis FSR Completion 945-952-263 Reproductive function in Completed Grant Magnus-Mi Morell, M US Nov-99 Oct-00 Data Lock 171,587 11-Oct-99 AED treated women with ller, L Sauer M, Giudice epilepsy L Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 55 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026061 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments HIV polyneuropathy In Progress Grant Schielke Germany Data Lock Information from London Meeting 13-Aug-01 attended by Interim SBS, AEM: patient accrual slow--currently Data Analysis only 30 pts FSR Completion Tension headaches In Progress Grant Arnold Germany Data Lock Information from London Meeting 13-Aug-01 attended by Interim SBS, AEM: slow enrollment Data Analysis FSR Completion 945-475-433 Carpal Tunnel Syndrome- In Progress Grant Australia Data Lock Information from neuropath. pain prophyl. London meeting (vs. placebo, DB 13-Aug-01 attended by crossover, Interim SBS, AEM: started at 8 wks., titr. to 4800 mg, end of '98 20 pts., 1 center) Data Analysis FSR Completion 945-475-433 Carpal Tunnel Syndrome- In Progress Grant Australia Data Lock Information from neuropath. pain prophyl. London meeting (vs. placebo, DB 13-Aug-01 attended by crossover, Interim SBS, AEM: started at 8 wks., titr. to 4800 mg, end of '98 20 pts., 1 center) Data Analysis FSR Completion Post-marketing In Progress Grant Korea (Jeil Data Lock surveillance Pharmaceuti cals) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 56 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026062 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments PMS In Progress Grant Phillipines Data Lock Interim Data Analysis FSR Completion A945-10. Evaluation of gabapentin Planned Grant Italy Data Lock Information from effect in the prevention of London meeting oxaliplatin induced 13-Aug-01 attended by neurotoxicity in Interim SBS, AEM: very gabapentin treated or expensive study--Italy untreated population Data Analysis cannnot support this study at all. Looking to see whether NYHQ will FSR Completion be able to fund the entire study. A945-1002 A double-blind Planned Grant Italy Data Lock Information from randomised trial London meeting comparing gabapentin 13-Aug-01 attended by versus placebo in the Interim SBS, AEM: from same prophylaxis and treatment Data Analysis protocol as #11--this of acute oxaliplatin half may not be induced neurotoxicity pursued. FSR Completion GBP vs CBZ in epilepsy Planned Grant Spain Data Lock Information from (double-blind study) London meeting 13-Aug-01 attended by Interim SBS, AEM: still no response on whether Data Analysis this has been approved. FSR Completion Insomnia (preference for Planned Grant Spain Data Lock GBP over BZD in insonmia) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 57 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026063 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Insomnia (preference for Planned Grant Spain Data Lock GBP over BZD in insonmia) Interim Data Analysis FSR Completion Participation of the Planned Grant Venezuela Data Lock endogenous pain modulatory system in experimentally induced Interim neuropathic pain. New perspectives on the Data Analysis mechanism of action of gabapentin FSR Completion Functional Proposed Grant Spain Data Lock Information from characterization of the London meeting GABA-mediated actions 13-Aug-01 attended by induced by gabapentin Interim SBS, AEM: awaiting (MOA study) response from Data Analysis NYHQ--submitted in July FSR Completion Post-hernia repair Proposed Grant UK Data Lock Information from (inguinaldynia) London meeting 13-Aug-01 attended by Interim SBS, AEM: good protocol, local grant Data Analysis study FSR Completion Amytriptyline comparator Proposed Grant UK Data Lock in Cancer Pain-full spectrum of cancer pain Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 58 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026064 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments AWB-monotherapy Completed Marketing Schmidt D Germany Data Lock Information from (400-500 London meeting pts--post-surveillance 13-Aug-01 attended by clincal experience trial) Interim SBS, AEM: framework provided, sales force Data Analysis data gathering FSR Completion 945-212 Partial/gen. epilepsy vs. Sponsored Australia Data Lock lamotrigine Internat. ICD study Interim Data Analysis FSR Completion 945-430 Migraine prophylaxis Cancelled Sponsored Spain Data Lock Interim Data Analysis FSR Completion 945-475-206 Australia Steps Complete Sponsored Australia Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: based on same protocol on Data Analysis US-blood levels awaited FSR Completion 945-418-308 Belsteps Complete Sponsored Belgium Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: like-Australian Data Analysis steps--open-label-data entry ongoing-stat. report end-2000 FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 59 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026065 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-420-007 Epilepsy (Add-on followed Completed Sponsored Italy Data Lock by lead cmpd withdrawal) Interim Data Analysis FSR Completion 945-437-466 Postoperative/post-traum Completed Sponsored Sweden, Data Lock Information from atic pain ('POP' Finland, London meeting study--120 pts enrolled, Norway, 13-Aug-01 attended by 90-100 evaluable) Denmark Interim SBS, AEM: code broken last Data Analysis week-results available in Sept. Results to be released at Sept FSR Completion investigators meeting. 945-01/11-001 Migraine-children, adoles. Completed Sponsored Spain Data Lock Information from 9 (open-label) London meeting 13-Aug-01 attended by Interim SBS, AEM: Very Data Analysis positive results; completed approx 1-2 mos ago FSR Completion 945-475-283 Headache-chronic, daily Completed Sponsored Australia Data Lock Information from (tension Headache) London meeting 13-Aug-01 attended by Interim SBS, AEM: data management Data Analysis ongoing-possibly completed-must check FSR Completion 945-411 Diabetes-neuropathic Completed Sponsored Mexico, Data Lock Information from pain, Venez. London meeting (fixed dose vs. titration, Equador, 13-Aug-01 attended by double-blind, 7 wks.) Columb, Interim SBS, AEM: 508 Chile, Peru, patients targeted: 304 Braz Data Analysis enrolled, 188 completed. Need full info on data from CRO. FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 60 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026066 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-405-401 Pediatric study Completed Sponsored South Africa Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: part of Shapiro study similar to Data Analysis Mexican pediatric study above FSR Completion 945-420-275 Post-herpetic neuralgia Completed Sponsored Italy Data Lock Interim Data Analysis FSR Completion 945-187/87 Epilepsy-refract.-long Completed Sponsored Mexico Data Lock Information from term London meeting OC safety in children 13-Aug-01 attended by (open-label safety) Interim SBS, AEM: Publ. Devel. Med. and Child Data Analysis Neuro. FSR Completion Sub-study of allodynia In Progress Sponsored Sweden, Data Lock Information from based on POP study (20 Finland, London meeting pts.) Norway, 13-Aug-01 attended by Denmark Interim SBS, AEM: recruitment complete by Data Analysis Nov--anticipated study results by Q2/02 FSR Completion 945-222 Spasticity In Progress Sponsored Spain Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: finalized Q1/01 Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 61 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026067 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-431 Restless Leg Syndrome In Progress Sponsored Spain Data Lock Information from (including sleep London meeting architecture) 13-Aug-01 attended by Interim SBS, AEM: finishing in Sept, results in Oct/Nov Data Analysis FSR Completion 945-424 Parkinson's Disease In Progress Sponsored Spain Data Lock Information from (L-dopa related London meeting dyskinesia) 13-Aug-01 attended by Interim SBS, AEM: delayed due to PI Data Analysis pregnancy--possibly to be complete Q1/02 FSR Completion 945-276 Cancer pain (Italian In Progress Sponsored Spain Data Lock Information from study) London meeting 13-Aug-01 attended by Interim SBS, AEM: March 2002 Data Analysis final patient accrual anticipated. FSR Completion 945-436-288 Epilepsy-monotherapy In Progress Sponsored France Data Lock Information from (open-label switch, not London meeting stringently 13-Aug-01 attended by controlled-experience Interim SBS, AEM: Auralie is trial) the contact Data Analysis FSR Completion 945-445-435 Dutch Steps In Progress Sponsored Netherlands Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: contact for Netherlands--Marnix Data Analysis Artz FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 62 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026068 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-468-429 Diabetes-neuropathic In Progress Sponsored Taiwan Data Lock Information from pain London meeting 13-Aug-01 attended by Interim SBS, AEM: 9/00 12/01-Need to find out Data Analysis if this has completed FSR Completion 945-420-276 Neuropathic Pain (Cancer In Progress Sponsored Spain/Italy 8 Data Lock Information from Pain) sites London meeting 13-Aug-01 attended by Interim SBS, AEM: ongoing 10/98-6/01 Data Analysis FSR Completion 945-445-280 Refl. Symp. Dystr. pain In Progress Sponsored Netherlands Data Lock Interim Data Analysis FSR Completion 945-291 Bipolar Disorder (1 year Ongoing Sponsored Spain/Italy 3 Data Lock Information from Tx) sites London meeting 13-Aug-01 attended by Interim SBS, AEM: patient accrual currently 35 but Data Analysis need 80 total Accrual problems due to Janssen blocking FSR Completion recruitment. Issue may have been somewhat resolved. Definitely Neuropathic pain Planned Sponsored Germany Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: initiated in May, CRFs Due Oct / Data Analysis Nov, anticpated results in Jan FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 63 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026069 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-301 Refractory Planned Sponsored Canada Data Lock Information from epilepsy-children aged 1 London meeting month to 4 yrs-open 13-Aug-01 attended by Interim SBS, AEM: submission-contact Data Analysis Tibor Kapussy of Canada for info. FSR Completion 945-401 Pediatric (contributed to Planned Sponsored Mexico Data Lock Information from US FDA submission) London meeting 13-Aug-01 attended by Interim SBS, AEM: submission Data Analysis FSR Completion Peripheral neuropathic Planned Sponsored Netherlands Data Lock Information from pain London meeting open study 13-Aug-01 attended by Interim SBS, AEM: unknown whether this has started Data Analysis FSR Completion 945-437-466 Neuropathic pain Planned Sponsored Phillipines Data Lock Interim Data Analysis FSR Completion Diabetes-neuropathic Planned Sponsored Thailand Data Lock pain Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 64 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026070 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Spasticity (60 pts Rejected Sponsored Nelles Germany Data Lock Information from proposed--early London meeting intervention in stroke pts 13-Aug-01 attended by to prevent spasticity and Interim SBS, AEM: LT to pain) re-review request for Data Analysis funding FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 65 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026071 Neurontin AIDS/HIV Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % AIDS Yes Primary 30 1.5 3 4.5 BIOSIS 8.018 3,207 Infectious Disease Specialists47 North America 59 Letters Chemical Abstracts Public Health Specialists 15 Europe 32 Current Contents Pathologists 15 Far East 3 EMBASE Immunologists 8 Rest of World 6 Index Medicus Oncologists 15 MEDLINE Science Citation Index AIDS and Behavior Yes Primary 50 6 6 12 CINAHL N/A N/A N/A N/A N/A N/A Reviews EMBASE Letters AIDS Care Yes Primary N/A 6 6 12 Biological Abstracts N/A 650 Psychologists N/A United States 50 Brief Reports CINAHL Social Scientists N/A United Kingdom 25 Current Contents Nurses N/A Rest of World 25 EMBASE Other N/A Index Medicus MEDLINE Science Citation Index AIDS Patient Care Yes Primary 50 2-3 2-3 4 - 6 CINAHL N/A 5,628 Primary Care Physicians 90 N/A N/A and STDs Letters EMBASE Researchers 10 Case Reports MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 66 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026072 Neurontin AIDS/HIV Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % AIDS Reader Yes Primary 70 1 3 4 EMBASE N/A 34,576 Family Physicians 31 United States 99 Reviews MEDLINE Internists 28 Rest of World 1 Letters Hematologists 11 Oncologists 10 Other 20 International Journal Yes Primary 45 1 3 4 Current Contents 1.019 1,050 N/A N/A United Kingdom 53 of STD and AIDS Letters EMBASE Europe 17 Case Reports Index Medicus North America 14 MEDLINE Rest of World 16 SciSearch Journal of Acquired Yes Primary 60 1 2 6 7-8 BIOSIS 3.046 2,931 Infectious Disease SpecialistsN/A United States 23 Immune Deficiency Reviews Current Contents Pathologists N/A Rest of World 77 Syndromes Letters EMBASE Biologists N/A Case Reports Index Medicus Epidemiologists N/A MEDLINE Virologists N/A Science Citation Index Researchers N/A SciSearch A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 67 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026073 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Diabetes Yes Primary 25 1 1.25 3 4 4.25 Biological Abstracts 7.715 7,500 Researchers N/A North America N/A Chemical Abstracts Physicians N/A Rest of World N/A Current Contents Other N/A EMBASE Index Medicus MEDLINE Science Citation Index Diabetes and Yes Reviews 60 6 6 12 Biological Abstracts N/A 1,500 Diabetologists N/A France 60 Metabolism Primary Chemical Abstracts Endocrinologists N/A Rest of World 40 Letters Current Contents Editorials EMBASE Index Medicus MEDLINE Science Citation Index Diabetes Care Yes Primary 25 1 1.25 3 4 4.25 Biological Abstracts 4.992 13,500 Physicians N/A North America N/A Letters Chemical Abstracts Researchers N/A Europe N/A Case Reports Current Contents Nurse Practitioners N/A EMBASE Index Medicus MEDLINE Science Citation Index Diabetes Research Yes Primary 45 4 3 7 Biological Abstracts 0.982 325 Diabetologists N/A N/A N/A and Clinical Practice Reviews BIOSIS Endocrinologists N/A Letters Chemical Abstracts Brief Reports Current Contents EMBASE Index Medicus MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 68 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026074 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Diabetic Medicine Yes Primary 17 2.5 3 - 4 5.5 6.5 Current Contents 2.732 2,100 N/A N/A United Kingdom 58 Reviews EMBASE Europe 19 Letters Index Medicus North America 10 Brief Reports MEDLINE Rest of World 13 Case Reports Science Citation Index Diabetologia Yes Primary 20 6 1.5 7.5 Biological Abstracts 5.721 7,300 Endocrinologists N/A Europe 69 Letters Chemical Abstracts Internists N/A North America 16 EMBASE Researchers N/A Asia 11 Index Medicus Rest of World 4 MEDLINE Endocrine Reviews Yes N/P N/P N/P N/P Biological Abstracts 19.524 4,711 Endocrinologists 100 North America 60 BIOSIS Rest of World 40 Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE Endocrinology Yes Primary 30 1 2.5 3.5 Biological Abstracts 4.790 4,872 Endocrinologists 100 North America 68 BIOSIS Rest of World 32 Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 69 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026075 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Journal of Clinical Yes Primary 33 1 3 4 Biological Abstracts 5.447 10,158 Endocrinologists 100 United States 67 Endocrinology and Letters BIOSIS Rest of World 33 Metabolism Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE Journal of Diabetes Yes Primary 85 1 2-3 3 - 4 BIOSIS 0.851 900 Diabetologists N/A United States 40 and its Reviews Current Contents Endocrinologists N/A Europe 35 Complications Letters EMBASE Nephrologists N/A Asia 16 Editorials Index Medicus Urologists N/A Rest of World 9 Case Reports MEDLINE Primary Care Physicians N/A SciSearch A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 70 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026076 Neurontin Epilepsy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Epilepsia Yes Primary N/A 1 4 2-6 3-10 Biological Abstracts 3.787 5,220 Neurologists 94 United States 85 Letters BIOSIS Psychologists 5 Rest of World 15 Case Reports Chemical Abstracts Other 1 Current Contents EMBASE Index Medicus MEDLINE Science Citation Index SciSearch Epilepsies Yes Primary 60 2 4 6 EMBASE N/A 1,000 Neurologists N/A Europe N/A Reviews Epileptologists N/A Rest of World N/A Brief Reports Other N/A Epilepsy and Yes Primary N/A N/A N/A N/A N/A N/A 1,500 Neurologists 40 N/A N/A Behavior Letters Neuropsychiatrists 30 Editorials Radiologists 10 Brief Reports Other 20 Case Reports Epilepsy Research Yes Primary 45 2 3 5 Biological Abstracts 2.866 520 Epileptologists N/A Europe 41 Reviews BIOSIS Neurologists N/A North America 34 Letters Chemical Abstracts Pharmacologists N/A Asia 18 Editorials Current Contents Psychiatrists N/A Rest of World 7 Brief Reports EMBASE Index Medicus MEDLINE Science Citation Index A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 71 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026077

what country is mentioned for study # 945-278?

jnjm0223

jnjm0223_p32, jnjm0223_p33, jnjm0223_p34, jnjm0223_p35, jnjm0223_p36, jnjm0223_p37, jnjm0223_p38, jnjm0223_p39, jnjm0223_p40, jnjm0223_p41, jnjm0223_p42, jnjm0223_p43, jnjm0223_p44, jnjm0223_p45, jnjm0223_p46, jnjm0223_p47, jnjm0223_p48, jnjm0223_p49, jnjm0223_p50, jnjm0223_p51, jnjm0223_p52, jnjm0223_p53, jnjm0223_p54, jnjm0223_p55, jnjm0223_p56, jnjm0223_p57, jnjm0223_p58, jnjm0223_p59, jnjm0223_p60, jnjm0223_p61, jnjm0223_p62, jnjm0223_p63, jnjm0223_p64, jnjm0223_p65, jnjm0223_p66, jnjm0223_p67, jnjm0223_p68, jnjm0223_p69, jnjm0223_p70, jnjm0223_p71

UK

Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Gabapentin for the treatment of Rowbotham MC 2 In development. Pain or Neurology AIDS/HIV painful HIV polyneuropathy Neuropathic Pain: HIV neuropathic pain study 2 In development. AIDS/HIV Neuropathic Pain: Treatment of diabetic neuropathy Nicholson B Knapp L 1 In development. JAMA 31-Dec-01 01-May-02 Diabetic Blonde L, Freeman R Rowbotham M, Mutisya E Neuropathy Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 32 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026038 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Gabapentin in painful diabetic Reckless J 2 In development. Diabetic Medicine Diabetic neuropathy: a randomized, Roder B, Maisonobe P Neuropathy double-blind, placebo controlled study (224) Neuropathic Pain: Phantom limb pain (UK) Critchley 1 In development. Phantom Limb Neuropathic Pain: Restless leg syndrome (Spain) 4-high Proposed. Restless Leg Syndrome Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 33 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026039 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Neuropathic Pain: Sleep quality and patient-reported Ehrenberg BL Glanzman R 2 Complete CONSORT Neurology 01-Aug-01 01-Nov-01 01-Mar-02 Sleep health status in periodic limb Wagner AK, Chang H, Piron S, Hsu T requirements. movement disorder treated with Corbett KR, Rogers WH gabapentin: a double-blind, randomized, placebo-controlled, cross-over study Psychiatric Gabapentin in the treatment of Marcotte D 2 In development. Primary Psychiatry 01-Oct-01 01-Dec-01 01-Apr-02 Disorders dementia and behavioral disturbance Psychiatric Psychiatric applications of Pande AC 3-high On hold. Disorders gabapentin Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 34 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026040 Neurontin Manuscript Tracking Grid. Sorted by Indication and Priority Expect. Expect. Expect. Indication Working Title/Description Authors Internal Reviewers Priority Current Status Target Journal Sub. Accep. Pub. Psychiatric Gabapentin and methylphenidate Hamrin V 2 In development. Disorders: Bipolar treatment of a preadolescent with Disorder ADHD and bipolar disorder Bold = Lead Author/Lead Internal Reviewer Medical Action Communications TBD = To Be Determined 31-Oct-01 Priority 1 = Top Priority 35 Priority 2 = In Development Priority 3 = On Hold Priority 4 = Proposed Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026041 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Myrick H, Henderson S, Brady KT, Malcolm R. Gabapentin in the treatment of Jan-01 cocaine dependence: a case series. J Clin Psychiatry. 2001;62:19-23. Crawford P, Brown S, Kerr M, Parke Davis Clinical Trials Group. A randomized Mar-01 open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy. Seizure. 2001;10:107-115. Appleton R, Fichtner K, LaMoreaux L, et al. Gabapentin as add-on therapy in Apr-01 children with refractory partial seizures: a 24-week, multicentre, open-label study. Dev Med Child Neurol. 2001;43:267-273. Lado FA, Sperber EF, Moshe SL. Anticonvulsant efficacy of gabapentin on Apr-01 kindling in the immature brain. Epilepsia. 2001;42:458-463. Kwan P, Sills GJ, Brodie MJ. The mechanisms of action of commonly used Apr-01 antiepileptic drugs. Pharmacol Ther. 2001;90:21-34. Medical Action Communications 31-Oct-01 36 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026042 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Haig GM, Bockbrader HN, Wesche DL, Boellner SW, Ouellet D, Brown RR, May-01 Randinitis EJ, Posvar EL. Single-dose gabapentin pharmacokinetics and safety in healthy infants and children. J Clin Pharmacol. 2001;41:507-514. Bridges D, Thompson SWN, Rice ASC. Mechanisms of neuropathic pain. Br J Jul-01 Anaesth. 2001;87:12-26. Schmidt D, Stefan H, Elger CE. Gabapentin-monotherapy in 503 patients with Aug-01 partial epilepsy dissatisfied with initial standard antiepileptic drug therapy. Nervenheilkunde. 2001;20:321-325. Maneuf YP, Hughes J, McKnight AT. Gabapentin inhibits the substance Aug-01 P-facilitated K(+) -evoked release of. Pain. 2001;93(2):191-196. Beran R. Australian study of titration to effect profile of safety (AUS-STEPS): Oct-01 high-dose gabapentin (Neurontin) in partial seizures. Epilepsia. In Press. Medical Action Communications 31-Oct-01 37 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pizer_LKnapp_0026043 Neurontin Manuscripts Year to Date Sorted by Publication Date Citation Publication Date Rice ASC, Maton S, Postherpetic Neuralgia Study Group. Gabapentin in Nov-01 postherpetic neuralgia: a randomised, double blind, placebo controlled study. Pain. In Press. Medical Action Communications 31-Oct-01 38 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026044 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-195 Double-blind, Meador K Data Lock randomized, two-period crossover comparison and behavioral effects of Interim gabapentin and carbamazepine in healthy Data Analysis volunteers FSR Completion Epilespy (BID/TID study) Data Lock Interim Data Analysis FSR Completion 945-421-002 GBP vs Valproate Spain Data Lock (add-on with CBZ, then remove CBZ and drop to monotherapy) Interim Data Analysis FSR Completion Phase III double-blind, Miller, R Data Lock 200,000. 16-Dec-96 placebo-controlled study 00-based assessing the efficacy of on 100 gabapentin in patients Interim patients with amotrophic lateral out of sclerosis (ALS) Data Analysis 200 required for study FSR Completion An open, matched control Magnus-Mi Holmes, L US Data Lock 433,943 01-Nov-95 23-Dec-99 study comparing the ller, L Harvey E, Keither cognitive abilities of D, Khoshbin S, children born to epileptic Adams J, Ryan L Interim mothers who received antiepileptic drug Data Analysis treatment to children born to non-epileptic mothers FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 39 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026045 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 073-170 An open, matched control Magnus-Mi Holmes, L US Data Lock study comparing the ller, L cognitive abilities of children exposed in utero Interim to anti epileptic monotherapy to children Data Analysis born to non-epileptic mothers FSR Completion 945-419-277 Complex/simple partial Accepted Greece Data Lock Information from seizures vs. CBZ London meeting (monotherapy), 13-Aug-01 attended by double-blind, 36 wks. Interim SBS, AEM: initiation delayed due to Data Analysis integration of research budgets. FSR Completion 945-92 Epilepsy Monotherapy vs Complete 14 Countries Data Lock Information from CBZ (290 pts) London meeting 13-Aug-01 attended by Interim SBS, AEM: poster presented from Data Analysis mid-term analysis of 100pts--study now complete-research FSR Completion report written 945-952-236 Neurontin for neurogenic Completed Herbert J Apr-96 Dec-98 Data Lock 78,500 pain in multiple sclerosis Interim Data Analysis FSR Completion 945-954-241 Neurontin in Essential Completed Uitti R Jul-98 Feb-99 Data Lock 48,000 temor Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 40 Source:https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026046 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-250 Gabapentin adjunctive Completed Ketter T Apr-98 Dec-99 Data Lock 90,691 treatment in patients with bipolar disorder Interim Data Analysis FSR Completion 945-954-252 In vivo determination of Completed Kuzniecky R Dec-96 Nov-97 Data Lock 216,610 human brain gaba Gilliam F concentrations in volunteers receiving Interim gabapentin:an escalating dose response study Data Analysis FSR Completion 945-400-281 VA COOP STUDY #428 Completed Ramsay E Jan-99 Dec-99 Data Lock 50,000 Interim Data Analysis FSR Completion 945-952-282 Gabapentin Completed Gidal B, Jul-95 Aug-00 Data Lock 87,993.1 pharmacology: Effects of Weissman J 5 GABA on human cerebral GABA concentrations Interim studies with NMR spectroscopy Data Analysis FSR Completion 945-400-WW2 SALINSKY BUDGET Completed Salinsky M Dec-96 Oct-98 Data Lock 159,364 TRF FR WE Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 41 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026047 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-090 Dose Intitiaition: Titration Completed Multicenter Jan-94 Dec-98 Data Lock 2,801,75 vs. Non-Titration 6 Interim Data Analysis FSR Completion 945-400-193 Neurontin STEPS (Study Completed Multicenter Jan-95 May-98 Data Lock 4,269,90 and of titration to 0 945-400-200 effectiveness and profile of safety) Interim Data Analysis FSR Completion 945-400-211 A Double-blind, Completed Carr D, Jan-96 Jan-99 Data Lock 1,967,40 randomized, placebo Rosenberg J, 0 controlled, parallel group, Dunteman E, multicenter trial to Harden N, Interim determine the efficacy Kreitzer J, Mann and safety of Neurontin JD, Obbens E, Data Analysis in subjects with peripheral Rowbotham M, neuropathy (Post-herpetic Ross E, Yokiel Neuralgia) J, Schell D, FSR Completion Singer E, Stewart RM, 945-400-217 MIGRAINE BID Completed Jan-97 Dec-99 Data Lock 1,849,73 0.03 Interim Data Analysis FSR Completion 945-400-220 MIGRAINE TID Completed Sep-96 Sep-98 Data Lock 699,598. 81 Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 42 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026048 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-953-231 Evaluation of the efficacy Completed Duntley Dec-96 Mar-99 Data Lock 46,650 of neurontin in the treatment of restless leg syndome and periodic Interim limb movement Data Analysis FSR Completion 945-952-233 Neurontin in the treatment Completed Feinberg Oct-96 Mar-99 Data Lock 35,000 of agitation in patients with demetia Interim Data Analysis FSR Completion 945-953-243 Double-blind, Completed Klapper JA Apr-98 Dec-98 Data Lock 1,100 randomized, placebo-controlled, parallel group trial to Interim determine the efficacy and safety of neurontin Data Analysis (gabapentin) in subjects with trigeminal neuralgia FSR Completion 945-954-244 Quantitative assessments Completed Longmire D Jul-96 Dec-96 Data Lock 15,000 of sympathetic pseudomotor changes induced by gabapentin in Interim patients with neuropathic pain Data Analysis FSR Completion 945-954-246 Adjunctive treatment for Completed Aug-98 Oct-99 Data Lock 0.01 bipolar disorder Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 43 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026049 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-954-247 A retrospective study of Completed Nuckolls J Nov-97 Jan-98 Data Lock 4,375 the effectiveness of gabapentin in the treatment of mood Interim disorders Data Analysis FSR Completion 945-954-249 A blinded randomized trial Completed Hines R Jul-99 Oct-99 Data Lock 2,000 to evaluate the efficacy of gabapentin versus ibuprofen in patients with Interim chronic pelvic pain Data Analysis FSR Completion 945-954-253 Category analysis of the Completed Longmire D Aug-97 Jun-98 Data Lock 15,000 effects of gabapentin on neuropathic pain: an open-label community Interim based outcomes study of over six hundred patient Data Analysis records FSR Completion 945-954-254 A double-blind, Completed Lyketsos Aug-98 Mar-99 Data Lock 0.01 placebo-controlled, parallel clinical trial using gabapentin to treat the Interim behavioral disturbances of out-patients with Data Analysis dementia FSR Completion 945-954-256 Gabapentin in the Completed Myrick H Jun-98 Dec-99 Data Lock 31,000 treatment of cocaine dependence Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 44 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026050 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-953-257 Evaluation of the efficacy Completed Ondo W Nov-96 Mar-99 Data Lock 63,000 of gabapentin for essential tremor Interim Data Analysis FSR Completion 945-952-261 Gabapentin therapy Completed Holmes May 97 Mar-99 Data Lock 22,740 following status epilepticus Interim Data Analysis FSR Completion 945-951-270 Open-label, Completed Gidal B May-98 Dec-99 Data Lock 7,214 non-randomized, pilot study to determine whether chronic neurontin Interim administration results in significant changes in Data Analysis various sex hormones FSR Completion 945-951-417 LEPPIK/SUDEP Completed Leppik I Oct-99 Dec-99 Data Lock 15,000 Interim Data Analysis FSR Completion 945-400-AA1 GABAPENTIN/CYT P450 Completed Dec-97 Feb-99 Data Lock 26,425 REOPENED Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 45 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026051 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-AAA GBP COMBINATION Completed Hammond Jan-98 Nov-98 Data Lock 35,219.1 STUDY FR. 1 0 Interim Data Analysis FSR Completion 945-400-EXT PUBLICATIONS Completed Holmes Jan-97 Apr-98 Data Lock 52,300.0 STARTED 1/9 1 Interim Data Analysis FSR Completion 945-951-NC1 BEYDOUN MONEY FR Completed Beydoun A Aug-96 Dec-96 Data Lock 13,915 X02E00 PE Interim Data Analysis FSR Completion 945-952-NE1 GORSIN WAS Completed Gorson K Dec-95 Apr-97 Data Lock 23,333.3 1YYE00-DIABET 4 Interim Data Analysis FSR Completion 945-954-PUB PUBLICATION-NEURON Completed Holmes L Jan-96 Oct-97 Data Lock 85,962.8 TIN INC T Marcotte D 9 Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 46 Source:https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026052 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-QQQ EXTERNAL STUDIES Completed Yaksh T Jul-96 Dec-96 Data Lock 48,000 BUD.TRANS Interim Data Analysis FSR Completion 945-954-SE3 EPILEPSY AND Completed May-97 Jun-97 Data Lock 34,856.5 WOMENS INFECTI 0 Interim Data Analysis FSR Completion 945-954-SE5 RYBACK BUDGET TRSF Completed Ryback R Aug-97 Jun-98 Data Lock 18,000 FR S Interim Data Analysis FSR Completion 945-954-SE8 CLOSED 4/00-NEUR IN Completed Nov-97 Oct-98 Data Lock 0 COCAINE Interim Data Analysis FSR Completion 945-954-SEA QUANTITATIVE Completed May-98 Dec-98 Data Lock 0 ASSESMENT OF S Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 47 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026053 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-X02 NEUR-COST BENEFIT Completed Arthur D. Little, Jun-94 Sep-96 Data Lock 300,000 Inc. Interim Data Analysis FSR Completion 945-400-X03 STEPS-MISC Completed Sep-94 Aug-95 Data Lock 299,000 NEURONTIN Interim Data Analysis FSR Completion 945-400-X04 USUAL CARE Completed Morris, III G Jan-94 Oct-99 Data Lock 65,319.1 Park K 2 Interim Data Analysis FSR Completion 945-400-X05 PREGNANCY REG Completed General Jan-95 Dec-95 Data Lock 100,049. Hospital Corp. 42 Interim Data Analysis FSR Completion 945-400-X07 WALS (MILLER) 200.0 Completed Miller R Jan-97 Dec-97 Data Lock 200,000 FROM Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 48 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026054 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-400-XXX PUBLICATION Completed Jan-95 Dec-95 Data Lock 100,000 SUPPORT Interim Data Analysis FSR Completion 945-224 GBP in Diabetic Completed Multicenter Data Lock Information from Neuropathy (pcbo study out of London meeting controlled-open-label Germany 13-Aug-01 attended by extension for 4 mos) Interim SBS, AEM: not to be published until Data Analysis PHN--very good data for sleep and QoL FSR Completion 945-025 Post-herpetic neuralgia Completed Rice, Maton UK Data Lock To be published in Nov-01 issue of Pain Interim Data Analysis FSR Completion 945-026 Mixed-symptoms study Completed Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: key target for publication-oovarall Data Analysis results not overwhelming but very positive for subset of FSR Completion pts with NeP Neuropathic pain vs. Completed Data Lock Information from plac., DB, crossover 6 London meeting wks. Disability Services 13-Aug-01 attended by Clinic Interim SBS, AEM: 17 pts. randomized;13 Data Analysis completed both 6-week arms. FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 49 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026055 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-262 Placebo-controlled trial of Completed Magnus-Mi Miller, R US, Canada Jun-99 Dec-99 Data Lock 15,000 gabapentin in spinal ller, L Bradley W, muscular atrophy Brooke M, Bryan W, Barohn R, Interim lannaccone S, Leshner R, Data Analysis Mendell J, Kissel J, Russman B, Samaha F, Smith FSR Completion S 945-955-250 Gabapentin adjunctive Completed Magnus-Mi Ketter, T US Apr-98 Dec-99 Data Lock 90,691 02-Jun-98 treatment in patients with ller, L Winsberg M. bipolar depression DeGolia S, Dunai M, O'Meara C, Interim Tate D, Strong C Data Analysis FSR Completion 945-954-237 Pregnancy and epilepsy Completed Montouris, G US Dec-98 Dec-00 Data Lock 45,000 20-Jul-98 15-Feb-99 in the treatment of seizures in women of childbearing age Interim Data Analysis FSR Completion 945-954-264 Reproductive hormones, Completed Magnus-Mi Pennell, P US Feb-99 Dec-99 Data Lock 68,000 01-Apr-99 antiepileptic drug levels ller, L Henry T, Litt B, and seizure occurance in Epstein C women with catamenial Interim epilepsy Data Analysis FSR Completion 945-952-232 A randomized controlled Completed Ehrenberg, B US Dec-95 Aug-00 Data Lock 75,000 09-Mar-98 pilot study of gabapentin (neurontin) in patients with restless leg Interim syndrome/periodic limb movement disorder Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 50 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026056 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-955-245 Randomized, Completed Magnus-Mi Rowbotham, R US Apr-99 Jun-00 Data Lock 275,000 double-blind study ller, L Sacks G, Young assessing "low dose" S versus "high dose" Interim gabapentin for the treatment of painful HIV Data Analysis neuropathy FSR Completion 945-951-304 Oral absorption of Completed Magnus-Mi Gidal, B US Oct-99 Jun-00 Data Lock 36,200 10-Sep-99 03-Dec-99 gabapentin solution: ller, L Sheth R pharmacokinetic impact of mixing with milk juice Interim or enteral supplements Data Analysis FSR Completion 945-954-242 Gabapentin for the Completed Magnus-Mi Hansen, H US Jun-99 Apr-00 Data Lock 35,000 08-Feb-99 01-Mar-99 treatment of fibromyalgia ller, L Wodecki R Interim Data Analysis FSR Completion 945-954-255 Retrospective study of the Completed Magnus-Mi Marcotte, D US Jun-99 Dec-99 Data Lock 20,000 15-Oct-99 15-Dec-00 effectiveness of ller, L gabapentin with dementia with behavioral Interim disturbance Data Analysis FSR Completion 945-953-228 Effect of gabapentin on Completed Diaz-Arrastia, R US Apr-99 Dec-99 Data Lock 20,000 13-Apr-99 12-Feb-01 plasma homocystine and Agostini M, folate levels Kokkinakis D Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 51 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026057 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-420-010 Neuropathic pain cancer In Progress Italy Data Lock Information from pts. (refractory to opiates, London meeting vs. placebo, 10 days, 13-Aug-01 attended by 600-1800 mg titr., add-on) Interim SBS, AEM: potential for final data end Q4/01 Data Analysis FSR Completion Efficacy and safety of In Progress Gudez-Santos M Philippines Data Lock gabapentin in comparison Hernandez M, with carbamazepine in Poblete A the management of pain Interim secondary to trigeminal neuralgia Data Analysis FSR Completion 945-278 Trigeminal neuralgia Cancelled Drug only Cunliffe UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: early termination-accrual Data Analysis problems (32 pts.); rept in prep. FSR Completion 945-241 Vulvadynia Cancelled Drug only Smith UK Data Lock Interim Data Analysis FSR Completion 945-279 Phantom limb pain Completed Drug only Critchley UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: presented this year-Michael Data Analysis Rowbotham has this data. Poster presented at EFIC (17 pts.). FSR Completion Publication in prep. Bold = Lead Investigator Medical Action Communications 31-Oct-01 52 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026058 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-425 CRPS vs. placebo In Progress Drug only Hill D UK Data Lock Information from crossover London meeting 13-Aug-01 attended by Interim SBS, AEM: all 10 pts. enrolled; completion Data Analysis anticipated next yr FSR Completion 945-285 Refl. Symp. Dys. In Progress Drug only Souter UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: ongoing--need to locate Data Analysis protocol-13 of 15 pts. enrolled; target compl. Feb. 2001 FSR Completion 945-410 Back pain-surgically In Progress Drug only Hester UK Data Lock Information from refractory London meeting 13-Aug-01 attended by Interim SBS, AEM: 15 to 20 Data Analysis patients currently recruited-10 of 27 pts. enrolled; target FSR Completion 945-420 HIV neuropathy In Progress Drug only Manji UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: recruitment complete but study still Data Analysis ongoing-completion Sept. 2001 FSR Completion 945-293 Essential tremor Planned Drug only Wills, Naashef UK Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: not yet started 40 pts. Data Analysis targeted FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 53 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026059 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Bipolar disorder Grant Walden Germany Data Lock (retrospective analysis) Interim Data Analysis FSR Completion 945-418-428 Add-on treatment children Grant Lagae Belgium Data Lock Interim Data Analysis FSR Completion 945-418-432 Perineal pain-open study Grant Herbaut Belgium Data Lock Interim Data Analysis FSR Completion A9451010 Gabapentin in Approved Grant Spain Data Lock Information from neuropathic pain London meeting (open-label study) 13-Aug-01 attended by Interim SBS, AEM: anticipated start in Sept Data Analysis FSR Completion Effects of GBP on NeP Cancelled Grant Spain Data Lock and sleep symptoms (double-blind) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 54 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026060 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-275-273 Epilepsy-elderly add-on Cancelled Grant Australia Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: terminated - low enrollment Data Analysis FSR Completion Cancer pain Completed Grant Kloke Germany Data Lock Information from (retrospective analysis) London Meeting 13-Aug-01 attended by Interim SBS, AEM: report received-in review to Data Analysis determine how strongly publication should be pursued FSR Completion 945-400-281 Treatment of seizures in Completed Grant Magnus-Mi Veteran affairs US Jan-98 Jan-01 Data Lock 125,000= 06-Dec-00 the elderly population ller, L cooperative 25,000/yr studies program for 5 Balish M, Towne Interim years + A, Salinsky M, 50,000 Felicetta J, Data Analysis additional Rodgers-Neame for N, McLean M. central Rutecki P, FSR Completion laborator Mamdani M, y Uthman B, Spitz 945-954-258 Use of gabapentin for Completed Grant Magnus-Mi Pellock, J US Nov-99 Oct-00 Data Lock 7,000 15-Dec-00 symptom control in ller, L Fusun Alehan, children with attention MD-Medical deficit hyperactivity College of Interim disorder-a pilot study Virginia, Richmond, VA Data Analysis FSR Completion 945-952-263 Reproductive function in Completed Grant Magnus-Mi Morell, M US Nov-99 Oct-00 Data Lock 171,587 11-Oct-99 AED treated women with ller, L Sauer M, Giudice epilepsy L Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 55 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026061 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments HIV polyneuropathy In Progress Grant Schielke Germany Data Lock Information from London Meeting 13-Aug-01 attended by Interim SBS, AEM: patient accrual slow--currently Data Analysis only 30 pts FSR Completion Tension headaches In Progress Grant Arnold Germany Data Lock Information from London Meeting 13-Aug-01 attended by Interim SBS, AEM: slow enrollment Data Analysis FSR Completion 945-475-433 Carpal Tunnel Syndrome- In Progress Grant Australia Data Lock Information from neuropath. pain prophyl. London meeting (vs. placebo, DB 13-Aug-01 attended by crossover, Interim SBS, AEM: started at 8 wks., titr. to 4800 mg, end of '98 20 pts., 1 center) Data Analysis FSR Completion 945-475-433 Carpal Tunnel Syndrome- In Progress Grant Australia Data Lock Information from neuropath. pain prophyl. London meeting (vs. placebo, DB 13-Aug-01 attended by crossover, Interim SBS, AEM: started at 8 wks., titr. to 4800 mg, end of '98 20 pts., 1 center) Data Analysis FSR Completion Post-marketing In Progress Grant Korea (Jeil Data Lock surveillance Pharmaceuti cals) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 56 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026062 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments PMS In Progress Grant Phillipines Data Lock Interim Data Analysis FSR Completion A945-10. Evaluation of gabapentin Planned Grant Italy Data Lock Information from effect in the prevention of London meeting oxaliplatin induced 13-Aug-01 attended by neurotoxicity in Interim SBS, AEM: very gabapentin treated or expensive study--Italy untreated population Data Analysis cannnot support this study at all. Looking to see whether NYHQ will FSR Completion be able to fund the entire study. A945-1002 A double-blind Planned Grant Italy Data Lock Information from randomised trial London meeting comparing gabapentin 13-Aug-01 attended by versus placebo in the Interim SBS, AEM: from same prophylaxis and treatment Data Analysis protocol as #11--this of acute oxaliplatin half may not be induced neurotoxicity pursued. FSR Completion GBP vs CBZ in epilepsy Planned Grant Spain Data Lock Information from (double-blind study) London meeting 13-Aug-01 attended by Interim SBS, AEM: still no response on whether Data Analysis this has been approved. FSR Completion Insomnia (preference for Planned Grant Spain Data Lock GBP over BZD in insonmia) Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 57 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026063 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Insomnia (preference for Planned Grant Spain Data Lock GBP over BZD in insonmia) Interim Data Analysis FSR Completion Participation of the Planned Grant Venezuela Data Lock endogenous pain modulatory system in experimentally induced Interim neuropathic pain. New perspectives on the Data Analysis mechanism of action of gabapentin FSR Completion Functional Proposed Grant Spain Data Lock Information from characterization of the London meeting GABA-mediated actions 13-Aug-01 attended by induced by gabapentin Interim SBS, AEM: awaiting (MOA study) response from Data Analysis NYHQ--submitted in July FSR Completion Post-hernia repair Proposed Grant UK Data Lock Information from (inguinaldynia) London meeting 13-Aug-01 attended by Interim SBS, AEM: good protocol, local grant Data Analysis study FSR Completion Amytriptyline comparator Proposed Grant UK Data Lock in Cancer Pain-full spectrum of cancer pain Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 58 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026064 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments AWB-monotherapy Completed Marketing Schmidt D Germany Data Lock Information from (400-500 London meeting pts--post-surveillance 13-Aug-01 attended by clincal experience trial) Interim SBS, AEM: framework provided, sales force Data Analysis data gathering FSR Completion 945-212 Partial/gen. epilepsy vs. Sponsored Australia Data Lock lamotrigine Internat. ICD study Interim Data Analysis FSR Completion 945-430 Migraine prophylaxis Cancelled Sponsored Spain Data Lock Interim Data Analysis FSR Completion 945-475-206 Australia Steps Complete Sponsored Australia Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: based on same protocol on Data Analysis US-blood levels awaited FSR Completion 945-418-308 Belsteps Complete Sponsored Belgium Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: like-Australian Data Analysis steps--open-label-data entry ongoing-stat. report end-2000 FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 59 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026065 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-420-007 Epilepsy (Add-on followed Completed Sponsored Italy Data Lock by lead cmpd withdrawal) Interim Data Analysis FSR Completion 945-437-466 Postoperative/post-traum Completed Sponsored Sweden, Data Lock Information from atic pain ('POP' Finland, London meeting study--120 pts enrolled, Norway, 13-Aug-01 attended by 90-100 evaluable) Denmark Interim SBS, AEM: code broken last Data Analysis week-results available in Sept. Results to be released at Sept FSR Completion investigators meeting. 945-01/11-001 Migraine-children, adoles. Completed Sponsored Spain Data Lock Information from 9 (open-label) London meeting 13-Aug-01 attended by Interim SBS, AEM: Very Data Analysis positive results; completed approx 1-2 mos ago FSR Completion 945-475-283 Headache-chronic, daily Completed Sponsored Australia Data Lock Information from (tension Headache) London meeting 13-Aug-01 attended by Interim SBS, AEM: data management Data Analysis ongoing-possibly completed-must check FSR Completion 945-411 Diabetes-neuropathic Completed Sponsored Mexico, Data Lock Information from pain, Venez. London meeting (fixed dose vs. titration, Equador, 13-Aug-01 attended by double-blind, 7 wks.) Columb, Interim SBS, AEM: 508 Chile, Peru, patients targeted: 304 Braz Data Analysis enrolled, 188 completed. Need full info on data from CRO. FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 60 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026066 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-405-401 Pediatric study Completed Sponsored South Africa Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: part of Shapiro study similar to Data Analysis Mexican pediatric study above FSR Completion 945-420-275 Post-herpetic neuralgia Completed Sponsored Italy Data Lock Interim Data Analysis FSR Completion 945-187/87 Epilepsy-refract.-long Completed Sponsored Mexico Data Lock Information from term London meeting OC safety in children 13-Aug-01 attended by (open-label safety) Interim SBS, AEM: Publ. Devel. Med. and Child Data Analysis Neuro. FSR Completion Sub-study of allodynia In Progress Sponsored Sweden, Data Lock Information from based on POP study (20 Finland, London meeting pts.) Norway, 13-Aug-01 attended by Denmark Interim SBS, AEM: recruitment complete by Data Analysis Nov--anticipated study results by Q2/02 FSR Completion 945-222 Spasticity In Progress Sponsored Spain Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: finalized Q1/01 Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 61 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026067 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-431 Restless Leg Syndrome In Progress Sponsored Spain Data Lock Information from (including sleep London meeting architecture) 13-Aug-01 attended by Interim SBS, AEM: finishing in Sept, results in Oct/Nov Data Analysis FSR Completion 945-424 Parkinson's Disease In Progress Sponsored Spain Data Lock Information from (L-dopa related London meeting dyskinesia) 13-Aug-01 attended by Interim SBS, AEM: delayed due to PI Data Analysis pregnancy--possibly to be complete Q1/02 FSR Completion 945-276 Cancer pain (Italian In Progress Sponsored Spain Data Lock Information from study) London meeting 13-Aug-01 attended by Interim SBS, AEM: March 2002 Data Analysis final patient accrual anticipated. FSR Completion 945-436-288 Epilepsy-monotherapy In Progress Sponsored France Data Lock Information from (open-label switch, not London meeting stringently 13-Aug-01 attended by controlled-experience Interim SBS, AEM: Auralie is trial) the contact Data Analysis FSR Completion 945-445-435 Dutch Steps In Progress Sponsored Netherlands Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: contact for Netherlands--Marnix Data Analysis Artz FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 62 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026068 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-468-429 Diabetes-neuropathic In Progress Sponsored Taiwan Data Lock Information from pain London meeting 13-Aug-01 attended by Interim SBS, AEM: 9/00 12/01-Need to find out Data Analysis if this has completed FSR Completion 945-420-276 Neuropathic Pain (Cancer In Progress Sponsored Spain/Italy 8 Data Lock Information from Pain) sites London meeting 13-Aug-01 attended by Interim SBS, AEM: ongoing 10/98-6/01 Data Analysis FSR Completion 945-445-280 Refl. Symp. Dystr. pain In Progress Sponsored Netherlands Data Lock Interim Data Analysis FSR Completion 945-291 Bipolar Disorder (1 year Ongoing Sponsored Spain/Italy 3 Data Lock Information from Tx) sites London meeting 13-Aug-01 attended by Interim SBS, AEM: patient accrual currently 35 but Data Analysis need 80 total Accrual problems due to Janssen blocking FSR Completion recruitment. Issue may have been somewhat resolved. Definitely Neuropathic pain Planned Sponsored Germany Data Lock Information from London meeting 13-Aug-01 attended by Interim SBS, AEM: initiated in May, CRFs Due Oct / Data Analysis Nov, anticpated results in Jan FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 63 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026069 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments 945-301 Refractory Planned Sponsored Canada Data Lock Information from epilepsy-children aged 1 London meeting month to 4 yrs-open 13-Aug-01 attended by Interim SBS, AEM: submission-contact Data Analysis Tibor Kapussy of Canada for info. FSR Completion 945-401 Pediatric (contributed to Planned Sponsored Mexico Data Lock Information from US FDA submission) London meeting 13-Aug-01 attended by Interim SBS, AEM: submission Data Analysis FSR Completion Peripheral neuropathic Planned Sponsored Netherlands Data Lock Information from pain London meeting open study 13-Aug-01 attended by Interim SBS, AEM: unknown whether this has started Data Analysis FSR Completion 945-437-466 Neuropathic pain Planned Sponsored Phillipines Data Lock Interim Data Analysis FSR Completion Diabetes-neuropathic Planned Sponsored Thailand Data Lock pain Interim Data Analysis FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 64 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026070 Neurontin Study Report Studies Sorted by Study Type and Status Budget Date Date Date Type/ Study Start Completion Amount Budget First Last Study # Study Title Status Funder Champion Investigators Country (ies) Date Date Dates Approved Approved Check Check Notes/Comments Spasticity (60 pts Rejected Sponsored Nelles Germany Data Lock Information from proposed--early London meeting intervention in stroke pts 13-Aug-01 attended by to prevent spasticity and Interim SBS, AEM: LT to pain) re-review request for Data Analysis funding FSR Completion Bold = Lead Investigator Medical Action Communications 31-Oct-01 65 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026071 Neurontin AIDS/HIV Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % AIDS Yes Primary 30 1.5 3 4.5 BIOSIS 8.018 3,207 Infectious Disease Specialists47 North America 59 Letters Chemical Abstracts Public Health Specialists 15 Europe 32 Current Contents Pathologists 15 Far East 3 EMBASE Immunologists 8 Rest of World 6 Index Medicus Oncologists 15 MEDLINE Science Citation Index AIDS and Behavior Yes Primary 50 6 6 12 CINAHL N/A N/A N/A N/A N/A N/A Reviews EMBASE Letters AIDS Care Yes Primary N/A 6 6 12 Biological Abstracts N/A 650 Psychologists N/A United States 50 Brief Reports CINAHL Social Scientists N/A United Kingdom 25 Current Contents Nurses N/A Rest of World 25 EMBASE Other N/A Index Medicus MEDLINE Science Citation Index AIDS Patient Care Yes Primary 50 2-3 2-3 4 - 6 CINAHL N/A 5,628 Primary Care Physicians 90 N/A N/A and STDs Letters EMBASE Researchers 10 Case Reports MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 66 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026072 Neurontin AIDS/HIV Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % AIDS Reader Yes Primary 70 1 3 4 EMBASE N/A 34,576 Family Physicians 31 United States 99 Reviews MEDLINE Internists 28 Rest of World 1 Letters Hematologists 11 Oncologists 10 Other 20 International Journal Yes Primary 45 1 3 4 Current Contents 1.019 1,050 N/A N/A United Kingdom 53 of STD and AIDS Letters EMBASE Europe 17 Case Reports Index Medicus North America 14 MEDLINE Rest of World 16 SciSearch Journal of Acquired Yes Primary 60 1 2 6 7-8 BIOSIS 3.046 2,931 Infectious Disease SpecialistsN/A United States 23 Immune Deficiency Reviews Current Contents Pathologists N/A Rest of World 77 Syndromes Letters EMBASE Biologists N/A Case Reports Index Medicus Epidemiologists N/A MEDLINE Virologists N/A Science Citation Index Researchers N/A SciSearch A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 67 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026073 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Diabetes Yes Primary 25 1 1.25 3 4 4.25 Biological Abstracts 7.715 7,500 Researchers N/A North America N/A Chemical Abstracts Physicians N/A Rest of World N/A Current Contents Other N/A EMBASE Index Medicus MEDLINE Science Citation Index Diabetes and Yes Reviews 60 6 6 12 Biological Abstracts N/A 1,500 Diabetologists N/A France 60 Metabolism Primary Chemical Abstracts Endocrinologists N/A Rest of World 40 Letters Current Contents Editorials EMBASE Index Medicus MEDLINE Science Citation Index Diabetes Care Yes Primary 25 1 1.25 3 4 4.25 Biological Abstracts 4.992 13,500 Physicians N/A North America N/A Letters Chemical Abstracts Researchers N/A Europe N/A Case Reports Current Contents Nurse Practitioners N/A EMBASE Index Medicus MEDLINE Science Citation Index Diabetes Research Yes Primary 45 4 3 7 Biological Abstracts 0.982 325 Diabetologists N/A N/A N/A and Clinical Practice Reviews BIOSIS Endocrinologists N/A Letters Chemical Abstracts Brief Reports Current Contents EMBASE Index Medicus MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 68 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026074 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Diabetic Medicine Yes Primary 17 2.5 3 - 4 5.5 6.5 Current Contents 2.732 2,100 N/A N/A United Kingdom 58 Reviews EMBASE Europe 19 Letters Index Medicus North America 10 Brief Reports MEDLINE Rest of World 13 Case Reports Science Citation Index Diabetologia Yes Primary 20 6 1.5 7.5 Biological Abstracts 5.721 7,300 Endocrinologists N/A Europe 69 Letters Chemical Abstracts Internists N/A North America 16 EMBASE Researchers N/A Asia 11 Index Medicus Rest of World 4 MEDLINE Endocrine Reviews Yes N/P N/P N/P N/P Biological Abstracts 19.524 4,711 Endocrinologists 100 North America 60 BIOSIS Rest of World 40 Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE Endocrinology Yes Primary 30 1 2.5 3.5 Biological Abstracts 4.790 4,872 Endocrinologists 100 North America 68 BIOSIS Rest of World 32 Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 69 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026075 Neurontin Diabetes/Endocrinoloqy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Journal of Clinical Yes Primary 33 1 3 4 Biological Abstracts 5.447 10,158 Endocrinologists 100 United States 67 Endocrinology and Letters BIOSIS Rest of World 33 Metabolism Chemical Abstracts Current Contents EMBASE Index Medicus MEDLINE Journal of Diabetes Yes Primary 85 1 2-3 3 - 4 BIOSIS 0.851 900 Diabetologists N/A United States 40 and its Reviews Current Contents Endocrinologists N/A Europe 35 Complications Letters EMBASE Nephrologists N/A Asia 16 Editorials Index Medicus Urologists N/A Rest of World 9 Case Reports MEDLINE Primary Care Physicians N/A SciSearch A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 70 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026076 Neurontin Epilepsy Types of % of Journal Profiles, Sorted by Title Peer- Unsolic. Primary mss *Primary mss *Primary mss *Primary mss **Impact Total Journal Title Review mss Accept. Accept. Sub. to Dec. Accept. to Pub. Total Pub. Time Indexed Factor Circ. Target Audience % Geographic Distribution % Epilepsia Yes Primary N/A 1 4 2-6 3-10 Biological Abstracts 3.787 5,220 Neurologists 94 United States 85 Letters BIOSIS Psychologists 5 Rest of World 15 Case Reports Chemical Abstracts Other 1 Current Contents EMBASE Index Medicus MEDLINE Science Citation Index SciSearch Epilepsies Yes Primary 60 2 4 6 EMBASE N/A 1,000 Neurologists N/A Europe N/A Reviews Epileptologists N/A Rest of World N/A Brief Reports Other N/A Epilepsy and Yes Primary N/A N/A N/A N/A N/A N/A 1,500 Neurologists 40 N/A N/A Behavior Letters Neuropsychiatrists 30 Editorials Radiologists 10 Brief Reports Other 20 Case Reports Epilepsy Research Yes Primary 45 2 3 5 Biological Abstracts 2.866 520 Epileptologists N/A Europe 41 Reviews BIOSIS Neurologists N/A North America 34 Letters Chemical Abstracts Pharmacologists N/A Asia 18 Editorials Current Contents Psychiatrists N/A Rest of World 7 Brief Reports EMBASE Index Medicus MEDLINE Science Citation Index A/R = Awaiting Research * Publication times are listed in months Medical Action Communications Information Subject to Change N/A = Not Available ** 2000 Journal Citation Reports 31-Oct-01 N/P = Not Permitted 71 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026077

Were CME Credits Offered?

rjmd0217

rjmd0217_p0, rjmd0217_p1, rjmd0217_p2

No, no

G EVENT 1:" Page'smits (+), 601964 PRE-EVENT INFORMATION Please complete these questions for all invilations, whether OT not you attended. Was A Pharmaceutical Company Associated With The Event? City/State: Yes Company Name: Parke Davis 192 Event Date (Month/Day/Year): 2 / 109 / 98 No The Invitation Was Made By A: Were CME Credits Offered? Pharmaceutical Sales Representative Yes Company Name: No Firm Firm other Name: than Pharmaceutical medical Company research Associatin up What Type Of Honorarlum Was Offerod? (Chock AL That Apply) Meals University/Medical Institution (eg., Vanderbilt University) Name: Charitable Contribution Cash/Check Clinical/Professional Association (e.g., The American Heart Association) Name: Medical Instruments (please specify): Other: (please specify) Gift Certificate (please specify for what): medical Suppler Textbooks (please specify): Tho Evont Was Sponsored By: (Check All That Apply) Pharmaccutical Company: Parke navi 192 Other: None University/Medical Institution: Dld You Attend The Event? Clinical/Prolessional Association: YES Because Of: (Check All That Managed Care Company: Interest In The Topic Other: (please specify) Type Of Honoraria Offered Tho Announcod Topic Was: (Check All Tha Appy) Topic Reputation Of Speakers General Therapeutic Area 48. CME Credits Offered (e.g., hypertension, heart failure, diabetes): It of Epilepsy Convenient Location A Therapeutic Class of Drugs Other (please specify): (e.g., ACE Inhibitors, diuretics): NO, Because Of: (Check All That Apply) A Specific Product Manufactured by The Pharnuceutical Company: 12233 Neurontin Lack Of Interest In The Topic Disease Management Program Scheduling Conflict (professional or personal) (treatment guldellnes, protocols, care maps, etc.): Type Of Honoraria Offered Other: No CME Credits Offered Evont Location: (Ploase Chock Appropriale Box And Record Spocific Namo On Uno Bolow): Inconvenient Location/Distance Hotel Restaurant Convention Mkt. Res. Facility Other (please specify): Home Office Other (Specify Name): Telephone Conference If You Attended, Please Continue With The Questions On The Following Pages. Pleaso Continuo With Tho Quostions To The Right S-L09819 Please Continue With The Questions For Event 1 On The Next Page. 15 CE 4 EVENT 1: Page 2 of 3 601964 PRODUCT INFORMATION Yes (Please complete the boxes in this section.) How many times Wore Specific Products Discussed? have you been No (Please go to the "General Theme" detailed on this At what level do At what level do box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? 1 Product Name: Neurontin Not Detailed Nonprescriber Nonprescriber THEME(S): (Piease Be As Specific As Possible) 12233 ply 1 Detail Low Low 2 Details Moderate Modorato Advance in tx of Epilepsy 3 Details High High >3 Details 2 Product Name: 2/98 Not Detailod Nonprescribor Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderato Moderate 3 Details High High >3 Details 3 p'oduct Name: Not Detailod Nonprescriber Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderato Moderato 3 Details High High >3 Details GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topics Discussed (Advanco in tx of opilepsy. - Focu in Neworks) S-L09818 15 Source:

what is the event number?

qnmd0217

qnmd0217_p0, qnmd0217_p1, qnmd0217_p2

2, Event 2

6 605675 EVENT 2: Page 2 of 3 How many other How many times If you checked increase Were specific products discussed? events have you have you been or decrease, what Yes (Please complete the boxes in this section.) attended on this detailed on this Do you prescribe How will your factors influenced No (Please go to the "General Theme" box product/topic in product in the or recommend Rx activity shift this change at the bottom of this page.) the last 6 months? last 6 months? this product? In the future? in Rx activity? 1. Product Name: Nevotin Please specify: Theme(s) Please be as specific as possible: 1 Other 1 Detail Currently Rx? Increase 106 2 Others 2Details Yes Decrease Urful in painful speater 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels pointed neuropathy No Others Not Detailed out its if "Yes." Avg. 12233cluk viseFulness # of Rxs written per month? REDACTED 3. Product Name: Please specify: Theme(s) Please be as specific as possible: I Other 1 Detail Currently Rx? Increase 2 Others 2 Details Yes Decrease 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels No Others Not Detailed If "Yes." Avg. # of Rxs written per month? GENERAL THEME(S) AND OTHER TOPICS DISCUSSED Dx & tx neuropathy 990 Please Continue With Questions For Event 2 On The Next Page. I I S-L10058 is Source: https://wwww.industrydocuments.ucsf.edu/docs/qnmd0217 EVENT 2: Page 3 of 3 The presentation was conducted by: (Check all that apply) How useful did you find the information you reccived at the event? Drug company representative Not useful 1 2 3 4 5 6 7 Extremely useful Local physician/rescarcher (specify name): P- The fran MD, Visiting plysician/rescarcher (specify name) : How objective were the presentations and discussious? Third-party moderator (specify name): Not objective 1 2 3 4 5 6 7 Extremely objective Other (please specify): To what degree was the event dedicated to promotion? I Number of speakers: Not promotional 1 2 3 4 5 6 7 Extremiely promotional Approximately, how many physicians attended the event? 10 Length of event (e.g., 3 hours, 2 days, etc.): 1hr To what degree was the event dedicated to education? Not educational 1 2 3 4 5 6 7 Extremely educational Wus a pharmaceutical representative present? Yes No To what extent will the information presented at this event impact your prescribing of the drug and/or therapeutic class? Which of the following were used during the presentation? No impact 1 2 3 4 5 6 7 High impact (Check all that apply) Vidcoconference National Local Regional Other: Taking into account everything about the event, what is your overall rating? Videotape/Slidc presentation Negative 1 2 3 4 5 6 7 Positive Internet Teleconference How would you rate the sponsoring company's image? NA One-on-one intervicw Poor 1 2 3 4 5 6 7 Excellent Peer discussion Clinical studies General Comments Other (please specify) : What support materials, if any, were used? (Check all that apply) What event factors had the greatest impact on your overall event rating? Vidcotape Speaker quality Computer Event theme Visual/Detail aid Peer interaction Print advertisement Event format Clinical reprint Support Materials (please specify): Giveaway (please specify) : Other (please specify): Other (please specify) : Handout Other Comments/Suggestions: Nonc S-L10059 Source: https://www.industrydocuments.ucsf.edu/docs/qnmd0217

approximately how many physicians attended the event?

qnmd0217

qnmd0217_p0, qnmd0217_p1, qnmd0217_p2

10

6 605675 EVENT 2: Page 2 of 3 How many other How many times If you checked increase Were specific products discussed? events have you have you been or decrease, what Yes (Please complete the boxes in this section.) attended on this detailed on this Do you prescribe How will your factors influenced No (Please go to the "General Theme" box product/topic in product in the or recommend Rx activity shift this change at the bottom of this page.) the last 6 months? last 6 months? this product? In the future? in Rx activity? 1. Product Name: Nevotin Please specify: Theme(s) Please be as specific as possible: 1 Other 1 Detail Currently Rx? Increase 106 2 Others 2Details Yes Decrease Urful in painful speater 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels pointed neuropathy No Others Not Detailed out its if "Yes." Avg. 12233cluk viseFulness # of Rxs written per month? REDACTED 3. Product Name: Please specify: Theme(s) Please be as specific as possible: I Other 1 Detail Currently Rx? Increase 2 Others 2 Details Yes Decrease 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels No Others Not Detailed If "Yes." Avg. # of Rxs written per month? GENERAL THEME(S) AND OTHER TOPICS DISCUSSED Dx & tx neuropathy 990 Please Continue With Questions For Event 2 On The Next Page. I I S-L10058 is Source: https://wwww.industrydocuments.ucsf.edu/docs/qnmd0217 EVENT 2: Page 3 of 3 The presentation was conducted by: (Check all that apply) How useful did you find the information you reccived at the event? Drug company representative Not useful 1 2 3 4 5 6 7 Extremely useful Local physician/rescarcher (specify name): P- The fran MD, Visiting plysician/rescarcher (specify name) : How objective were the presentations and discussious? Third-party moderator (specify name): Not objective 1 2 3 4 5 6 7 Extremely objective Other (please specify): To what degree was the event dedicated to promotion? I Number of speakers: Not promotional 1 2 3 4 5 6 7 Extremiely promotional Approximately, how many physicians attended the event? 10 Length of event (e.g., 3 hours, 2 days, etc.): 1hr To what degree was the event dedicated to education? Not educational 1 2 3 4 5 6 7 Extremely educational Wus a pharmaceutical representative present? Yes No To what extent will the information presented at this event impact your prescribing of the drug and/or therapeutic class? Which of the following were used during the presentation? No impact 1 2 3 4 5 6 7 High impact (Check all that apply) Vidcoconference National Local Regional Other: Taking into account everything about the event, what is your overall rating? Videotape/Slidc presentation Negative 1 2 3 4 5 6 7 Positive Internet Teleconference How would you rate the sponsoring company's image? NA One-on-one intervicw Poor 1 2 3 4 5 6 7 Excellent Peer discussion Clinical studies General Comments Other (please specify) : What support materials, if any, were used? (Check all that apply) What event factors had the greatest impact on your overall event rating? Vidcotape Speaker quality Computer Event theme Visual/Detail aid Peer interaction Print advertisement Event format Clinical reprint Support Materials (please specify): Giveaway (please specify) : Other (please specify): Other (please specify) : Handout Other Comments/Suggestions: Nonc S-L10059 Source: https://www.industrydocuments.ucsf.edu/docs/qnmd0217

what is the number of speakers?

qnmd0217

qnmd0217_p0, qnmd0217_p1, qnmd0217_p2

1

6 605675 EVENT 2: Page 2 of 3 How many other How many times If you checked increase Were specific products discussed? events have you have you been or decrease, what Yes (Please complete the boxes in this section.) attended on this detailed on this Do you prescribe How will your factors influenced No (Please go to the "General Theme" box product/topic in product in the or recommend Rx activity shift this change at the bottom of this page.) the last 6 months? last 6 months? this product? In the future? in Rx activity? 1. Product Name: Nevotin Please specify: Theme(s) Please be as specific as possible: 1 Other 1 Detail Currently Rx? Increase 106 2 Others 2Details Yes Decrease Urful in painful speater 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels pointed neuropathy No Others Not Detailed out its if "Yes." Avg. 12233cluk viseFulness # of Rxs written per month? REDACTED 3. Product Name: Please specify: Theme(s) Please be as specific as possible: I Other 1 Detail Currently Rx? Increase 2 Others 2 Details Yes Decrease 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels No Others Not Detailed If "Yes." Avg. # of Rxs written per month? GENERAL THEME(S) AND OTHER TOPICS DISCUSSED Dx & tx neuropathy 990 Please Continue With Questions For Event 2 On The Next Page. I I S-L10058 is Source: https://wwww.industrydocuments.ucsf.edu/docs/qnmd0217 EVENT 2: Page 3 of 3 The presentation was conducted by: (Check all that apply) How useful did you find the information you reccived at the event? Drug company representative Not useful 1 2 3 4 5 6 7 Extremely useful Local physician/rescarcher (specify name): P- The fran MD, Visiting plysician/rescarcher (specify name) : How objective were the presentations and discussious? Third-party moderator (specify name): Not objective 1 2 3 4 5 6 7 Extremely objective Other (please specify): To what degree was the event dedicated to promotion? I Number of speakers: Not promotional 1 2 3 4 5 6 7 Extremiely promotional Approximately, how many physicians attended the event? 10 Length of event (e.g., 3 hours, 2 days, etc.): 1hr To what degree was the event dedicated to education? Not educational 1 2 3 4 5 6 7 Extremely educational Wus a pharmaceutical representative present? Yes No To what extent will the information presented at this event impact your prescribing of the drug and/or therapeutic class? Which of the following were used during the presentation? No impact 1 2 3 4 5 6 7 High impact (Check all that apply) Vidcoconference National Local Regional Other: Taking into account everything about the event, what is your overall rating? Videotape/Slidc presentation Negative 1 2 3 4 5 6 7 Positive Internet Teleconference How would you rate the sponsoring company's image? NA One-on-one intervicw Poor 1 2 3 4 5 6 7 Excellent Peer discussion Clinical studies General Comments Other (please specify) : What support materials, if any, were used? (Check all that apply) What event factors had the greatest impact on your overall event rating? Vidcotape Speaker quality Computer Event theme Visual/Detail aid Peer interaction Print advertisement Event format Clinical reprint Support Materials (please specify): Giveaway (please specify) : Other (please specify): Other (please specify) : Handout Other Comments/Suggestions: Nonc S-L10059 Source: https://www.industrydocuments.ucsf.edu/docs/qnmd0217

what is the length of the event?

qnmd0217

qnmd0217_p0, qnmd0217_p1, qnmd0217_p2

1 hr

6 605675 EVENT 2: Page 2 of 3 How many other How many times If you checked increase Were specific products discussed? events have you have you been or decrease, what Yes (Please complete the boxes in this section.) attended on this detailed on this Do you prescribe How will your factors influenced No (Please go to the "General Theme" box product/topic in product in the or recommend Rx activity shift this change at the bottom of this page.) the last 6 months? last 6 months? this product? In the future? in Rx activity? 1. Product Name: Nevotin Please specify: Theme(s) Please be as specific as possible: 1 Other 1 Detail Currently Rx? Increase 106 2 Others 2Details Yes Decrease Urful in painful speater 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels pointed neuropathy No Others Not Detailed out its if "Yes." Avg. 12233cluk viseFulness # of Rxs written per month? REDACTED 3. Product Name: Please specify: Theme(s) Please be as specific as possible: I Other 1 Detail Currently Rx? Increase 2 Others 2 Details Yes Decrease 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels No Others Not Detailed If "Yes." Avg. # of Rxs written per month? GENERAL THEME(S) AND OTHER TOPICS DISCUSSED Dx & tx neuropathy 990 Please Continue With Questions For Event 2 On The Next Page. I I S-L10058 is Source: https://wwww.industrydocuments.ucsf.edu/docs/qnmd0217 EVENT 2: Page 3 of 3 The presentation was conducted by: (Check all that apply) How useful did you find the information you reccived at the event? Drug company representative Not useful 1 2 3 4 5 6 7 Extremely useful Local physician/rescarcher (specify name): P- The fran MD, Visiting plysician/rescarcher (specify name) : How objective were the presentations and discussious? Third-party moderator (specify name): Not objective 1 2 3 4 5 6 7 Extremely objective Other (please specify): To what degree was the event dedicated to promotion? I Number of speakers: Not promotional 1 2 3 4 5 6 7 Extremiely promotional Approximately, how many physicians attended the event? 10 Length of event (e.g., 3 hours, 2 days, etc.): 1hr To what degree was the event dedicated to education? Not educational 1 2 3 4 5 6 7 Extremely educational Wus a pharmaceutical representative present? Yes No To what extent will the information presented at this event impact your prescribing of the drug and/or therapeutic class? Which of the following were used during the presentation? No impact 1 2 3 4 5 6 7 High impact (Check all that apply) Vidcoconference National Local Regional Other: Taking into account everything about the event, what is your overall rating? Videotape/Slidc presentation Negative 1 2 3 4 5 6 7 Positive Internet Teleconference How would you rate the sponsoring company's image? NA One-on-one intervicw Poor 1 2 3 4 5 6 7 Excellent Peer discussion Clinical studies General Comments Other (please specify) : What support materials, if any, were used? (Check all that apply) What event factors had the greatest impact on your overall event rating? Vidcotape Speaker quality Computer Event theme Visual/Detail aid Peer interaction Print advertisement Event format Clinical reprint Support Materials (please specify): Giveaway (please specify) : Other (please specify): Other (please specify) : Handout Other Comments/Suggestions: Nonc S-L10059 Source: https://www.industrydocuments.ucsf.edu/docs/qnmd0217

was a pharmaceutical representative present?

qnmd0217

qnmd0217_p0, qnmd0217_p1, qnmd0217_p2

No, no

6 605675 EVENT 2: Page 2 of 3 How many other How many times If you checked increase Were specific products discussed? events have you have you been or decrease, what Yes (Please complete the boxes in this section.) attended on this detailed on this Do you prescribe How will your factors influenced No (Please go to the "General Theme" box product/topic in product in the or recommend Rx activity shift this change at the bottom of this page.) the last 6 months? last 6 months? this product? In the future? in Rx activity? 1. Product Name: Nevotin Please specify: Theme(s) Please be as specific as possible: 1 Other 1 Detail Currently Rx? Increase 106 2 Others 2Details Yes Decrease Urful in painful speater 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels pointed neuropathy No Others Not Detailed out its if "Yes." Avg. 12233cluk viseFulness # of Rxs written per month? REDACTED 3. Product Name: Please specify: Theme(s) Please be as specific as possible: I Other 1 Detail Currently Rx? Increase 2 Others 2 Details Yes Decrease 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels No Others Not Detailed If "Yes." Avg. # of Rxs written per month? GENERAL THEME(S) AND OTHER TOPICS DISCUSSED Dx & tx neuropathy 990 Please Continue With Questions For Event 2 On The Next Page. I I S-L10058 is Source: https://wwww.industrydocuments.ucsf.edu/docs/qnmd0217 EVENT 2: Page 3 of 3 The presentation was conducted by: (Check all that apply) How useful did you find the information you reccived at the event? Drug company representative Not useful 1 2 3 4 5 6 7 Extremely useful Local physician/rescarcher (specify name): P- The fran MD, Visiting plysician/rescarcher (specify name) : How objective were the presentations and discussious? Third-party moderator (specify name): Not objective 1 2 3 4 5 6 7 Extremely objective Other (please specify): To what degree was the event dedicated to promotion? I Number of speakers: Not promotional 1 2 3 4 5 6 7 Extremiely promotional Approximately, how many physicians attended the event? 10 Length of event (e.g., 3 hours, 2 days, etc.): 1hr To what degree was the event dedicated to education? Not educational 1 2 3 4 5 6 7 Extremely educational Wus a pharmaceutical representative present? Yes No To what extent will the information presented at this event impact your prescribing of the drug and/or therapeutic class? Which of the following were used during the presentation? No impact 1 2 3 4 5 6 7 High impact (Check all that apply) Vidcoconference National Local Regional Other: Taking into account everything about the event, what is your overall rating? Videotape/Slidc presentation Negative 1 2 3 4 5 6 7 Positive Internet Teleconference How would you rate the sponsoring company's image? NA One-on-one intervicw Poor 1 2 3 4 5 6 7 Excellent Peer discussion Clinical studies General Comments Other (please specify) : What support materials, if any, were used? (Check all that apply) What event factors had the greatest impact on your overall event rating? Vidcotape Speaker quality Computer Event theme Visual/Detail aid Peer interaction Print advertisement Event format Clinical reprint Support Materials (please specify): Giveaway (please specify) : Other (please specify): Other (please specify) : Handout Other Comments/Suggestions: Nonc S-L10059 Source: https://www.industrydocuments.ucsf.edu/docs/qnmd0217

what is the rating given for usefulness of the information recieved at the event?

qnmd0217

qnmd0217_p0, qnmd0217_p1, qnmd0217_p2

6

6 605675 EVENT 2: Page 2 of 3 How many other How many times If you checked increase Were specific products discussed? events have you have you been or decrease, what Yes (Please complete the boxes in this section.) attended on this detailed on this Do you prescribe How will your factors influenced No (Please go to the "General Theme" box product/topic in product in the or recommend Rx activity shift this change at the bottom of this page.) the last 6 months? last 6 months? this product? In the future? in Rx activity? 1. Product Name: Nevotin Please specify: Theme(s) Please be as specific as possible: 1 Other 1 Detail Currently Rx? Increase 106 2 Others 2Details Yes Decrease Urful in painful speater 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels pointed neuropathy No Others Not Detailed out its if "Yes." Avg. 12233cluk viseFulness # of Rxs written per month? REDACTED 3. Product Name: Please specify: Theme(s) Please be as specific as possible: I Other 1 Detail Currently Rx? Increase 2 Others 2 Details Yes Decrease 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels No Others Not Detailed If "Yes." Avg. # of Rxs written per month? GENERAL THEME(S) AND OTHER TOPICS DISCUSSED Dx & tx neuropathy 990 Please Continue With Questions For Event 2 On The Next Page. I I S-L10058 is Source: https://wwww.industrydocuments.ucsf.edu/docs/qnmd0217 EVENT 2: Page 3 of 3 The presentation was conducted by: (Check all that apply) How useful did you find the information you reccived at the event? Drug company representative Not useful 1 2 3 4 5 6 7 Extremely useful Local physician/rescarcher (specify name): P- The fran MD, Visiting plysician/rescarcher (specify name) : How objective were the presentations and discussious? Third-party moderator (specify name): Not objective 1 2 3 4 5 6 7 Extremely objective Other (please specify): To what degree was the event dedicated to promotion? I Number of speakers: Not promotional 1 2 3 4 5 6 7 Extremiely promotional Approximately, how many physicians attended the event? 10 Length of event (e.g., 3 hours, 2 days, etc.): 1hr To what degree was the event dedicated to education? Not educational 1 2 3 4 5 6 7 Extremely educational Wus a pharmaceutical representative present? Yes No To what extent will the information presented at this event impact your prescribing of the drug and/or therapeutic class? Which of the following were used during the presentation? No impact 1 2 3 4 5 6 7 High impact (Check all that apply) Vidcoconference National Local Regional Other: Taking into account everything about the event, what is your overall rating? Videotape/Slidc presentation Negative 1 2 3 4 5 6 7 Positive Internet Teleconference How would you rate the sponsoring company's image? NA One-on-one intervicw Poor 1 2 3 4 5 6 7 Excellent Peer discussion Clinical studies General Comments Other (please specify) : What support materials, if any, were used? (Check all that apply) What event factors had the greatest impact on your overall event rating? Vidcotape Speaker quality Computer Event theme Visual/Detail aid Peer interaction Print advertisement Event format Clinical reprint Support Materials (please specify): Giveaway (please specify) : Other (please specify): Other (please specify) : Handout Other Comments/Suggestions: Nonc S-L10059 Source: https://www.industrydocuments.ucsf.edu/docs/qnmd0217

what event factors had the greatest impact on overall event rating?

qnmd0217

qnmd0217_p0, qnmd0217_p1, qnmd0217_p2

Speaker quality, speaker quality

6 605675 EVENT 2: Page 2 of 3 How many other How many times If you checked increase Were specific products discussed? events have you have you been or decrease, what Yes (Please complete the boxes in this section.) attended on this detailed on this Do you prescribe How will your factors influenced No (Please go to the "General Theme" box product/topic in product in the or recommend Rx activity shift this change at the bottom of this page.) the last 6 months? last 6 months? this product? In the future? in Rx activity? 1. Product Name: Nevotin Please specify: Theme(s) Please be as specific as possible: 1 Other 1 Detail Currently Rx? Increase 106 2 Others 2Details Yes Decrease Urful in painful speater 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels pointed neuropathy No Others Not Detailed out its if "Yes." Avg. 12233cluk viseFulness # of Rxs written per month? REDACTED 3. Product Name: Please specify: Theme(s) Please be as specific as possible: I Other 1 Detail Currently Rx? Increase 2 Others 2 Details Yes Decrease 3 Others 3 Details No Maintain >3 Others >3 Details Current Levels No Others Not Detailed If "Yes." Avg. # of Rxs written per month? GENERAL THEME(S) AND OTHER TOPICS DISCUSSED Dx & tx neuropathy 990 Please Continue With Questions For Event 2 On The Next Page. I I S-L10058 is Source: https://wwww.industrydocuments.ucsf.edu/docs/qnmd0217 EVENT 2: Page 3 of 3 The presentation was conducted by: (Check all that apply) How useful did you find the information you reccived at the event? Drug company representative Not useful 1 2 3 4 5 6 7 Extremely useful Local physician/rescarcher (specify name): P- The fran MD, Visiting plysician/rescarcher (specify name) : How objective were the presentations and discussious? Third-party moderator (specify name): Not objective 1 2 3 4 5 6 7 Extremely objective Other (please specify): To what degree was the event dedicated to promotion? I Number of speakers: Not promotional 1 2 3 4 5 6 7 Extremiely promotional Approximately, how many physicians attended the event? 10 Length of event (e.g., 3 hours, 2 days, etc.): 1hr To what degree was the event dedicated to education? Not educational 1 2 3 4 5 6 7 Extremely educational Wus a pharmaceutical representative present? Yes No To what extent will the information presented at this event impact your prescribing of the drug and/or therapeutic class? Which of the following were used during the presentation? No impact 1 2 3 4 5 6 7 High impact (Check all that apply) Vidcoconference National Local Regional Other: Taking into account everything about the event, what is your overall rating? Videotape/Slidc presentation Negative 1 2 3 4 5 6 7 Positive Internet Teleconference How would you rate the sponsoring company's image? NA One-on-one intervicw Poor 1 2 3 4 5 6 7 Excellent Peer discussion Clinical studies General Comments Other (please specify) : What support materials, if any, were used? (Check all that apply) What event factors had the greatest impact on your overall event rating? Vidcotape Speaker quality Computer Event theme Visual/Detail aid Peer interaction Print advertisement Event format Clinical reprint Support Materials (please specify): Giveaway (please specify) : Other (please specify): Other (please specify) : Handout Other Comments/Suggestions: Nonc S-L10059 Source: https://www.industrydocuments.ucsf.edu/docs/qnmd0217

what is the number mentioned at the top right corner?

hjmd0217

hjmd0217_p0, hjmd0217_p1, hjmd0217_p2

602425

7 EVENT 1: Pagelof3 602425 PRE-EVENT INTORMATION Please coirplete these questions for all invitations, whether or not you attended. Was A Pharmacoutical Company, Associated With The Event? Company Name: Parke - Davis 192 City/State: Fennville, MI Yes Event Date 11/4/97 No The Invitation Was Mado By A: Were CME Credits Offered? Pharmaccutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical Company Firm Name: Boron- Le Pore 1774 What Type Of Honorarlum Was Offered? (Cruck Ar That ^pply) Meals University/Medical Institution (e.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Prolessional Association (e.g., The American Heart Association) Nainc: Medical Instruments (please specify): Other: (please specify) Gift Certificate (please specify for what): Audis Dyest Tape The Event Was Sponsored Company: By: (Check Parke-Davis All That Apply) 192 Textbooks (please specify): Other: Pharmaceutical None University/Medical Institution: Dld You Attend The Event? Clinical/Professional Association: YES, Because Of: (Check All Thut ^pply) Managed Care Company: Interest In The Topic Other: (please specify) Type Of Honoraria Offered The Announced Topic Was: (Chock All That Apply) Toplc Reputation Of Speakers General Therapeutic Area 48 Epilepsy Treatment CME Credits Offered i (e.g., hypertension, heart failure, diabetes): Advareement Convenient Location A Therapeutic Class of Drugs Other (please specify): (e.g., ACE inhibitors, diuretics): NO, Because Of: (Check All That Apply) A Specific Product Manufactured by The Pharmaceutical Company: Lack Of Interest In The Topic Disease Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honoraria Offered Other: No CME Credits Offered Inconvenient Location/Distanco Evont Location: (Ploase Chuck Appropriale Box And Record Spedific Name On Une Bolow): Hotel Mkt. Res. Facility Other (please specify): Restaurant Convention Home Office Other (Specify Name): telecompsone If You Attended, Please Continue With The Questions On The Following Pages. Ploaso Continue With Tho Quaétions To The Right. Please Continue With The Questions For Event 1 On The Next Page. I- S-L09775 Source: https://www.industrydocuments.ucsf.edu/docs/hjmdQ217 EVENT 1: Page 2 of 3 602425 PRODUCT NFORMATION Yes (Please complete the boxes in this section.) How many times Wore Specilic Products Discussed? No (Please go to the "General Theme" have you been detailed on this At what level do At what level do 12233 p/y box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? Product Name: Neurontin Dose tid 4800 mg/dl Not Detailed THEME(S): Nonprescribor Nonprescriber (Please Be As Specific As Possible) Effective as add on agent to Dilantin as 1 Detail Low Low Neuprimary as is not therepy protein bound + is excritedunmentald in urine 2 Details Moderale Modorate Doesnot induce Lepatic enzymes. allothese are factors in look 3 Details High High 3 Details No Gloodland dry interastional moniticing is needed: Thus preventing expond of laboratory tasts Product Name: Not Detailed THEME(S): Nonproscriber Nonprescribor (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderate Moderate 3 Details High High 3 Details Product Name: Not Detailed Nonprescriber Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderate Moderate 3 Details High High >3 Details GENERAL THEME(S) AND OTHER TOPICS DISCUSSED 48 up to 25% of cases are not adequately controlled c monothinapyste polytherapy Epilopsy is 3rd most common neurologic discase (after stabes T Algheimer D General Theme(s) and Other Topia Discussed objectived of treatment 1) Elizinate or reduce sligares 3)avoid treatmentlside affects 3) Maintain a restore psychosocial 9 Moat antiseigure medications have dose related: side effects. S.L09774 Please Continue With The Questions For Event 1 On The Next Page, 15

What is the pharmaceuticals company name?

hjmd0217

hjmd0217_p0, hjmd0217_p1, hjmd0217_p2

parke davis, Parke Davis, Parke-Davis 192

7 EVENT 1: Pagelof3 602425 PRE-EVENT INTORMATION Please coirplete these questions for all invitations, whether or not you attended. Was A Pharmacoutical Company, Associated With The Event? Company Name: Parke - Davis 192 City/State: Fennville, MI Yes Event Date 11/4/97 No The Invitation Was Mado By A: Were CME Credits Offered? Pharmaccutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical Company Firm Name: Boron- Le Pore 1774 What Type Of Honorarlum Was Offered? (Cruck Ar That ^pply) Meals University/Medical Institution (e.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Prolessional Association (e.g., The American Heart Association) Nainc: Medical Instruments (please specify): Other: (please specify) Gift Certificate (please specify for what): Audis Dyest Tape The Event Was Sponsored Company: By: (Check Parke-Davis All That Apply) 192 Textbooks (please specify): Other: Pharmaceutical None University/Medical Institution: Dld You Attend The Event? Clinical/Professional Association: YES, Because Of: (Check All Thut ^pply) Managed Care Company: Interest In The Topic Other: (please specify) Type Of Honoraria Offered The Announced Topic Was: (Chock All That Apply) Toplc Reputation Of Speakers General Therapeutic Area 48 Epilepsy Treatment CME Credits Offered i (e.g., hypertension, heart failure, diabetes): Advareement Convenient Location A Therapeutic Class of Drugs Other (please specify): (e.g., ACE inhibitors, diuretics): NO, Because Of: (Check All That Apply) A Specific Product Manufactured by The Pharmaceutical Company: Lack Of Interest In The Topic Disease Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honoraria Offered Other: No CME Credits Offered Inconvenient Location/Distanco Evont Location: (Ploase Chuck Appropriale Box And Record Spedific Name On Une Bolow): Hotel Mkt. Res. Facility Other (please specify): Restaurant Convention Home Office Other (Specify Name): telecompsone If You Attended, Please Continue With The Questions On The Following Pages. Ploaso Continue With Tho Quaétions To The Right. Please Continue With The Questions For Event 1 On The Next Page. I- S-L09775 Source: https://www.industrydocuments.ucsf.edu/docs/hjmdQ217 EVENT 1: Page 2 of 3 602425 PRODUCT NFORMATION Yes (Please complete the boxes in this section.) How many times Wore Specilic Products Discussed? No (Please go to the "General Theme" have you been detailed on this At what level do At what level do 12233 p/y box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? Product Name: Neurontin Dose tid 4800 mg/dl Not Detailed THEME(S): Nonprescribor Nonprescriber (Please Be As Specific As Possible) Effective as add on agent to Dilantin as 1 Detail Low Low Neuprimary as is not therepy protein bound + is excritedunmentald in urine 2 Details Moderale Modorate Doesnot induce Lepatic enzymes. allothese are factors in look 3 Details High High 3 Details No Gloodland dry interastional moniticing is needed: Thus preventing expond of laboratory tasts Product Name: Not Detailed THEME(S): Nonproscriber Nonprescribor (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderate Moderate 3 Details High High 3 Details Product Name: Not Detailed Nonprescriber Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderate Moderate 3 Details High High >3 Details GENERAL THEME(S) AND OTHER TOPICS DISCUSSED 48 up to 25% of cases are not adequately controlled c monothinapyste polytherapy Epilopsy is 3rd most common neurologic discase (after stabes T Algheimer D General Theme(s) and Other Topia Discussed objectived of treatment 1) Elizinate or reduce sligares 3)avoid treatmentlside affects 3) Maintain a restore psychosocial 9 Moat antiseigure medications have dose related: side effects. S.L09774 Please Continue With The Questions For Event 1 On The Next Page, 15

what is th event date?

hjmd0217

hjmd0217_p0, hjmd0217_p1, hjmd0217_p2

11/4/97

7 EVENT 1: Pagelof3 602425 PRE-EVENT INTORMATION Please coirplete these questions for all invitations, whether or not you attended. Was A Pharmacoutical Company, Associated With The Event? Company Name: Parke - Davis 192 City/State: Fennville, MI Yes Event Date 11/4/97 No The Invitation Was Mado By A: Were CME Credits Offered? Pharmaccutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical Company Firm Name: Boron- Le Pore 1774 What Type Of Honorarlum Was Offered? (Cruck Ar That ^pply) Meals University/Medical Institution (e.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Prolessional Association (e.g., The American Heart Association) Nainc: Medical Instruments (please specify): Other: (please specify) Gift Certificate (please specify for what): Audis Dyest Tape The Event Was Sponsored Company: By: (Check Parke-Davis All That Apply) 192 Textbooks (please specify): Other: Pharmaceutical None University/Medical Institution: Dld You Attend The Event? Clinical/Professional Association: YES, Because Of: (Check All Thut ^pply) Managed Care Company: Interest In The Topic Other: (please specify) Type Of Honoraria Offered The Announced Topic Was: (Chock All That Apply) Toplc Reputation Of Speakers General Therapeutic Area 48 Epilepsy Treatment CME Credits Offered i (e.g., hypertension, heart failure, diabetes): Advareement Convenient Location A Therapeutic Class of Drugs Other (please specify): (e.g., ACE inhibitors, diuretics): NO, Because Of: (Check All That Apply) A Specific Product Manufactured by The Pharmaceutical Company: Lack Of Interest In The Topic Disease Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honoraria Offered Other: No CME Credits Offered Inconvenient Location/Distanco Evont Location: (Ploase Chuck Appropriale Box And Record Spedific Name On Une Bolow): Hotel Mkt. Res. Facility Other (please specify): Restaurant Convention Home Office Other (Specify Name): telecompsone If You Attended, Please Continue With The Questions On The Following Pages. Ploaso Continue With Tho Quaétions To The Right. Please Continue With The Questions For Event 1 On The Next Page. I- S-L09775 Source: https://www.industrydocuments.ucsf.edu/docs/hjmdQ217 EVENT 1: Page 2 of 3 602425 PRODUCT NFORMATION Yes (Please complete the boxes in this section.) How many times Wore Specilic Products Discussed? No (Please go to the "General Theme" have you been detailed on this At what level do At what level do 12233 p/y box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? Product Name: Neurontin Dose tid 4800 mg/dl Not Detailed THEME(S): Nonprescribor Nonprescriber (Please Be As Specific As Possible) Effective as add on agent to Dilantin as 1 Detail Low Low Neuprimary as is not therepy protein bound + is excritedunmentald in urine 2 Details Moderale Modorate Doesnot induce Lepatic enzymes. allothese are factors in look 3 Details High High 3 Details No Gloodland dry interastional moniticing is needed: Thus preventing expond of laboratory tasts Product Name: Not Detailed THEME(S): Nonproscriber Nonprescribor (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderate Moderate 3 Details High High 3 Details Product Name: Not Detailed Nonprescriber Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderate Moderate 3 Details High High >3 Details GENERAL THEME(S) AND OTHER TOPICS DISCUSSED 48 up to 25% of cases are not adequately controlled c monothinapyste polytherapy Epilopsy is 3rd most common neurologic discase (after stabes T Algheimer D General Theme(s) and Other Topia Discussed objectived of treatment 1) Elizinate or reduce sligares 3)avoid treatmentlside affects 3) Maintain a restore psychosocial 9 Moat antiseigure medications have dose related: side effects. S.L09774 Please Continue With The Questions For Event 1 On The Next Page, 15

were CME credits offered?

hjmd0217

hjmd0217_p0, hjmd0217_p1, hjmd0217_p2

No, no

7 EVENT 1: Pagelof3 602425 PRE-EVENT INTORMATION Please coirplete these questions for all invitations, whether or not you attended. Was A Pharmacoutical Company, Associated With The Event? Company Name: Parke - Davis 192 City/State: Fennville, MI Yes Event Date 11/4/97 No The Invitation Was Mado By A: Were CME Credits Offered? Pharmaccutical Sales Representative Yes Company Name: No Firm other than Pharmaceutical Company Firm Name: Boron- Le Pore 1774 What Type Of Honorarlum Was Offered? (Cruck Ar That ^pply) Meals University/Medical Institution (e.g., Vanderbilt University) Charitable Contribution Name: Cash/Check Clinical/Prolessional Association (e.g., The American Heart Association) Nainc: Medical Instruments (please specify): Other: (please specify) Gift Certificate (please specify for what): Audis Dyest Tape The Event Was Sponsored Company: By: (Check Parke-Davis All That Apply) 192 Textbooks (please specify): Other: Pharmaceutical None University/Medical Institution: Dld You Attend The Event? Clinical/Professional Association: YES, Because Of: (Check All Thut ^pply) Managed Care Company: Interest In The Topic Other: (please specify) Type Of Honoraria Offered The Announced Topic Was: (Chock All That Apply) Toplc Reputation Of Speakers General Therapeutic Area 48 Epilepsy Treatment CME Credits Offered i (e.g., hypertension, heart failure, diabetes): Advareement Convenient Location A Therapeutic Class of Drugs Other (please specify): (e.g., ACE inhibitors, diuretics): NO, Because Of: (Check All That Apply) A Specific Product Manufactured by The Pharmaceutical Company: Lack Of Interest In The Topic Disease Management Program Scheduling Conflict (professional or personal) (treatment guidelines, protocols, care maps, etc): Type Of Honoraria Offered Other: No CME Credits Offered Inconvenient Location/Distanco Evont Location: (Ploase Chuck Appropriale Box And Record Spedific Name On Une Bolow): Hotel Mkt. Res. Facility Other (please specify): Restaurant Convention Home Office Other (Specify Name): telecompsone If You Attended, Please Continue With The Questions On The Following Pages. Ploaso Continue With Tho Quaétions To The Right. Please Continue With The Questions For Event 1 On The Next Page. I- S-L09775 Source: https://www.industrydocuments.ucsf.edu/docs/hjmdQ217 EVENT 1: Page 2 of 3 602425 PRODUCT NFORMATION Yes (Please complete the boxes in this section.) How many times Wore Specilic Products Discussed? No (Please go to the "General Theme" have you been detailed on this At what level do At what level do 12233 p/y box at the bottom of this page.) product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? Product Name: Neurontin Dose tid 4800 mg/dl Not Detailed THEME(S): Nonprescribor Nonprescriber (Please Be As Specific As Possible) Effective as add on agent to Dilantin as 1 Detail Low Low Neuprimary as is not therepy protein bound + is excritedunmentald in urine 2 Details Moderale Modorate Doesnot induce Lepatic enzymes. allothese are factors in look 3 Details High High 3 Details No Gloodland dry interastional moniticing is needed: Thus preventing expond of laboratory tasts Product Name: Not Detailed THEME(S): Nonproscriber Nonprescribor (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderate Moderate 3 Details High High 3 Details Product Name: Not Detailed Nonprescriber Nonprescriber THEME(S): (Please Be As Specific As Possible) 1 Detail Low Low 2 Details Moderate Moderate 3 Details High High >3 Details GENERAL THEME(S) AND OTHER TOPICS DISCUSSED 48 up to 25% of cases are not adequately controlled c monothinapyste polytherapy Epilopsy is 3rd most common neurologic discase (after stabes T Algheimer D General Theme(s) and Other Topia Discussed objectived of treatment 1) Elizinate or reduce sligares 3)avoid treatmentlside affects 3) Maintain a restore psychosocial 9 Moat antiseigure medications have dose related: side effects. S.L09774 Please Continue With The Questions For Event 1 On The Next Page, 15

were specific products discussed?

jmmd0217

jmmd0217_p2

Yes, yes

EVENT 1: Page 2 of 3 PRODUCT INFORMATION Wero Spocific Products Discussed? Yes (Please complete the boxes in this section.) How many times No (Please go to the "General Theme" have you been box at the bottom of this page.) detailed on this At what level do At what level do product in the last you currently Rx you plan to try or 6 months? this product? continue to Rx? REDACTED ( 3 Product Name: nemmten THEME(S): Not Detailed Nonprescriber Nonprescribor (Please Bc As Specific As Possible) 1 Detail Low Low 2 Details Modorato Modorate 12233 nly bepalar II. Annou atting + effe time lop for 3 Dotails High High >3 Dotails GENERAL THEME(S) AND OTHER TOPICS DISCUSSED General Theme(s) and Other Topics Discussed bB S-L09988 Please Continue With The Questiona For Foont 1 are The Noxt Paga 0-8 Source: ttps://www.industrydocuments.ucsf.edu/docs/jmmd0217

what is the phase number?

gxyd0217

gxyd0217_p10, gxyd0217_p11, gxyd0217_p12, gxyd0217_p13, gxyd0217_p14, gxyd0217_p15, gxyd0217_p16, gxyd0217_p17, gxyd0217_p18

17

10 SITE SELECTION CRITERIA FOR ATORVASTATIN , PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: John Rogers Address: Albany Medical College NY 12208 Phone: or 262 5031 Fax: Study Coordinator(s): Yes Practice Specialty: Gastrcenterology ( Lipid specialist) Study experience: Extensive (PI $ CARE study) PD studies: NO Number of active studies: 1 Any competing studies: Pt. Population: # of patients in practice 3000 plus VA pt. base most common treatment # of newly diagnosed method of recruitment Patient base plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? } Locked cabinets is the drug storage locked? (Y/N) Y central lab experience?(who) IRB requirements, can a national IRB be used? Local IRB meeting schedule who approves study budgets? Investigator Dr Rogers is head of Lipid Clinice and has a Comments: VA population - Very influented to bischell h Allany area Large Dyslipidemic population draws from CBU Associate Director: Phone: minarities dabities 11 women SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Marc Weinberg Address: 1076 North Main Street Previdence RI 02904 Phone: (401) 861-7711 Fax: (401) 421 - 5710 Study Coordinator(s): Renee Haneich Practice Specialty: Hypertension and Nephrology Study experience: Extensive - Dr. Weusburg has 3 full-ture Research assistants PD studies: ( Has propoled a small Accupal study Number of active studies: Any competing studies: 7 Yes (Merck already enolled) Pt. Population: # of patients in practice 20,000 toral - Many disslepidence most common treatment and diabetics # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are records stored? where are study drugs stored? study I calcuts locked is the drug storage locked? (Y/N) Yes central lab experience?(who) Various includers Smuhkline IRB requirements, can a national IRB be used? Several Central IRBS Local IRB meeting schedule 2 weet IRB turnaund who approves study budgets? Renee Haneich /Dr. Weinburg Comments: Dr. Wenburg is Very influential S Rhode Island and 'statens': Can call on significant diabetic & meventy population sallending aleas , Has extensive experence with CBU Associate Director: Phone: women dubbtics p minnities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Rhode Island Hospital Doctor's Name: Dr. David Brill as a member of Carchology Foundation Address: 845 North Main Street Providence RI 02904 Phone: (401) 751- 0023 Fax: Study Coordinator(s): Yes ( 4 full-tune nuses when group) Practice Specialty: Cardiology Study experience: Extensive but varies among different members of the group PD studies: 0 Number of active studies: 0 Any competing studies: Pt. Population # of patients in practice 15,000 most common treatment # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? Locked where study drugs stored? 5 Cabinits are is the drug storage locked? (Y/N) Y central lab experience?(who) Rhode Kland hobital or others IRB requirements, can a national IRB be used? National IRB Local IRB meeting schedule who approves study budgets? This group incorporates up to 17 Caddroggsists and (Nerns Comments: They are 4 the process of setting up a Lepid clinic including the cardiologists at RI hospital. and are extremely important for business & this area. CBU Associate Director: Phone: Source: https:llwwwindustrydocuments.ucsf.edu/docs/gxyd021 women derbitics 13 SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Robert Weiss Address: Two Great Falls Plaza Auburn , ME 04210 Phone: (207) 782 4022 Fax: (207) 784 3537 Study Coordinator(s): Carole Ridley Practice Specialty: cardiology ( lip.d specialit) Study experience: Extensive ( Currently doing ALLHAT) Employs 2 full ture end 1 parF-time research associate PD studies: 0 Number of active studies: 6-8 Any competing studies: ALLHAT , (ecently line a small flurastatin study Pt. Population: # of patients in practice 250 1 month large % we dyslipidemic (95%) most common treatment # of newly diagnosed method of recruitment Patient bare plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 Locked cabnet in where are study drugs sto: ??? J Locked office is the drug storage locked? (Y/N) Y central lab experience?(whc CORVING BIORAN IRB requirements, can a national IRB be used? Local but could one nationa Local IRB meeting schedule Monthly who approves study budgets? Dr. Welss Comments: Dr. Wess is extremely influential in Hus alea CBU Associate Director: Phone: Source: https:l/www.industrydocuments.ucsf.edu/docs/gxyd0217 women diabetics 14 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Francine Welty, MD Address: One Autumn st Boston mA 02215 Phone: (617) 632 - 7659 Fax: (617) 632 - 7675 Study Coordinator(s): for No Practice Specialty: Lipids Study experience: extensive PD studies: yes Number of active studies: 2 Any competing studies: 0 Lipid Population: # of patients in practice 1000-1500 most common treatment dutlexer. LOPID, 3 HMGS # of newly diagnosed 10 /month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study records stored? locked cabinet where are study drugs stored? J is the drug storage locked? (Y/N) central lab experience?(who) Smithklene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? business mgr Comments: CBU Associate Director: Phone: Source: women deabities 15 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Sudhir Bansal , MD Address: 215 Tolgate Rd Warwer RI 02886 Phone: (401) 732 - 6828 (401) 732 - 0880 Fax: Study Coordinator(s): yes Practice Specialty: Endocrenalogy /Internal Medicine Study experience: yes PD studies: No Number of active studies: / Any competing studies: D Lipid Population: # of patients in practice 1,000-1500 most common treatment HINGS # of newly diagnosed 15/mmth method of recruitment pt bise could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are where are study drugs stored? study records stored? Zlocked benes is the drug storage locked? (Y/N) Y central lab experience?(who) SmithKline IRB requirements, can a national IRB be used? y Local IRB meeting schedule who approves study budgets? Bransal Comments: CBU Associate Director: Phone: diabetics. minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE 17 IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Richard De Amices, MD Address: 4 Courthase lane Chelmsford MA 01824 Phone: (508) 459 - 8400 Fax: (508) 459 - 2340 Study Coordinator(s): yes Practice Specialty: Im Study experience: yes PD studies: yes Number of active studies: / Any competing studies: Q Lipid Population: # of patients in practice DIEED 1,000-1500 most common treatment MMGs # of newly diagnosed 15/month method of recruitment St phase could site ID 20-30 Site specifics: where where are study drugs stored? are study records stored? pts 3 locked alchet y in 6 months? (Y/N) is the drug storage locked? (Y/N) y central lab experience?( (who) Smithklene IRB requirements, can a national IRB be used? yes Local IRB meeting schedule who approves study budgets? himself Comments: CBU Associate Director: Phone: Source: women diabetics minorities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE 18 INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Peter Ganz Address: Brigham and Women's Hospital 225 Longwood Ave Boston MA 02115 Phone: (617) 732 1133 Fax: Study Coordinator(s): Peter Store MD , Dancelle Delagrange Practice Specialty: Cardialogist Study experience: Extensive PD studies: Just approved for atervastatin in $15 unstable argus stud Number of active studies: Any competing studies: Pt. Population: # of patients in practice 4,000/gr. in Cath lab - Also Clinic most common treatment # of newly diagnosed method of recruitment P1- base and extensive referaTs could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 where are study drugs stored? technical cabunes is the drug storage locked? (Y/N) Jy central lab experience?(who) Brigham's lab IRB réquirements, can a national IRB be used? Brupan's IRB Local IRB meeting schedule ever, Minth who approves study budgets? Dr. Ganz Comments: Just approved for Ann Actor unstable argan study Therefore not as big a priority CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxyd0217 diabetics women minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS 10 THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Paul Loch, MD Address: 26QQueen3 Street Worcester MA 01604 Phone: (28) 755 - 0201 Fax: Study Coordinator(s): Elizabeth Mahi (508)755-0201 Practice Specialty: IM (subspecially -Diabetes) Study experience: phase, 11 IV PD studies: 0 Number of active studies: 6 Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment HMGs, diet, LOPID # of newly diagnosed 5/uk method of recruitment pt base could site ID 20-30 pts in 6 Site specifics: where are study records stored? N where are study drugs stored? J is the drug storage locked? (Y/N) varies depending M tral Y central lab experience?(who) IRB requirements, can a national IRB be used? yes Local IRB meeting schedule once/month who approves study budgets? Dr lock Comments: Dr lock conducts research Through The Clinical pharmacology study group CBU Associate Director: Phone:

what is the practice speciality?

gxyd0217

gxyd0217_p10, gxyd0217_p11, gxyd0217_p12, gxyd0217_p13, gxyd0217_p14, gxyd0217_p15, gxyd0217_p16, gxyd0217_p17, gxyd0217_p18

IM

10 SITE SELECTION CRITERIA FOR ATORVASTATIN , PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: John Rogers Address: Albany Medical College NY 12208 Phone: or 262 5031 Fax: Study Coordinator(s): Yes Practice Specialty: Gastrcenterology ( Lipid specialist) Study experience: Extensive (PI $ CARE study) PD studies: NO Number of active studies: 1 Any competing studies: Pt. Population: # of patients in practice 3000 plus VA pt. base most common treatment # of newly diagnosed method of recruitment Patient base plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? } Locked cabinets is the drug storage locked? (Y/N) Y central lab experience?(who) IRB requirements, can a national IRB be used? Local IRB meeting schedule who approves study budgets? Investigator Dr Rogers is head of Lipid Clinice and has a Comments: VA population - Very influented to bischell h Allany area Large Dyslipidemic population draws from CBU Associate Director: Phone: minarities dabities 11 women SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Marc Weinberg Address: 1076 North Main Street Previdence RI 02904 Phone: (401) 861-7711 Fax: (401) 421 - 5710 Study Coordinator(s): Renee Haneich Practice Specialty: Hypertension and Nephrology Study experience: Extensive - Dr. Weusburg has 3 full-ture Research assistants PD studies: ( Has propoled a small Accupal study Number of active studies: Any competing studies: 7 Yes (Merck already enolled) Pt. Population: # of patients in practice 20,000 toral - Many disslepidence most common treatment and diabetics # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are records stored? where are study drugs stored? study I calcuts locked is the drug storage locked? (Y/N) Yes central lab experience?(who) Various includers Smuhkline IRB requirements, can a national IRB be used? Several Central IRBS Local IRB meeting schedule 2 weet IRB turnaund who approves study budgets? Renee Haneich /Dr. Weinburg Comments: Dr. Wenburg is Very influential S Rhode Island and 'statens': Can call on significant diabetic & meventy population sallending aleas , Has extensive experence with CBU Associate Director: Phone: women dubbtics p minnities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Rhode Island Hospital Doctor's Name: Dr. David Brill as a member of Carchology Foundation Address: 845 North Main Street Providence RI 02904 Phone: (401) 751- 0023 Fax: Study Coordinator(s): Yes ( 4 full-tune nuses when group) Practice Specialty: Cardiology Study experience: Extensive but varies among different members of the group PD studies: 0 Number of active studies: 0 Any competing studies: Pt. Population # of patients in practice 15,000 most common treatment # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? Locked where study drugs stored? 5 Cabinits are is the drug storage locked? (Y/N) Y central lab experience?(who) Rhode Kland hobital or others IRB requirements, can a national IRB be used? National IRB Local IRB meeting schedule who approves study budgets? This group incorporates up to 17 Caddroggsists and (Nerns Comments: They are 4 the process of setting up a Lepid clinic including the cardiologists at RI hospital. and are extremely important for business & this area. CBU Associate Director: Phone: Source: https:llwwwindustrydocuments.ucsf.edu/docs/gxyd021 women derbitics 13 SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Robert Weiss Address: Two Great Falls Plaza Auburn , ME 04210 Phone: (207) 782 4022 Fax: (207) 784 3537 Study Coordinator(s): Carole Ridley Practice Specialty: cardiology ( lip.d specialit) Study experience: Extensive ( Currently doing ALLHAT) Employs 2 full ture end 1 parF-time research associate PD studies: 0 Number of active studies: 6-8 Any competing studies: ALLHAT , (ecently line a small flurastatin study Pt. Population: # of patients in practice 250 1 month large % we dyslipidemic (95%) most common treatment # of newly diagnosed method of recruitment Patient bare plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 Locked cabnet in where are study drugs sto: ??? J Locked office is the drug storage locked? (Y/N) Y central lab experience?(whc CORVING BIORAN IRB requirements, can a national IRB be used? Local but could one nationa Local IRB meeting schedule Monthly who approves study budgets? Dr. Welss Comments: Dr. Wess is extremely influential in Hus alea CBU Associate Director: Phone: Source: https:l/www.industrydocuments.ucsf.edu/docs/gxyd0217 women diabetics 14 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Francine Welty, MD Address: One Autumn st Boston mA 02215 Phone: (617) 632 - 7659 Fax: (617) 632 - 7675 Study Coordinator(s): for No Practice Specialty: Lipids Study experience: extensive PD studies: yes Number of active studies: 2 Any competing studies: 0 Lipid Population: # of patients in practice 1000-1500 most common treatment dutlexer. LOPID, 3 HMGS # of newly diagnosed 10 /month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study records stored? locked cabinet where are study drugs stored? J is the drug storage locked? (Y/N) central lab experience?(who) Smithklene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? business mgr Comments: CBU Associate Director: Phone: Source: women deabities 15 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Sudhir Bansal , MD Address: 215 Tolgate Rd Warwer RI 02886 Phone: (401) 732 - 6828 (401) 732 - 0880 Fax: Study Coordinator(s): yes Practice Specialty: Endocrenalogy /Internal Medicine Study experience: yes PD studies: No Number of active studies: / Any competing studies: D Lipid Population: # of patients in practice 1,000-1500 most common treatment HINGS # of newly diagnosed 15/mmth method of recruitment pt bise could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are where are study drugs stored? study records stored? Zlocked benes is the drug storage locked? (Y/N) Y central lab experience?(who) SmithKline IRB requirements, can a national IRB be used? y Local IRB meeting schedule who approves study budgets? Bransal Comments: CBU Associate Director: Phone: diabetics. minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE 17 IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Richard De Amices, MD Address: 4 Courthase lane Chelmsford MA 01824 Phone: (508) 459 - 8400 Fax: (508) 459 - 2340 Study Coordinator(s): yes Practice Specialty: Im Study experience: yes PD studies: yes Number of active studies: / Any competing studies: Q Lipid Population: # of patients in practice DIEED 1,000-1500 most common treatment MMGs # of newly diagnosed 15/month method of recruitment St phase could site ID 20-30 Site specifics: where where are study drugs stored? are study records stored? pts 3 locked alchet y in 6 months? (Y/N) is the drug storage locked? (Y/N) y central lab experience?( (who) Smithklene IRB requirements, can a national IRB be used? yes Local IRB meeting schedule who approves study budgets? himself Comments: CBU Associate Director: Phone: Source: women diabetics minorities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE 18 INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Peter Ganz Address: Brigham and Women's Hospital 225 Longwood Ave Boston MA 02115 Phone: (617) 732 1133 Fax: Study Coordinator(s): Peter Store MD , Dancelle Delagrange Practice Specialty: Cardialogist Study experience: Extensive PD studies: Just approved for atervastatin in $15 unstable argus stud Number of active studies: Any competing studies: Pt. Population: # of patients in practice 4,000/gr. in Cath lab - Also Clinic most common treatment # of newly diagnosed method of recruitment P1- base and extensive referaTs could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 where are study drugs stored? technical cabunes is the drug storage locked? (Y/N) Jy central lab experience?(who) Brigham's lab IRB réquirements, can a national IRB be used? Brupan's IRB Local IRB meeting schedule ever, Minth who approves study budgets? Dr. Ganz Comments: Just approved for Ann Actor unstable argan study Therefore not as big a priority CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxyd0217 diabetics women minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS 10 THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Paul Loch, MD Address: 26QQueen3 Street Worcester MA 01604 Phone: (28) 755 - 0201 Fax: Study Coordinator(s): Elizabeth Mahi (508)755-0201 Practice Specialty: IM (subspecially -Diabetes) Study experience: phase, 11 IV PD studies: 0 Number of active studies: 6 Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment HMGs, diet, LOPID # of newly diagnosed 5/uk method of recruitment pt base could site ID 20-30 pts in 6 Site specifics: where are study records stored? N where are study drugs stored? J is the drug storage locked? (Y/N) varies depending M tral Y central lab experience?(who) IRB requirements, can a national IRB be used? yes Local IRB meeting schedule once/month who approves study budgets? Dr lock Comments: Dr lock conducts research Through The Clinical pharmacology study group CBU Associate Director: Phone:

what is the number of active studies?

gxyd0217

gxyd0217_p10, gxyd0217_p11, gxyd0217_p12, gxyd0217_p13, gxyd0217_p14, gxyd0217_p15, gxyd0217_p16, gxyd0217_p17, gxyd0217_p18

1

10 SITE SELECTION CRITERIA FOR ATORVASTATIN , PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: John Rogers Address: Albany Medical College NY 12208 Phone: or 262 5031 Fax: Study Coordinator(s): Yes Practice Specialty: Gastrcenterology ( Lipid specialist) Study experience: Extensive (PI $ CARE study) PD studies: NO Number of active studies: 1 Any competing studies: Pt. Population: # of patients in practice 3000 plus VA pt. base most common treatment # of newly diagnosed method of recruitment Patient base plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? } Locked cabinets is the drug storage locked? (Y/N) Y central lab experience?(who) IRB requirements, can a national IRB be used? Local IRB meeting schedule who approves study budgets? Investigator Dr Rogers is head of Lipid Clinice and has a Comments: VA population - Very influented to bischell h Allany area Large Dyslipidemic population draws from CBU Associate Director: Phone: minarities dabities 11 women SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Marc Weinberg Address: 1076 North Main Street Previdence RI 02904 Phone: (401) 861-7711 Fax: (401) 421 - 5710 Study Coordinator(s): Renee Haneich Practice Specialty: Hypertension and Nephrology Study experience: Extensive - Dr. Weusburg has 3 full-ture Research assistants PD studies: ( Has propoled a small Accupal study Number of active studies: Any competing studies: 7 Yes (Merck already enolled) Pt. Population: # of patients in practice 20,000 toral - Many disslepidence most common treatment and diabetics # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are records stored? where are study drugs stored? study I calcuts locked is the drug storage locked? (Y/N) Yes central lab experience?(who) Various includers Smuhkline IRB requirements, can a national IRB be used? Several Central IRBS Local IRB meeting schedule 2 weet IRB turnaund who approves study budgets? Renee Haneich /Dr. Weinburg Comments: Dr. Wenburg is Very influential S Rhode Island and 'statens': Can call on significant diabetic & meventy population sallending aleas , Has extensive experence with CBU Associate Director: Phone: women dubbtics p minnities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Rhode Island Hospital Doctor's Name: Dr. David Brill as a member of Carchology Foundation Address: 845 North Main Street Providence RI 02904 Phone: (401) 751- 0023 Fax: Study Coordinator(s): Yes ( 4 full-tune nuses when group) Practice Specialty: Cardiology Study experience: Extensive but varies among different members of the group PD studies: 0 Number of active studies: 0 Any competing studies: Pt. Population # of patients in practice 15,000 most common treatment # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? Locked where study drugs stored? 5 Cabinits are is the drug storage locked? (Y/N) Y central lab experience?(who) Rhode Kland hobital or others IRB requirements, can a national IRB be used? National IRB Local IRB meeting schedule who approves study budgets? This group incorporates up to 17 Caddroggsists and (Nerns Comments: They are 4 the process of setting up a Lepid clinic including the cardiologists at RI hospital. and are extremely important for business & this area. CBU Associate Director: Phone: Source: https:llwwwindustrydocuments.ucsf.edu/docs/gxyd021 women derbitics 13 SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Robert Weiss Address: Two Great Falls Plaza Auburn , ME 04210 Phone: (207) 782 4022 Fax: (207) 784 3537 Study Coordinator(s): Carole Ridley Practice Specialty: cardiology ( lip.d specialit) Study experience: Extensive ( Currently doing ALLHAT) Employs 2 full ture end 1 parF-time research associate PD studies: 0 Number of active studies: 6-8 Any competing studies: ALLHAT , (ecently line a small flurastatin study Pt. Population: # of patients in practice 250 1 month large % we dyslipidemic (95%) most common treatment # of newly diagnosed method of recruitment Patient bare plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 Locked cabnet in where are study drugs sto: ??? J Locked office is the drug storage locked? (Y/N) Y central lab experience?(whc CORVING BIORAN IRB requirements, can a national IRB be used? Local but could one nationa Local IRB meeting schedule Monthly who approves study budgets? Dr. Welss Comments: Dr. Wess is extremely influential in Hus alea CBU Associate Director: Phone: Source: https:l/www.industrydocuments.ucsf.edu/docs/gxyd0217 women diabetics 14 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Francine Welty, MD Address: One Autumn st Boston mA 02215 Phone: (617) 632 - 7659 Fax: (617) 632 - 7675 Study Coordinator(s): for No Practice Specialty: Lipids Study experience: extensive PD studies: yes Number of active studies: 2 Any competing studies: 0 Lipid Population: # of patients in practice 1000-1500 most common treatment dutlexer. LOPID, 3 HMGS # of newly diagnosed 10 /month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study records stored? locked cabinet where are study drugs stored? J is the drug storage locked? (Y/N) central lab experience?(who) Smithklene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? business mgr Comments: CBU Associate Director: Phone: Source: women deabities 15 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Sudhir Bansal , MD Address: 215 Tolgate Rd Warwer RI 02886 Phone: (401) 732 - 6828 (401) 732 - 0880 Fax: Study Coordinator(s): yes Practice Specialty: Endocrenalogy /Internal Medicine Study experience: yes PD studies: No Number of active studies: / Any competing studies: D Lipid Population: # of patients in practice 1,000-1500 most common treatment HINGS # of newly diagnosed 15/mmth method of recruitment pt bise could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are where are study drugs stored? study records stored? Zlocked benes is the drug storage locked? (Y/N) Y central lab experience?(who) SmithKline IRB requirements, can a national IRB be used? y Local IRB meeting schedule who approves study budgets? Bransal Comments: CBU Associate Director: Phone: diabetics. minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE 17 IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Richard De Amices, MD Address: 4 Courthase lane Chelmsford MA 01824 Phone: (508) 459 - 8400 Fax: (508) 459 - 2340 Study Coordinator(s): yes Practice Specialty: Im Study experience: yes PD studies: yes Number of active studies: / Any competing studies: Q Lipid Population: # of patients in practice DIEED 1,000-1500 most common treatment MMGs # of newly diagnosed 15/month method of recruitment St phase could site ID 20-30 Site specifics: where where are study drugs stored? are study records stored? pts 3 locked alchet y in 6 months? (Y/N) is the drug storage locked? (Y/N) y central lab experience?( (who) Smithklene IRB requirements, can a national IRB be used? yes Local IRB meeting schedule who approves study budgets? himself Comments: CBU Associate Director: Phone: Source: women diabetics minorities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE 18 INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Peter Ganz Address: Brigham and Women's Hospital 225 Longwood Ave Boston MA 02115 Phone: (617) 732 1133 Fax: Study Coordinator(s): Peter Store MD , Dancelle Delagrange Practice Specialty: Cardialogist Study experience: Extensive PD studies: Just approved for atervastatin in $15 unstable argus stud Number of active studies: Any competing studies: Pt. Population: # of patients in practice 4,000/gr. in Cath lab - Also Clinic most common treatment # of newly diagnosed method of recruitment P1- base and extensive referaTs could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 where are study drugs stored? technical cabunes is the drug storage locked? (Y/N) Jy central lab experience?(who) Brigham's lab IRB réquirements, can a national IRB be used? Brupan's IRB Local IRB meeting schedule ever, Minth who approves study budgets? Dr. Ganz Comments: Just approved for Ann Actor unstable argan study Therefore not as big a priority CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxyd0217 diabetics women minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS 10 THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Paul Loch, MD Address: 26QQueen3 Street Worcester MA 01604 Phone: (28) 755 - 0201 Fax: Study Coordinator(s): Elizabeth Mahi (508)755-0201 Practice Specialty: IM (subspecially -Diabetes) Study experience: phase, 11 IV PD studies: 0 Number of active studies: 6 Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment HMGs, diet, LOPID # of newly diagnosed 5/uk method of recruitment pt base could site ID 20-30 pts in 6 Site specifics: where are study records stored? N where are study drugs stored? J is the drug storage locked? (Y/N) varies depending M tral Y central lab experience?(who) IRB requirements, can a national IRB be used? yes Local IRB meeting schedule once/month who approves study budgets? Dr lock Comments: Dr lock conducts research Through The Clinical pharmacology study group CBU Associate Director: Phone:

who approves study budget?

gxyd0217

gxyd0217_p10, gxyd0217_p11, gxyd0217_p12, gxyd0217_p13, gxyd0217_p14, gxyd0217_p15, gxyd0217_p16, gxyd0217_p17, gxyd0217_p18

himself, Himself

10 SITE SELECTION CRITERIA FOR ATORVASTATIN , PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: John Rogers Address: Albany Medical College NY 12208 Phone: or 262 5031 Fax: Study Coordinator(s): Yes Practice Specialty: Gastrcenterology ( Lipid specialist) Study experience: Extensive (PI $ CARE study) PD studies: NO Number of active studies: 1 Any competing studies: Pt. Population: # of patients in practice 3000 plus VA pt. base most common treatment # of newly diagnosed method of recruitment Patient base plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? } Locked cabinets is the drug storage locked? (Y/N) Y central lab experience?(who) IRB requirements, can a national IRB be used? Local IRB meeting schedule who approves study budgets? Investigator Dr Rogers is head of Lipid Clinice and has a Comments: VA population - Very influented to bischell h Allany area Large Dyslipidemic population draws from CBU Associate Director: Phone: minarities dabities 11 women SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Marc Weinberg Address: 1076 North Main Street Previdence RI 02904 Phone: (401) 861-7711 Fax: (401) 421 - 5710 Study Coordinator(s): Renee Haneich Practice Specialty: Hypertension and Nephrology Study experience: Extensive - Dr. Weusburg has 3 full-ture Research assistants PD studies: ( Has propoled a small Accupal study Number of active studies: Any competing studies: 7 Yes (Merck already enolled) Pt. Population: # of patients in practice 20,000 toral - Many disslepidence most common treatment and diabetics # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are records stored? where are study drugs stored? study I calcuts locked is the drug storage locked? (Y/N) Yes central lab experience?(who) Various includers Smuhkline IRB requirements, can a national IRB be used? Several Central IRBS Local IRB meeting schedule 2 weet IRB turnaund who approves study budgets? Renee Haneich /Dr. Weinburg Comments: Dr. Wenburg is Very influential S Rhode Island and 'statens': Can call on significant diabetic & meventy population sallending aleas , Has extensive experence with CBU Associate Director: Phone: women dubbtics p minnities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Rhode Island Hospital Doctor's Name: Dr. David Brill as a member of Carchology Foundation Address: 845 North Main Street Providence RI 02904 Phone: (401) 751- 0023 Fax: Study Coordinator(s): Yes ( 4 full-tune nuses when group) Practice Specialty: Cardiology Study experience: Extensive but varies among different members of the group PD studies: 0 Number of active studies: 0 Any competing studies: Pt. Population # of patients in practice 15,000 most common treatment # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? Locked where study drugs stored? 5 Cabinits are is the drug storage locked? (Y/N) Y central lab experience?(who) Rhode Kland hobital or others IRB requirements, can a national IRB be used? National IRB Local IRB meeting schedule who approves study budgets? This group incorporates up to 17 Caddroggsists and (Nerns Comments: They are 4 the process of setting up a Lepid clinic including the cardiologists at RI hospital. and are extremely important for business & this area. CBU Associate Director: Phone: Source: https:llwwwindustrydocuments.ucsf.edu/docs/gxyd021 women derbitics 13 SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Robert Weiss Address: Two Great Falls Plaza Auburn , ME 04210 Phone: (207) 782 4022 Fax: (207) 784 3537 Study Coordinator(s): Carole Ridley Practice Specialty: cardiology ( lip.d specialit) Study experience: Extensive ( Currently doing ALLHAT) Employs 2 full ture end 1 parF-time research associate PD studies: 0 Number of active studies: 6-8 Any competing studies: ALLHAT , (ecently line a small flurastatin study Pt. Population: # of patients in practice 250 1 month large % we dyslipidemic (95%) most common treatment # of newly diagnosed method of recruitment Patient bare plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 Locked cabnet in where are study drugs sto: ??? J Locked office is the drug storage locked? (Y/N) Y central lab experience?(whc CORVING BIORAN IRB requirements, can a national IRB be used? Local but could one nationa Local IRB meeting schedule Monthly who approves study budgets? Dr. Welss Comments: Dr. Wess is extremely influential in Hus alea CBU Associate Director: Phone: Source: https:l/www.industrydocuments.ucsf.edu/docs/gxyd0217 women diabetics 14 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Francine Welty, MD Address: One Autumn st Boston mA 02215 Phone: (617) 632 - 7659 Fax: (617) 632 - 7675 Study Coordinator(s): for No Practice Specialty: Lipids Study experience: extensive PD studies: yes Number of active studies: 2 Any competing studies: 0 Lipid Population: # of patients in practice 1000-1500 most common treatment dutlexer. LOPID, 3 HMGS # of newly diagnosed 10 /month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study records stored? locked cabinet where are study drugs stored? J is the drug storage locked? (Y/N) central lab experience?(who) Smithklene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? business mgr Comments: CBU Associate Director: Phone: Source: women deabities 15 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Sudhir Bansal , MD Address: 215 Tolgate Rd Warwer RI 02886 Phone: (401) 732 - 6828 (401) 732 - 0880 Fax: Study Coordinator(s): yes Practice Specialty: Endocrenalogy /Internal Medicine Study experience: yes PD studies: No Number of active studies: / Any competing studies: D Lipid Population: # of patients in practice 1,000-1500 most common treatment HINGS # of newly diagnosed 15/mmth method of recruitment pt bise could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are where are study drugs stored? study records stored? Zlocked benes is the drug storage locked? (Y/N) Y central lab experience?(who) SmithKline IRB requirements, can a national IRB be used? y Local IRB meeting schedule who approves study budgets? Bransal Comments: CBU Associate Director: Phone: diabetics. minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE 17 IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Richard De Amices, MD Address: 4 Courthase lane Chelmsford MA 01824 Phone: (508) 459 - 8400 Fax: (508) 459 - 2340 Study Coordinator(s): yes Practice Specialty: Im Study experience: yes PD studies: yes Number of active studies: / Any competing studies: Q Lipid Population: # of patients in practice DIEED 1,000-1500 most common treatment MMGs # of newly diagnosed 15/month method of recruitment St phase could site ID 20-30 Site specifics: where where are study drugs stored? are study records stored? pts 3 locked alchet y in 6 months? (Y/N) is the drug storage locked? (Y/N) y central lab experience?( (who) Smithklene IRB requirements, can a national IRB be used? yes Local IRB meeting schedule who approves study budgets? himself Comments: CBU Associate Director: Phone: Source: women diabetics minorities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE 18 INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Peter Ganz Address: Brigham and Women's Hospital 225 Longwood Ave Boston MA 02115 Phone: (617) 732 1133 Fax: Study Coordinator(s): Peter Store MD , Dancelle Delagrange Practice Specialty: Cardialogist Study experience: Extensive PD studies: Just approved for atervastatin in $15 unstable argus stud Number of active studies: Any competing studies: Pt. Population: # of patients in practice 4,000/gr. in Cath lab - Also Clinic most common treatment # of newly diagnosed method of recruitment P1- base and extensive referaTs could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 where are study drugs stored? technical cabunes is the drug storage locked? (Y/N) Jy central lab experience?(who) Brigham's lab IRB réquirements, can a national IRB be used? Brupan's IRB Local IRB meeting schedule ever, Minth who approves study budgets? Dr. Ganz Comments: Just approved for Ann Actor unstable argan study Therefore not as big a priority CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxyd0217 diabetics women minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS 10 THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Paul Loch, MD Address: 26QQueen3 Street Worcester MA 01604 Phone: (28) 755 - 0201 Fax: Study Coordinator(s): Elizabeth Mahi (508)755-0201 Practice Specialty: IM (subspecially -Diabetes) Study experience: phase, 11 IV PD studies: 0 Number of active studies: 6 Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment HMGs, diet, LOPID # of newly diagnosed 5/uk method of recruitment pt base could site ID 20-30 pts in 6 Site specifics: where are study records stored? N where are study drugs stored? J is the drug storage locked? (Y/N) varies depending M tral Y central lab experience?(who) IRB requirements, can a national IRB be used? yes Local IRB meeting schedule once/month who approves study budgets? Dr lock Comments: Dr lock conducts research Through The Clinical pharmacology study group CBU Associate Director: Phone:

where are study records and study drugs stored?

gxyd0217

gxyd0217_p10, gxyd0217_p11, gxyd0217_p12, gxyd0217_p13, gxyd0217_p14, gxyd0217_p15, gxyd0217_p16, gxyd0217_p17, gxyd0217_p18

locked cabinet

10 SITE SELECTION CRITERIA FOR ATORVASTATIN , PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: John Rogers Address: Albany Medical College NY 12208 Phone: or 262 5031 Fax: Study Coordinator(s): Yes Practice Specialty: Gastrcenterology ( Lipid specialist) Study experience: Extensive (PI $ CARE study) PD studies: NO Number of active studies: 1 Any competing studies: Pt. Population: # of patients in practice 3000 plus VA pt. base most common treatment # of newly diagnosed method of recruitment Patient base plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? } Locked cabinets is the drug storage locked? (Y/N) Y central lab experience?(who) IRB requirements, can a national IRB be used? Local IRB meeting schedule who approves study budgets? Investigator Dr Rogers is head of Lipid Clinice and has a Comments: VA population - Very influented to bischell h Allany area Large Dyslipidemic population draws from CBU Associate Director: Phone: minarities dabities 11 women SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Marc Weinberg Address: 1076 North Main Street Previdence RI 02904 Phone: (401) 861-7711 Fax: (401) 421 - 5710 Study Coordinator(s): Renee Haneich Practice Specialty: Hypertension and Nephrology Study experience: Extensive - Dr. Weusburg has 3 full-ture Research assistants PD studies: ( Has propoled a small Accupal study Number of active studies: Any competing studies: 7 Yes (Merck already enolled) Pt. Population: # of patients in practice 20,000 toral - Many disslepidence most common treatment and diabetics # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are records stored? where are study drugs stored? study I calcuts locked is the drug storage locked? (Y/N) Yes central lab experience?(who) Various includers Smuhkline IRB requirements, can a national IRB be used? Several Central IRBS Local IRB meeting schedule 2 weet IRB turnaund who approves study budgets? Renee Haneich /Dr. Weinburg Comments: Dr. Wenburg is Very influential S Rhode Island and 'statens': Can call on significant diabetic & meventy population sallending aleas , Has extensive experence with CBU Associate Director: Phone: women dubbtics p minnities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Rhode Island Hospital Doctor's Name: Dr. David Brill as a member of Carchology Foundation Address: 845 North Main Street Providence RI 02904 Phone: (401) 751- 0023 Fax: Study Coordinator(s): Yes ( 4 full-tune nuses when group) Practice Specialty: Cardiology Study experience: Extensive but varies among different members of the group PD studies: 0 Number of active studies: 0 Any competing studies: Pt. Population # of patients in practice 15,000 most common treatment # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? Locked where study drugs stored? 5 Cabinits are is the drug storage locked? (Y/N) Y central lab experience?(who) Rhode Kland hobital or others IRB requirements, can a national IRB be used? National IRB Local IRB meeting schedule who approves study budgets? This group incorporates up to 17 Caddroggsists and (Nerns Comments: They are 4 the process of setting up a Lepid clinic including the cardiologists at RI hospital. and are extremely important for business & this area. CBU Associate Director: Phone: Source: https:llwwwindustrydocuments.ucsf.edu/docs/gxyd021 women derbitics 13 SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Robert Weiss Address: Two Great Falls Plaza Auburn , ME 04210 Phone: (207) 782 4022 Fax: (207) 784 3537 Study Coordinator(s): Carole Ridley Practice Specialty: cardiology ( lip.d specialit) Study experience: Extensive ( Currently doing ALLHAT) Employs 2 full ture end 1 parF-time research associate PD studies: 0 Number of active studies: 6-8 Any competing studies: ALLHAT , (ecently line a small flurastatin study Pt. Population: # of patients in practice 250 1 month large % we dyslipidemic (95%) most common treatment # of newly diagnosed method of recruitment Patient bare plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 Locked cabnet in where are study drugs sto: ??? J Locked office is the drug storage locked? (Y/N) Y central lab experience?(whc CORVING BIORAN IRB requirements, can a national IRB be used? Local but could one nationa Local IRB meeting schedule Monthly who approves study budgets? Dr. Welss Comments: Dr. Wess is extremely influential in Hus alea CBU Associate Director: Phone: Source: https:l/www.industrydocuments.ucsf.edu/docs/gxyd0217 women diabetics 14 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Francine Welty, MD Address: One Autumn st Boston mA 02215 Phone: (617) 632 - 7659 Fax: (617) 632 - 7675 Study Coordinator(s): for No Practice Specialty: Lipids Study experience: extensive PD studies: yes Number of active studies: 2 Any competing studies: 0 Lipid Population: # of patients in practice 1000-1500 most common treatment dutlexer. LOPID, 3 HMGS # of newly diagnosed 10 /month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study records stored? locked cabinet where are study drugs stored? J is the drug storage locked? (Y/N) central lab experience?(who) Smithklene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? business mgr Comments: CBU Associate Director: Phone: Source: women deabities 15 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Sudhir Bansal , MD Address: 215 Tolgate Rd Warwer RI 02886 Phone: (401) 732 - 6828 (401) 732 - 0880 Fax: Study Coordinator(s): yes Practice Specialty: Endocrenalogy /Internal Medicine Study experience: yes PD studies: No Number of active studies: / Any competing studies: D Lipid Population: # of patients in practice 1,000-1500 most common treatment HINGS # of newly diagnosed 15/mmth method of recruitment pt bise could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are where are study drugs stored? study records stored? Zlocked benes is the drug storage locked? (Y/N) Y central lab experience?(who) SmithKline IRB requirements, can a national IRB be used? y Local IRB meeting schedule who approves study budgets? Bransal Comments: CBU Associate Director: Phone: diabetics. minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE 17 IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Richard De Amices, MD Address: 4 Courthase lane Chelmsford MA 01824 Phone: (508) 459 - 8400 Fax: (508) 459 - 2340 Study Coordinator(s): yes Practice Specialty: Im Study experience: yes PD studies: yes Number of active studies: / Any competing studies: Q Lipid Population: # of patients in practice DIEED 1,000-1500 most common treatment MMGs # of newly diagnosed 15/month method of recruitment St phase could site ID 20-30 Site specifics: where where are study drugs stored? are study records stored? pts 3 locked alchet y in 6 months? (Y/N) is the drug storage locked? (Y/N) y central lab experience?( (who) Smithklene IRB requirements, can a national IRB be used? yes Local IRB meeting schedule who approves study budgets? himself Comments: CBU Associate Director: Phone: Source: women diabetics minorities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE 18 INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Peter Ganz Address: Brigham and Women's Hospital 225 Longwood Ave Boston MA 02115 Phone: (617) 732 1133 Fax: Study Coordinator(s): Peter Store MD , Dancelle Delagrange Practice Specialty: Cardialogist Study experience: Extensive PD studies: Just approved for atervastatin in $15 unstable argus stud Number of active studies: Any competing studies: Pt. Population: # of patients in practice 4,000/gr. in Cath lab - Also Clinic most common treatment # of newly diagnosed method of recruitment P1- base and extensive referaTs could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 where are study drugs stored? technical cabunes is the drug storage locked? (Y/N) Jy central lab experience?(who) Brigham's lab IRB réquirements, can a national IRB be used? Brupan's IRB Local IRB meeting schedule ever, Minth who approves study budgets? Dr. Ganz Comments: Just approved for Ann Actor unstable argan study Therefore not as big a priority CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxyd0217 diabetics women minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS 10 THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Paul Loch, MD Address: 26QQueen3 Street Worcester MA 01604 Phone: (28) 755 - 0201 Fax: Study Coordinator(s): Elizabeth Mahi (508)755-0201 Practice Specialty: IM (subspecially -Diabetes) Study experience: phase, 11 IV PD studies: 0 Number of active studies: 6 Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment HMGs, diet, LOPID # of newly diagnosed 5/uk method of recruitment pt base could site ID 20-30 pts in 6 Site specifics: where are study records stored? N where are study drugs stored? J is the drug storage locked? (Y/N) varies depending M tral Y central lab experience?(who) IRB requirements, can a national IRB be used? yes Local IRB meeting schedule once/month who approves study budgets? Dr lock Comments: Dr lock conducts research Through The Clinical pharmacology study group CBU Associate Director: Phone:

what is the number of newly diagonised?

gxyd0217

gxyd0217_p10, gxyd0217_p11, gxyd0217_p12, gxyd0217_p13, gxyd0217_p14, gxyd0217_p15, gxyd0217_p16, gxyd0217_p17, gxyd0217_p18

15/month

10 SITE SELECTION CRITERIA FOR ATORVASTATIN , PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: John Rogers Address: Albany Medical College NY 12208 Phone: or 262 5031 Fax: Study Coordinator(s): Yes Practice Specialty: Gastrcenterology ( Lipid specialist) Study experience: Extensive (PI $ CARE study) PD studies: NO Number of active studies: 1 Any competing studies: Pt. Population: # of patients in practice 3000 plus VA pt. base most common treatment # of newly diagnosed method of recruitment Patient base plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? } Locked cabinets is the drug storage locked? (Y/N) Y central lab experience?(who) IRB requirements, can a national IRB be used? Local IRB meeting schedule who approves study budgets? Investigator Dr Rogers is head of Lipid Clinice and has a Comments: VA population - Very influented to bischell h Allany area Large Dyslipidemic population draws from CBU Associate Director: Phone: minarities dabities 11 women SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Marc Weinberg Address: 1076 North Main Street Previdence RI 02904 Phone: (401) 861-7711 Fax: (401) 421 - 5710 Study Coordinator(s): Renee Haneich Practice Specialty: Hypertension and Nephrology Study experience: Extensive - Dr. Weusburg has 3 full-ture Research assistants PD studies: ( Has propoled a small Accupal study Number of active studies: Any competing studies: 7 Yes (Merck already enolled) Pt. Population: # of patients in practice 20,000 toral - Many disslepidence most common treatment and diabetics # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are records stored? where are study drugs stored? study I calcuts locked is the drug storage locked? (Y/N) Yes central lab experience?(who) Various includers Smuhkline IRB requirements, can a national IRB be used? Several Central IRBS Local IRB meeting schedule 2 weet IRB turnaund who approves study budgets? Renee Haneich /Dr. Weinburg Comments: Dr. Wenburg is Very influential S Rhode Island and 'statens': Can call on significant diabetic & meventy population sallending aleas , Has extensive experence with CBU Associate Director: Phone: women dubbtics p minnities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Rhode Island Hospital Doctor's Name: Dr. David Brill as a member of Carchology Foundation Address: 845 North Main Street Providence RI 02904 Phone: (401) 751- 0023 Fax: Study Coordinator(s): Yes ( 4 full-tune nuses when group) Practice Specialty: Cardiology Study experience: Extensive but varies among different members of the group PD studies: 0 Number of active studies: 0 Any competing studies: Pt. Population # of patients in practice 15,000 most common treatment # of newly diagnosed method of recruitment Pt. base could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? Locked where study drugs stored? 5 Cabinits are is the drug storage locked? (Y/N) Y central lab experience?(who) Rhode Kland hobital or others IRB requirements, can a national IRB be used? National IRB Local IRB meeting schedule who approves study budgets? This group incorporates up to 17 Caddroggsists and (Nerns Comments: They are 4 the process of setting up a Lepid clinic including the cardiologists at RI hospital. and are extremely important for business & this area. CBU Associate Director: Phone: Source: https:llwwwindustrydocuments.ucsf.edu/docs/gxyd021 women derbitics 13 SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Robert Weiss Address: Two Great Falls Plaza Auburn , ME 04210 Phone: (207) 782 4022 Fax: (207) 784 3537 Study Coordinator(s): Carole Ridley Practice Specialty: cardiology ( lip.d specialit) Study experience: Extensive ( Currently doing ALLHAT) Employs 2 full ture end 1 parF-time research associate PD studies: 0 Number of active studies: 6-8 Any competing studies: ALLHAT , (ecently line a small flurastatin study Pt. Population: # of patients in practice 250 1 month large % we dyslipidemic (95%) most common treatment # of newly diagnosed method of recruitment Patient bare plus referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 Locked cabnet in where are study drugs sto: ??? J Locked office is the drug storage locked? (Y/N) Y central lab experience?(whc CORVING BIORAN IRB requirements, can a national IRB be used? Local but could one nationa Local IRB meeting schedule Monthly who approves study budgets? Dr. Welss Comments: Dr. Wess is extremely influential in Hus alea CBU Associate Director: Phone: Source: https:l/www.industrydocuments.ucsf.edu/docs/gxyd0217 women diabetics 14 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Francine Welty, MD Address: One Autumn st Boston mA 02215 Phone: (617) 632 - 7659 Fax: (617) 632 - 7675 Study Coordinator(s): for No Practice Specialty: Lipids Study experience: extensive PD studies: yes Number of active studies: 2 Any competing studies: 0 Lipid Population: # of patients in practice 1000-1500 most common treatment dutlexer. LOPID, 3 HMGS # of newly diagnosed 10 /month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study records stored? locked cabinet where are study drugs stored? J is the drug storage locked? (Y/N) central lab experience?(who) Smithklene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? business mgr Comments: CBU Associate Director: Phone: Source: women deabities 15 SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Sudhir Bansal , MD Address: 215 Tolgate Rd Warwer RI 02886 Phone: (401) 732 - 6828 (401) 732 - 0880 Fax: Study Coordinator(s): yes Practice Specialty: Endocrenalogy /Internal Medicine Study experience: yes PD studies: No Number of active studies: / Any competing studies: D Lipid Population: # of patients in practice 1,000-1500 most common treatment HINGS # of newly diagnosed 15/mmth method of recruitment pt bise could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are where are study drugs stored? study records stored? Zlocked benes is the drug storage locked? (Y/N) Y central lab experience?(who) SmithKline IRB requirements, can a national IRB be used? y Local IRB meeting schedule who approves study budgets? Bransal Comments: CBU Associate Director: Phone: diabetics. minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE 17 IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Richard De Amices, MD Address: 4 Courthase lane Chelmsford MA 01824 Phone: (508) 459 - 8400 Fax: (508) 459 - 2340 Study Coordinator(s): yes Practice Specialty: Im Study experience: yes PD studies: yes Number of active studies: / Any competing studies: Q Lipid Population: # of patients in practice DIEED 1,000-1500 most common treatment MMGs # of newly diagnosed 15/month method of recruitment St phase could site ID 20-30 Site specifics: where where are study drugs stored? are study records stored? pts 3 locked alchet y in 6 months? (Y/N) is the drug storage locked? (Y/N) y central lab experience?( (who) Smithklene IRB requirements, can a national IRB be used? yes Local IRB meeting schedule who approves study budgets? himself Comments: CBU Associate Director: Phone: Source: women diabetics minorities SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE 18 INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Peter Ganz Address: Brigham and Women's Hospital 225 Longwood Ave Boston MA 02115 Phone: (617) 732 1133 Fax: Study Coordinator(s): Peter Store MD , Dancelle Delagrange Practice Specialty: Cardialogist Study experience: Extensive PD studies: Just approved for atervastatin in $15 unstable argus stud Number of active studies: Any competing studies: Pt. Population: # of patients in practice 4,000/gr. in Cath lab - Also Clinic most common treatment # of newly diagnosed method of recruitment P1- base and extensive referaTs could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 where are study drugs stored? technical cabunes is the drug storage locked? (Y/N) Jy central lab experience?(who) Brigham's lab IRB réquirements, can a national IRB be used? Brupan's IRB Local IRB meeting schedule ever, Minth who approves study budgets? Dr. Ganz Comments: Just approved for Ann Actor unstable argan study Therefore not as big a priority CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxyd0217 diabetics women minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS 10 THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Paul Loch, MD Address: 26QQueen3 Street Worcester MA 01604 Phone: (28) 755 - 0201 Fax: Study Coordinator(s): Elizabeth Mahi (508)755-0201 Practice Specialty: IM (subspecially -Diabetes) Study experience: phase, 11 IV PD studies: 0 Number of active studies: 6 Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment HMGs, diet, LOPID # of newly diagnosed 5/uk method of recruitment pt base could site ID 20-30 pts in 6 Site specifics: where are study records stored? N where are study drugs stored? J is the drug storage locked? (Y/N) varies depending M tral Y central lab experience?(who) IRB requirements, can a national IRB be used? yes Local IRB meeting schedule once/month who approves study budgets? Dr lock Comments: Dr lock conducts research Through The Clinical pharmacology study group CBU Associate Director: Phone:

what is the practice speciality?

gxyd0217

gxyd0217_p2, gxyd0217_p3, gxyd0217_p4, gxyd0217_p5, gxyd0217_p6

lipids, Lipids

women minorities 2 diabitics SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Gay Balady, MD Address: 88 E. Neuton St boston MA 02118 Phone: (617) 638-7490 Ear (617) 438 - 8968 Study Coordinator(s): yes Practice Specialty: Lipids Study experience: yes PD studies: D Number of active studies: Any competing studies: Lipid Population: # of patients in practice 3000-4000 most common treatment HMGs , Uut # of newly diagnosed 10/month method of recruitment could site ID 20-30 pt bast pts in 6 months? (Y/N) y Site specifics: where are study where are study drugs records stored? stored? 3 locked cabinet is the drug storage locked? (Y/N) central lab experience?(who) IRB requirements, can a national IRB be used? NO Local IRB meeting schedule once/month who approves study budgets? Dr. Beandy & business mgr Comments: - large minouty population CBU Associate Director: Phone: women minorities MASS. GENERAL 3 disbitics SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Richard Pasternack Address: Massachusetts General Hospital 55 Fruit Street Boston MA 02114 Phone: (617) 726 3784 Fax: (017) 724 0371 Study Coordinator(s): Theresa Bishop Practice Specialty: Cardiology (speciality in freventative Cardiology) Study experience: Extensive ( good experience wuh HMG's ) PD studies: Number of active studies: 5 Any competing studies: Pt. Population: # of patients in practice 1,000 hypercholesteralemus most common treatment # of newly diagnosed method of recruitment Cardiac Unit (his private practice 1 advestucing lig could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 locked where are study drugs stored? J cabsigt is the drug storage locked? (Y/N) central lab experience?(who Use various IRB requirements, can a national IRB be used? Mass General IRB Local IRB meeting schedule Twice Monty who approves study budgets? Dr - Pasternah . Comments: CBU Associate Director: Phone: derbetics women 4 Joslen Clinic SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: On Ganda, MD - Director of Lipid Cline Address: One Joslen Pl. Boston MA 02215 Phone: (617)732-2537 Fax: (417) 732 - 2659 Study Coordinator(s) yes-several@CRC Practice Specialty: Endocrinalogy -Lipids Study experience: Extenser PD studies: - National speaker on PD's Lipid Speakers' Burea Number of active studies: Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment Lopid - MMGS # of newly diagnosed 5/month method of recruitment could site ID 20-30 pt. base pts in 6 months? (Y/N) Y Site specifics: where are study records stored? where are study drugs stored? 3 locked cabinet is the drug storage locked? (Y/N) Y central lab experience?(who) smithrene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? Dr. Gandai businessing Comments: CBU Associate Director: Phone: duabetics women 5 minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Address: Mary M Gowan, MD Manchester NH 03102 100 Mc Gregorst Phone: (603) 669 - 0413 Fax: (603)628-2350 Study Coordinator(s): Monique Pacheco Practice Specialty: Cardiology Study experience: extensive PD studies: 0 Number of active studies: Any competing studies: 0 3 pending Lipid Population: # of patients in practice 2,000 most common treatment HMGs # of newly diagnosed 5/month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study drugs stored? where are study records stored? Zlacksatinet is the drug storage locked? (Y/N) central lab experience?(who) IRB requirements, can a national IRB be used? smonkline/grier Local IRB meeting schedule who approves study budgets? f 2mos sees 40 pts/week Shirtey Shaa vp of curdenc services Comments: CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxydQ217. women PI for CARE study minorites diabitics SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Frank Sacks Address: Brigham and Women's Hospital 75 Francis St Boston MA 02115 Phone: (+17) 432 1420 Fax: Study Coordinator(s): Various the Practice Specialty: Endocrurologist Study experience: Extensive including PI n CARE PD studies: 0 Number of active studies: Any competing studies: CARE study Pt. Population: # of patients in practice 1,000 most common treatment # of newly diagnosed method of recruitment Pt. bare / referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? locked cabusets/offire is the drug storage locked? (Y/N) Y central lab experience?(who) Various IRB requirements, can a national IRB be used? Brighen IRB Local IRB meeting schedule monthly who approves study budgets? Dr. Jacks Comments: CBU Associate Director: Phone:

what is the number of newly diagonised?

gxyd0217

gxyd0217_p2, gxyd0217_p3, gxyd0217_p4, gxyd0217_p5, gxyd0217_p6

10/month

women minorities 2 diabitics SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Gay Balady, MD Address: 88 E. Neuton St boston MA 02118 Phone: (617) 638-7490 Ear (617) 438 - 8968 Study Coordinator(s): yes Practice Specialty: Lipids Study experience: yes PD studies: D Number of active studies: Any competing studies: Lipid Population: # of patients in practice 3000-4000 most common treatment HMGs , Uut # of newly diagnosed 10/month method of recruitment could site ID 20-30 pt bast pts in 6 months? (Y/N) y Site specifics: where are study where are study drugs records stored? stored? 3 locked cabinet is the drug storage locked? (Y/N) central lab experience?(who) IRB requirements, can a national IRB be used? NO Local IRB meeting schedule once/month who approves study budgets? Dr. Beandy & business mgr Comments: - large minouty population CBU Associate Director: Phone: women minorities MASS. GENERAL 3 disbitics SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Richard Pasternack Address: Massachusetts General Hospital 55 Fruit Street Boston MA 02114 Phone: (617) 726 3784 Fax: (017) 724 0371 Study Coordinator(s): Theresa Bishop Practice Specialty: Cardiology (speciality in freventative Cardiology) Study experience: Extensive ( good experience wuh HMG's ) PD studies: Number of active studies: 5 Any competing studies: Pt. Population: # of patients in practice 1,000 hypercholesteralemus most common treatment # of newly diagnosed method of recruitment Cardiac Unit (his private practice 1 advestucing lig could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 locked where are study drugs stored? J cabsigt is the drug storage locked? (Y/N) central lab experience?(who Use various IRB requirements, can a national IRB be used? Mass General IRB Local IRB meeting schedule Twice Monty who approves study budgets? Dr - Pasternah . Comments: CBU Associate Director: Phone: derbetics women 4 Joslen Clinic SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: On Ganda, MD - Director of Lipid Cline Address: One Joslen Pl. Boston MA 02215 Phone: (617)732-2537 Fax: (417) 732 - 2659 Study Coordinator(s) yes-several@CRC Practice Specialty: Endocrinalogy -Lipids Study experience: Extenser PD studies: - National speaker on PD's Lipid Speakers' Burea Number of active studies: Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment Lopid - MMGS # of newly diagnosed 5/month method of recruitment could site ID 20-30 pt. base pts in 6 months? (Y/N) Y Site specifics: where are study records stored? where are study drugs stored? 3 locked cabinet is the drug storage locked? (Y/N) Y central lab experience?(who) smithrene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? Dr. Gandai businessing Comments: CBU Associate Director: Phone: duabetics women 5 minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Address: Mary M Gowan, MD Manchester NH 03102 100 Mc Gregorst Phone: (603) 669 - 0413 Fax: (603)628-2350 Study Coordinator(s): Monique Pacheco Practice Specialty: Cardiology Study experience: extensive PD studies: 0 Number of active studies: Any competing studies: 0 3 pending Lipid Population: # of patients in practice 2,000 most common treatment HMGs # of newly diagnosed 5/month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study drugs stored? where are study records stored? Zlacksatinet is the drug storage locked? (Y/N) central lab experience?(who) IRB requirements, can a national IRB be used? smonkline/grier Local IRB meeting schedule who approves study budgets? f 2mos sees 40 pts/week Shirtey Shaa vp of curdenc services Comments: CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxydQ217. women PI for CARE study minorites diabitics SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Frank Sacks Address: Brigham and Women's Hospital 75 Francis St Boston MA 02115 Phone: (+17) 432 1420 Fax: Study Coordinator(s): Various the Practice Specialty: Endocrurologist Study experience: Extensive including PI n CARE PD studies: 0 Number of active studies: Any competing studies: CARE study Pt. Population: # of patients in practice 1,000 most common treatment # of newly diagnosed method of recruitment Pt. bare / referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? locked cabusets/offire is the drug storage locked? (Y/N) Y central lab experience?(who) Various IRB requirements, can a national IRB be used? Brighen IRB Local IRB meeting schedule monthly who approves study budgets? Dr. Jacks Comments: CBU Associate Director: Phone:

where are the study records and study drugs stored?

gxyd0217

gxyd0217_p2, gxyd0217_p3, gxyd0217_p4, gxyd0217_p5, gxyd0217_p6

locked cabinet

women minorities 2 diabitics SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Gay Balady, MD Address: 88 E. Neuton St boston MA 02118 Phone: (617) 638-7490 Ear (617) 438 - 8968 Study Coordinator(s): yes Practice Specialty: Lipids Study experience: yes PD studies: D Number of active studies: Any competing studies: Lipid Population: # of patients in practice 3000-4000 most common treatment HMGs , Uut # of newly diagnosed 10/month method of recruitment could site ID 20-30 pt bast pts in 6 months? (Y/N) y Site specifics: where are study where are study drugs records stored? stored? 3 locked cabinet is the drug storage locked? (Y/N) central lab experience?(who) IRB requirements, can a national IRB be used? NO Local IRB meeting schedule once/month who approves study budgets? Dr. Beandy & business mgr Comments: - large minouty population CBU Associate Director: Phone: women minorities MASS. GENERAL 3 disbitics SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Richard Pasternack Address: Massachusetts General Hospital 55 Fruit Street Boston MA 02114 Phone: (617) 726 3784 Fax: (017) 724 0371 Study Coordinator(s): Theresa Bishop Practice Specialty: Cardiology (speciality in freventative Cardiology) Study experience: Extensive ( good experience wuh HMG's ) PD studies: Number of active studies: 5 Any competing studies: Pt. Population: # of patients in practice 1,000 hypercholesteralemus most common treatment # of newly diagnosed method of recruitment Cardiac Unit (his private practice 1 advestucing lig could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 locked where are study drugs stored? J cabsigt is the drug storage locked? (Y/N) central lab experience?(who Use various IRB requirements, can a national IRB be used? Mass General IRB Local IRB meeting schedule Twice Monty who approves study budgets? Dr - Pasternah . Comments: CBU Associate Director: Phone: derbetics women 4 Joslen Clinic SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: On Ganda, MD - Director of Lipid Cline Address: One Joslen Pl. Boston MA 02215 Phone: (617)732-2537 Fax: (417) 732 - 2659 Study Coordinator(s) yes-several@CRC Practice Specialty: Endocrinalogy -Lipids Study experience: Extenser PD studies: - National speaker on PD's Lipid Speakers' Burea Number of active studies: Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment Lopid - MMGS # of newly diagnosed 5/month method of recruitment could site ID 20-30 pt. base pts in 6 months? (Y/N) Y Site specifics: where are study records stored? where are study drugs stored? 3 locked cabinet is the drug storage locked? (Y/N) Y central lab experience?(who) smithrene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? Dr. Gandai businessing Comments: CBU Associate Director: Phone: duabetics women 5 minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Address: Mary M Gowan, MD Manchester NH 03102 100 Mc Gregorst Phone: (603) 669 - 0413 Fax: (603)628-2350 Study Coordinator(s): Monique Pacheco Practice Specialty: Cardiology Study experience: extensive PD studies: 0 Number of active studies: Any competing studies: 0 3 pending Lipid Population: # of patients in practice 2,000 most common treatment HMGs # of newly diagnosed 5/month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study drugs stored? where are study records stored? Zlacksatinet is the drug storage locked? (Y/N) central lab experience?(who) IRB requirements, can a national IRB be used? smonkline/grier Local IRB meeting schedule who approves study budgets? f 2mos sees 40 pts/week Shirtey Shaa vp of curdenc services Comments: CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxydQ217. women PI for CARE study minorites diabitics SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Frank Sacks Address: Brigham and Women's Hospital 75 Francis St Boston MA 02115 Phone: (+17) 432 1420 Fax: Study Coordinator(s): Various the Practice Specialty: Endocrurologist Study experience: Extensive including PI n CARE PD studies: 0 Number of active studies: Any competing studies: CARE study Pt. Population: # of patients in practice 1,000 most common treatment # of newly diagnosed method of recruitment Pt. bare / referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? locked cabusets/offire is the drug storage locked? (Y/N) Y central lab experience?(who) Various IRB requirements, can a national IRB be used? Brighen IRB Local IRB meeting schedule monthly who approves study budgets? Dr. Jacks Comments: CBU Associate Director: Phone:

when is the local IRB meeting scheduled?

gxyd0217

gxyd0217_p2, gxyd0217_p3, gxyd0217_p4, gxyd0217_p5, gxyd0217_p6

once/month

women minorities 2 diabitics SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Gay Balady, MD Address: 88 E. Neuton St boston MA 02118 Phone: (617) 638-7490 Ear (617) 438 - 8968 Study Coordinator(s): yes Practice Specialty: Lipids Study experience: yes PD studies: D Number of active studies: Any competing studies: Lipid Population: # of patients in practice 3000-4000 most common treatment HMGs , Uut # of newly diagnosed 10/month method of recruitment could site ID 20-30 pt bast pts in 6 months? (Y/N) y Site specifics: where are study where are study drugs records stored? stored? 3 locked cabinet is the drug storage locked? (Y/N) central lab experience?(who) IRB requirements, can a national IRB be used? NO Local IRB meeting schedule once/month who approves study budgets? Dr. Beandy & business mgr Comments: - large minouty population CBU Associate Director: Phone: women minorities MASS. GENERAL 3 disbitics SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Richard Pasternack Address: Massachusetts General Hospital 55 Fruit Street Boston MA 02114 Phone: (617) 726 3784 Fax: (017) 724 0371 Study Coordinator(s): Theresa Bishop Practice Specialty: Cardiology (speciality in freventative Cardiology) Study experience: Extensive ( good experience wuh HMG's ) PD studies: Number of active studies: 5 Any competing studies: Pt. Population: # of patients in practice 1,000 hypercholesteralemus most common treatment # of newly diagnosed method of recruitment Cardiac Unit (his private practice 1 advestucing lig could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? 2 locked where are study drugs stored? J cabsigt is the drug storage locked? (Y/N) central lab experience?(who Use various IRB requirements, can a national IRB be used? Mass General IRB Local IRB meeting schedule Twice Monty who approves study budgets? Dr - Pasternah . Comments: CBU Associate Director: Phone: derbetics women 4 Joslen Clinic SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: On Ganda, MD - Director of Lipid Cline Address: One Joslen Pl. Boston MA 02215 Phone: (617)732-2537 Fax: (417) 732 - 2659 Study Coordinator(s) yes-several@CRC Practice Specialty: Endocrinalogy -Lipids Study experience: Extenser PD studies: - National speaker on PD's Lipid Speakers' Burea Number of active studies: Any competing studies: Lipid Population: # of patients in practice 1500 most common treatment Lopid - MMGS # of newly diagnosed 5/month method of recruitment could site ID 20-30 pt. base pts in 6 months? (Y/N) Y Site specifics: where are study records stored? where are study drugs stored? 3 locked cabinet is the drug storage locked? (Y/N) Y central lab experience?(who) smithrene IRB requirements, can a national IRB be used? No Local IRB meeting schedule once/month who approves study budgets? Dr. Gandai businessing Comments: CBU Associate Director: Phone: duabetics women 5 minorities SITE SELECTION CRITERIA FOR Atorvastatin PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV TROGLITAZONE PROGRAMS. Doctor's Name: Address: Mary M Gowan, MD Manchester NH 03102 100 Mc Gregorst Phone: (603) 669 - 0413 Fax: (603)628-2350 Study Coordinator(s): Monique Pacheco Practice Specialty: Cardiology Study experience: extensive PD studies: 0 Number of active studies: Any competing studies: 0 3 pending Lipid Population: # of patients in practice 2,000 most common treatment HMGs # of newly diagnosed 5/month method of recruitment pt base could site ID 20-30 pts in 6 months? (Y/N) Y Site specifics: where are study drugs stored? where are study records stored? Zlacksatinet is the drug storage locked? (Y/N) central lab experience?(who) IRB requirements, can a national IRB be used? smonkline/grier Local IRB meeting schedule who approves study budgets? f 2mos sees 40 pts/week Shirtey Shaa vp of curdenc services Comments: CBU Associate Director: Phone: Source:https://wwwindustrydocuments.ucsf.edu/docs/gxydQ217. women PI for CARE study minorites diabitics SITE SELECTION CRITERIA FOR ATORVASTATIN PHASE IIIB/IV INVESTIGATORS THIS FORM IS TO BE COMPLETED IN ITS ENTIRITY FOR THOSE PHYSICIANS YOU WOULD LIKE TO HAVE CONSIDERED FOR THE MEDICAL RESEARCH PHASE IIIB/IV ATORVASTATIN PROGRAMS. Doctor's Name: Frank Sacks Address: Brigham and Women's Hospital 75 Francis St Boston MA 02115 Phone: (+17) 432 1420 Fax: Study Coordinator(s): Various the Practice Specialty: Endocrurologist Study experience: Extensive including PI n CARE PD studies: 0 Number of active studies: Any competing studies: CARE study Pt. Population: # of patients in practice 1,000 most common treatment # of newly diagnosed method of recruitment Pt. bare / referals could site ID 20-30 pts in 6 months? (Y/N) Yes Site specifics: where are study records stored? where are study drugs stored? locked cabusets/offire is the drug storage locked? (Y/N) Y central lab experience?(who) Various IRB requirements, can a national IRB be used? Brighen IRB Local IRB meeting schedule monthly who approves study budgets? Dr. Jacks Comments: CBU Associate Director: Phone:

Mention the "website" given for "Collegium Internationale Neuro-Psychopharmacologicum" Congress?

jnjm0223

jnjm0223_p107, jnjm0223_p108, jnjm0223_p109, jnjm0223_p110, jnjm0223_p111, jnjm0223_p112, jnjm0223_p113

www.cinp.org

Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site American Academy of Family AAFP Yes Yes Yes Family Physicians 100 North America 99 14,886 4,500 www.aafp.org Physicians. Annual Scientific Rest of World 1 Assembly. American College of Physicians- ACP-ASIM No Yes Yes Internists 95 United States 93 10,000 7,000 www.acponline.org American Society of Internal Medicine Other 5 Rest of World 7 Annual Session. International Society of Internal ICIM Yes Yes Yes Internists 95 Japan 70 7,000 5,000 www.acponline.org/isin Medicine. Biennial Congress. Other 5 North America 10 Europe 10 Rest of World 10 Primary Medicine Today East. Pri-Med East No Yes Yes Primary Care 55 United States 100 8,000 6,991 www.pri-med.com Annual Meeting. Pediatricians 9 Other 36 Primary Medicine Today MidWest. Pri-Med No Yes Yes Primary Care 61 United States 100 5,216 5,112 www.pri-med.com Annual Meeting. MidWest Pediatricians 10 Primary Care Other 29 Primary Medicine Today South. Pri-Med South No Yes Yes Primary Care 56 United States 100 5,000 4,512 www.pri-med.com Annual Meeting. Pediatricians 8 Other 36 Primary Medicine Today West. Annual Pri-Med West No Yes Yes Primary Care 65 United States 100 9,000 8,369 www.pri-med.com Meeting. Pediatricians 10 Other 25 Society of General Internal Medicine. SGIM Yes No No Primary Care N/A North America 90 1,700 1,700 www.sgim.org Annual Meeting. Rest of World 10 WONCA Asia Pacific Regional WONCA-Asia A/R A/R A/R Primary Care N/A A/R A/R 1,000 800 www.wonca.org Conference. Annual. WONCA Europe. Annual Conference. WONCA-Europe Yes Yes Yes Primary Care N/A Europe 50 3,000 3,000 ww.wonca.org Other Rest of World 50 WONCA World Congress of Family WONCA-World Yes Yes No Family Physicians 100 North America 10 5,000 4,000 www.wonca.org Doctors. Triennial. Rest of World 90 American Academy of Child and AACAP Yes No Yes Psychiatrists 90 North America 60 3,000 3,000 www.aacap.org Adolescent Psychiatry. Annual Other 10 Europe 15 Meeting. Asia 15 Other 10 American Psychiatric Association. APA Yes Yes Yes Psychrists 90 N/A N/A 19,000 19,000 www.psych.org Annual Meeting. Other 10 Psychiatry Anxiety Disorders Association of ADAA Yes Yes Yes Physicians N/A United States 100 600 600 www.adaa.org America National Conference. Annual. Medical Students N/A Association of European Psychiatrists. AEP Yes Yes Yes Researchers N/A Europe 87 2,600 2,575 www.aep.lu Biennial Congress. Other N/A North America 4 Asia 5 Rest of World 4 A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 107 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026113 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Collegium Internationale Neuro- CINP Yes Yes Yes Psychiatrists N/A North America N/A 5,000 5,000 www.cinp.org Psychopharmacologicum. Biennial Other N/A United Kingdom N/A Congress. European College of ECNP Yes Yes Yes N/A N/A N/A N/A 5,000 5,000 www.encp.nl Neuropsychopharmacology. Annual Congress. Institute on Psychiatric Services. IPS Yes Yes Yes Psychiatrists N/A North America 95 2,000 2,000 www.psych.org Annual Meeting. Psychologists N/A Rest of World 5 Other N/A International Conference on Bipolar ICBD Yes No Yes Psychiatrists N/A United States N/A 859 700 ww.wpic.pitt.edu Disorder. Biennial. Psychologists N/A Rest of World N/A Social Workers N/A Medical Students N/A International Congress of ICN A/R A/R A/R Psychiatrists N/A International N/A A/R A/R www.kenes.com Neuropsychiatry. Biennial. Psychiatry (cont.) International Forum on Mood and IFMAD Yes Yes Yes Psychiatrists 100 United States N/A 650 600 www.aisc.it Anxiety Disorders. Annual Meeting. Europe N/A Rest of World N/A New Clinical Drug Evaluation Unit. NCDEU Yes No No Government N/A N/A N/A 1,200 1,200 www.nimh.nih.gov Annual Meeting. Industry N/A Stress and Anxiety Research Society. STAR Yes No No Psychologists 100 Europe 52 200 200 www.star-society.org Annual International Conference. Asia 22 North America 11 Africa 7 Rest of World 8 US Psychiatric and Mental Health USPMHC Yes Yes Yes Psychiatrists 63 Europe N/A 3,000 3,000 www.cmeinc.com Congress. Annual. Psychologists 9 United States N/A Nurses 17 Social Workers 4 Other 7 World Congress of Psychiatry. WCP Yes Yes Yes Psychiatrists N/A N/A N/A 10,000 10,000 www.wpanet.org Triennial. Government N/A Other N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 108 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026114 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Associated Professional Sleep APSS Yes Yes Yes Researchers 33 North America 88 4,000 3,200 www.apss.org Societies. Annual Meeting. Pulmonologists 21 Rest of World 12 Neurologists 16 Psychologists 8 Neuroscientists 8 Psychiatrists 8 Other 6 Sleep European Sleep Research Society. ESRS Yes Yes Yes Physicians N/A International N/A 950 N/A www.esrs.org Biennial Congress. Neurologists N/A Biologists N/A Psychologists N/A World Conference Sleep Odyssey. WCSO Yes Yes Yes Researchers N/A Unied States N/A A/R A/R www.wfsrs.org Quadrennial. Physicians N/A Europe N/A Rest of World N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 109 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026115 DATE 29-Oct-01 REF Neurontin PSC Meeting CLIENT Pfizer MTG DATE 19-Sep-01 VENUE Pfizer PRESENT Pfizer: L Tive, E Mutisya, S Brigandi, MEDICAL ACTION S Piron, M Garcia, J Kaplan, M COMMUNICATIONS Rowbotham, L Knapp, A Fannon, A Crespo, D Probert, J Marino, C Blanckmeister, C Banta MAC: M Vinegra, S Valerio, S Steen, A Masonis, J Mierop, S Tyler COPIED TO E Shapiro, K Kennon, R Glanzman, M Ulrey, K Taylor, M Balkenhol, H Duda Racki, T Hylan, T Hsu, L Collins ACTION REPORT SUBJECT Neurontin PSC Meeting 1.0 Introduction The following action report summarizes the decisions, issues and action items discussed during the Neurontin Publications Subcommittee (PSC) meeting held on September 19. During the meeting the following topics were covered: 2002 congress presentations Issues regarding specific manuscripts Future meeting between NYHQ and Ann Arbor Key message development update Journal and congress profiling update Bibliography development update 2.0 2002 Congress Presentations Joan Kaplan (JK) initiated the discussion by informing the team that the 2001 International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP) has been cancelled. However, the 2 posters scheduled to be presented at that meeting should be included in future presentation plans. The team developed the following plan for poster presentations in 2002: 2.1 American Academy of Neurology (AAN) Dosing response/exposure response (Neuropathic Pain) QOL data from the 5 pivotal trials (Neuropathic Pain) - Steve Piron SP (SP) mentioned that Brett Stacey had expressed an interest in this the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 fizer_LKnapp_0026116 type of subanalysis. SP will contact Stacey to further explore his interest. 2.2 American Pain Society (APS) Efficacy data from the 5 pivotal trials - This poster was originally targeted for ICMTNP. Both the abstract and poster have been completed. MAC will provide reformatting and production support MAC as needed. 2.3 International Association for the Study of Pain (IASP) Practical dosing and titration POPP (tentative, pending subanalysis results) 2.4 American Academy of Family Practioners (AAFP) Screening tool - Stephen Valerio (SV) and Amy Masonis (AEM) of MAC both advised the team that this is a very difficult meeting in terms of acceptance of presentations. The academy has rigorous rules regarding both representation of data and pharmaceutical company funding of accepted presentations. 2.5 American Diabetes Association (ADA) Latin America diabetic neuropathy study Pooled results from the 2 diabetic neuropathy trials MAC will determine the abstract deadlines and meeting dates for ADA MAC and forward these to the team. 2.6 Other Possible Presentations In addition to the above; the following presentations will be added to the list for 2002, pending the following actions: Sleep study - MAC will contact Dr. Erhenberg to find out whether he has previously presented these data at a congress, and if not, MAC whether he would be interested in doing so. MAC will also solicit his preference as to which meeting he would like to present the data. HIV-neuropathy study - This poster was originally to be presented at ICMTNP. Elizabeth Mutisya (EM) will ask Prof. Rowbotham if he EM would prefer to present these data at American Academy of Neurology (AAN), American Pain Society (APS), or International Association for the Study of Pain (IASP). In addition, MAC will MAC follow-up with the International AIDS Conference (IAIDSC) regarding its rules for re-presentation. The team strongly felt that it would be advantageous to have these data presented at this meeting as well. Action Report: 19-Sep-01 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026117 Philippine post-marketing surveillance EM will review these data to determine whether there is any EM potential for presentation material. CRPS placebo cross-over Michael Rowbotham (MR) will follow-up with Prof. Hill to find out MR whether he has any presentation plans for these data. 3.0 Manuscript Issues 3.1 Latin America Diabetic Neuropathy EM informed the team that the preliminary data have just come in and further analysis needs to be done. While the manuscript is currently targeted for the JAMA special issue, the December 31 deadline may be tight. After the data have been reviewed; MAC will distribute a MAC journal query form so that a list of potential back-up journals can be developed. Leslie Tive (LT) was identified as the lead reviewer. EM, Lloyd Knapp (LK), SP, Angela Crespo (AC) and Lingshi Tan (LT) were identified as reviewers. John Marino (JM) recommended that a Brazilian and Mexican be selected as authors. LT also suggested Klaus as an author, even though he no longer is a Pfizer employee. 3.2 Treatment of Diabetic Neuropathy Review for JAMA The team agreed that Larry Blonde and Roy Freeman should co-author this paper, with Bruce Nicholson to provide the viewpoints of an endocrinologist, an anesthesiologist, and a neurologist respectively. LK will be the lead reviewer; MR and EM will also review the manuscript. MR pointed out that the focus of the review should be to convince diabetologists that the treatment of the neuropathic pain associated with diabetes should consist of more than the underlying condition; therapy should be directed toward relieving the symptom itself. 3.3 Gabapentin Review SV reminded the team that the journal Expert Opinion on Pharmacotherapy had solicited a review from Dr. Nicholson, who then asked for Pfizer's help. It was decided that since this was an industry- focused journal, this manuscript was not a priority for the team. It was MAC decided that MAC would look into using a previous review by Nicholson as the backbone for this review and would add some new data to update it. 3.4 Dosing Manuscripts SV informed the team that he had spoken with Dr. McLean, who suggested that the 2 dosing manuscripts be combined since the fundamental issue underlying the manuscripts is the same, namely, intrasubject variability. AC and the team disagreed, arguing that the the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pizer_LKnapp_0026118 clinical issues associated with the 2 conditions were quite different. SV MAC suggested that he would get back to Dr. McLean and mention that Pfizer would first like to write 2 clinically focused reviews and then follow-up with a more detailed, kinetically based review next year. The team agreed to this plan. [Post-meeting note: SV has left a message for Dr. McLean and is awaiting a response.] 3.5 POPP Study The team decided that this manuscript would be placed on hold until the subanalysis is completed. The team selected The Journal of Pain and Symptom Management as the target journal with Pain Medicine as a backup. 3.6 European Journal of Pain Supplement The team was updated regarding the status of the supplement. MAC has received reviewer comments. These will be sent to Stephen MAC Brigandi (SB) who will forward them to Embryon. [Post-meeting note: SB both of these actions have been completed.] The final version will be sent to LT for final approval next week. 4.0 Meeting with NYHQ and Ann Arbor The meeting to discuss the transfer of study data and to determine whether there are studies that have not been published has been confirmed for the afternoon of October 3. The meeting to discuss the subanalyses will be arranged independently. 5.0 Key Messages Update Most of the key message meetings have taken place, and the approved list is undergoing final revisions. Corporate messages will be reviewed by a small committee via e-mail or teleconference. The entire list will be reviewed by a single committee in order to finalize it; however, the list will be revisited in the future. 6.0 Profile and Bibliography Update MAC presented the latest journal and congress profiles and reminded the team that profiling is continuing. MAC also presented the latest screen shots from the bibliography. LT requested a special meeting to discuss the bibliography, independent of other publication issues. In addition; MAC was actioned to provide a small working model to be MAC tested at the meeting. Stephen Valerio Medical Projects Director the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026119

Mention the "Acronym" given for "Collegium Internationale Neuro-Psychopharmacologicum" Congress?

jnjm0223

jnjm0223_p107, jnjm0223_p108, jnjm0223_p109, jnjm0223_p110, jnjm0223_p111, jnjm0223_p112, jnjm0223_p113

CINP

Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site American Academy of Family AAFP Yes Yes Yes Family Physicians 100 North America 99 14,886 4,500 www.aafp.org Physicians. Annual Scientific Rest of World 1 Assembly. American College of Physicians- ACP-ASIM No Yes Yes Internists 95 United States 93 10,000 7,000 www.acponline.org American Society of Internal Medicine Other 5 Rest of World 7 Annual Session. International Society of Internal ICIM Yes Yes Yes Internists 95 Japan 70 7,000 5,000 www.acponline.org/isin Medicine. Biennial Congress. Other 5 North America 10 Europe 10 Rest of World 10 Primary Medicine Today East. Pri-Med East No Yes Yes Primary Care 55 United States 100 8,000 6,991 www.pri-med.com Annual Meeting. Pediatricians 9 Other 36 Primary Medicine Today MidWest. Pri-Med No Yes Yes Primary Care 61 United States 100 5,216 5,112 www.pri-med.com Annual Meeting. MidWest Pediatricians 10 Primary Care Other 29 Primary Medicine Today South. Pri-Med South No Yes Yes Primary Care 56 United States 100 5,000 4,512 www.pri-med.com Annual Meeting. Pediatricians 8 Other 36 Primary Medicine Today West. Annual Pri-Med West No Yes Yes Primary Care 65 United States 100 9,000 8,369 www.pri-med.com Meeting. Pediatricians 10 Other 25 Society of General Internal Medicine. SGIM Yes No No Primary Care N/A North America 90 1,700 1,700 www.sgim.org Annual Meeting. Rest of World 10 WONCA Asia Pacific Regional WONCA-Asia A/R A/R A/R Primary Care N/A A/R A/R 1,000 800 www.wonca.org Conference. Annual. WONCA Europe. Annual Conference. WONCA-Europe Yes Yes Yes Primary Care N/A Europe 50 3,000 3,000 ww.wonca.org Other Rest of World 50 WONCA World Congress of Family WONCA-World Yes Yes No Family Physicians 100 North America 10 5,000 4,000 www.wonca.org Doctors. Triennial. Rest of World 90 American Academy of Child and AACAP Yes No Yes Psychiatrists 90 North America 60 3,000 3,000 www.aacap.org Adolescent Psychiatry. Annual Other 10 Europe 15 Meeting. Asia 15 Other 10 American Psychiatric Association. APA Yes Yes Yes Psychrists 90 N/A N/A 19,000 19,000 www.psych.org Annual Meeting. Other 10 Psychiatry Anxiety Disorders Association of ADAA Yes Yes Yes Physicians N/A United States 100 600 600 www.adaa.org America National Conference. Annual. Medical Students N/A Association of European Psychiatrists. AEP Yes Yes Yes Researchers N/A Europe 87 2,600 2,575 www.aep.lu Biennial Congress. Other N/A North America 4 Asia 5 Rest of World 4 A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 107 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026113 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Collegium Internationale Neuro- CINP Yes Yes Yes Psychiatrists N/A North America N/A 5,000 5,000 www.cinp.org Psychopharmacologicum. Biennial Other N/A United Kingdom N/A Congress. European College of ECNP Yes Yes Yes N/A N/A N/A N/A 5,000 5,000 www.encp.nl Neuropsychopharmacology. Annual Congress. Institute on Psychiatric Services. IPS Yes Yes Yes Psychiatrists N/A North America 95 2,000 2,000 www.psych.org Annual Meeting. Psychologists N/A Rest of World 5 Other N/A International Conference on Bipolar ICBD Yes No Yes Psychiatrists N/A United States N/A 859 700 ww.wpic.pitt.edu Disorder. Biennial. Psychologists N/A Rest of World N/A Social Workers N/A Medical Students N/A International Congress of ICN A/R A/R A/R Psychiatrists N/A International N/A A/R A/R www.kenes.com Neuropsychiatry. Biennial. Psychiatry (cont.) International Forum on Mood and IFMAD Yes Yes Yes Psychiatrists 100 United States N/A 650 600 www.aisc.it Anxiety Disorders. Annual Meeting. Europe N/A Rest of World N/A New Clinical Drug Evaluation Unit. NCDEU Yes No No Government N/A N/A N/A 1,200 1,200 www.nimh.nih.gov Annual Meeting. Industry N/A Stress and Anxiety Research Society. STAR Yes No No Psychologists 100 Europe 52 200 200 www.star-society.org Annual International Conference. Asia 22 North America 11 Africa 7 Rest of World 8 US Psychiatric and Mental Health USPMHC Yes Yes Yes Psychiatrists 63 Europe N/A 3,000 3,000 www.cmeinc.com Congress. Annual. Psychologists 9 United States N/A Nurses 17 Social Workers 4 Other 7 World Congress of Psychiatry. WCP Yes Yes Yes Psychiatrists N/A N/A N/A 10,000 10,000 www.wpanet.org Triennial. Government N/A Other N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 108 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026114 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Associated Professional Sleep APSS Yes Yes Yes Researchers 33 North America 88 4,000 3,200 www.apss.org Societies. Annual Meeting. Pulmonologists 21 Rest of World 12 Neurologists 16 Psychologists 8 Neuroscientists 8 Psychiatrists 8 Other 6 Sleep European Sleep Research Society. ESRS Yes Yes Yes Physicians N/A International N/A 950 N/A www.esrs.org Biennial Congress. Neurologists N/A Biologists N/A Psychologists N/A World Conference Sleep Odyssey. WCSO Yes Yes Yes Researchers N/A Unied States N/A A/R A/R www.wfsrs.org Quadrennial. Physicians N/A Europe N/A Rest of World N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 109 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026115 DATE 29-Oct-01 REF Neurontin PSC Meeting CLIENT Pfizer MTG DATE 19-Sep-01 VENUE Pfizer PRESENT Pfizer: L Tive, E Mutisya, S Brigandi, MEDICAL ACTION S Piron, M Garcia, J Kaplan, M COMMUNICATIONS Rowbotham, L Knapp, A Fannon, A Crespo, D Probert, J Marino, C Blanckmeister, C Banta MAC: M Vinegra, S Valerio, S Steen, A Masonis, J Mierop, S Tyler COPIED TO E Shapiro, K Kennon, R Glanzman, M Ulrey, K Taylor, M Balkenhol, H Duda Racki, T Hylan, T Hsu, L Collins ACTION REPORT SUBJECT Neurontin PSC Meeting 1.0 Introduction The following action report summarizes the decisions, issues and action items discussed during the Neurontin Publications Subcommittee (PSC) meeting held on September 19. During the meeting the following topics were covered: 2002 congress presentations Issues regarding specific manuscripts Future meeting between NYHQ and Ann Arbor Key message development update Journal and congress profiling update Bibliography development update 2.0 2002 Congress Presentations Joan Kaplan (JK) initiated the discussion by informing the team that the 2001 International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP) has been cancelled. However, the 2 posters scheduled to be presented at that meeting should be included in future presentation plans. The team developed the following plan for poster presentations in 2002: 2.1 American Academy of Neurology (AAN) Dosing response/exposure response (Neuropathic Pain) QOL data from the 5 pivotal trials (Neuropathic Pain) - Steve Piron SP (SP) mentioned that Brett Stacey had expressed an interest in this the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 fizer_LKnapp_0026116 type of subanalysis. SP will contact Stacey to further explore his interest. 2.2 American Pain Society (APS) Efficacy data from the 5 pivotal trials - This poster was originally targeted for ICMTNP. Both the abstract and poster have been completed. MAC will provide reformatting and production support MAC as needed. 2.3 International Association for the Study of Pain (IASP) Practical dosing and titration POPP (tentative, pending subanalysis results) 2.4 American Academy of Family Practioners (AAFP) Screening tool - Stephen Valerio (SV) and Amy Masonis (AEM) of MAC both advised the team that this is a very difficult meeting in terms of acceptance of presentations. The academy has rigorous rules regarding both representation of data and pharmaceutical company funding of accepted presentations. 2.5 American Diabetes Association (ADA) Latin America diabetic neuropathy study Pooled results from the 2 diabetic neuropathy trials MAC will determine the abstract deadlines and meeting dates for ADA MAC and forward these to the team. 2.6 Other Possible Presentations In addition to the above; the following presentations will be added to the list for 2002, pending the following actions: Sleep study - MAC will contact Dr. Erhenberg to find out whether he has previously presented these data at a congress, and if not, MAC whether he would be interested in doing so. MAC will also solicit his preference as to which meeting he would like to present the data. HIV-neuropathy study - This poster was originally to be presented at ICMTNP. Elizabeth Mutisya (EM) will ask Prof. Rowbotham if he EM would prefer to present these data at American Academy of Neurology (AAN), American Pain Society (APS), or International Association for the Study of Pain (IASP). In addition, MAC will MAC follow-up with the International AIDS Conference (IAIDSC) regarding its rules for re-presentation. The team strongly felt that it would be advantageous to have these data presented at this meeting as well. Action Report: 19-Sep-01 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026117 Philippine post-marketing surveillance EM will review these data to determine whether there is any EM potential for presentation material. CRPS placebo cross-over Michael Rowbotham (MR) will follow-up with Prof. Hill to find out MR whether he has any presentation plans for these data. 3.0 Manuscript Issues 3.1 Latin America Diabetic Neuropathy EM informed the team that the preliminary data have just come in and further analysis needs to be done. While the manuscript is currently targeted for the JAMA special issue, the December 31 deadline may be tight. After the data have been reviewed; MAC will distribute a MAC journal query form so that a list of potential back-up journals can be developed. Leslie Tive (LT) was identified as the lead reviewer. EM, Lloyd Knapp (LK), SP, Angela Crespo (AC) and Lingshi Tan (LT) were identified as reviewers. John Marino (JM) recommended that a Brazilian and Mexican be selected as authors. LT also suggested Klaus as an author, even though he no longer is a Pfizer employee. 3.2 Treatment of Diabetic Neuropathy Review for JAMA The team agreed that Larry Blonde and Roy Freeman should co-author this paper, with Bruce Nicholson to provide the viewpoints of an endocrinologist, an anesthesiologist, and a neurologist respectively. LK will be the lead reviewer; MR and EM will also review the manuscript. MR pointed out that the focus of the review should be to convince diabetologists that the treatment of the neuropathic pain associated with diabetes should consist of more than the underlying condition; therapy should be directed toward relieving the symptom itself. 3.3 Gabapentin Review SV reminded the team that the journal Expert Opinion on Pharmacotherapy had solicited a review from Dr. Nicholson, who then asked for Pfizer's help. It was decided that since this was an industry- focused journal, this manuscript was not a priority for the team. It was MAC decided that MAC would look into using a previous review by Nicholson as the backbone for this review and would add some new data to update it. 3.4 Dosing Manuscripts SV informed the team that he had spoken with Dr. McLean, who suggested that the 2 dosing manuscripts be combined since the fundamental issue underlying the manuscripts is the same, namely, intrasubject variability. AC and the team disagreed, arguing that the the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pizer_LKnapp_0026118 clinical issues associated with the 2 conditions were quite different. SV MAC suggested that he would get back to Dr. McLean and mention that Pfizer would first like to write 2 clinically focused reviews and then follow-up with a more detailed, kinetically based review next year. The team agreed to this plan. [Post-meeting note: SV has left a message for Dr. McLean and is awaiting a response.] 3.5 POPP Study The team decided that this manuscript would be placed on hold until the subanalysis is completed. The team selected The Journal of Pain and Symptom Management as the target journal with Pain Medicine as a backup. 3.6 European Journal of Pain Supplement The team was updated regarding the status of the supplement. MAC has received reviewer comments. These will be sent to Stephen MAC Brigandi (SB) who will forward them to Embryon. [Post-meeting note: SB both of these actions have been completed.] The final version will be sent to LT for final approval next week. 4.0 Meeting with NYHQ and Ann Arbor The meeting to discuss the transfer of study data and to determine whether there are studies that have not been published has been confirmed for the afternoon of October 3. The meeting to discuss the subanalyses will be arranged independently. 5.0 Key Messages Update Most of the key message meetings have taken place, and the approved list is undergoing final revisions. Corporate messages will be reviewed by a small committee via e-mail or teleconference. The entire list will be reviewed by a single committee in order to finalize it; however, the list will be revisited in the future. 6.0 Profile and Bibliography Update MAC presented the latest journal and congress profiles and reminded the team that profiling is continuing. MAC also presented the latest screen shots from the bibliography. LT requested a special meeting to discuss the bibliography, independent of other publication issues. In addition; MAC was actioned to provide a small working model to be MAC tested at the meeting. Stephen Valerio Medical Projects Director the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026119

Mention the "Total Attend." given for "Collegium Internationale Neuro-Psychopharmacologicum" Congress?

jnjm0223

jnjm0223_p107, jnjm0223_p108, jnjm0223_p109, jnjm0223_p110, jnjm0223_p111, jnjm0223_p112, jnjm0223_p113

5,000

Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site American Academy of Family AAFP Yes Yes Yes Family Physicians 100 North America 99 14,886 4,500 www.aafp.org Physicians. Annual Scientific Rest of World 1 Assembly. American College of Physicians- ACP-ASIM No Yes Yes Internists 95 United States 93 10,000 7,000 www.acponline.org American Society of Internal Medicine Other 5 Rest of World 7 Annual Session. International Society of Internal ICIM Yes Yes Yes Internists 95 Japan 70 7,000 5,000 www.acponline.org/isin Medicine. Biennial Congress. Other 5 North America 10 Europe 10 Rest of World 10 Primary Medicine Today East. Pri-Med East No Yes Yes Primary Care 55 United States 100 8,000 6,991 www.pri-med.com Annual Meeting. Pediatricians 9 Other 36 Primary Medicine Today MidWest. Pri-Med No Yes Yes Primary Care 61 United States 100 5,216 5,112 www.pri-med.com Annual Meeting. MidWest Pediatricians 10 Primary Care Other 29 Primary Medicine Today South. Pri-Med South No Yes Yes Primary Care 56 United States 100 5,000 4,512 www.pri-med.com Annual Meeting. Pediatricians 8 Other 36 Primary Medicine Today West. Annual Pri-Med West No Yes Yes Primary Care 65 United States 100 9,000 8,369 www.pri-med.com Meeting. Pediatricians 10 Other 25 Society of General Internal Medicine. SGIM Yes No No Primary Care N/A North America 90 1,700 1,700 www.sgim.org Annual Meeting. Rest of World 10 WONCA Asia Pacific Regional WONCA-Asia A/R A/R A/R Primary Care N/A A/R A/R 1,000 800 www.wonca.org Conference. Annual. WONCA Europe. Annual Conference. WONCA-Europe Yes Yes Yes Primary Care N/A Europe 50 3,000 3,000 ww.wonca.org Other Rest of World 50 WONCA World Congress of Family WONCA-World Yes Yes No Family Physicians 100 North America 10 5,000 4,000 www.wonca.org Doctors. Triennial. Rest of World 90 American Academy of Child and AACAP Yes No Yes Psychiatrists 90 North America 60 3,000 3,000 www.aacap.org Adolescent Psychiatry. Annual Other 10 Europe 15 Meeting. Asia 15 Other 10 American Psychiatric Association. APA Yes Yes Yes Psychrists 90 N/A N/A 19,000 19,000 www.psych.org Annual Meeting. Other 10 Psychiatry Anxiety Disorders Association of ADAA Yes Yes Yes Physicians N/A United States 100 600 600 www.adaa.org America National Conference. Annual. Medical Students N/A Association of European Psychiatrists. AEP Yes Yes Yes Researchers N/A Europe 87 2,600 2,575 www.aep.lu Biennial Congress. Other N/A North America 4 Asia 5 Rest of World 4 A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 107 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026113 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Collegium Internationale Neuro- CINP Yes Yes Yes Psychiatrists N/A North America N/A 5,000 5,000 www.cinp.org Psychopharmacologicum. Biennial Other N/A United Kingdom N/A Congress. European College of ECNP Yes Yes Yes N/A N/A N/A N/A 5,000 5,000 www.encp.nl Neuropsychopharmacology. Annual Congress. Institute on Psychiatric Services. IPS Yes Yes Yes Psychiatrists N/A North America 95 2,000 2,000 www.psych.org Annual Meeting. Psychologists N/A Rest of World 5 Other N/A International Conference on Bipolar ICBD Yes No Yes Psychiatrists N/A United States N/A 859 700 ww.wpic.pitt.edu Disorder. Biennial. Psychologists N/A Rest of World N/A Social Workers N/A Medical Students N/A International Congress of ICN A/R A/R A/R Psychiatrists N/A International N/A A/R A/R www.kenes.com Neuropsychiatry. Biennial. Psychiatry (cont.) International Forum on Mood and IFMAD Yes Yes Yes Psychiatrists 100 United States N/A 650 600 www.aisc.it Anxiety Disorders. Annual Meeting. Europe N/A Rest of World N/A New Clinical Drug Evaluation Unit. NCDEU Yes No No Government N/A N/A N/A 1,200 1,200 www.nimh.nih.gov Annual Meeting. Industry N/A Stress and Anxiety Research Society. STAR Yes No No Psychologists 100 Europe 52 200 200 www.star-society.org Annual International Conference. Asia 22 North America 11 Africa 7 Rest of World 8 US Psychiatric and Mental Health USPMHC Yes Yes Yes Psychiatrists 63 Europe N/A 3,000 3,000 www.cmeinc.com Congress. Annual. Psychologists 9 United States N/A Nurses 17 Social Workers 4 Other 7 World Congress of Psychiatry. WCP Yes Yes Yes Psychiatrists N/A N/A N/A 10,000 10,000 www.wpanet.org Triennial. Government N/A Other N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 108 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026114 Neurontin Critical Congress Profiles Congresses, Sorted by Congress Specialty and Title Satellite Total Abstracts Symposia Geographic Total Prof. Specialty Congress Acronym Accepted Permitted Exhibits Target Audience % Audience % Attend. Attend. Web site Associated Professional Sleep APSS Yes Yes Yes Researchers 33 North America 88 4,000 3,200 www.apss.org Societies. Annual Meeting. Pulmonologists 21 Rest of World 12 Neurologists 16 Psychologists 8 Neuroscientists 8 Psychiatrists 8 Other 6 Sleep European Sleep Research Society. ESRS Yes Yes Yes Physicians N/A International N/A 950 N/A www.esrs.org Biennial Congress. Neurologists N/A Biologists N/A Psychologists N/A World Conference Sleep Odyssey. WCSO Yes Yes Yes Researchers N/A Unied States N/A A/R A/R www.wfsrs.org Quadrennial. Physicians N/A Europe N/A Rest of World N/A A/R= Awaiting Research N/A= Not Available Medical Action Communications Information Subject to Change 31-Oct-01 109 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp 0026115 DATE 29-Oct-01 REF Neurontin PSC Meeting CLIENT Pfizer MTG DATE 19-Sep-01 VENUE Pfizer PRESENT Pfizer: L Tive, E Mutisya, S Brigandi, MEDICAL ACTION S Piron, M Garcia, J Kaplan, M COMMUNICATIONS Rowbotham, L Knapp, A Fannon, A Crespo, D Probert, J Marino, C Blanckmeister, C Banta MAC: M Vinegra, S Valerio, S Steen, A Masonis, J Mierop, S Tyler COPIED TO E Shapiro, K Kennon, R Glanzman, M Ulrey, K Taylor, M Balkenhol, H Duda Racki, T Hylan, T Hsu, L Collins ACTION REPORT SUBJECT Neurontin PSC Meeting 1.0 Introduction The following action report summarizes the decisions, issues and action items discussed during the Neurontin Publications Subcommittee (PSC) meeting held on September 19. During the meeting the following topics were covered: 2002 congress presentations Issues regarding specific manuscripts Future meeting between NYHQ and Ann Arbor Key message development update Journal and congress profiling update Bibliography development update 2.0 2002 Congress Presentations Joan Kaplan (JK) initiated the discussion by informing the team that the 2001 International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP) has been cancelled. However, the 2 posters scheduled to be presented at that meeting should be included in future presentation plans. The team developed the following plan for poster presentations in 2002: 2.1 American Academy of Neurology (AAN) Dosing response/exposure response (Neuropathic Pain) QOL data from the 5 pivotal trials (Neuropathic Pain) - Steve Piron SP (SP) mentioned that Brett Stacey had expressed an interest in this the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 fizer_LKnapp_0026116 type of subanalysis. SP will contact Stacey to further explore his interest. 2.2 American Pain Society (APS) Efficacy data from the 5 pivotal trials - This poster was originally targeted for ICMTNP. Both the abstract and poster have been completed. MAC will provide reformatting and production support MAC as needed. 2.3 International Association for the Study of Pain (IASP) Practical dosing and titration POPP (tentative, pending subanalysis results) 2.4 American Academy of Family Practioners (AAFP) Screening tool - Stephen Valerio (SV) and Amy Masonis (AEM) of MAC both advised the team that this is a very difficult meeting in terms of acceptance of presentations. The academy has rigorous rules regarding both representation of data and pharmaceutical company funding of accepted presentations. 2.5 American Diabetes Association (ADA) Latin America diabetic neuropathy study Pooled results from the 2 diabetic neuropathy trials MAC will determine the abstract deadlines and meeting dates for ADA MAC and forward these to the team. 2.6 Other Possible Presentations In addition to the above; the following presentations will be added to the list for 2002, pending the following actions: Sleep study - MAC will contact Dr. Erhenberg to find out whether he has previously presented these data at a congress, and if not, MAC whether he would be interested in doing so. MAC will also solicit his preference as to which meeting he would like to present the data. HIV-neuropathy study - This poster was originally to be presented at ICMTNP. Elizabeth Mutisya (EM) will ask Prof. Rowbotham if he EM would prefer to present these data at American Academy of Neurology (AAN), American Pain Society (APS), or International Association for the Study of Pain (IASP). In addition, MAC will MAC follow-up with the International AIDS Conference (IAIDSC) regarding its rules for re-presentation. The team strongly felt that it would be advantageous to have these data presented at this meeting as well. Action Report: 19-Sep-01 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026117 Philippine post-marketing surveillance EM will review these data to determine whether there is any EM potential for presentation material. CRPS placebo cross-over Michael Rowbotham (MR) will follow-up with Prof. Hill to find out MR whether he has any presentation plans for these data. 3.0 Manuscript Issues 3.1 Latin America Diabetic Neuropathy EM informed the team that the preliminary data have just come in and further analysis needs to be done. While the manuscript is currently targeted for the JAMA special issue, the December 31 deadline may be tight. After the data have been reviewed; MAC will distribute a MAC journal query form so that a list of potential back-up journals can be developed. Leslie Tive (LT) was identified as the lead reviewer. EM, Lloyd Knapp (LK), SP, Angela Crespo (AC) and Lingshi Tan (LT) were identified as reviewers. John Marino (JM) recommended that a Brazilian and Mexican be selected as authors. LT also suggested Klaus as an author, even though he no longer is a Pfizer employee. 3.2 Treatment of Diabetic Neuropathy Review for JAMA The team agreed that Larry Blonde and Roy Freeman should co-author this paper, with Bruce Nicholson to provide the viewpoints of an endocrinologist, an anesthesiologist, and a neurologist respectively. LK will be the lead reviewer; MR and EM will also review the manuscript. MR pointed out that the focus of the review should be to convince diabetologists that the treatment of the neuropathic pain associated with diabetes should consist of more than the underlying condition; therapy should be directed toward relieving the symptom itself. 3.3 Gabapentin Review SV reminded the team that the journal Expert Opinion on Pharmacotherapy had solicited a review from Dr. Nicholson, who then asked for Pfizer's help. It was decided that since this was an industry- focused journal, this manuscript was not a priority for the team. It was MAC decided that MAC would look into using a previous review by Nicholson as the backbone for this review and would add some new data to update it. 3.4 Dosing Manuscripts SV informed the team that he had spoken with Dr. McLean, who suggested that the 2 dosing manuscripts be combined since the fundamental issue underlying the manuscripts is the same, namely, intrasubject variability. AC and the team disagreed, arguing that the the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pizer_LKnapp_0026118 clinical issues associated with the 2 conditions were quite different. SV MAC suggested that he would get back to Dr. McLean and mention that Pfizer would first like to write 2 clinically focused reviews and then follow-up with a more detailed, kinetically based review next year. The team agreed to this plan. [Post-meeting note: SV has left a message for Dr. McLean and is awaiting a response.] 3.5 POPP Study The team decided that this manuscript would be placed on hold until the subanalysis is completed. The team selected The Journal of Pain and Symptom Management as the target journal with Pain Medicine as a backup. 3.6 European Journal of Pain Supplement The team was updated regarding the status of the supplement. MAC has received reviewer comments. These will be sent to Stephen MAC Brigandi (SB) who will forward them to Embryon. [Post-meeting note: SB both of these actions have been completed.] The final version will be sent to LT for final approval next week. 4.0 Meeting with NYHQ and Ann Arbor The meeting to discuss the transfer of study data and to determine whether there are studies that have not been published has been confirmed for the afternoon of October 3. The meeting to discuss the subanalyses will be arranged independently. 5.0 Key Messages Update Most of the key message meetings have taken place, and the approved list is undergoing final revisions. Corporate messages will be reviewed by a small committee via e-mail or teleconference. The entire list will be reviewed by a single committee in order to finalize it; however, the list will be revisited in the future. 6.0 Profile and Bibliography Update MAC presented the latest journal and congress profiles and reminded the team that profiling is continuing. MAC also presented the latest screen shots from the bibliography. LT requested a special meeting to discuss the bibliography, independent of other publication issues. In addition; MAC was actioned to provide a small working model to be MAC tested at the meeting. Stephen Valerio Medical Projects Director the Action Report: 19-Sep-01 Source: https://www.industrydocuments.ucsf.edu/docs/jnjm0223 Pfizer_LKnapp_0026119