THE CRISIS IN BIOMEDICAL RESEARCH FUNDING-A
COMMENTARY* NATHANIEL I. BERLIN** MIAMI
PROLOGUE My presentation at the Association's meeting came about in a somewhat different and perhaps unusual way and given that way this paper will follow closely what I said more than may be the usual. When Dr. Hook called for subject matter for this meeting I submitted to him a book review that I had written for the Journal of the American Medical Association (1) and Clinical Research-A Commentary that I had written for the Journal of Cancer Education (2). As he prepared the agenda for the meeting he had comparable subject material presented to him by Dr. Petersdorf entitled "The Crisis in Biomedical Research Funding" (3). The result was that he asked me if I would present an extended commentary to Dr. Petersdorfs paper and this I was prepared to do. However, while on vacation in San Francisco and just prior to the meeting, Dr. Hook called me and informed me that Dr. Petersdorf's wife was not well and asked if I would take his place on the program. I did do so and what follows is the presentation that I made largely as I made it. THE TALK I am particularly pleased to have the opportunity to speak to you. I have had a few days to prepare these remarks. This may be the only paper that will be without slides. I have had an opportunity to see Dr. Petersdorfs paper and I will try to blend some of his thoughts with mine. Our conclusions are remarkably similar. As I prepared my thoughts I began by going to the dictionary and looked up the definition of crisis (4). Not surprisingly there were a medical definition of which my example is the defervescence associated with fever as in pneumococcal pneumonia as it was treated in an earlier era when I was an intern. There were other definitions and I selected two which well epitomize the present. They are "the period of strain following the culmination of a period of business prosperity when forced liquidation occurs" and "an unstable or crucial time or state of affairs whose outcome will make a decisive difference for better or for worse". * From the Sylvester Comprehensive Cancer Center University of Miami, Miami, Florida
** Address for reprints: Sylvester Comprehensive Cancer Center, University of Miami
School of Medicine, P.O. Box 016960 (D-72), Miami, FL 33101 191
192
NATHANIEL I. BERLIN
The first time that I can recall that crisis was used to describe the funding of biomedical research is Leon Rosenberg's OP-ED piece in the New York Times about a year ago (Sept. 2, 1990, entitled "Medical Research is in Ruins") (5). The second is Barbara Culliton's address at the AFCR Public Policy Symposium in May of this year (1991) entitled "The Crisis in Biomedical Research Real but Overstated" (6), and the last is Petersdorfs paper of today "The Crisis in Biomedical Research Funding" (3). [There may be many others-these are the ones that have come to my attention.] Today we are in a crisis and the definitions that I quoted are to my way of thinking a good description. But I will differ from some. The crisis is of our own making. When Dr. Hook suggested that I comment on Bob's paper, I jotted down a few thoughts. Today rather than commenting briefly I will amplify those thoughts. I will focus my attention on clinical research and clinical investigators but not neglect the basic sciences entirely. The thoughts that I jotted down and in the same order as I did are: 1. There is a crisis 2. It is of our own making 3. Clinical Research is not an attractive career 4. There has been a substantial decrease in the percentage of NIH grants to doctors of medicine 5. There are too many people applying for grants 6. For clinical investigators there is competition for their time. That is patient care competing for research time now expressed as "protected time" 7. There is a need to provide for career stability 8. There is a need to stabilize institutional support 9. There is a need to restructure the grants process (this is vague at this point but may be clearer later) 10. Grants review I have already stated that there is a crisis and in my opinion it is of our own making. Why? I think we must adopt the position that the population of the Biomedical Research Community is in or is approaching a steady state, that is, that there will not be a growth in numbers but we have constantly sought increased funding and at a rate possibly greater than inflation, even when the increasing cost of salaries, supplies, and the ever-escalating cost of the equipment required is included. There is a simple explanation. Population growth can be explained in Malthusian terms (7). Researchers want-need-require graduate student and fellows and when they in turn become researchers they want graduate
CRISIS IN BIOMEDICAL RESEARCH
193
students and fellows and so in Malthusian terms the population increases geometrically while the agricultural side, in our case funding, has increased linearly or not at all in constant dollars in recent years. (Fig. 1 of Petersdorf's paper) (3). Much attention has been paid to training grants and there are projections of the number of trainees needed or desirable. These I will not discuss. What I have not seen are estimates or data on the duration of the active, that is, the productive phase of an investigator's career. Among my colleagues in my age group there were few who were active more than twenty-five years. This must be built into the calculation of the number of trainees required. The longer the active phase, the smaller the number of trainees required to keep the biomedical research community in a steady state. Next, clinical research is not, at present, an attractive career. There are a number of reasons for this starting with the burden of the debt acquired in medical school and for some in college. A long clinical training period, no less than three to five years, the need for "protected time", the fact that the M.D. is not a research degree and the complexity of currently laboratory technology are some of the deterrents. The end result is that only twenty-five percent of NIH grants go to M.D.'s (8). I am firmly convinced that we need to offer physician investigators an opportunity for a stable career. Three year grants are inherently unstable, the renewal rates are low, at least, for first renewals. Next, we need some mechanism for stable institutional support and I do not mean indirect cost rates. And last what brought me to being before you today was the desire on my part to use as a springboard a book review that I wrote for the Journal of the American Medical Association of a book entitled "Research Proposals by Thomas Ogden of the University of Southern California." I would like to read three excerpts from that review (1): 1) "Today when medical research funding is said to be in a crisis, when only a small fraction of NIH grant applications are funded and a career in biomedical research is much less attractive to young people this book serves as a much needed text. Dr. Ogden's theme can be expressed in the terms of form and substance. Good science-substance can be hampered in the review process by a poorly prepared proposal-form. Poor or ordinary science can not be helped. Thus how to put one's best foot forward is the theme." 2) "This text is a compendium of what he has learned. The advice he gives is candid, simple and will be supported by most experienced investigators and grant reviewers. Some will be surprised, others shocked by the candor. Two examples are: "It is unusual for anyone other than the assigned reviewers to read an entire proposal care-
194
NATHANIEL I. BERLIN
fully. Some of the members will look at a given proposal for the first time as it is presented in the meeting. Their scrutiny is superficial to say the least, and is limited to about ten minutes" (9). "In 1991, the across-the-board fund reductions may be as high as 14%. This is enough to adversely affect most projects. Applicants should pad their budgets to absorb these anticipated cuts. Padding is a dangerous but necessary subterfuge"." (10) 3) The candor and frankness of some of the advice if it had been collected in a single chapter could be considered to be a serious criticism of the review process and for that reason the senior staff of the NIH should be encouraged to read this book and while the NIH Grant Peer Review Study Team (report dated Dec 1978) is now more than 12 years old some of the criticisms voiced at that time if not many remain (12). What is being done, Freireich has reviewed various aspects of clinical research in the Journal of the National Cancer Institute (12). The NCI held a conference devoted to the problems of clinical research as has the Institute of Medicine (13) and the NCI has proposed a new training program (14). What has been done and what has been proposed has been helpful but in my opinion not sufficient. The NIH must seek some way and I recognize the difficulty in providing some stable support to our institutions, medical schools and universities on a formula basis and not a formula that rewards the "haves". There is a model which should be examined and that is the Walter and Eliza Hall Institute of Medical Research in Melbourne where half of the budget is derived from a grant by the Australian government. Last, how have I come to this position? I have never applied for a research grant. I will acknowledge three NIH fellowships, a post-doctoral that got me through graduate school at Berkeley, a senior that took me to Mill Hill for a sabbatical year and a Forgarty Senior International late in my career which took me to the Walter and Eliza Hall Institute and my entire productive research career was at institutions with stable support, the Donner Laboratory at the University of California, the National Institute of Medical Research (Mill Hill, London) the National Cancer Institute and the Walter and Eliza Hall Institute of Medical Research, Melbourne. Jim Shannon recognized these problems, and tried but did not succeed in developing a solution. He often said that he desired to build the science base in the universities and he did do that. To summarize, we are in a crisis. It is of our own making. The biomedical research community is in a steady state but the growth pressures continue. We need to examine what it will take to bring some measure of stability to individuals and institutions. We need to determine
CRISIS IN BIOMEDICAL RESEARCH
195
what is needed to make a career in clinical research attractive to young physicians. And last we need to examine how grants are reviewed. Thank you... You must forgive me for my errors. This was written while I was on vacation without access to some of the primary data. In any event it represents my opinion, some may say my bias, others hope and last a quote from Peterdorf's last paragraph: "The current funding problems are serious and their impact on both individual scientists and the nations's biomedical research effort are significant. Quick fixes will not ensure a vigorous research climate in the years to come. We need to look long and hard at the future and ask tough questions about what it will take to stabilize all elements of our national research effort" (3).
EPILOGUE On returning home I have edited this but only to a small degree. I have included the references that I think are relevant to the material that I have mentioned. I have included in the references the definition of Malthusian. I now recognize that Rosenberg did not use the word "crisis" in his N.Y. Times OP-ED piece-but it should be read-it is brief, substantive-and many will say a passionate call for action and certainly described the crisis.
1. 2. 3. 4. 5.
6. 7.
8.
REFERENCES Berlin NI: Book Review: Research Proposals: A Guide to Success by Thomas E. Ogden. JAMA 1991; 266:575. Berlin NI: Clinical Research-A Commentary. J. Cancer Education, to be published. Petersdorf RG: The Crisis in Biomedical Research Funding (Trans Am Clin Climatol Assoc 1991; 103-in press. Webster New Collegiate Dictionary, Merriam Co., 1975. Rosenberg LE: Medical Research is in Ruins, N. Y. Times, Sept. 2, 1990 Section IV, OP-ED Page. Culliton BJ: The Crisis in Biomedical Research: Real But Overstated. Clinical Research 1991; 39:517. Random House Dictionary of the English Language [Malthusian- of or pertaining to the theories of TR Malthus, which state the population tends to increase faster, at a geometrical ratio, than the means of subsistence, which increases at an arithmetical ratio, and that this will result in an inadequate supply of the goods supporting life, unless war, famine, or disease reduce the population, or the increase of population is checked by sexual restraint.] Random House, 1966. Wyngaarden JB: The Clinical Investigator as an Endanagered Species. NEJM 1979;
301:1254. 9. Ogden TE: Research Proposals, pg. 20, Raven Press, New York 1991. 10. Ogden TE: Ibid, pg. 47. 11. Grants Peer Review: Phase II of the Report to the Director, NIH, Dec. 1978.
196
NATHANIEL I. BERLIN
12. Freireich EJ: A Study of the Status of Clinical Cancer Research within the United States (1990). JNCI 1991; 83: 829. 13. IOM 88-07, Report of A Study-Resources for Clinical Investigations. 1988. 14. Kimes BW, Cairoli V, Freireich EJ, Karp J and Yang SS. Training in Clinical Research in Oncology. Cancer Research. 1991; 51: 753. 15. The Walter and Eliza Hall Institute of Medical Research Annual Review, July 1990June 1991.
COMMENTARY* NATHANIEL I. BERLIN** MIAMI
PROLOGUE My presentation at the Association's meeting came about in a somewhat different and perhaps unusual way and given that way this paper will follow closely what I said more than may be the usual. When Dr. Hook called for subject matter for this meeting I submitted to him a book review that I had written for the Journal of the American Medical Association (1) and Clinical Research-A Commentary that I had written for the Journal of Cancer Education (2). As he prepared the agenda for the meeting he had comparable subject material presented to him by Dr. Petersdorf entitled "The Crisis in Biomedical Research Funding" (3). The result was that he asked me if I would present an extended commentary to Dr. Petersdorfs paper and this I was prepared to do. However, while on vacation in San Francisco and just prior to the meeting, Dr. Hook called me and informed me that Dr. Petersdorf's wife was not well and asked if I would take his place on the program. I did do so and what follows is the presentation that I made largely as I made it. THE TALK I am particularly pleased to have the opportunity to speak to you. I have had a few days to prepare these remarks. This may be the only paper that will be without slides. I have had an opportunity to see Dr. Petersdorfs paper and I will try to blend some of his thoughts with mine. Our conclusions are remarkably similar. As I prepared my thoughts I began by going to the dictionary and looked up the definition of crisis (4). Not surprisingly there were a medical definition of which my example is the defervescence associated with fever as in pneumococcal pneumonia as it was treated in an earlier era when I was an intern. There were other definitions and I selected two which well epitomize the present. They are "the period of strain following the culmination of a period of business prosperity when forced liquidation occurs" and "an unstable or crucial time or state of affairs whose outcome will make a decisive difference for better or for worse". * From the Sylvester Comprehensive Cancer Center University of Miami, Miami, Florida
** Address for reprints: Sylvester Comprehensive Cancer Center, University of Miami
School of Medicine, P.O. Box 016960 (D-72), Miami, FL 33101 191
192
NATHANIEL I. BERLIN
The first time that I can recall that crisis was used to describe the funding of biomedical research is Leon Rosenberg's OP-ED piece in the New York Times about a year ago (Sept. 2, 1990, entitled "Medical Research is in Ruins") (5). The second is Barbara Culliton's address at the AFCR Public Policy Symposium in May of this year (1991) entitled "The Crisis in Biomedical Research Real but Overstated" (6), and the last is Petersdorfs paper of today "The Crisis in Biomedical Research Funding" (3). [There may be many others-these are the ones that have come to my attention.] Today we are in a crisis and the definitions that I quoted are to my way of thinking a good description. But I will differ from some. The crisis is of our own making. When Dr. Hook suggested that I comment on Bob's paper, I jotted down a few thoughts. Today rather than commenting briefly I will amplify those thoughts. I will focus my attention on clinical research and clinical investigators but not neglect the basic sciences entirely. The thoughts that I jotted down and in the same order as I did are: 1. There is a crisis 2. It is of our own making 3. Clinical Research is not an attractive career 4. There has been a substantial decrease in the percentage of NIH grants to doctors of medicine 5. There are too many people applying for grants 6. For clinical investigators there is competition for their time. That is patient care competing for research time now expressed as "protected time" 7. There is a need to provide for career stability 8. There is a need to stabilize institutional support 9. There is a need to restructure the grants process (this is vague at this point but may be clearer later) 10. Grants review I have already stated that there is a crisis and in my opinion it is of our own making. Why? I think we must adopt the position that the population of the Biomedical Research Community is in or is approaching a steady state, that is, that there will not be a growth in numbers but we have constantly sought increased funding and at a rate possibly greater than inflation, even when the increasing cost of salaries, supplies, and the ever-escalating cost of the equipment required is included. There is a simple explanation. Population growth can be explained in Malthusian terms (7). Researchers want-need-require graduate student and fellows and when they in turn become researchers they want graduate
CRISIS IN BIOMEDICAL RESEARCH
193
students and fellows and so in Malthusian terms the population increases geometrically while the agricultural side, in our case funding, has increased linearly or not at all in constant dollars in recent years. (Fig. 1 of Petersdorf's paper) (3). Much attention has been paid to training grants and there are projections of the number of trainees needed or desirable. These I will not discuss. What I have not seen are estimates or data on the duration of the active, that is, the productive phase of an investigator's career. Among my colleagues in my age group there were few who were active more than twenty-five years. This must be built into the calculation of the number of trainees required. The longer the active phase, the smaller the number of trainees required to keep the biomedical research community in a steady state. Next, clinical research is not, at present, an attractive career. There are a number of reasons for this starting with the burden of the debt acquired in medical school and for some in college. A long clinical training period, no less than three to five years, the need for "protected time", the fact that the M.D. is not a research degree and the complexity of currently laboratory technology are some of the deterrents. The end result is that only twenty-five percent of NIH grants go to M.D.'s (8). I am firmly convinced that we need to offer physician investigators an opportunity for a stable career. Three year grants are inherently unstable, the renewal rates are low, at least, for first renewals. Next, we need some mechanism for stable institutional support and I do not mean indirect cost rates. And last what brought me to being before you today was the desire on my part to use as a springboard a book review that I wrote for the Journal of the American Medical Association of a book entitled "Research Proposals by Thomas Ogden of the University of Southern California." I would like to read three excerpts from that review (1): 1) "Today when medical research funding is said to be in a crisis, when only a small fraction of NIH grant applications are funded and a career in biomedical research is much less attractive to young people this book serves as a much needed text. Dr. Ogden's theme can be expressed in the terms of form and substance. Good science-substance can be hampered in the review process by a poorly prepared proposal-form. Poor or ordinary science can not be helped. Thus how to put one's best foot forward is the theme." 2) "This text is a compendium of what he has learned. The advice he gives is candid, simple and will be supported by most experienced investigators and grant reviewers. Some will be surprised, others shocked by the candor. Two examples are: "It is unusual for anyone other than the assigned reviewers to read an entire proposal care-
194
NATHANIEL I. BERLIN
fully. Some of the members will look at a given proposal for the first time as it is presented in the meeting. Their scrutiny is superficial to say the least, and is limited to about ten minutes" (9). "In 1991, the across-the-board fund reductions may be as high as 14%. This is enough to adversely affect most projects. Applicants should pad their budgets to absorb these anticipated cuts. Padding is a dangerous but necessary subterfuge"." (10) 3) The candor and frankness of some of the advice if it had been collected in a single chapter could be considered to be a serious criticism of the review process and for that reason the senior staff of the NIH should be encouraged to read this book and while the NIH Grant Peer Review Study Team (report dated Dec 1978) is now more than 12 years old some of the criticisms voiced at that time if not many remain (12). What is being done, Freireich has reviewed various aspects of clinical research in the Journal of the National Cancer Institute (12). The NCI held a conference devoted to the problems of clinical research as has the Institute of Medicine (13) and the NCI has proposed a new training program (14). What has been done and what has been proposed has been helpful but in my opinion not sufficient. The NIH must seek some way and I recognize the difficulty in providing some stable support to our institutions, medical schools and universities on a formula basis and not a formula that rewards the "haves". There is a model which should be examined and that is the Walter and Eliza Hall Institute of Medical Research in Melbourne where half of the budget is derived from a grant by the Australian government. Last, how have I come to this position? I have never applied for a research grant. I will acknowledge three NIH fellowships, a post-doctoral that got me through graduate school at Berkeley, a senior that took me to Mill Hill for a sabbatical year and a Forgarty Senior International late in my career which took me to the Walter and Eliza Hall Institute and my entire productive research career was at institutions with stable support, the Donner Laboratory at the University of California, the National Institute of Medical Research (Mill Hill, London) the National Cancer Institute and the Walter and Eliza Hall Institute of Medical Research, Melbourne. Jim Shannon recognized these problems, and tried but did not succeed in developing a solution. He often said that he desired to build the science base in the universities and he did do that. To summarize, we are in a crisis. It is of our own making. The biomedical research community is in a steady state but the growth pressures continue. We need to examine what it will take to bring some measure of stability to individuals and institutions. We need to determine
CRISIS IN BIOMEDICAL RESEARCH
195
what is needed to make a career in clinical research attractive to young physicians. And last we need to examine how grants are reviewed. Thank you... You must forgive me for my errors. This was written while I was on vacation without access to some of the primary data. In any event it represents my opinion, some may say my bias, others hope and last a quote from Peterdorf's last paragraph: "The current funding problems are serious and their impact on both individual scientists and the nations's biomedical research effort are significant. Quick fixes will not ensure a vigorous research climate in the years to come. We need to look long and hard at the future and ask tough questions about what it will take to stabilize all elements of our national research effort" (3).
EPILOGUE On returning home I have edited this but only to a small degree. I have included the references that I think are relevant to the material that I have mentioned. I have included in the references the definition of Malthusian. I now recognize that Rosenberg did not use the word "crisis" in his N.Y. Times OP-ED piece-but it should be read-it is brief, substantive-and many will say a passionate call for action and certainly described the crisis.
1. 2. 3. 4. 5.
6. 7.
8.
REFERENCES Berlin NI: Book Review: Research Proposals: A Guide to Success by Thomas E. Ogden. JAMA 1991; 266:575. Berlin NI: Clinical Research-A Commentary. J. Cancer Education, to be published. Petersdorf RG: The Crisis in Biomedical Research Funding (Trans Am Clin Climatol Assoc 1991; 103-in press. Webster New Collegiate Dictionary, Merriam Co., 1975. Rosenberg LE: Medical Research is in Ruins, N. Y. Times, Sept. 2, 1990 Section IV, OP-ED Page. Culliton BJ: The Crisis in Biomedical Research: Real But Overstated. Clinical Research 1991; 39:517. Random House Dictionary of the English Language [Malthusian- of or pertaining to the theories of TR Malthus, which state the population tends to increase faster, at a geometrical ratio, than the means of subsistence, which increases at an arithmetical ratio, and that this will result in an inadequate supply of the goods supporting life, unless war, famine, or disease reduce the population, or the increase of population is checked by sexual restraint.] Random House, 1966. Wyngaarden JB: The Clinical Investigator as an Endanagered Species. NEJM 1979;
301:1254. 9. Ogden TE: Research Proposals, pg. 20, Raven Press, New York 1991. 10. Ogden TE: Ibid, pg. 47. 11. Grants Peer Review: Phase II of the Report to the Director, NIH, Dec. 1978.
196
NATHANIEL I. BERLIN
12. Freireich EJ: A Study of the Status of Clinical Cancer Research within the United States (1990). JNCI 1991; 83: 829. 13. IOM 88-07, Report of A Study-Resources for Clinical Investigations. 1988. 14. Kimes BW, Cairoli V, Freireich EJ, Karp J and Yang SS. Training in Clinical Research in Oncology. Cancer Research. 1991; 51: 753. 15. The Walter and Eliza Hall Institute of Medical Research Annual Review, July 1990June 1991.
