The Academic Physician-Investigator: A Crisis Not To Be Ignored

Young physicians may not be seeking careers in research in sufficient numbers to sustain the needs and momentum of medical research. Clinical investigation has always provided excitement and hope for medicine. The health of all persons depends on clinical investigation, research done to improve the well-being of humans. This definition broadly includes basic research that searches for answers in biological organisms that can have implications for human health. However, physicians have the responsibility to interpret basic science observations appropriately and apply them to humans if they are to be translated into meaningful discoveries. Without dedicated physicians who are committed to clinical research and its goal of improved health, the extension of basic science to the treatment of patients will be limited. Basic science research increased at an unprecedented rate in the last 50 years as a result of many factors, the two most important being the American research university supported by the U.S. government and the pharmaceutical industry, which learned quickly the value of highly focused research directed at human disease and the control of certain physiologic functions. The federal expenditure for medical research in 1940 was $3 million. The total national expenditure from all sources that year was $45 million [1]. In 1990, federal support for health-related research was $11.3 billion, of which the largest component was from the National Institutes of Health (NIH), the budget for which was slightly more than $7 billion; and total national financial support was $22.5 billion, representing nearly a 500-fold or 50 000% increase in 50 years [2]. These figures would indicate superficially that health research has never been better. However, the physician who wants to participate actively in improving the human condition faces many difficulties. For this essay, the clinical investigator is the physician who may be doing basic research or clinical, patient-related research. Historical Perspective Clinical research is a new discipline. Before the mid-1950s, advances in patient diagnosis, treatment, and care were based on imprecise and often biased observations. The first randomized clinical trial, which was an evaluation of streptomycin in tuberculosis, was published by the British in 1948 [3]. The first randomized clinical study in the United States was reported in 1951; it was a study designed to determine the effectiveness of penicillin in pneumococcal pneumonia [4]. Researchers realized during this time that a large number of patients entered into a clinical study allowed them to draw their conclusions more quickly and increased the chance that the findings would be important. Furthermore, investigators soon appreciated the power of statistical analysis, which permitted the evaluation of large groups to determine, with some degree of certainty, small differences among treatments. Soon clinical research was accepted as a legitimate academic discipline, and two large national cooperative clinical research groups were formed. The Acute Leukemia Group published the results of the first randomized treatment trial for leukemia in 1958 [5]. In 1960, the Eastern Cooperative Oncology Group reported their randomized study of the treatment of adults with solid tumors [6]. Elegant clinical studies had been conducted previously, such as that by Shannon and colleagues [7] for the treatment of malaria, but the rigorous scientific approach required to determine the validity of small differences and to simultaneously evaluate multiple variables had never been appreciated by clinical investigators. This was an exciting time in the development of clinical investigation. It offered a rigorous methodology to extend laboratory discoveries to humans. The nation was proud of these collective achievements in medicine. The number of medical schools increased from 77 to the current 126. The Hill-Burton Act allowed use of federal funds to help redevelop our hospital infrastructure, a necessity for the expansion of the nation's health initiative. Although there was no federally established and articulated goal, such as that of the space program, there was an understanding that the United States was devoted to achieving better health. The rapid development of the effective polio vaccine, introduced by Salk in 1955 [8], solidified the public's belief that enhanced health care and health research were important. This was an answer to a growing national concern about health and helplessness. The consequence of these and other successful discoveries was the creation of a new industry, the health services and research industry. Now our desire to pay the costs related to health care may be saturated, but we continue to demand better health care and more health research. We now face a monetary crisis and a crisis in which too few physicians are willing to make research in health a career. Furthermore, this crisis might be ignored if the mandate to produce more primary care physicians is unilaterally accepted without considering the effects this will have on other equally important health-related goals of our country. Research Funding It is a fact that physicians on medical school faculties are having increasing difficulty in obtaining funding to support their research and therefore themselves. The money to support medical school faculty comes from four primary sources: the NIH, private foundations, private industry, and clinical activity. The chance of receiving funding from the NIH for a new investigator-initiated application (R01) in 1990 was 14.2%, even though the application was considered worthy of being done (that is, it was not disapproved). This is considerably less than the 40% success rate in 1965 and 1975 [2]. If the application was a renewal of a previously funded grant, the success rate in 1990 was 35% [2], which is in marked contrast to the nearly 70% funding rate for renewal grants submitted in 1965 and 1975 (Figure 1). Figure 1. New and renewal investigator-initiated research grant applications (R01) to the National Institutes of Health (U.S. Dept. of Health and Human Services). By outcome: disapproved, unfunded, and funded from 1965 through 1990 The number of NIH grants funded in each year during the last decade has not changed substantially. In 1990, of the 25 725 total, 15 888 were R01s, of which 4845 were newly funded R01 grants, which includes both new and renewal applications, and 2083 were first awards [2]. In 1991, for which the most recent data are available, 2225 new R01s and 449 new first awards were made [9]. The new grant is less likely to be funded than is the continuation of an ongoing NIH-funded project. This is discouraging information to the new clinical investigator. A few grants have gone to program grants (771 in 1990), but the funds appropriated for this mechanism clearly do not substitute for the current reduced funding rate to new applicants. Nearly one third (9066) of all grants are not R01s but rather are other grants, which includes center grants, special projects, and disease-oriented requests for proposals (Figure 2). Figure 2. Grants funded by the National Institutes of Health by type of grant: investigator-initiated (R01), Program Project Grant (PO1), and others from 1981 through 1990. The percentage of new R01 applications submitted by physicians, including those with both MD and PhD degrees, has remained nearly 25% of the total since 1980 [10]. The priority scores of MD applications are nearly identical to the applications made by researchers with a PhD degree, which shows no particular preference for funding based on the degree. However, the assumption that only 14% of new R01 applications were funded in 1990 would indicate that only 386 new applications of the 2762 submitted from physicians were funded in that year. The information is not available, but it would be reasonable to assume that many of these new applications were from established investigators and not from new physicians just beginning an investigative career. In 1991, there were nearly 41 000 full-time faculty of clinical departments in U.S. medical schools [11, 12], of which 12 892 were faculty of departments of internal medicine (or 102 per medical school) [12, 13]. Faculty with both MD and PhD degrees in internal medicine departments numbered only 954. If 50% of the 386 new grant applications funded by the NIH were from new faculty, 193 physicians would have felt their decision to begin an academic career in clinical investigation was wise. I wonder what the other 1400 young physician-scientists whose applications were denied funding by the NIH considered in 1990? If these young faculty wish to pursue their dream of clinical investigation in an academic setting, they have only a few choices available. The research proposal can be resubmitted with adherence to the recommendations of the reviewers. The percentage of amended grants resubmitted in the new R01 pool has increased from 16.4% in 1980 to 34.4% in 1990; for competing applications, the increase has gone from 17.5% in 1980 to 41% in 1990 [10] (Figure 3). Figure 3. Outcome of resubmitted and amended investigator-initiated grant applications (R01s) that were previously funded from 1980 through 1990 . Of concern is the fact that 56% of amended renewal R01 applications are funded compared with the success rate of 35% for unamended renewal applications of a currently funded grant, and the 14% success rate for the initially submitted new R01 grant. The perception that a resubmission of a renewal grant after an initial nonfunding cycle is likely to be funded is clearly a valid assumption. As a result, researchers commonly apply one cycle early so the amended resubmission can be submitted so that funding will not be interrupted. This environment is not encouraging to new investigators. How could an application be so fundamentally flawed that funding is not provided, yet 6 months