Clinical Investigators— The Endangered Species Revisited

The premise that clinical research needs to be strengthened was placed squarely on the medical agenda more than 2 decades ago. In his landmark paper "The Clinical Investigator as an Endangered Species," Wyngaarden¹ described a number of problems that he believed jeopardized the future of clinical research. These included declining interest in biomedical research and decreases in the number of postdoctoral training awards granted to young clinicians. The solution he proposed, implementing a series of steps to encourage young physicians to pursue biomedical research careers, has in many respects been adopted. For example, the National Institutes of Health (NIH) has developed a number of new grant mechanisms, such as the K23 and K24 awards, designed to encourage clinical investigators to compete for peer-reviewed funding. This measure and numerous others, implemented by funding agencies and by individual academic health centers, have succeeded in the sense that today clinical investigators are not extinct. To the contrary, by a number of objective measures, they are thriving. For example, at the Johns Hopkins University School of Medicine, the amount of support for sponsored projects that involve human subjects comprises more than half the total amount awarded. This is not surprising, given the greater number of clinical faculty compared with basic science faculty. However, the clinical research would not pass peer review if it was of lower quality than nonclinical research.

Clinical research may be more robust than originally perceived. This perception, as detailed in the article by Campbell and colleagues² in this issue of THE JOURNAL, continues to be that clinical research conducted in academic health centers is of lower quality and facing greater challenges than nonclinical research. The possibility that this perception may be inaccurate has not been tested. Nonetheless, the powerful metaphor created by Wyngaarden¹ survives obscuring the fact that the subject of the metaphor, the clinician investigator, also survives and even thrives.

However, it is not sufficient that clinical research merely survive, but rather clinical research warrants serious attention, including new measures to ensure that it continues to flourish. Accordingly, the goal for the future must be to provide the resources needed for clinical research to use, build upon, and bring into the clinic the extraordinary new knowledge issuing from basic science laboratories.

The critical question becomes what new measures will ensure that clinical research realizes its potential at a time when its potential is so vast that it is impossible to know, with certainty, what shape it will take, much less where it will lead? Importantly, this question is being posed within a health care system that is characterized by dramatic changes, some of which may pose additional challenges to the conduct of clinical research. The constraints of the current health care environment cannot be readily changed; however, the environment is not a dictum, but rather a framework in which leaders in academic centers are making decisions and implementing policies.

One aspect of the current biomedical environment that affects virtually every activity at academic health centers is accountability. Although the idea of accountability seems mundane in contrast to the wonders of scientific discovery that are the pride of academic health centers, it is the hallmark of the academic environment and the standard that leaders in academic health centers now strive to meet.

The concept of accountability is straightforward. Academic leaders are accountable for time and resources. In an era in which financial pressures dominate, every aspect of the academic health center, including research, is affected. The reality is that the conduct of clinical research is extremely expensive, in terms of costs and personnel hours. For example, the cost per subject of running a phase 1 trial ranges from $5000 to $20 000. While some well-defined phase 1 trials only require half a dozen or so patients, most trials require many more, resulting in huge costs. Many phase 2 trials are as expensive per subject as phase 1 trials. While the per subject cost of a typical phase 3 trial is considerably less, the difference is quickly offset because these trials often require the participation of thousands of patients. In addition to these enormous direct costs, the indirect cost rate (institutional administration and regulatory compliance activities supporting the trials) amounts to about one fifth of the direct costs. The problem posed by the enormous cost of conducting clinical research in an environment in which accountability and cost containment are key priorities needs to be resolved.

Another critical issue involves the training of clinician-researchers, which is both complex and time-consuming. The breadth of training required to pursue a career in clinical investigation is not well appreciated. The length of this training is often not rewarded in the promotions process. The subject of training clinician-researchers has received considerable attention in recent years due to concern about the shortage of academic clinical investigators. A particularly promising means of addressing this problem is a new NIH grant, the K30 Clinical Research Curriculum Award.³ This award recognizes the length of training required to prepare a clinician scientist. To date, 55 academic health centers have received K30 awards to develop graduate training programs in clinical investigations.³ Programs that lead to both board eligibility in a medical specialty and a PhD in clinical investigation require 4 years of study and consist of a full year of didactic instruction followed by a mentored original research project. The didactic year provides an intensive sequence of study including courses in clinical research methods, epidemiology, biostatistics, principles of drug discovery, and research ethics. This intensive course of study is not only considered appropriate for training a physician to carry out patient-oriented research, it is regarded as the standard.

Outside the confines of such programs, it is easy to overlook the extraordinary range of knowledge required to perform rigorous clinical research. In contrast, clinicians typically are provided with courses in grant writing, sometimes supplemented with grant writing assistance and help in identifying funding sources. Clinicians are then expected to compete for peer-reviewed funding and, if they are lucky enough to attain it, are expected to carry out the investigation within the same time frame as basic science researchers. Many are surprised when these clinician-researchers fall short and search for reasons such as changes taking place within the health care environment or in funding agencies, which are chastised for misunderstanding clinical research. Leaders of academic health centers understand very well the multidisciplinary facets of clinical research. While the tools and training to conduct research are provided only to a select group of clinical fellows, the very rationale for creating rigorous clinical investigator training programs is ignored. When clinicians are expected to attain the same standards of clinical investigation by providing some of them with only a grant-writing course and, if resources permit, grant writing assistance, the system fails.

Every physician with an interest in conducting clinical research cannot participate in a training program that requires 4 years of study. There is a middle ground between an extensive program that grants a PhD in clinical investigation and one that provides only a grant-writing course. One possible solution might be to restructure the fourth year of medical school to create a separate curriculum for students interested in pursuing clinical research and extend this curriculum into residency training. This strategy would integrate an intensive course of research study into an ongoing curriculum and would do so at a time when students know or at least can test whether they are interested in pursuing this path. Providing students and residents with the knowledge they need to undertake clinical research at the start of their careers would support their career development and, at the same time, enhance the quality of clinical research.

The idea of incorporating some training in clinical investigation into the medical school curriculum and residency training is one means to help ensure the productivity of clinical research in the future. The notion of trying to safeguard the future of an activity that is growing in unpredictable ways is daunting, but the idea of not trying is more so, given the pace and potential of scientific discovery.