President's page: cardiovascular research--is something missing?

One has only to compare the 1980 American College of Cardiology (ACC) Annual Scientific Session program to the 1997 program in Anaheim to be amazed at the marked increase in the number of scientific abstracts presented (400 compared with 2,138). Why, then, is there widespread concern about the future of cardiovascular research in the United States? (1–4). Before addressing this question, it is important to distinguish among the various types of research that have emerged since 1980. First is basic research, involving genetics and molecular biology. Basic research was virtually absent from the 1980 meeting. This type of research receives the highest funding priority from both the National Institutes of Health (NIH) and the American Heart Association (AHA). Investigators can be either MDs or PhDs, but the considerable extra training required, beyond the usual training in clinical cardiology, makes this an unlikely course for financially indebted cardiovascular trainees to pursue. The second category involves experimental animal studies, which in 1980 was “basic” research. Such investigators must now have a reasonable understanding of molecular biology, in addition to physiology, and may be either a PhD or MD. Once again, the extra training requirements for this type of research are a disincentive for MDs. Whether any incentive exists to enter either type of basic research is strongly influenced by the closeness of the collaboration between the basic researchers and the clinicians at the trainee’s institution. Third is clinical research that involves human subjects and human diseases and is virtually always conducted by MDs. Clinical investigators study the epidemiology, pathogenesis of disease and mechanisms of disease management. These studies usually do not require large numbers of patients, but may incur substantial hospital or outpatient costs. Traditionally, clinical research has relied heavily on support from clinical revenues donated by the clinical faculty in addition to outside grant support. This type of research is one of the easiest starting points for cardiovascular trainees interested in research. Clinical research requires a thorough understanding of pathophysiology and clinical manifestations of disease supported by a background knowledge of molecular cardiology. In addition, the clinical investigator is generally involved in direct patient care and teaching. From this group, some individuals evolve into “master clinicians” who are able to recognize new manifestations of diseases and intuitively understand the value of new diagnostic procedures or therapies. These are the investigators who bring the questions from the bedside to the research laboratory and, conversely, from the basic laboratory to the bedside. It is this type of investigation for which funding and academic encouragement has dramatically declined since 1980 (1,2). Two new disciplines of research have emerged since 1980— clinical trials and outcomes research. Clinical trials are currently the most glamorous form of cardiovascular research. In fact, cardiovascular medicine leads all other fields in the number and scope of its clinical trials. The researchers are MDs (mostly those who formerly would have performed clinical research). Clinical trials have been an extremely valuable addition to clinical research, but they do have limitations that are not generally appreciated. Trials are often initiated before the mechanism of action of the treatment is fully understood, leading to an inappropriate cessation of research into a promising therapy (e.g., flosequinan, vesnarinone). The patient populations in clinical trials are usually heavily skewed toward the least complex patients and often suffer from referral bias. Thus, only a small percentage of clinical questions can be subjected to trials. Many trials are funded directly by the medical industry, which may have a different agenda than clinicians (5–7). Trials currently enjoy strong support from both the NIH and industry. A worrisome trend is that nonphysician entrepreneurs may steal this show, which could further cloud the interpretation of trials (8). Finally, there is outcomes research—arguably, this has always been a goal of clinical research. Although outcomes research can be prospective, it is commonly a retrospective, observational analysis. It often deals with practical clinical issues for the purpose of improving daily practice. This is a form of research favored by managed care. Outcomes analyses performed from large clinical databases have provided exAddress for correspondence: Dr. Richard P. Lewis, Ohio State University, 1654 Upham Drive, Room 643, Columbus, Ohio 43210-1250. JACC Vol. 29, No. 2 February 1997:457–8 457