Over the last half century, the support of clinical trials has shifted from the National Institutes of Health to the pharmaceutical and device industries. Federal funding for the basic research still remains the foundation upon which clinical research and clinical trials are built. However, the translation of basic research to the bedside has largely become the domain of industry.
In its newly acquired role, industry has relied upon clinical investigators to advise and design clinical trials that will responsibly and accurately answer the question posed by new scientific discoveries that derive from the laboratory and small clinical studies. The design of these trials depends largely on the mutual cooperation of the scientist and the industry sponsor. Although both participants come from different backgrounds, there is a confluence of motives on the part of the investigators and industry. Nevertheless, industry, not devoid of altruism, has as its motivation the corporate profits it needs for survival. The clinical investigators, usually specialists in a particular area, enter this alliance trying to answer important medical questions, using the clinical trial as a platform on which these questions can be answered.
This symbiosis between independent scientists and industry has been immensely successful. It has provided physicians and patients with a multitude of drugs and devices that have resulted in the impressive decrease in cardiac mortality in the past 50 years. At the same time, these trials have provided important science that has defined the natural history of disease, explained mechanism of action of new molecules and devices, and raised important questions for future avenues of scientific exploration.
There is a common understanding that motivates both participants to continue moving forward in the pursuit of new medical knowledge. Part of that understanding is the responsibility for expeditious reporting of clinical trial results. The aroma that emanates from the recent ENHANCE study, widely covered in the lay press and on the front page of CARDIOLOGY NEWS, raises serious concerns about how that study was carried out and the future direction of randomized clinical trials.
In this case, the data on the proof of efficacy of the study drug are not our main concern. Those data will require much further inquiry. However, we are concerned about the delay in reporting and the apparent conflict that has arisen between the industry sponsor and the clinical scientists chosen to direct the study. Much of what we know is derived from comments in the lay press and statements from congressional sources. There may be more relevant information yet to come. However, with what we now know, there was an inordinate delay of more than a year in reporting these data.
Often within the framework of the Science-Industry agreements, there is a moratorium on reporting of 30–60 days on the part of both sides. But a year is excessive. During that time, the principal investigators protested the delay as the industrial sponsor accelerated its advertising of the particular drug.
As the results of randomized clinical trials draw near, the participants have mixed emotions. If the study is positive, all the players are eager to report the result. If negative, the scientist who has worked on the study still may see science coming from negative results. The sponsor, federally or industry funded, would like to bury the data. Like it or not, the responsibility to report the data is undeniable. Either way, the results traditionally end up on the program of the circus that we know as the Late Breaking Clinical Trials at one or another of our national meetings.
The delay in reporting the results of ENHANCE, for whatever reason, has had a chilling effect on the continued support of randomized clinical trials on the part of both the scientist and the public. This methodology is so central to the attainment of improvement in quality care of cardiac patients that anything that challenges its authenticity and reliability diminished those efforts. Recruitment of American patients into randomized clinical trials has driven many of these studies to Europe and Asia, where the relevancy of outcome data to the American patients can be challenged. It has also limited the ability of young American clinical scientists to participate in these studies.
This may be a time to begin to codify the relationships between the sponsor and the clinical scientists who participate in randomized clinical trials. Perhaps we have taken that relationship for granted for too long without fully articulating the motivation and responsibilities of all the participants in this very important method of clinical research.