A Taint on Industry-Sponsored Clinical Trials

Many critics of industry sponsorship of clinical trials have gathered statistics suggesting a biasing of results in favor of the company's drugs or treatment. But Duke Medical Center researchers have gone to the heart of the issue--presenting evidence that industrial sponsorship can even warp the basic management of clinical trials.

In an article in the October 24, 2002, issue of the New England Journal of Medicine, they reported the results of a survey of 108 member institutions of the Association of American Medical Colleges. The aim was to assess the extent to which their contracts with clinical-trial sponsors complied with key provisions of accepted guidelines designed to protect the integrity of research and the rights and interests of academic investigators. The guidelines--promulgated by the International Committee of Medical Journal Editors (ICMJE)--are used by more than 500 medical journals as a standard for researchers submitting papers for publication.

The Duke research team, led by Kevin A. Schulman, professor of medicine, asked the institutions:

• whether authors of reports of multi-center trials had access to all trial data;
• whether the authors or an independent committee controlled editorial and publication decisions;
• whether investigators were fully involved in the design and conduct of the trials.

The Duke team found that such provisions rarely ended up in academic medical centers' agreements with industry sponsors. "We didn't expect to find full compliance with the guidelines, but we were surprised by the extent to which the agreements entered into by medical schools did not protect the independence of investigators in clinical studies and the integrity of their research," says Schulman. "We hope [this study] will offer medical schools a road map for how they might improve their agreements with industry sponsors." The study was funded by the Duke Clinical Research Institute (DCRI).

According to senior author and DCRI director Robert Califf, it is important for all researchers to have access to all the data in a multi-center study. "Publishing data, positive or negative, that are collected at a single site as part of a multi-center trial is not sound scientific practice," Califf says. "The number of patients enrolled at a single site is almost never large enough to yield statistically significant results."

Industry sponsors typically control decisions regarding the publication of data from clinical trials, the researchers found. The agreements also did not ensure dissemination of findings from research on stored biological materials, often collected during clinical trials for potential future research.

" Institutional agreements often fail to ensure researchers access to the final data from clinical trials, and there is also no guarantee that the collected data will ever be published or made available for professional use," says study co-author Jeremy Sugarman '82, M.D. '86, director of the Center for the Study of Medical Ethics and Humanities at Duke Medical Center. "Patients often participate in clinical trials not only for personal benefit, but also because they believe they are contributing to scientific knowledge as a whole. If trial data are not made available to others, this may break an implicit promise to research participants that their contributions will be used in such a way."

The Duke study also found scant adherence to the ICMJE recommendation for the participation of investigators in the design of trials. Only 2 percent required the presence of an independent executive committee as a condition of participation in a trial; only 1 percent required a data- and safety-monitoring board.