Experts Wrangle With Conflict of Interest in Clinical Trials

How is conflict of interest-or the perception of it-to be addressed when academia and industry collaborate on drug development? This was the question posed by Cheryl Bushnell, MD, assistant professor of neurology at Duke Medical Center in Durham, North Carolina, who chaired a brainstorming session on the issue at the 9th annual meeting of the American Society for Experimental Neurotherapeutics (ASENT), which took place March 8-10 in Washington, DC.

"Do academicians lose their independence or the perception of independence when they participate in industry-sponsored research?" she asked, adding that tightening pursestrings of the NIH is exacerbating the problem. Researchers face a challenge whereby the credibility of their research may be questioned because of its source of funding or purely because they received monetary compensation for the work.

Indeed, later in the program, Bushnell asked the audience who, by a show of hands, felt that research conducted by industry-paid academicians was biased. The majority of those participating in the poll believed so-and these persons, for the most part, were representatives from academia and industry who purposefully come together through ASENT to troubleshoot issues regarding advances in neurotherapeutics, including how to get from concept to clinical trial to market.

Bushnell's panel members, co-chair Mitchell F. Brin, MD, senior vice president and development and therapeutic area head at Allergan in Irvine, California; Karl Kieburtz, MD, MPH, professor of neurology at the University of Rochester in New York; and Steven DeKoskey, MD, director of the Division of Geriatrics and Neuropsychiatry at the University of Pittsburgh, all agreed that bias is inevitable. Kieburtz in particular noted that conflict of interest is not merely about monetary compensation and expectations about outcomes of drug trials but involves a wide range of factors, including personal beliefs, lifestyle, and class.

Although DeKoskey argued that pharmaceutical companies generally design studies well because "they listen to their consultants" (ie, academicians working with them) and toe the line with the FDA and other regulatory bodies, the discussion turned to the age-old question: how to get to the truth and even, what is truth?

Bias, whether conscious or unconscious, is inherent in research projects and compromises "truth," they agreed. Trial design, even if it is by-the-book, may not ultimately provide clinically relevant truth because study end points might be narrow and focused on a spin established by the funders, Bushnell argued. Pushing back on trial design might be a self-imposed responsibility of the participating academician in an attempt to maintain integrity, independence-and good science-Bushnell suggested. More discussion was given to the problem and perceptions surrounding monetary compensation.

On the one hand, researchers from academia who accept or end up accumulating large sums of money ($10,000 or more) for their time and effort are typically forced to relinquish opportunities to be published in professional journals in accordance with the statutes of the academic institutions to which they belong. On the other hand, researchers who work gratis or who donate their "take" from industry-sponsored research to their institution are held to a different, sometimes more ambiguous, standard.

But is the integrity of the research of the academician who puts compensation for work done in his pocket really less credible than that of the researcher who designates surrogate recipients of his compensation? After all, time is money. Still, there is the nasty suspicion, particularly among the public sector, that because profit is an end-goal of industry, something shady is going on in its research endeavors. Whether actual or not, this is the perception, Bushnell stressed, and there is the rub.

One participant from the audience-a representative from industry who asked not to be identified in print-noted that in her experience, academicians are experts in finding loopholes in the system to accept money in ways they're ordinarily not allowed to. "It goes beyond conflict of interest between academia and industry; it occurs within academia alone," she said. Putting caps on the amount of compensation that can be received by a person does not solve the problem because, as noted, the funds can be allotted to a third party without prompting questions. The industry representative said that stronger and more meaningful regulation about how academicians work with industry needs to be established within academic institutions.

In regard to finding truth and avoiding bias, the representative noted that patient advocacy groups are good sources-although this was countered by Robin A. Elliot, executive director of the Parkinson's Disease Foundation, who remarked that some advocacy groups hold fast to certain study findings for a myriad of reasons even though those findings may no longer be relevant.

In discussing how to validate study findings, the audience discussed the difficulty of replicating studies when funders are content with outcomes. A physician in the audience noted that single studies do not really produce too much in the way of clinically relevant information; rather, cumulative studies do, and they also reveal oversights and glitches in study designs and needs not met or problems not identified in individual studies.

Finally, 2 gentlemen, David M. Gersten, a judge from the Third District Court of Appeals in Miami, and Christopher Gallen, MD, PhD, president and chief executive officer of Neuromed Pharmaceuticals in Conshohocken, Pennsylvania, separately addressed the audience and stressed that the bottom line was not only disclosure and transparency but also avoiding any appearance of conflict of interest. This came down to recommending that academicians be selective about the research in which they become involved in relation to other projects and assignments.

In addition, the panel and audience seemed to be in agreement that more realistic and transparent regulations and restrictions should be devised and that academicians involved in industry-sponsored research have a strong presence in bringing integrity and truth to trial design and outcomes measures.