As drug industry’s influence over research grows, so does the potential for bias

Over a decade, controversies over blockbuster drugs such as Vioxx, Avandia and Celebrex erupted amid charges that the companies had shaped their research to obscure the dangerous side effects.

When the company is footing the bill, the opportunities for bias are manifold: Company executives seeking to promote their drugs can design research that makes their products look better. They can select like-minded academics to perform the work. And they can run the statistics in ways that make their own drugs look better than they are. If troubling signs about a drug arise, they can steer clear of further exploration.

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Conflicted influences

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The connections between article authors and pharmaceutical companies.

Maybe the most widely reported research controversy arose over the arthritis drug Vioxx, which had been featured positively in a NEJM article. The article reported the results of a trial that was funded by Merck and was co-written by two company researchers.

Five years later, journal editors reported discovering that the authors had omitted key incidences of heart troubles, creating “misleading” conclusions about the drug’s safety. Before the drug was pulled from the market, according to a review by an FDA investigator, it caused an extra 27,000 heart attacks and cardiac-related deaths.

Other industry-funded papers published in NEJM have led to conclusions that were later contradicted. Research published in NEJM regarding bestsellers such as the anemia drug Epogen and heart drug Natrecor has been challenged later by studies performed by other researchers.

“Unfortunately, the entire evidence base has been perverted,” said Joseph Ross, a professor at Yale Medical School who has studied the issue.

Just because industry-funded researchers arrived at conclusions that were later discarded does not mean that money biased their findings. Researchers get things wrong for lots of reasons — errors are a part of science.

But Ross notes that corporate bias can be particularly strong. The odds of coming to a conclusion favorable to the industry are 3.6 times greater in research sponsored by the industry than in research sponsored by government and nonprofit groups, according to a published analysis by Justin Bekelman, a professor at the University of Pennsylvania, and colleagues.

Moreover, at the same time that companies have been funding a larger share of research, they have shifted the job of conducting trials away from nonprofit academic hospitals to for-profit “contract research organizations.” Critics say that with this change, corporate bias is less likely to be challenged.

Academics have “contributed to the quality, intellectual rigor, and impact of . . . clinical trials,” the editors of the nation’s top medical journals, including NEJM, wrote in an editorial in 2001. “But, as economic pressures mount, this may be a thing of the past.”

With the for-profit companies competing to run the trials, “corporate sponsors have been able to dictate the terms,” the editorial said.

In recent years, more than half of the money the industry spends on outside research goes to for-profit organizations rather than universities and other academic centers.