Doctors without borders: why you can't trust medical journals anymore

Washington Monthly, April, 2004 by Shannon Brownlee

"These are not benign people who are interested in helping people with their new wonder drugs," says Drummond Rennie. "The drug companies are run by hard-nosed marketers, not by the physicians and the scientists. They use what works, and money works." Rennie, who has a thatch of unkempt white hair and remnants of the accent of his native Leeds, England, got a clear picture of the extent to which drug companies will go to control the results of studies they fund in 1993, when a colleague at University of California San Francisco tried to publish a paper in JAMA in 1993 on the metabolic activity of four different forms of thyroid hormone. Betty J. Dong, a pharmacologist, had been contracted in 1987 by Flint Laboratories to run a clinical trial comparing Synthroid, Flint's synthetic version of thyroid hormone, to that of three competing formulations. At the time, Synthroid was the market leader and the most expensive drug in its class. Dong and Flint signed a lengthy agreement detailing the design of the study, and both sides fully expected the results would show that Synthroid was superior.

But all four drugs turned out to be essentially equivalent. In 1990, as Dong prepared a paper for JAMA, the company that was at first so eager to solicit her help, launched a vigorous campaign to discredit the study. Flint then rushed its own paper into press at a less prestigious journal, concluding--surprise!--that Synthroid was superior. After numerous attempts to address the company's criticisms, Dong finally submitted her paper to JAMA, only to withdraw it three months later when the firm threatened to sue for breach of contract. It took the FDA and U.S. Department of Health and Human Services to get the company to back down. Dong's paper did not see print in JAMA until 1997.

In this case, it might seem as if the only real harm to the public during the seven years that elapsed from the time Dong completed her study to its publication was higher prices to patients and insurers. To Rennie's way of thinking, the Dong imbroglio and others like it have a more insidious effect by sending a chilling message to scientists, namely, don't bite the hand that feeds you. In a recent survey of clinical researchers, nearly 20 percent of respondents admitted to delaying publication of their results by more than six months at least once in the last three years to allow for patent application, protect their scientific lead, or to slow the dissemination of results that would hurt sales of their sponsor's product--often without overt pressure from the company. "If you're getting a lot of money from a corporate sponsor, it's easy to get the impression that you'll get even more for future research if you don't write up the negative results," says Rennie--and that your hinds will dry up if you do.

The bottom line is that articles appearing in medical journals contain a lot of happy talk about medical products. At least eight studies have shown that industry-sponsored research that gets published tends to produce pro-industry conclusions, according to a review by Yale University researchers that appeared last year in the JAMA. By reanalyzing data from eight separate studies of the effect of conflict of interest on 1,140 published scientific papers, the researchers found that papers based on industry-sponsored research are significantly more likely to reflect favorably on a sponsoring company's drug or device than research that is supported by a nonprofit entity or the federal government.