UCSF investigators: Drug companies distort trial information

A team of medical investigators at the University of California, San Francisco, has accused drug companies of bias by distorting the results of their trials in medical journals, which many doctors rely on to determine whether to prescribe new drugs.

As a result, the researchers say, patients may sometimes be taking medicines they don’t need - or with unwanted side effects - that their doctors have prescribed on the basis of inadequate information.

The UCSF team, led by Lisa A. Bero of the medical center’s Institute for Health Policy Studies, probed the details of 164 drug trials involving as many as 1,500 patients over a two-year period and then examined reports on those trials that were published in medical journals, as well as those that remained unpublished.

Researchers assessed each trial included in the efficacy trials submitted to the U.S. Food and Drug Administration in approved new drug applications for its publication status, primary outcome(s) reported and their statistical significance, and conclusions. Seventy-eight percent (128/164) of efficacy trials contained in FDA reviews of NDAs were published, according to the study. “Publication bias not only limits the number and scope of studies available for review by clinicians, but also affects the results of systematic reviews and meta-analyses,” the study’s researchers said. Forty-one primary outcomes from the NDAs were omitted from the papers.

Papers included 155 outcomes that were in the NDAs, 15 additional outcomes that favored the test drug, and two other neutral or unknown additional outcomes. Excluding outcomes with unknown significance, there were 43 outcomes in the NDAs that did not favor the NDA drug. Of those, 20 (47 percent) not included in the papers.

Discrepancies were discovered between the trial information reviewed by the FDA and information found in published trials tended to lead to more favorable presentations of the NDA drugs in the publications. Thus, the information that is readily available in the scientific literature to health care professionals is incomplete and potentially biased. In theory, there should be no difference between what the regulators are told about a new drug’s strengths and weaknesses and what doctors and other researchers read in journals.

But Bero’s study found a gap between the two. By looking at all the new-drug applications approved by the FDA in 2001 and 2002, the researchers got hold of a comprehensive set of data.

Their conclusions were published in the current issue of PLoS Medicine, an online medical journal.