Thursday, December 18, 2008

Did Your Doctor Get Unbiased Information Before Recommending Gardasil?

A new UCSF study led by Lisa A. Bero has uncovered one of those ugly little realities of the medical world: doctors frequently make decisions about which drugs to prescribe based on “skewed” reports that are essentially written by the drug companies and then published in medical journals.

Drug companies report the results of drug trials to the FDA. Once the drug has been approved the companies put together reports written either by physicians involved in the development of the drug, or by specialized companies that attribute authorship to doctors who have participated in the trials. Such articles typically emphasize the positive reports of the trials.

Bero’s team found that bias was shown both by lack of publication of trials with unfavorable outcomes and by selective reporting of data. Trials with favorable outcomes were about five times more likely than those with unfavorable outcomes to be published; there were often many discrepancies between the results the FDA received and the published data; and one-fourth of the results of trials testing the effectiveness of new drugs were not published at all within five years after the FDA approved them.

“Overall, these findings suggest that the information on the efficacy of new drugs that is readily available to clinicians and patients through the published scientific literature is incomplete and potentially biased,” concludes the editors’ summary of Bero’s paper about the study, which was published in the open access online medical journal of the Public Library of Science, PLoS Medicine.

“Bias, Spin, and Misreporting”, the title of An-Wen Chan’s commentary (also found on the PloS Medicine site) about the UCSF study pretty much sums it up. “Biased reporting of results from NDA trials is particularly concerning because these journal articles are the only peer-reviewed source of information on recently approved drugs for health care providers, who will have had limited clinical experience with these new treatments. There are also substantial cost implications if the efficacy is overestimated and the drugs overused, as new molecular entities are among the most expensive pharmaceuticals on the market,” he writes.

Although in theory doctors have access to absolutely all the information that the FDA saw in order to approve the drug, in practice time constraints mean that most must rely on published literature and information provided by pharmaceutical representatives when considering new drugs.

Want to Know More Details?

Here’s more of the PloS Medicine’s editors’ summary: “The researchers identified all the efficacy trials included in NDAs for totally new drugs that were approved by the FDA in 2001 and 2002 and searched the scientific literature for publications between July 2006 and June 2007 relating to these trials. Only three-quarters of the efficacy trials in the NDAs were published; trials with favorable outcomes were nearly five times as likely to be published as those without favorable outcomes. Although 155 primary outcomes were in both the papers and the NDAs, 41 outcomes were only in the NDAs. Conversely, 17 outcomes were only in the papers; 15 of these favored the test drug. Of the 43 primary outcomes reported in the NDAs that showed no statistically significant benefit for the test drug, only half were included in the papers; for five of the reported primary outcomes, the statistical significance differed between the NDA and the paper and generally favored the test drug in the papers. Finally, nine out of 99 conclusions differed between the NDAs and the papers; each time, the published conclusion favored the test drug…

…These findings indicate that the results of many trials of new drugs are not published 5 years after FDA approval of the drug. Furthermore, unexplained discrepancies between the data and conclusions in NDAs and in medical journals are common and tend to paint a more favorable picture of the new drug in the scientific literature than in the NDAs. Overall, these findings suggest that the information on the efficacy of new drugs that is readily available to clinicians and patients through the published scientific literature is incomplete and potentially biased.”—from the Editor’s Summary of the UCSF study in PloS Medicine.

What do you think? Do doctors rely on “skewed” information when prescribing new medications? Has the controversy over Gardasil ensured that doctors have studied it more closely than an obscure new drug?

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