Selective publication means unfavorable drug studies rarely get published

Jan 20 2008

A new report claims that almost a third of the research done on antidepressant drugs is never published in medical literature and most of those unpublished reports are unfavorable.

The report by a team of researchers from Oregon Health & Science University says even in the studies which are published, unfavorable results have been recast to make the drug appear more effective than it really is.

The researchers say whether and how studies are published depends on how they turn out according to the published literature, as nearly all studies conducted (94 percent) had positive treatment results, but FDA data showed that in fact only about half (51 percent) of the studies were positive.

Positive studies, with just one exception, were all published whereas most studies that were not positive (33 out of 36) were either not published or were published as if they were positive, in conflict with the FDA conclusions - these 33 studies involved 5,212 patients.

Lead researcher Dr. Erick Turner, who is an assistant professor of psychiatry, physiology and pharmacology, says even if this is not a deliberate ploy, it is bad news for patients.

The research team say selective publication can lead doctors to make inappropriate decisions when they prescribe, which may not be in the best interest of their patients or public health.

The notion that unfavorable test results get 'tucked under the carpet' is not a novel one and the researchers were able to explore the suspicion further by looking at a Food and Drug Administration registry where companies log details of any drug tests before trials are begun.

They also conducted a systematic literature search to identify whether results of these studies had been published in medical journals.

For trials of 12 widely prescribed antidepressant drugs that had been published, they compared the published version of the results with the FDA version of the results.

In this way they were able to see which experiments approved by the FDA between 1987 and 2004 were ultimately publicised in the medical literature and this was the main criteria the researchers planned to measure success.

Of the 74 studies that started for the 12 antidepressants, 38 produced positive results for the drug and all but one of those studies were published.

Of the 36 studies with negative or questionable results, as assessed by the FDA, only three were published, another 11 were revised and re-written as if the drug had worked.

The team says not only were positive results more likely to be published, but studies that were not positive were often published in a manner which conveyed a positive outcome.

The researchers found of the seven negative studies on GlaxoSmithKline's Paxil, five were never published and of three studies on GSK's Wellbutrin SR, the two negative ones were not published.

The team also found of five studies for Pfizer's Zoloft, the three showing the drug to be ineffective were not published and a fourth study, ruled as questionable by the FDA, was written and published to make it appear that the drug worked.

GlaxoSmithKline says it posts the data from all of its trials, positive or negative, on the Internet and says it agrees that public disclosure of clinical trial results for marketed medicines is essential.

Turner also says the surprisingly large number of negative studies does not mean that antidepressants are ineffective.

The team found that with each drug, when all studies were combined using a statistical technique called meta-analysis, they proved to be better than a placebo, but based on the FDA data, less effective than it would appear from the published literature.

Though Turner and his colleagues did not uncover who was to blame for not publishing the studies they suggest the reviewers and editors of medical journals may have played a role by deciding they would rather publish favorable results.

Turner says whatever the reason doctors and patients must have access to evidence that is complete and unbiased when they are weighing the risks and benefits of treatment.

The report is published in the New England Journal of Medicine.