A review of 909 clinical trials for 90 meds approved by the FDA between 1998 and 2000 found that more than half of the studies concluding a drug was ineffective were never published in medical journals. The review was published inPLoS Medicine.
The researchers combed through the FDA web site and searched published medical literature up to mid-2006 to determine if and when the results of each trial were published. What did they find? Although 76 percent of pivotal trials appeared in medical journals, usually within 3 years of FDA approval, only 43 percent of all submitted trials had been published.
Trials with statistically significant results were nearly twice as likely to have been published as those without statistically significant results, and pivotal trials were 3 times more likely to have been published as non-pivotal trials, 5 years after approval. In addition, a larger sample size increased the likelihood of publication. Having statistically significant results and larger sample sizes also increased the likelihood of publication of the pivotal trials, the researchers concluded.
"We found that there was indeed a pattern that favorable studies were more likely to be published than unfavorable trials,'' Ida Sim, associate professor of internal medicine at UCSF and the lead author of the analysis, tells Bloomberg News. "This is something that is essentially structural in the way clinical trial information is disseminated to the public.''
You may recall that the recently passed FDA Amendments Act created a trial registry and requires drugmakers to submit results, which PhRMA's Ken Johnson tells Bloomberg his trade group supports. But Sim says a brief summary of results posted on a government web site isn't the same as full publication in a medical journal.
"Medical journals are one of the most influential ways that clinicians and the public get evidence about which drugs work or don't,'' she tells Bloomberg, partly because of the attention published studies attract from the media. And she adds the new law may give drugmakers less motivation to submit studies to journals because they can argue the web site summaries amount to full disclosure.
"If there's less of an incentive to publish a negative study, the ratio of positive to unfavorable results might actually increase,'' she warns.
The study, by the way, didn't examine whether trials were submitted and rejected by journal editors or simply weren't submitted at all, Bloomberg notes. Sim explains that previous research has shown the primary reason for publication bias is that companies or investigators don't submit them.