Publication bias emerges again in clinical research

Related tags Clinical trial Fda Us

Clinical trials that support the effectiveness of drugs filed for approval in the US are more likely to be published than those that are less supportive, according to researchers at the University of California at San Francisco.

The team looked at 90 drug applications involving over 900 different clinical trials between 1998 and 2000, and identified whether or not the study had subsequently been published.

They found that when the drug under investigation performed well the trial was more likely to be published in a medical journals within the following five years. However, trials where the new drug performed less well were not so likely to be published, raising the suggestion that publication bias had been taking place.

Overall, 43 per cent of all the trials conducted were subsequently published, with the proportion rising to 76 per cent among larger, so-called ‘pivotal’ trials, they said in the study, which was published in PLoS Medicine.

Overall, 66 per cent of trials with statistically significant findings in support of the drug, which accounted for three quarters of the sample studied, subsequently appeared in medical journals. But the publication rate fell to 36 per cent among the remaining quarter of studies that failed to reach statistical significance.

“We sought to determine the proportion of trials submitted to the FDA in support of newly approved drugs that are published in biomedical journals that a typical clinician, consumer, or policy maker living in the US would reasonably search,” said the researchers, led by Ida Sim of UCSF’s division of general internal medicine.

“We ... found strong evidence of publication bias,” they concluded. “Trials with statistically significant results were more likely to be published than trials with nonsignificant results, as were trials with larger sample sizes.”

The study could reopen the often acrimonious debate about transparency and publication bias erupted earlier this decade amid accusations that the drug industry was selective in making its clinical trials public. That led to a companies committing to make details of all their studies public, through databases such as www.clinicaltrials.gov.

However, the researchers note that recent regulatory measures – namely the FDA Amendments Act of 2007 that mandates basic public results reporting for all trials supporting FDA-approved drugs and devices - could set things right.

“Under the new law, basic results for all trials must be posted by one year after trial completion or approval of the drug or device,” they note.

However, they warn that the law could in fact, paradoxically, hinder the publication of trial results.

Sponsors might feel less compelled to publish equivocal results because the data will already be in the public domain, they suggest, so an even greater proportion of ‘positive’ results might end up appearing in the medical literature.

“When more detailed protocol information must also be posted on ClinicalTrials.gov, to start no later than October 2010, the effect on publication practices is even harder to anticipate,” they write.

For now it is interesting to have data supporting the view that publication existed ahead of the new law. Time will tell what the landscape will be like after it is fully implemented.