Transparency over negative results in antidepressant trials is improving, data show

Analysis of trial data shows that there has been an increase in reporting of negative outcomes in antidepressant trials, from 11% in trials published between 1987 and 2002 to 47% in research published between 2008 and 2013.
Clinical trial concept

There has been an increase in transparent publishing of negative results in trials of antidepressant medicines, an analysis suggests.

Having compared data published from 30 phase II and III clinical trials of antidepressants approved by the US Food and Drug Administration (FDA) between 2008 and 2013, researchers discovered that there had been an increase in reporting of negative outcomes compared with published trials of antidepressants that were approved between 1987 and 2002.

Researchers from the University of Oxford, as well as the United States, Japan and Switzerland, looked at 30 clinical trials on desvenlafaxine, vilazodone, levomilnacipran and vortioxetine that had been reported to regulators as part of the medicine’s approval process. They discovered that 50% of these trials were regarded as ‘negative’, or not significant on the primary outcome, by the FDA.

However, of the 30 trials under analysis, 8 were either unpublished or misrepresented in the scientific literature as positive, leaving 7 — equating to 47% — reporting as ‘negative’. Of 74 trials of approved antidepressants that were published between 1987 and 2002, 11% were reported as negative.

Writing in PLoS Medicine on 19 January 2022, Andrea Cipriani, co-author of the study and professor of psychiatry at the University of Oxford, said standards around what was considered acceptable in clinical trial reporting were changing.

“Nowadays, there is greater awareness of reporting bias in the scientific literature — not only in psychiatry but across all medicine — and there has been a cultural change,” she said.

“Numerous policy changes have been implemented, which have played a major role in bringing about the increase in transparency. However, we do not have full transparency yet. Researchers, patients and clinicians should not naively accept published research findings at face value.”

The researchers also noted that while their new findings are encouraging, they still hint at a fundamental shortcoming in the reliance on studies selectively reported in scientific literature, as opposed to the unvarnished results of clinical trials that are provided to regulators.

Commenting on the findings, David Taylor, director of pharmacy and professor of psychopharmacology at South London and Maudsley NHS Foundation Trust, said the use of trial registers had helped reduced selective publishing in this field. Trial registers are usually nationally-run registers of clinical trials that meet set criteria of content, quality, validity and more.

Selective publishing of positive trial results inflates estimates of a drug’s efficacy,” he said.

“This is especially important when one considers that often only published trials are included in meta-analyses — the highest level of evidence.

“This study shows that selective publishing of positive trials of antidepressants still occurs but is less common with newer drugs than it was with tricyclics and the first SSRIs [selective serotonin reuptake inhibitors].”

He added: “Antidepressants are effective but their effect is somewhat less than only published trials suggest.” 

Read more: MHRA to launch consultation on changes to clinical trial legislation

Last updated
The Pharmaceutical Journal, PJ, January 2022, Vol 308, No 7957;308(7957)::DOI:10.1211/PJ.2022.1.125705

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