Massive Number of Antidepressant Meta-Analyses Biased By Industry

A massive number of meta-analyses of antidepressant clinical trials have financial conflicts of interest and are unduly influenced by pharmaceutical companies, according to a review to be published in an upcoming issue of the Journal of Clinical Epidemiology.  Researchers also found that meta-analyses with industry ties almost never report any negative findings in their abstracts.

As researchers, regulators, and practitioners have become more aware of the biasing effects of financial conflicts of interest on psychiatric drug research, many have come to rely on meta-analyses that synthesize the data of several clinical trials. This is particularly true for antidepressant drug trials, where meta-analyses are used to shape clinical guidelines, and prescribing practices.

“Apparently, meta-analyses have become so popular that they can become a prime marketing tool,” researchers write in a new review of meta-analyses.

A new study led by Shanil Ebrahim of Stanford University reveals that meta-analyses are not immune to industry influence.  Until now, no studies have attempted to assess the extent and effects of industry involvement in meta-analyses of antidepressant trials.

The antidepressant market in the United States is enormous.  With some estimating that the market is close to $10 billion dollars per year.  The market is growing despite the fact that, in the last decade, several high-powered meta-analyses have questioned the effectiveness of the drugs and raised concerns about serious side effects, including suicide.

Ebrahim and his colleagues suggest that the influence of these studies may have spurred the pharmaceutical companies to become more involved in producing meta-analyses.

“Given that influential meta-analyses can be performed with more limited resources and faster than randomized trials, it is conceivable that the industry could easily help generate a large number of meta-analyses to support its products.”

The researchers collected every meta-analysis of randomized control trials evaluating antidepressants published since 2007. They included research on SSRIs, SNRIs, atypical antidepressants, tricyclic and tetracyclic antidepressants, monoamine oxidase inhibitors, melatonergic and nonmelatonergic antidepressants, and any antipsychotics approved for antidepressants, like quetiapine. They excluded studies that compared antidepressant drugs to alternative treatments, such as psychotherapy.

Ebrahim and his colleagues found that seventy-nine percent (147 out of 185) of all antidepressant meta-analyses published in the last seven years were generated by the pharmaceutical industry.

The nearly two hundred meta-analyses broke down like this:

• 51 (28%) did not report sponsorship in the publication, but 11 of these, upon further investigation, included authors with ties to industry
• 46 (25%) were sponsored by the manufacturer of the assessed drug
• 41 (22%) received no funding
• 33 (18%) supported by a government agency
• 20 (11%) funded by a not-for-profit organization
• 3 (2%) sponsored a for-profit organization other than the manufacturer

 

The researchers also identified several trends in the studies with industry authors that suggest bias in favor of the drugs. Meta-analyses that included an author with industry ties were twenty-two times less likely to make a negative statement about the drug in their abstract.

Even when the researchers excluded studies that had an employee of a drug manufacturer on the research team, they still found that studies with a financial conflict of interest (i.e. previous grants or speakers fees) were significantly less likely to make negative statements about the drugs.  In the 38 studies where no industry ties were identified, half reached a negative conclusion in their abstract.

The researchers conclude:

“Multiple reviews have shown that industry-sponsored trials are associated with higher treatment success and report more favorable efficacy results, even when the results of industry-sponsored studies were not really that favorable. It seems that the same enhancement of favorable conclusions is operating also in the level of meta-analyses.”

 

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Ebrahim, S., Bance, S., Athale, A., Malachowski, C., & Ioannidis, J. P. (2015). Meta-analyses with industry involvement are massively published and report no caveats for antidepressants. Journal of Clinical Epidemiology. (Abstract)