Meta-reviews and meta-analyses as superspreaders of medical misinformation

Jon Jureidini & Leemon McHenry
A 2020 article published in Frontiers in Psychiatry by Boaden et al.: 'Anti-depressants in Children and Adolescents:  A Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment' purported to contrast the efficacy and tolerability of several antidepressants in treating children and adolescents diagnosed with different psychiatric disorders. In response to this article, we submitted a letter to the Editor of Frontiers (for publication) concerning the integrity of Boaden et al.’s analysis. We have received no response to our letter that was sent 8 October 2020 (see below) and it was not published by Frontiers.

Kamila Markram (CEO) & Mirjam Eckert (Publishing Director), Frontiers Media SA.

Dear Drs Markram and Eckert,

Meta-Reviews and Meta-Analyses as Superspreaders of Medical Misinformation

Meta-reviews and meta-analyses are reliable only in so far as the randomized clinical trials that are the subject of review are reliable.  Since, however, randomized clinical trials produced by the pharmaceutical industry are notoriously suspect, they cannot be relied upon. And when pharmaceutical industry sponsored clinical trials have been demonstrated as flawed or fraudulent, it is especially important that these results are not part of any meta-analysis, meta-review or any other citation that influences physicians’ prescribing behavior. 

In this regard we wish to register our concerns with the recently-published article, Boaden et al., Anti-depressants in Children and Adolescents:  A Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment.  Boaden et al.’s meta-review included nine systematic reviews and meta-analyses, many of which made the same mistake. For example, the Cipriani et al. meta-analysis (2016) included in the meta-review reports on 5260 children and adolescents (9-18 years) with a primary diagnosis of major depressive disorder according to standardized diagnostic criteria and includes data for efficacy, tolerability and suicidality from RCTs that have been misreported or are highly suspected of misreporting. Buried in the numbers of Boaden et al and Cipriani et al. are two industry-sponsored trials, GlaxoSmithKline’s paroxetine study 329 and Forest Laboratories citalopram CIT-MD-18, both of which have been deconstructed to reveal egregious misreporting of safety and efficacy results.

There is no reason to believe that other trials included in the meta-analyses are free of misrepresentation. Furthermore, most of these publications underreport harms and meta-analyses anyway tend to ignore harms.

The medical literature seems to have an unlimited appetite for meta-analysing and reviewing these studies, with different authors digesting them in slightly different ways that sometimes do and sometimes do not conclude that various drugs are a little bit effective and/or better than another drug. The resultant body of work unfortunately has little to contribute to a reliable evidence base.

JON N. JUREIDINI, MB, PhD (Adelaide, Australia)

LEEMON B. McHENRY, PhD (Los Angeles, California)