On Cochrane and 'facts' and 'politics' in evidence-based medicine

The controversy surrounding the reported expulsion of Peter Gøtzsche from the Cochrane Collaboration (or should that just be Cochrane?) is something that I've been following for a few days now (see here). Cochrane, under the heading "Trusted evidence. Informed decisions. Better health", represents one of the premier go-to sources for evidence-based healthcare advice on a range of topics. Some of those topics have been previous fodder for this blog too (see here and see here for examples).

I don't profess to have any unique insight into the various goings-on leading to the reported expulsion of Gøtzsche and resignations of fellow members beyond that which has been discussed in various sections of the science media (see here and see here and see here). From what I gather, things look like they've been 'brewing' for a while with regards to Cochrane and the views and opinions expressed by some of those who are seemingly departing. Such a public spat however, is unlikely to be good for science or evidence-based medicine, and indeed may have some wider implications for some fundamentals of science and science communication...

One of the possible [late] precipitating events mentioned around the Gøtzsche saga was the publication of a quite scathing article by Lars Jørgensen and colleagues [1] (including Gøtzsche as an author) questioning the published results of a recent Cochrane review [2] titled: "Prophylactic vaccination against human papillomaviruses [HPV] to prevent cervical cancer and its precursors". The original review by Marc Arbyn et al garnered media headlines when published (see here) as per conclusions such as: "There is high‐certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26." A comforting finding by all accounts. Accompanying such efficacy data were other statements made by the authors on the basis of the evidence reviewed that: "The vaccines do not increase the risk of serious adverse events, miscarriage or pregnancy termination."

Jørgensen and colleagues however put forward their [peer-reviewed] view that the Arbyn paper fell short of the expected standards from Cochrane: "We do not find the Cochrane HPV vaccine review to be ‘Trusted evidence’, as it was influenced by reporting bias [3] and biased trial designs." They highlighted several 'issues' with the original review stretching from trial selection for the review, to the assessment of "serious and systemic adverse events" to potential "conflicts of interest." Similar sentiments had been voiced about other Cochrane reviews too that were subsequently pulled from the scientific literature. Feathers were inevitably ruffled (see here) by the Jørgensen paper, even as far as prompting a response from the journal that published the paper [4] about the peer-review process leading to publication of the critique. Things are getting serious when a journal has to defend its publication of a paper.

Without wishing to reduce this saga to any one event, I don't think it would be unreasonable to assume that the Jørgensen paper might have influenced matters quite considerably; perhaps even bringing them to a head. As per involvement on the Boesen paper [5] Gøtzsche is no stranger to calling out Cochrane reviews that seemingly don't make the grade, alongside also voicing opinions on various other matters down the years. To quote: "... in another book, [he] likened the pharmaceutical industry to "organized crime""; such forthright statements stretching back some years are unlikely to have made too many friends in certain circles.

As per the title of this post mentioning the words 'facts' and 'politics', one particular write-up of this saga I think hits the nail on the head. The opinion piece from Trish Greenhalgh [6] presents the two sides to this 'dispute': on the one hand is that the “crisis” is "philosophical (relating to the nature of facts)" and on the other, "political (relating to organisational governance)." The philosophical side of things is pretty evident as per the publication of the Jørgensen paper as a counter to the Arbyn paper. Greenhalgh mentions about how "Gøtzsche might be classified as an evidence-based medicine purist" given his views and sizeable contribution to various "statements on how to undertake and publish research." In this respect, his published views on the original Arbyn paper (and similarly in other reviews) seem to detail scientific standards not being met, or at least not being met to his and his co-authors standards. And certainly on points such as access to trial results and data, he's seemingly not alone in his concern (see here).

On the political side of things, well, at the time of writing we just don't know enough to reasonably comment. Greenhalgh mentions that: "The political explanation for Cochrane’s crisis relates to the tension between governing an organisation and respecting individual members’ academic freedom to express dissent." The fact that such dissent has over the years covered various important public health topics - "cast doubts about the safety of a vaccine against human papillomavirus (HPV), a cause of cervical cancer, and says psychiatry has “gone astray” by coercing patients into taking medication, such as antidepressants, they don’t want to use and that cause “brain damage” over the long run" - is likely to have really stretched those organisational relationships with Gøtzsche. Not least because immunisation and antidepressant use reflect important pillars of modern public healthcare and, historically, uptake of such medicines is very, very susceptible to differences in scientific views, opinions and beyond.

As to the idea mentioned by Greenhalgh that: "We should cut it [Cochrane] some slack while it gets its house in order", I'm not exactly sure how it's going to approach this 'house in order' requirement and what this means for the future credibility of Cochrane. Based solely on the 'facts' side of this saga, it strikes me that organisations like Cochrane actually need people like Peter Gøtzsche and their "evidence-based medicine purist" beliefs. They need them in order to critically (really critically) boil down the ever-growing research literature into scientifically sound statements for public and policy consumption without fear or favour. Minus such voices, it's more likely that evidence-based messages originating from such initiatives are perhaps going to be weakened, which in turn means that population healthcare is potentially going to suffer. Moreover, I assume also that just because Gøtzsche is reportedly not part of Cochrane any more does not mean that he won't be heard from again in the peer-reviewed domain...

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[1] Jørgensen L. et al. The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias. BMJ Evidence-Based Medicine. 2018. July 27.

[2] Arbyn M. et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018 May 9;5:CD009069.

[3] Jørgensen L. et al. Index of the human papillomavirus (HPV) vaccine industry clinical study programmes and non-industry funded studies: a necessary basis to address reporting bias in a systematic review. Syst Rev. 2018 Jan 18;7(1):8.

[4] Heneghan C. & Onakpoya I. Editors’ response to concerns over the publication of the Cochrane HPV vaccine review was incomplete and ignored important evidence of bias. BMJ Evidence-Based Medicine. 2018. Sept 12.

[5] Boesen K. et al. The Cochrane Collaboration withdraws a review on methylphenidate for adults with attention deficit hyperactivity disorder. Evid Based Med. 2017 Aug;22(4):143-147.

[6] Greenhalgh T. The Cochrane Collaboration—what crisis? BMJ. 2018. Sept 17.

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