Reinvigorating Cochrane
BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3966 (Published 20 September 2018) Cite this as: BMJ 2018;362:k3966
All rapid responses
Since not everyone these days seems to understand the nature of irony, it may be well to point up the irony in the words “what crisis?” in the title of Trish Greenhalgh’s opinion piece (https://blogs.bmj.com/bmj/2018/09/17/trish-greenhalgh-the-cochrane-colla...), by reviewing their history.
After runs on the pound in 1975 and 1976, with inflation at 27%, the Labour Government of the day borrowed money from the IMF. In return, the IMF demanded cuts in public spending, with a 5% limit on pay rises. However, during the “winter of discontent” in 1978-9, strikes in various sectors led to higher settlements. Oil tanker drivers, for example, were given rises of up to 20%. More strikes followed—healthcare workers, refuse collectors, grave diggers. Hospitals were picketed, rubbish piled up in the streets, bodies lay unburied in mortuaries. Amid all this, Prime Minister Jim Callaghan went to an economic conference in Guadeloupe. When he returned he was asked what he was going to do. "I don't think other people in the world," he said, "would share the view [that] there is mounting chaos." The headline in the Sun newspaper the following day read "Crisis? What crisis?" Callaghan was condemned as being out of touch. The Labour Government soon fell.
There is a crisis in Cochrane, and it is to be hoped that it will not bring that institution down too. The Board of Cochrane must act quickly, to show that they are not out of touch. They have two choices: either to publicly acknowledge the validity of scientific debate, swallow their pride, apologise to Peter Gøtzsche and his colleagues, and reinstate him; or to resign en masse and allow a new board to take things forward. Speedy action is vital for the survival of the reputation of what used to be called, and should still be called, the Collaboration.
Competing interests: Competing interests: JKA is an honorary member of the Centre for Evidence Based Medicine (CEBM), which is in the Nuffield Department of Primary Care Health Sciences in Oxford, of which Trish Greenhalgh is also a member; he is an honorary associate editor of BMJ Evidence Based Medicine; he has co-authored two papers with Tom Jefferson, who is also a member of the CEBM, on vaginal mesh (BMJ Open 2017; 7(12): e017125) and complex systematic reviews (BMJ Evidence Based Medicine 2018; 23(4): 127-30); he has not collaborated or published with Lars Jørgensen or Peter Gøtzsche.
Dear Madam
PSA and Prostate Cancer Screening in the UK
We write with concern that the series of articles in the BMJ on 22/9/18 do not reflect the true situation on screening and early diagnosis of prostate cancer (PCa).
Whilst the Editorial on page 366 is balanced and factual, reporting the benefits of mpMRI, transperineal biopsy, active surveillance and new treatments that have dramatically reduced the harms of over-diagnosis and over-treatment, the BMJ’s “Editor’s Choice” is a brief, dogmatic, anti-screening conclusion that is dangerously misleading.
The “Systematic Review and Meta-analysis” on page 367 further misleads. The printed review is a synopsis of an extensive study in which the authors admit “The major limitations of this review stem from the included trials themselves”. This statement should have been published because only 5 trials have been included of which 2 (CAP and Lundgren) entailed only a single PSA which does not fulfil the criteria for an adequate screening programme. The third study, PLCO, was notoriously contaminated so its conclusions are not acceptable. The Quebec study is outdated and follow-up too short. Not included in the meta-analysis were the Gothenburg1 and Rotterdam2 studies showing 52% and 51% falls in PCa mortality whilst the latest study from California of over 400,000 men quotes a 64% fall in PCa mortality3!
None of the established screening programmes rely on GPs for delivery. We cannot reasonably expect GPs to reflect recent advances in specialist practice or be familiar with international guidelines on PCa screening when counselling men requesting a PSA test. However, we should expect the BMJ to provide balanced reporting on the benefits of screening which now appear to outweigh the harms. We should not forget that over 11,800 men die from this thoroughly unpleasant cancer and UK cure rates languish below most other advanced countries. On behalf of the National Federation of Prostate Cancer Support Groups (NFPCSG), we expect to see properly informed and balanced reporting in the future.
Yours sincerely
Frank Chinegwundoh MBE, Consultant Urologist, NFPCSG Clinical Advisory Board
Roger Wotton, Chairman, NFPCSG
References:
1. Hugosson J et al. Scand J Urol 2018; 52(1): 27-37
2. European Urology. 2014; 65: 329-336
3. Alpert P F et al. Urology. 2018; 118: 119-126
Competing interests: No competing interests
In regards to the Cochrane crisis, Ray Moynihan says: "The much bigger crisis here is the threat to the reliability of healthcare evidence and public trust posed by the unhealthy financial entanglement between industry and those who evaluate and use its products."[1]
Exactly. Consider for instance the recently published Cochrane HPV vaccine review which is compromised by conflicts of interest.
Lauri Markowitz, an employee of the US Centers for Disease Control and Prevention who is involved in the promotion of HPV vaccine products, was an author on the original protocol for this Cochrane review, and reviewed the results and discussion sections of the final review.
I have challenged David Tovey, Editor in Chief of Cochrane, about Lauri Markowitz' involvement in this review since February 2016.
The CDC is a US government agency. As I detail in my recent rapid responses published on The BMJ, the US government benefits from royalties from the sales of HPV vaccines, via the US National Institutes of Health (NIH). (See my detailed Rapid Responses on Nigel Hawkes' BMJ article: HPV vaccine safety: Cochrane launches urgent investigation into review after criticisms: https://www.bmj.com/content/362/bmj.k3472/rapid-responses )
It's alarming that Cochrane reviews of vaccine products such as the HPV vaccines are being influenced by the promoters of these products, e.g. Lauri Markowitz of the US CDC.
With the ever-increasing number of vaccine products and revaccinations being added to vaccination schedules around the world, we desperately need independent and objective evaluation of these products. Vaccines more than any other product demand scrutiny as governments move to compulsorily impose these products on the community, as is happening in Australia, the United States, Italy and elsewhere.
While Ray Moynihan says "To see the future of Cochrane threatened foreshadows a disaster for all of us", I suggest we face a greater disaster if Cochrane is allowed to continue to give the green light to vaccine products via biased reviews, and thereby unduly influence vaccination policy.
In fact, does Cochrane plan to protect vaccine products from scrutiny in future? In November 2015, Cochrane announced it had closed the section which undertook systematic reviews of vaccine products.[2] It's remarkable that Cochrane decided that vaccine products do not merit objective evaluation, who at Cochrane decided to let vaccine products off the evaluation hook?
And how interesting that the recently favourable - and conflicted - Cochrane HPV vaccine review made it through to publication...
Cochrane is in crisis.
Can this compromised organisation be salvaged to return to its stated mission, i.e. to reliably provide the community with accurate and unbiased information to support informed decision-making?[3]
References:
1. Ray Moynihan. Let's stop the burning and bleeding at Cochrane - there's too much at stake: https://blogs.bmj.com/bmj/2018/09/17/ray-moynihan-lets-stop-the-burning-...
2.Closure of the Vaccines Field, November 18, 2015: https://community.cochrane.org/news/closure-vaccines-field
3. Cochrane - About us: https://www.cochrane.org/about-us
Competing interests: No competing interests
Two things strike me about this debacle. The first is the danger presented by creeping corporatization to an organization’s scientific character. Transformations of the kind Cochrane has gone through are not easy to get right, and the recent events suggest something has gone awry along the way.
The second is the problem of how industry trials should be assessed. Drug marketing is evidence-driven these days. Trial designs and journal article content are determined by drug manufacturers themselves – assisted by academic partners, who generally head the author byline, but are replaceable, and have clear conflicts of interest. We rely on organizations like Cochrane to analyze the evidence unsparingly and identify risks of bias. Company trial reports, regulatory submissions and patient-level data are a better basis for review than journal articles, and a klaxon should be sounded if these are withheld by manufacturers. If Cochrane were to fail in its rigor, then its large, cash-generating paywall library of reviews would be in danger of becoming exploited as a de facto drug marketing channel.
Cochrane is aware of these challenges, debates them, has bias tools in place, is working on updates, and campaigns for greater data transparency – but I think industry science is likely to remain a controversial issue. It is surely inadvisable, for instance, for Cochrane to allow academics with conflicts of interest to author its reviews.
Everybody wishes Cochrane well. The organization needs to reaffirm itself as a scientific, not a corporate endeavour. I can’t comment on the nitty-gritty of the dispute with Peter Gotzsche, but would like to see a solution in which he is reinstated. There have been calls for resignations, but frankly, like scrappers after a pub car park dust-up, I’d like to see everyone involved calm down, patch things up, have a beer together and turn the page.
Competing interests: I am a former industry consultant and writer, and continue to support innovative pharmaceutical research. I am also a critic of drug marketing practices, particularly in the setting of clinical trials and journal literature.
Never mind about Cochrane [1], what about the safety of the young people receiving HPV vaccines [2]? It seems as if the medical profession has become intensely preoccupied with itself, while there is a much more important public issue. In the light of the BMJ Evidence Based Medicine publication, can doctors ethically administer these products without addressing a lot of uncomfortable problems with their patients?
[1] Fiona Godlee, 'Reinvigorating Cochrane', BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3966 (Published 20 September 2018)
[2] Lars Jørgensen, Peter C. Gøtzsche, Tom Jefferson, 'The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias', https://ebm.bmj.com/content/ebmed/early/2018/07/27/bmjebm-2018-111012.fu...
Competing interests: No competing interests
I watched from afar as the events unfolded online and off last weekend at the Cochrane Colloquium. I had a keen interest as having worked on several Cochrane Reviews, but more so as a Conference Scholar who examined the dynamics and processes around the conflicts of interest debate at the 2003 Cochrane Colloquium in Barcelona (and its follow-up), in my book (Nicolson, 2017) and a related LSE Impact blog (Nicolson, 2016). Not being in Edinburgh in person, I can only imagine events surrounding this conference probably had considerable impact on many in attendance, and more so their conversations at the time.
People have expressed sadness at the turn of events regarding the individuals in question, and that too was my reaction. But I was not surprised that conflicts of interest remain unresolved. Cochrane were slow in addressing the conflicts issue – it took them until 2003 when many other areas of research had addressed this sometime before. And their actions since the debate did not unequivocally resolve the issue, although it did remove funding from the pharmaceutical industry.
It is impossible not to have some conflict of interests in any walk of life. The challenges that face the Organisation on conflicts remain ideological and practical. In the weeks, months and years to come, Cochrane has some difficult decisions to make. If anything, this is an existential crisis for the Collaboration. And as such, it is probably momentary, and so will pass. If Cochrane can learn from its history, it might be able to reinvigorate itself.
DJ Nicolson. 2017. Academic Conferences as Neoliberal Commodities. Palgrave Macmillan
DJ Nicolson. 2016. The last great unknown? The impact of academic conferences. LSE Impact Blog. http://blogs.lse.ac.uk/impactofsocialsciences/2016/08/16/the-last-great-...
Competing interests: No competing interests
Re: Reinvigorating Cochrane
The inevitable consequence of a takeover by an Executive which persists in changing the ethos of an organisation is that there will be intensifying resistance to that change by adherents to the `old` ethos such that it will end in fierce dispute, as we have witnessed.
Ethos is defined as ` the characteristic spirit of a culture, era, or community as manifested in its attitudes and aspirations`. In this case, either the original ethos is reinstated with the newcomers conceding, or the newcomers continue to force changes incompatible with the `old` ethos. As Alastair Matheson stated [1] in response to Fiona Godlee`s. Editor`s Choice [2] `the organisation needs to reaffirm itself as a scientific not a corporate endeavour`, i.e. turn away from its new aspirations. But, in my view, there is no `patching up` possible: there has to be a clear, authoritative intent to go one way or the other. Who exactly is to steer Cochrane`s reinvigorated course will depend on which course direction is taken, which ethos triumphs, who surmounts these obstacles. Those individuals who cannot accept the guiding ethos will have no place.
[1] Alastair Matheson`s rapid response to [2] https://www.bmj.com/content/362/bmj.k3966/rr-1
[2] Fiona Godlee. Reinvigorating Cochrane. BMJ 2018;362:k396
Competing interests: No competing interests