The relevant correspondence is below:
On 5 Nov 2016, at 13:18, Holgate S.T. <
S.Holgate@soton.ac.uk> wrote:
Dear Jonathan,
As you will no doubt know we are trying to put together a national effort to undertake a multi-omics study in CFS/ME. This will involve both adults and children and require about 10,000 patients with controls. I have assembled a great team of researchers including George Davey-Smith, Andrew Morrison, Chris Ponting, the MRC Metabolomics Centre in Birmingham, Somolomics etc. to set about this. I attach a draft of a description of it (although this will need input for from others yet and the FAQs).
As you will see below, for reasons that baffle us there is an internet campaign (a petition, I believe - OMEGA
https://spoonseeker.com/2016/11/02/why-we-all-need-to-sign-the-omega-petition/ and
http://www.investinme.org/IIME-Newslet-1609-02.htm/) to try and stop us from doing this. I am perplexed in particular by the statement on the Invest in M.E. website "MEGA will...suck away all funding for ME research for the next few years and give an impression that something is being done that will produce benefits for people with ME". We have not even written the protocol yet, let alone seek funding. It seems that Invest in ME is involved in this, though I don't know why. I should add that MEGA nor the CMRC has any connection with PACE or Peter White now he has retired. As you will see from the attached brief description we will be establishing a patient's panel to help us and to have patients and their carers involved throughout.
In your capacity as an advisor to Invest in ME, could you please shed some light on this? We would be pleased to involve Invest in M.E. in the initiative if seen as helpful. I am copying this email to Charles Shepherd of the M.E Association and Sonya Choudhury of Action for M.E. as well as Mark Edwards, and Hugh Perry and Neha Issar-Brown from MRC some of our advisors who have been helping us.
Thank you very much,
I look forward to hearing from you.
Kindest Regards,
Stephen.
Dear Stephen,
Further to the previous email, I am now able to give you my thoughts on the MEGA proposal.
I have advised IiME on research strategy but I am not involved in decision-making. Views expressed by IiME are not my views, although they may overlap. So my comments below are based on my own perspective on the recent debate and a desire to facilitate good research into CFS/ME.
My understanding is that the MEGA grouping was formed in order to facilitate an application for funding by certain investigators, not so far clearly identified, for a large-scale genetic/metabolic project. That project will obviously need to be submitted in the normal competitive way and be judged on its merits by peer review.
I appreciate that individuals like you and I may have a facilitatory role in getting investigators to collaborate. However, I do see problems when distinctions between potential grant applicants, potential commissioners of grants and representatives of potential funding bodies get blurred. Serious problems have arisen in this context with Arthritis Research UK and appear endemic to EU collaborations. In theory everyone can join a consortium or collaborative but in practice funding goes to specific individuals and that tends to be determined by internal politics rather than open competition. That is a matter of concern not just to scientists but also to patients and carers who may benefit from open competition in funding strategy.
The current spate of comments about the MEGA proposal appears to have been precipitated by the MEGA team itself. A petition was put on the internet asking for patient support, presumably so that evidence of support could be used to strengthen an application for funding. However, patients and carers (and also independent scientists such as myself) are concerned both by the fact that, as you say, no protocol for the project has yet been written, and by the way the petition only asks for a positive response. In the context of the normal peer review process, gathering support in this way would not be acceptable. Within the patient and carer community there are a number of highly intelligent individuals, many of whom understand the relevant scientific and methodological problems in great detail. I think it is reasonable for them to feel unhappy about a ‘consultation’ process that does not take them seriously.
As a result a counter-petition has appeared, which I believe has received about the same number of signatures as the original. I think the MEGA team needs to reflect on why that should be and appreciate that it should have come as no surprise. If IiME have made comments I suspect they were triggered in the same way. The point that any MEGA project will use up funds that are potentially available to any applicant does not seem to me unreasonable. A comprehensive study based on samples from a large cohort is clearly a good idea, but money is unlikely to be available for multiple studies. A Biobank project is already in existence, which is designed to re-invest money from initial project funding into rolling expansion but there is no mention of it or the researchers involved in the MEGA postings. That seems on the face of it a waste of common resources.
There may be a perception within the CMRC that it is the obvious source of an application of this sort. However, most of my contacts are with the international research community (through IiME, EMERG, EUROMENE and IACFS/ME) where at least some would view CMRC (along with NIH) as parochial and out of step. The main problem for CMRC is clearly the association with trials of psychological therapies using poor methodology. Peter White and Simon Wessely have put it about that criticism of these trials is malicious. I think it was useful to have the independent opinion of the Information Officer at the QMUL FOI appeal in April to the effect that this suggestion is at best a red herring and at worst deliberate misinformation. The trials do have poor methodology and do not provide reliable evidence; the patients and carers are right to point this out.
What I think is particularly relevant in the present context is that the claims that criticism is unreasonable reveals a refusal to acknowledge, on the part of trial authors and colleagues, that they understand the nature of the methodological flaws involved. Anyone can make mistakes in science: we have all designed poor experiments. Competent scientists are, however, expected to be able to
understand in retrospect why they are poor. As a grant referee, I would seriously doubt the suitability of applicants who claim to be unable to understand basic methodological flaws.
You have made it clear that Peter White is no longer involved MEGA. What is not clear is Esther Crawley’s position, but various comments suggest that she may be heavily involved in cohort selection. Esther was a registrar with us. She is intelligent and motivated. However, judging by what she has recently communicated to the media and to other investigators, and also by some of her recent publications, it is unclear that she recognises the flaws in studies of CBT and related therapies. To be credible within the scientific community I think she needs to demonstrate that she fully understands the poor quality of most of the work in the area.
To be specific, we do not want to see a project set up that, like PACE, appears superficially to be well designed, with large numbers, randomisation etc., yet suffers from one or more basic flaws that can introduce systematic bias of a sort that destroys the project. CFS/ME is, as you well know, more or less the worst case scenario for risk of systematic bias in terms of cohort selection, outcome assessment and so on. Reading the recent review by Esther and George Davey-Smith I was not convinced of an adequate appreciation of just how serious the problems are. I spent my career piecing together causal factors in rheumatoid arthritis, and, even there, things were not straightforward. The simplistic model of genes and environmental triggers is inadequate.
I have made some comments about the MEGA proposal elsewhere, on the basis of the information that has been put out. I am happy to discuss these further but will not enlarge here. The issue that worries me most is that of cohort identification. I understand that it has been suggested that patients should be recruited from CFS/ME clinics. My experience with specialist colleagues who diagnose CFS/ME is that diagnosis is often heavily coloured by (varying) irrational personal views about the nature of the illness. Moreover, clinics are unlikely to reflect the true demographics without systematic bias that might involve both genetics and comorbidities. In RA the Norfolk Arthritis Register used a directly population-based cohort.
My position within the CFS/ME research community is as an invited outsider with no personal interest in funding or publication. As such, like you, my motivation is purely to encourage the best science. I think the MEGA proposal has to be a welcome one in principle. But it has to compete on a level playing field, through appropriate channels, and be judged on the merits of a detailed proposal. Continuing concerns about the quality of science from the patient and carer community are in my view legitimate and constructive. Both scientific and patient communities are entitled to have evidence that methodology is robust and presentation transparent. Even with that evidence there may still be some who for historical reasons remain sceptical but there is no reason why that should be a barrier to application for funding.
To put things in a nutshell, the way to ‘End the damaging battle over chronic fatigue syndrome’ to quote Esther’s New Scientist article, is for Esther, and the CMRC as a whole, to put out a clear statement that the shortcomings of past (and perhaps ongoing) studies of psychological and exercise therapies are
understood and taken on board in future plans. Regardless of whether or not we think regular talking sessions and exercise management may well be helpful in the path to recovery, if we are to set a standard for CFS/ME research then we need to acknowledge that the evidence from trials from the PACE team and colleagues in the Netherlands is not reliable enough to be useful. The transition to good science we are all striving for needs to be complete and uncompromising - and seen to be so.
Very best wishes,
Jo
Dear Jo,
It was most kind of you to provide me with such a helpful response to my enquiry, thank you.
Kind Regards,
Stephen.
