The MEGA (ME/CFS Epidemiology and Genetics Alliance) ‘big data' research study – some comments from Dr Charles Shepherd following last week's third annual scientific meeting of the UK CFS/ME Research Collaborative
I can understand all the concerns, criticisms and questions about the MEGA study that are being expressed by the ME/CFS patient community on internet discussion forums.
I can also assure people that they will be transferred back to those at the CMRC (CFS/ME Research Collaborative) who are involved in preparing what is probably going to be the largest ever research grant application relating to ME/CFS here in the UK.
There are clearly a number of key decisions still to be made. And .if anyone followed the proceedings at the CMRC conference in Newcastle last week. they will know that I raised the crucial issue of patient selection criteria (narrow or broad) with Professor George Davey Smith and Dr Esther Crawley during the discussion section.
The key point I want to make at this stage is that the MEGA study is an important and complex new item of ME/CFS research that is going to make use of a wide range of relatively new and exciting technologies – metabolomics, proteomics, genomics, epigenetics etc.
The MEGA study will also involve some very high profile BIOMEDICAL scientists of international repute – several of whom are completely new to ME/CFS.
Researchers who will be involved include:
* Genomics – Prof George Davey-Smith (Bristol), Prof Chris Ponting (Edinburgh), Prof Colin Smith (Brighton)
* Epigenetics – Prof Caroline Relton (Bristol)
* Proteomics – Mr Tony Bartlett (Somalogic)
* Metabolomics – Dr Rick Dunn (Birmingham)
* Routinely collected data – Prof Andrew Morris (Edinburgh) and Prof David Ford (Swansea)
* Infection – Prof Paul Moss (Birmingham)
* Sleep – Prof Jim Horne (Loughborough)
* Pain – Prof Maria Fitzgerald (UCL)
* Prof Julia Newton (Newcastle)
The MEGA study has also attracted the very positive attention of the Wellcome Trust _ the largest provider of non governmental funding for biomedical research here in the UK and the largest research funding charity in the world
Wellcome Trust: >https://wellcome.ac.uk
And the numbers of patients involved is going to be huge – around 10,000 adults and 2,000 children.
However, when it comes to the aims and objectives of the research, there are some serious misunderstandings and inaccuracies being circulated on the internet as to how this ‘big data' is going to be collected, analysed and used. This is NOT a treatment trial in any sense of the word and it has nothing to do with PACE, CBT or GET.
If we are going to make progress in trying to sort out the different clinical and pathological sub-groups/phenotypes that currently come under the very messy umbrella of ME/CFS, as well as those with unexplained chronic fatigue, AND in the process develop diagnostic biomarkers that could then be used as objective diagnostic tests to identify specific sub-groups of patients that come under this ME/CFS umbrella, ALONG WITH helping to identify specific forms of treatment that are aimed at these specific sub-groups, we are going to have to look at the whole spectrum of patients who are currently being diagnosed with ME, CFS or ME/CFS, and possibly unexplained chronic fatigue as well.
So the numbers need to be huge and a study of this nature may also need to include people with chronic fatigue states whom we will then want to exclude for both our benefit and for their benefit.
In my opinion, getting this right will clearly be dependent on having very detailed clinical information accompanying the biological samples – as is the case with the ME/CFS Biobank where we can check what diagnostic criteria (and symptoms) accompanies each individual blood sample that has been collected and stored.
I am not yet clear as to how this will be done in this study, which Is why I asked the question on patient selection at the conference. The nearest information we have was the reply from Dr Esther Crawley in which she stated that patients will meet NHS diagnostic criteria for ME/CFS and will be recruited from the NHS hospital-based referral centres for people with ME/CFS
So I would ask the ME/CFS patient community to see how the protocol develops and what information and inclusion criteria are going to be used.
If you are happy with the final research proposal, then there will obviously be ways of expressing public support.
If not, there will be ways of saying so as well!
As Professor Jonathan Edwards has said on the Phoenix Rising forum:
“I think the project must be welcome but I am surprised by this sort of canvassing for support. So far no details are available of who would do what. Surely patients are entitled to judge a project on the basis of a written application, just as scientists do”
So I hope that those people who are wanting to simply strangle this proposal before it has even been properly finalised will think very carefully about what they are doing – especially if this is mainly because they disagree with the inclusion of certain specific researchers.
It is difficult enough getting new and distinguished scientists and researchers, and major research funders such as the Wellcome Trust, interested in this subject without trying to scare them off almost as soon as they express a serious desire to get stuck into in a huge multidisciplinary project such as this, and the protocol is still being developed.
If people want to express concerns, criticisms, or have questions to ask, then I suggest that this should be done in the form of an open letter to the Board of the CMRC, which could be signed by anyone expresing such concerns, rather than a petition.
Dr Charles Shepherd
Hon Medical Adviser
The ME Association
I think that it’s fair to say that the handling of the announcement of the MEGA research project has been abysmal. It is an insult to the intelligence of the M.E. community.
Given past events, and consequently people’s perfectly understandable suspicions where anyone involved in the PACE trial is concerned, posting of the change.org petition, asking them to support a trial in which Prof White is involved was utterly stupid.
I agree that not enough is yet known about the MEGA proposal, and so those who are being persuaded to support it via the petition are doing so in ignorance. However, that won’t be a factor when those numbers are used to support an application for funding to the MRC – irrespective of whether the proposal is a good one or not.
Agreed
I think this is an insult to our intelligence.
These are my comments that I have previously posted on Phoenix Rising;
Thank you for your post Dr Shepherd, getting some interaction on this subject is very much appreciated.
“charles shepherd said: ↑
This is NOT a treatment trial in any sense of the word and it has nothing to do with PACE, CBT or GET.”
So I have to ask, why the involvement of BPS supporters? You, given your greater interaction with the patient community, must have had an appreciation of the response large sections of the community would have to their involvement. As far as I, as well as many others, can see there is no benefit to this project by their involvement at all.
“charles shepherd said: ↑
So I would ask the ME/CFS patient community to see how the protocol develops and what information and inclusion criteria are going to be used”
“charles shepherd said: ↑
f you are happy with the final research proposal then there will obviously be ways of expressing public support”
“charles shepherd said: ↑
If not there will be ways of saying so as well!”
So why are we being asked to endorse it now before all of this is established.
“charles shepherd said: ↑
So I hope that those people who are wanting to simply strangle this proposal before it has even been properly finalised will think very carefully about what they are doing – especially if this is mainly because they disagree with the inclusion of certain specific researchers”
Personally, I think you are seriously misrepresenting the majority reaction of the community here. The vast number of comments that I have seen are confirming that we are desperate for biomedical research and would offer our support, as long as there are no BPS supporters involved. If those involved in the CMRC can not understand this stance then I would suggest that they would benefit from engaging with patient population more.
“charles shepherd said: ↑
It is difficult enough getting new and distinguished scientists and researchers, and major research funders such as the Wellcome Trust, interested in this subject without trying to scare them off almost as soon as they express a serious desire to get stuck into in a huge multidisciplinary project such as this, and the protocol is still being developed”
No, as I comment above, the majority of comments are pro-biomedical research but anti-BPS. There is a section which are highly suspicious particularly because there is insufficient detail released so far and yet we are asked to endorse it via the petition. Action for ME’s involvement also sours patient engagement for historical reasons.
“charles shepherd said: ↑
If people want to express concerns, criticisms, or have questions to ask, then I suggest that this should be done in the form of an open letter to the Board of the CMRC, which could be signed by anyone expresing such concerns, rather than a petition”
And the difference between the two is lost on me, especially, to labour the point, when a petition is being used to gather our support. Why did MEGA not use an open letter, so that anyone who supported their project could then sign it?
I really do appreciate you taking the time to engage with us but the fact that you have had to just highlights the problems that exist. The way that this has been dealt with by CMRC/MEGA suggests how poorly they think of the patient community as a whole.
(All my own opinion as well as my own interpretation of general moods in the patient population)
Well said
Well said, and not all your own opinion. It’s mine too and I like you very much read that as the reaction of the vast majority of the ME community, or at least the ones I have seen comment.
Given this project is about attracting researchers new to the field, I think it is even more important to exclude those from the BPS school.
They could sway naieve folk who are unaware of the politics and previous machinations from such “eminent” people, and who regard the qualifications and labels they wear as authority.
Yes. We need ME Ass to protect us. Newcomers turn to ME Ass for guidance.
I agree wholeheartedly with the above responses. No BPS involvement, no AFME involvement, Peter White, Esther Crawley, PACE trial researchers etc.
“I am not yet clear as to how this will be done in this study, which Is why I asked the question on patient selection at the conference. The nearest information we have was the reply from Dr Esther Crawley in which she stated that patients will meet NHS diagnostic criteria for ME/CFS and will be recruited from the NHS hospital-based referral centres for people with ME/CFS”
NHS diagnostic criteria? You mean NICE Guidelines which have been drawn up by the PACE trial, BPS school, CBT and GET and frankly everything and everyone that is wrong with the whole treatment and diagnosis of ME. Sounds great, yeah. Basically anyone with any undiagnosed, incorrectly diagnosed or wastebasket “CFS” illness that has “unexplained fatigue for six months or more” can be recruited, just as was done for the PACE trial. Sorry but no thanks.
Exactly this. What we don’t want any more of is poorly designed research that only muddies the waters, discourages funding future well-designed research, leads to discrediting patients, and which won’t add any true findings to the picture. If it isn’t based on the international consensus criteria it is not appropriate in any way, regardless of who is or isn’t on the advisory or research team. If it doesn’t screen patients on ICC ME guidelines, then it isn’t ME research.
I appreciate that this study may produce interesting results, but it would be enormously helpful to use, say, the Revised London criteria, to ascertain how many may have classic ME (as opposed to chronic fatigue due to stress or diet). Alternatively, we may find different changes in those with post-viral onset compared to gradual onset. I sense that many of us are keen to see how the various subsets compare. It’s cheap, takes little time and I can’t see a reason for not stratifying the samples. After all, it was recommended by Fukuda et al 1994.
Thanks, Charles.
I agree this study has huge potential and it’s great to see new biomedical talent come into the mecfs field.
“the reply from Dr Esther Crawley in which she stated that patients will meet NHS diagnostic criteria for ME/CFS and will be recruited from the NHS hospital-based referral centres for people with ME/CFS” I didn’t hear that (looking forward to the conference videos being posted) but it reassures me too.
Equally, I don’t think MEGA have made a great job of communicating the study to patients, and I understand why many feel aggrieved at being asked to back a study. I like the idea of an open letter.
This is not reassuring. It is ineffective science if it isn’t based on ICC on ME guidelines, because it can only be compared to other research data and used effectively if all research projects are using the same definable disease. Only recruiting from NHS clinics effectively rules out anyone who has refused GET or CBT or who has been sick long enough to have been discharged because they have finished their assigned therapies or counselling and have been discharged from their local service. By only selecting from NHS CFS service referrals, it will be excluding the most severely effected patients once again, because they will have been unable to attend those services or “treatments”. Completely aside from the fact that they are focussing on one symptom (fatigue) that isn’t even considered the cardinal symptom of ME (i.e. post exertional neuroimmune exhaustion). Bad science all around.
Agreed
Firstly recruiting from the NHS clinics doesn’t rule people who refuse CBT/GET. I’ve been under an NHS clinic for 5 years and have always refused GET and CBT as have many others there. Secondly post exertional fatigue is a required symptom for an CFS/ME diagnosis in the NICE guidelines so how anyone can claim it’s not considered is beyond me.
This sounds likes it’s written by Weesley – ‘scaring researchers away’ so, not only are you tied up with White and Crawley, the funder is Wellcome trust who for those who don’t know awarded the book prize this year to Suzzane O’Sullivan, author of ‘It’s all in your head, psychosomatic disorders explored’ which contains an entire chapter on ME. Here’s the thread on PR if you want to read more about that;
http://www.healthrising.org/forums/threads/th-countess-of-mars-letter-to-dr-suzanne-osullivan.2655/
So, you’re asking us to ignore the PACE trial, the FINE trial, all of the trials Crawley has been funded for and has provided no futher answers, the trials Wessely has been funded for, because we know he’s involved from Jane Colby’s report;
http://forums.phoenixrising.me/index.php?threads/behind-the-scenes-setting-up-the-uk-cfs-me-research-collaborative-uk-cmrc-tymes-trust.32302/
But we should trust Action for ME who cheated us, and has done for forty years?
Crawley Research;
https://frownatsmile.wordpress.com/tag/dr-esther-crawley/
http://trialsjournal.biomedcentral.com/articles/10.1186/1745-6215-14-415
http://bmjopen.bmj.com/content/1/2/e000252.short
http://bmchealthservres.biomedcentral.com/articles/10.1186/1472-6963-11-217
http://adc.bmj.com/content/98/6/425.full
http://adc.bmj.com/content/93/5/419.short
http://pediatrics.aappublications.org/content/130/1/e71.short
http://link.springer.com/article/10.1007/s00787-009-0029-4
http://adc.bmj.com/content/95/4/245.short
http://bmchealthservres.biomedcentral.com/articles/10.1186/1472-6963-11-308
http://adc.bmj.com/content/early/2010/07/24/adc.2009.173161.extract
http://adc.bmj.com/content/92/12/1058.short
http://adc.bmj.com/content/99/2/171.abstract
http://ccp.sagepub.com/content/early/2012/10/19/1359104512460862.abstract
http://ccp.sagepub.com/content/16/2/215.short
http://www.magonlinelibrary.com/doi/abs/10.12968/hmed.2006.67.9.21994
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=9202412&fileId=S1463423613000121
http://ep.bmj.com/content/90/4/ep92.
http://bmjopen.bmj.com/content/2/4/e001417.full
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2214.2011.01298.x/abstract?userIsAuthenticated=false&deniedAccessCustomisedMessage=
http://adc.bmj.com/content/98/7/561.full
http://pediatrics.aappublications.org/content/137/2/1.51.abstract
http://www.bris.ac.uk/social-community-medicine/people/esther-m-crawley/pub/292703
http://trialsjournal.biomedcentral.com/articles/10.1186/1745-6215-16-S2-P71
http://download-redirector.springer.com/redirect?ddsId=art:10.1186/1745-6215-14-444&originUrl=
http://trialsjournal.biomedcentral.com/article/10.1186/1745-6215-14-444&contentType=pdf
http://ep.bmj.com/content/early/2012/09/04/archdischild-2012-302484.short
http://www.bmj.com/content/342/bmj.d3956?tab=response-form#bmj_el_266989
http://bmchealthservres.biomedcentral.com/articles/10.1186/1472-6963-11-217
http://adc.bmj.com/content/94/10/752.short
http://adc.bmj.com/content/94/10/757.short
https://adc.bmj.com/content/98/6/425.full
And finally, you’re asking us to accept the Oxford criteria for patient selection?
Oxford definition is CFS research and not ME research. The NIH has already rejected findings on CBT and GET because they used the Oxford definition. If it isn’t using ICC definition then it isn’t ME research and ME patients should not be asked to support it.
No more psych research, no more psychosomatic researchers, no more poorly designed studies, no more studies with wastebasket diagnoses groups.
Agreed
andy131877- Would you mind explaining what you mean by: “Action for ME’s involvement also sours patient engagement for historical reasons”? I am trying to be as well-informed as I can -particularly regarding MEGA – and I don’t know this reference.
why involve in any way the participation of the psych lobby, when they have produced highly fraudulent paper which prevented access to care and effective treatments not only to all patients with ME in the UK, but all around the world?
Why are patients been ask for forgiveness when the harm is still happening and when there is absolutely no excuse coming from these people?
This is a bit eery to say the least. It makes me wonder who is corrupt and who is not.
Sincerely, Kati
It feels unconscionable to allow anyone that supported the #PACEtrial anywhere near anything to do with ME.
Lets not forget about the ‘with holding wheelchairs comment’, and the so called ‘vexatious ME terrorists’
PWME have been terrorised by these peoples ‘work’.
Plus they still insist and wish us to believe that the PACE data shows CBT & GET as a route to recovery. No apology, just us all being told we’ve got it wrong AGAIN!
Many PWME, and parents of children with ME, live in fear of losing their children, family and support, thanks to these people.
And we don’t need another research project into people with fatigue, we have ICC, let’s use it
Dear Mr Shepherd,
I honestly can’t believe you’re actually asking us to support research that is currently being led by Esther Crawley… There are no words strong enough to express my disappointment.
Led by? As far as I was aware there’s no primary investigator as yet?
Leaving all history aside, it makes no sense to me that people from the psychiatric or psychological field are involved in this study. If a similar study was being done on cancer or diabetes, it would be restricted to researchers in the relevant field, surely?
It makes sense to me not to tar everyone with the same brush. I know at least one person in the “psychological field” where people with ME have jumped on the assumption he supports CBT and GET when in fact he argues against it.
By carte blanche assuming anyone with a specialism in psychiatry or psychology is automatically going to try to support CBT or GET could actually be counterproductive because they could hold the very elements of debate needed to counteract the damaging support of CBT and GET.
However, I can see the point of people distrusting those already with a vested interest in believing they have evidence connected to the PACE trial which would automatically create suspicion in the ME community.
I think the controversy around the MEGA project demonstrates several things:
1) Money is power. The Wellcome Trust would probably not offer funding if the researchers did not include Wessely-school researchers.
2) This is a war. Most PWME do not accept that CBT and GET are effective treatments for M.E. Wessely-school practictioners insist that they are. Therefore we are in a state of war. PWME CANNOT back down because they’re fighting for their LIVES (in some cases quite LITERALLY) and Wessely-school practioners will not back down. Sure it’s not an armed conflict but it satisfies every other aspect of the definition of war.
3) When psychiatrists abuse their power it leads to total war. Sounds like wild melodrama on my part? Well, it’s a fact that they wield such power that it has to be extremely constrained by legislation (The Mental Health Act). They have the power to deprive people of liberty and, perhaps, ultimately of life (witness Karina Hansen, and ask the question: Are their people with M.E. who are now dead but would be alive were it not for the PACE trial and all that went before it i.e. the sum total of negative effects Wessely-school practioners have had on the global M.E. situation for the past 50 years?).
In light of the PACE trial and the entire story of M.E, does the Mental Health Act need revising to further constrain the power of psychiatrists? I’d be interested to hear other’s comments.
4) A little leaven leavens the whole lump. The CMRC was a compromise outfit from the start by including people like Esther Crawley and that rule that members must not join campaigns against other researcher’s work. This rule was utterly unacceptable for one reason: a campaign may be NECESSARY and JUSTIFIED. The preeminent example being the campaign against the PACE trial!
I am supporting this study because it will examine patients in great detail and should help to identify different subgroups under the diagnosis of ME/CFS. I also like that the collaborative consists of researchers from different fields and is trying to bring in new researchers. We need their differing perspectives and an interdisciplinary exchange and debate of ideas to stimulate progress into understanding of our condition. If you are concerned that there is too much focus on psychology in this illness surely this is a great opportunity to get the voices of our physiologies heard in the research data.
Patients of what? Fatigue? Again?
We need research into people with ME using ICC. We don’t need more research into fatigue and then being told it applies to ME.
Patients diagnosed with CFS/ME. Yes we have ICC but remember that’s still only a diagnosis based on symptoms. This will be looking at the underlying biology of the population of people diagnosed with CFS/ME to find the biological underpinnings not selecting a group based on a symptom profile. Many, if not most, researchers consider it likely that CFS/ME is a heterogeneous set of conditions and one of the roles of MEGA is to try and elucidate the biological basis of the conditions being diagnosed as CFS/ME and whether it is a single condition with graded severity or multiple conditions. Simply because you adopt a tight set of symptoms as your criteria doesn’t rule this out it only increases your risk of missing a vital component of the condition.
The only way the CMRC and the MEGA project will gain the confidence of PWME is if both are reconstituted to totally and systematically exclude Wessely-school researchers.
This is where we’ve arrived at now with M.E.. The PACE debacle has produced a fault line in science and medicine. Are we going to conflate physical and mental illness or are they capable of real and meaningful distinction?
Whatever our answers to this question the one thing we must not tolerate is lack of integrity in science. Science, and ultimately life itself, depends on personal integrity. The rigour of cross-examination in a court of law (the First-Tier Tribunal) has made definitive what was known already by PWME and their advocates but could not be proven.
Equally we cannot tolerate secretiveness in science. Peer review is a cardinal feature of science and without it we are in the realm of authoritarianism.
Why not expand on the Biobank we already have? Didn’t that get £1 million last year?
I’m with Dr Shepherd. We need a large data set as a basis for research; even 12,000 isn’t enough. Okay, so some researchers have decided that CBT and GET are cures. We all know who they are, their methods have been discredited, so what’s the problem? Apparently funding may depend on them being involved. Deal with it.
What really annoys me is that any research always has to run the gauntlet of the politics, usually at the hands of people who don’t even have the disease!
Well said!
I wrote to the CMRC a few days ago. No reply so far, not even an acknowledgment.
Charles, I am sorry. I have thought long and hard about this and I just don’t feel I can support it while it seems that the most severely ill are not going to be included.
“I think the project must be welcome but I am surprised by this sort of canvassing for support. So far no details are available of who would do what. Surely patients are entitled to judge a project on the basis of a written application, just as scientists do”
I am not sure why you quoted this, It seems to me to argue against supporting it until we know more. As you say, wait until the protocol develops.
Dr Shepherd quotes Prof Jonathan Edwards above, please see Prof Jonathan Edwards’ comment on the petition opposing MEGA site where he encourages people to sign the petition opposing MEGA. (Invest in ME research are also opposing MEGA)
I do so want to support this study, I think it has tremendous potential, and includes a number of eminent biomedical researchers. We need to sort out the different sub groups, why some respond to certain therapies and others don’t, why some get better over time, others get worse, why some have persistent symptoms and others relapse and remit. A broad & longitudinal study could yield a lot of important clues.
I am not even against a psychiatrist being involved in the study because ME, like many other physical illnesses, affects the brain & nervous system. But I am totally against including any psychiatrist who believes in psychological causation and perpetuation of the illness, maladaptive illness beliefs, and the BPS model in general. And I believe it would be very unethical to include any professional who is connected to or supported the PACE Trial, which has now been been roundly discredited.
Is it possible to salvage the best parts of this proposed study without the inclusion of any supporters of the BPS model, they have had their say and had their day?
The history of the MEA has been one of sustained pragmatic engagement with clinicians, researchers, Government and the NHS. At times the MEA has had to energetically oppose misinformation, misrepresentation, poor treatment practice and bad research, all of this was carried out without losing the high ground of sound reason and argument. The proposed MEGA initiative does not present anything that should change the MEA’s established practice of engagement and involvement.
In the last year or so Charles Shepherd has taken on the task of engaging with ME/CFS patients and carers who are largely non MEA members on the Phoenix Rising (PR) internet forum. While internet forums frequently claim huge memberships and even huger readerships, participation in discussions is usually limited to a number of more vocal individuals whose numbers are measured in mere tens, that seems to apply to PR. Charles’ measured contributions stand out as an example of good sense and remarkable patience in the face of the only just contained hostility that gets directed at those patient organisations which are judged not to conform to the online group ideal. Discussion about the MEGA proposal has followed predictable lines; the involvement of psychologists has damned the project, the MRC and its personnel are derided as enablers or fellow travellers of a psychiatric lobby and the involvement of patient organisations including the MEA is frequently presented as ‘collaboration’ in its most negative sense.
It would be wrong for the MEA to not acknowledge that there some patients and carers who have antipathy to MEGA, to the CMRC and to the MEA and other patient organisations. However as an organisation founded on clear principles, the MEA should not without very good cause change its position of broad engagement, and this must include participation in the MEGA project. Participation should not be read as the MEA giving unconditional approval to any and everything that is presented in the names of the CMRC and MEGA. To fulfil its role of patient advocacy the MEA has to be free to openly criticise what it sees as wrong and efforts to exclude from participation (as has been reported on at least once) in the CMRC or MEGA, those patient organisations whose representatives are outspoken, should be strongly resisted. Any action on the part of any participant in the CMRC or MEGA who seeks to play off different organisations against each other or to exclude organisations for following their duties to speak up on behalf of their members and target beneficiaries, should be subject to unequivocal public rebuke.
Undoubtedly the PACE trial will cast a long shadow over UK ME/CFS research, the failures of PACE, notably the arrogant dismissal of patient concerns and the failure on the part of the project team to maintain good relationships with a broad range of patient organisations should inform the MEA’s oversight of the MEGA project. Had PACE included a genuine pacing arm rather than the ersatz invention of the trial designers, £5 million of research funds would not have been wholly wasted. The MEA needs to be involved in MEGA to provide a consistent reminder that patient perspectives help make good science.