What should be done about the MEGA (ME/CFS Epidemiology and Genetics Alliance) project? Concerns and response

Update October 21, 2016: Professor Jonathan Edwards is now urging signing the petition opposing MEGA. Find the petition here.

7976304-special-edition-stampEarly this morning some thoughtful comments were approved at my PLOS Mind the Brain blog concerning the MEGA (ME/CFS Epidemiology and Genetics Alliance) project. After careful consideration, I felt these comments should not be left simply buried there, but put into a larger conversation. Below I have posted them, along with a directly relevant statement from Dr. Charles Shepherd.

I am not a ME/CFS patient or parent of a patient, I’m not even a resident of the UK. But I have been drawn into a long and complex struggle, starting with a comment that I made on Twitter, a rejection of Simon Wessely’s direct message to me that I should not get involved in the controversy over the PACE trial, and my making of a request for data that the PACE investigators had promised would be available as a condition of publishing in PLOS One. The PACE investigators publicly labeled my legitimate request as “vexatious” and almost a year later have not turned the data over.

mega-image-481x230At the outset, I should note that Professor George Davey Smith has key responsibility for the genomics section of this complex project. I have the greatest respect for his intellect and intellectual integrity. I have learned immensely from him.

However, I have serious concerns about other personnel involved in this project in terms of their recent conduct as physicians and scientists. Among other issues, the nature of their role in the project needs to be clarified. Conditions need to be in place that they will not use their role to inflict further abuse and bad science on the patient and scientific communities. Other personnel must step in and demonstrate that patients have an appropriate role in the design, implementation, and interpretation of the data published in peer-reviewed journals in a timely fashion. Patients should be heard, welcomed to  high-level participation in research, and not just used.

Concerns, criticisms and questions about the MEGA study are being expressed by the ME/CFS [   Myalgic encephalomyelitis)/Chronic Fatigue Syndrome] patient community on internet discussion forums.

Some clear inaccuracies are circulating, but there are some big issues yet to be settled.

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. –Dr Charles Shepherd

And

“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” – Professor Jonathan Edwards

A comment left at the PLOS Mind the Brain

There are now also concerns about Esther Crawley’s involvement in the MEGA project, which is presented as an omics and big data approach to stratifying ME/CFS patients.

Esther Crawley and Peter White are involved in this project as ME/CFS experts, despite significant patient opposition. That these are even involved calls into question the integrity of the rest of the team. White has engaged in fraud in the PACE trial. Crawley’s unethical behaviour is well described in this blog’s article.

That aside, the concern is that they (or other BPS model proponents) will introduce flawed definitions of the illness and its symptoms into the project. Crawley and White certainly have a history of downplaying, ignoring, or psychologizing physical symptoms of this illness, or simply conflating this life destroying illness with the not uncommon and often transient symptom of tiredness. On the project’s petition page, the important symptom “post-exertional malaise”, which is an objectively measurable, typically delayed, decline in function with an increase in symptom severity, is referred to as “post-exertional stress”. Redefining words and concepts in a misleading manner is something the PACE authors have done repeatedly, so one wonders if we’re already seeing the redefinition of an important physical symptom to make it fit into a narrative preferred by PACE authors and their colleagues. A vague term such as “post-exertional stress” certainly fits well into a “health anxiety” narrative of patients supposedly worrying excessively about ordinary muscle soreness after exercise, and mistaking this for symptoms of an illness.

Such a narrative would be particularly easy to construct if permissive case definitions were used. The project plans to recruit patients from NHS referral centers, which are operating according to the BPS / PACE paradigm, with NICE criteria which are permissive. NICE instructs doctors to only refer patients to these centers when they are mildly or moderately affect and believe that CBT and GEt are appropriate. For this, and other reasons, it is likely that this recruitment strategy will exclude or underrepresent the more severely ill.

In a large and important project, a solid foundation of knowledge and methodology is more important than ever.

There are also concerns about the patient advisory groups. Patient involvement is important according to MEGA study authors, and two patient advisory groups will be created. No details have been given on how patient representatives will be chosen. It would be problematic if the authors chose patient representatives that are not considered trustworthy by the larger patient community.

We suspect they will be drawn from the AFME and AYME charities. Many patients don’t trust these organizations. Crawley is medical officer of AYME, and AFME has a history of collaborating with PACE authors and generally being lenient and ignoring problems with the BPS approach and the PACE trial. AFME approved of the removal of actometers from the PACE trial with dubious justifications. It was repeatedly mentioned that patient advisors in the MEGA project will be able to prevent certain data from being collected and certain tests being performed. Will we see important questions not being asked, important data not being collected, important tests not being done because these undemocratic patient advisor groups with ties to the PACE authors believe that doing so is in the best interest of patients?

In general it is a problem that communications go through the untrusted intermediary AFME.

ME/CFS Research in the UK needs to divorce completely from the failing BPS model of the illness. Patients hate it, it’s scientifically flawed, and has produced no results when reasonably standards of evidence are applied. Consider that over 12000 patients signed a petition to the Lancet against the PACE trial, while the MEGA study has collected only 2130 signatures (with number of signatures essentially having stopped). The distrust of the BPS model is so great that any project touched by its influence becomes tainted. The MEGA study team should reconsider its current approach and whom it collaborates with.

Give this MEGA project a chance to fly – don’t try to strangle it at birth, says Dr Charles Shepherd | 3 October 2016

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

So far, Dr. Shepherd’s statement has attracted numerous comments, which you can see by going to the website. However, I would like to, reproduce one comment by a noted patient citizen scientist.

Simon McGrath October 3, 2016 at 5:35 pm

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.

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26 thoughts on “What should be done about the MEGA (ME/CFS Epidemiology and Genetics Alliance) project? Concerns and response

  1. Thanks for raising the subject, Prof Coyne.
    I also respect Simon McGrath, but that reply does not reassure me as it does him. In fact it encapsulates my concerns.
    First, it underlines the central role to be played by Crawley, who is a fatigue researcher and not an ME researcher, and who has been involved in junk trials such as SMILE.
    Second, I think the use of broad criteria serves only to confuse and not to clarify, turning the study into a fatigue-including-CFS/ME study.
    Third, the clinics are based on the current NICE recommendations, including CBT and GET. The sample will inevitably be biased: excluding those with severe ME and those of us, like me, who know there is no treatment currently available and would not waste time and effort in going to a clinic

    Liked by 8 people

  2. Nice guidelines have been declared by NICE themselves as not fit for purpose, so it hardly reassures me that this dx criteria will likely be being used. Adult patients only attend at clinics for completion of or refusal to do CBT/GET course then they are discharged…so those of long duration would also not be captured.
    We are, with this current selection of ME advisors, in danger of having the biggest biobank of biopsychosocial defined samples masquerading as ME ones….
    Things need to be made a lot clearer before anyone is asked to sign up to this, and the biobased scientists would be wise to check who they are associating with if they are not to bring their own excellent reputations into disrepute.
    This intitial liaison exercise is poorly thought through and it is such a shame as all those with ME are anxious to be able to commit to what could be an excellent biomedical based study.

    Liked by 6 people

  3. What I believe needs to happen for this project to gain widespread patient support:

    BPS model influences need to be removed entirely (that specifically includes White and Crawley). There will be no significant support if this doesn’t happen.

    Trustworthy patient advisor groups need to be formed, and their role described clearly. They can also handle the communication aspect.

    There needs to be a solid strategy for recruiting patients from across the whole spectrum of illness, including patients that are too ill to visit a clinic, and those who do not fit into the BPS paradigm that has dominated the health care offered to patients until now. We patients have fallen through the cracks of the health care system, recruiting those who have not (yet) fallen through will exclude patients with certain characteristics. Sadly with this illness, it cannot be assumed that there is working health care system in place.

    A more detailed study plan should be published. Public support can be sought at this point. If the plan is good the project will receive strong public support from the patient community. The Open Medicine Foundation has a similar omics approach to research ME/CFS and has been able to raise $5 million since 2012.

    In case anyone is wondering. BPS stands for biopsychosocial. In practice it seems to mean that persistent unexplained symptoms are assumed to be caused by ongoing psychological and social factors.

    Liked by 2 people

  4. My concerns go beyond who’s involved and how are they recruiting

    My concerns regarding the study as a long-term severely affected patient who has already seen what should have been the best part of my life wasted, is if this will essentially freeze the uk CFS/ME (their usual terminology) field & predicament for us for the next five years? And are we committing five years to subgroup an excessively broad fatigue spectrum that we don’t need to lump M.E in with anyway, except those ideoligally committed to lumping together fatigue syndromes as some in the uk are? What can people from severe ME expect from uk in terms of treatment for their illness if all the focus goes on subgrouping chronic fatigue (severe ME is still hugely marginalised in U.K. although it’s 25% of sufferers and the suffering/debility is huge) – is it really the best way to focus efforts and what else will happen in the meantime, anything ?

    By freezing the field I mean by dominating the general attention & focus (as it has this year), gobbling up the research funds and keeping us in a “CFS fatigue spectrum umbrella” approach (with essentially no recognition of ME or SEID or stricter criteria in terms of services and research) until this research is published and the field supposedly stratified better. Of course developments in other areas such as the to be published rituximab trial and the probably unexpected forced release and reanalysing of PACE data might force change.
    But The uk establishment (differing from other parts of the world) has always insisted on the broadest criteria fatigue spectrum approach and the charities support that argueing this will remain until differences are proven though science. Will this study stall change (not discounting its possible contribution to CFS science) which will maintain status quo till its published in uk until in the 2020s? IOM report in USA has driven change there saying a systemic exertion intolerance disease can already be recognised and diagnosed and researched. MRC & NHS & BMJ etc have yet to define and treat & research this patient group in any such serious terms but is it going to be years off now? .

    Liked by 4 people

  5. I think it is imperative that those organising and carrying out this research need to first take the time to look at the scientific evidence and history of ME, to understand what has been going on, why patients are so unhappy with the situation as it is being presented. It is highly likely they have been fed a very distorted view of the scientific evidence and about nutty militant, dangerous patients.

    If they look at the scientific evidence as outlined in IOM/P2P etc they will see ME is a serious multi system disease, not behavioural, then they should publicly, unequivocally reject the BPS model, their diagnostic criteria and the expertise and opinions of those associated with it.

    The MRC and other funding bodies also need to clearly reject the BPS model. The longer they support this untenable view the worse they look, now’s the time to reject it.

    PEM is a diagnostic symptom for this disease and therefore the diagnostic criteria for the trial must reflect this, not some wide BPS catch all type definition. Naviaux’s research is showing one disease with the heterogeneity being due to individual genetics overlaying the common metabolic abnormalities, not multiple different diseases. So the argument of needing very wide diagnostic criteria doesn’t wash.

    Liked by 7 people

  6. If the involvement of Crawley and White, and the biopsychosocial model doesn’t scare you enough, the use of the NHS diagnostic criteria and the fact that they are recruiting from among centers that only believe this is a psych illness, and that also only take mild to moderate, short- term patients, should definitely scare you….
    ….not to mention that they are already using deceptive language in their definition of PEM, and in their attempts to try to convince patients that this is different (when thus far it seems to be more of the same….the same which has harmed many patients and spread false information to Drs, the same which has wasted tons of money, time, and other resources that should be going to finding real help for sick patients, the same that has put a huge stigma on this illness and that stigma has prevented many good researchers from trying to help us & many good Drs from caring about trying to properly treat us, the same garbage that has convinced many that we are either faking it, mentally ill, lazy, and/or just afraid to exercise…..more of all the same)

    If the idea behind this is to include a variety of patients, then using the totally watered down definition that does not even come close to truly defining this illness is not the way to do that. Their definition not only leaves out true PEM and many of the real physical abnormalities that exist in ME, but it also excludes the more severely ill, and it includes many who do not have anything more than garden variety tiredness (which most of the general population could qualify for at some point.) Seriously, it’s like if they did a study on cancer that included everyone who is a little tired or on TB that included anyone who ever had a mild cough. Have so few learned anything from the massive disaster that was PACE?

    Liked by 4 people

  7. The ME/CFS Research Collaborative was set up, by the usual psychiatric suspects, at the time when the first rituximab trial was presented at the Invest in ME Conference, and was clearly a (successful) attempt to ensure that research funds would be diverted away from Invest in ME (whose annual London conferences, by the way, are never reported in the UK Media – how has that been engineered?). Early minutes and administrative records of the ME/CFS Research Collaborative will indicate how the psychiatrists behind it proposed to present a front of respectable sientific research, which was aided by presentations by genuine researchers from the US who were unaware of the role they would be playing within the psychiatric power games in the UK. There was a successful attempt to keep PD White in the background during the first Conference. There is documentation by the TYMES Trust who looked into this carefully and ascertained, for example, that the ME/CFS Research Collaboration arranged to have one set of minutes to be circulated only to the members, while another would be prepared for public presentation, supporting the view that this organisation is nothing more than a front for the psychiatric group.
    I am somewhat disturbed that Dr. Shepherd appears not to be aware of the nature of this group (and would be reluctant to believe that he is actively supporting them, but it looks as though he is). I understand that his organisation had £50,000 raised for biomedical research, which would have been a great help to Invest in ME…the organisation that has a real commitment to biomedical research progress…but which may have been used instead to support the ‘research’ efforts of the ME/CFS Research Collaborative. Yet again, the Wessely group of psychiatrists are monopolising vast amounts of research funding which clearly is intended to support the BPS view and continue the abuse of ME patients, including children, by ‘treatments’ which will almost guarantee their deterioration into severe ME.
    These guys don’t rest for five minutes, and are desperate to prevent, at any cost to patients, the loss of their expensive empire based on the psychiatric view of ME/CFS.
    The reanalysis of PACE should put a stop to this, as would any objective study of the outcomes of these treatments, especially for those who drop out. Let’s see full reporting of harms before going any further.
    The people who have become alert to the real nature and purpose of this study and refused to offer it further support are absolutely right.

    Liked by 5 people

    • The timing of the MEGA study petition is also interesting. I’m sure White is glad that patients are busy with this rather than his now exposed fraud in the PACE trial.

      Liked by 3 people

    • The article above has been labelled as written by me, but mistakenly labelled as written by Tammie. There is an earlier post written by Tammie, with which I rully agree, but it was labelled as having been written by me. Tammie has liked my article (thanks, Tammie!) but that seems to having turned into her being labelled as author of mine, and my being labelled as the author of hers. I’d be grateful for this to be sorted out, and doubtless Tammie would, too! This comment reply seems to be going to be listed as me misusing her site, followed by her misuing mine! WordPress, please sort this out!

      Liked by 1 person

  8. My own personal opinion, is that “strangling” a large trial is to be preferred over allowing that large trial to be co-opted by powerful forces with an agenda other than getting to the bottom of the science so as to actually help patients.

    Allowing those who want to push a psychosocial agenda to co-opt this trial will set the field back two or four times longer than the trial takes. 😦 😦 😦 😦

    Liked by 4 people

  9. We can no longer support any research that is not able to be compared globally to other research, as it only obfuscates the general picture of M.E. We can no longer support research which excludes moderate and severe patients. We can no longer support research that includes patients without M.E. We cannot consider anyone who persists in ignoring patient preference and primarily referring to heart disease as CFS or CFS/ME to be operating under a non-BPM model, to be someone who truly believes in the veracity patient experiences or to understand the severity of the impact of this disease. Researchers who refuse to use the ICC definitions and symptom descriptions do not have patient’s best interests in mind, do not have respect for best practice in research design. Anyone who works with someone in any capacity who is responsible for the fraud of the PACE trial cannot be trusted to have patient’s best interest in mind. And any study this amount of money being thrown in by the government cannot be assumed to be free from the sort of an ethical interference by the DWP in the insurance companies that we have already seen in PACE. If the research is looking broadly at “fatigue” rather than focussing on the specific neuroimmune symptoms of ME, then severe doubt is cast on the actual reading that the research team has done on ME (in other words not much) and on their validity as ME researchers. If they can’t be bothered to study the ICC document, how can they be doing this research???

    It would be as if I, as a paleoanthropologist, asked for millions of £ in funding to go search for a new sub species Homo habilis fossils without specifying where on the planet I planned on looking, having not read anything about the locations of the hominins I was searching for, and being unfamiliar with their anatomy or the relative anatomies of species from the same time period so that I could identify them when found. And I was going to include any ape-like fossils I found in my hypodigm, as long as they had one shared but non-defining characteristic. And then justifying my lack of knowledge or qualifications of the subject matter by saying that “new researchers need encouragement so that the field can grow”. And I then kept calling the fossils I was searching for Dead Apes instead of Homo habilis sp. And I didn’t believe in Evolution and my advisors were Creationists.

    This is what they’re asking ME patients to continue to be subjected to. This is what they’re wasting research money on. This is NOT science. This money needs to go to well designed biomedical research performed by qualified, experienced researchers who actually respect patients and understand the full range of symptoms that make up ME.

    Liked by 4 people

  10. We can no longer support any research that is not able to be compared globally to other research, as it only obfuscates the general picture of M.E. We can no longer support research which excludes moderate and severe patients. We can no longer support research that includes patients without M.E. We cannot consider anyone who persists in ignoring patient preference and primarily referring to our disease as CFS or CFS/ME to be operating under a non-BPM model, to be someone who truly believes in the veracity patient experiences or to understand the severity of the impact of this disease. Researchers who refuse to use the ICC definitions and symptom descriptions do not have patient’s best interests in mind, do not have respect for best practice in research design. Anyone who works with someone in any capacity who is responsible for the fraud of the PACE trial cannot be trusted to have patient’s best interest in mind. And any study this amount of money being thrown in by the government cannot be assumed to be free from the sort of an ethical interference by the DWP in the insurance companies that we have already seen in PACE. If the research is looking broadly at “fatigue” rather than focussing on the specific neuroimmune symptoms of ME, then severe doubt is cast on the actual reading that the research team has done on ME (in other words not much) and on their validity as ME researchers. If they can’t be bothered to study the ICC document, how can they be doing this research???

    It would be as if I, as a paleoanthropologist, asked for millions of £ in funding to go search for a new sub species Homo habilis fossils without specifying where on the planet I planned on looking, having not read anything about the locations of the hominins I was searching for, and being unfamiliar with their anatomy or the relative anatomies of species from the same time period so that I could identify them when found. And I was going to include any ape-like fossils I found in my hypodigm, as long as they had one shared but non-defining characteristic. And then justifying my lack of knowledge or qualifications of the subject matter by saying that “new researchers need encouragement so that the field can grow”. And I then kept calling the fossils I was searching for Dead Apes instead of Homo habilis sp. And I didn’t believe in Evolution and my advisors were Creationists.

    This is what they’re asking ME patients to continue to be subjected to. This is what they’re wasting research money on. This is NOT science. This money needs to go to well designed biomedical research performed by qualified, experienced researchers who actually respect patients and understand the full range of symptoms that make up ME.

    Liked by 4 people

    • I agree.

      I too have concerns about trust, but I also have scientific concerns as well.

      From the genomics I have been involved with so far, populations from different ethnicities will be needed.

      There will the problem of deciding whether a finding of a given p value has any relevance to the disease at all, especially as important mixtures of mutations (mutation combinations) may be missed altogether by such strategies. Some key pathways of lower p value could be lost amongst spurious findings of high p value which merely represent ‘tag along’ flotsam.

      Data mining alone is going to be futile.

      There has to be a pre study strategy of how to properly evaluate the data and to used informed searching methods, so to avoid lucky dipping based on statistics alone. There will be a need to focus on what is meaningful and relevant to the condition, and I can’t see White or Crawley having any clue as to where to look. They have been avoiding organic science for decades, and will be the worst to advise us on how to examine the data.

      Liked by 7 people

  11. I think it is time for a lawsuit. Doesn’t anyone in the UK or US have any connections to human rights and civil issue law firms to sue NHS, SMC, PACE Trial authors, CDC and NIH? ANYONE!

    I believe all of these organizations worldwide are covering for one another and don’t want to face a biological disease because they find it too expensive to research and a diversion from cancer, AIDS and diabetes which are the research grant and pharmaceutical company money making machines.

    After 30 years they are hoping this all just goes away or they can keep everything “cheap” and covered by psychiatry.

    When you spread US disabled and compromised patients out over 50 states it isn’t such a burden even if ME/CFS patients cost $20 billion a year. It is spread out among disability and its denial process, food stamps, state disability funds, loss in wages, etc.

    British medicine is a social failure in that they let psychiatrists and the media run it because it is cheaper than real medical research. Who can’t deliver babies and fix a broken arm or treat cancer for that matter! Medicine is more than that and the NHS is broke and even though deep down they know they are dealing with a disease they can’t admit it due to saving face and money. All they have to do is say they were wrong, they are sorry and they don’t know what to do. It’s only the truth.

    Liked by 4 people

  12. This MEGA team has curiously opted for a petition site to canvass for support for this study. This is rather unusual, considering that a majority of patients disagree in the inclusion of Peter White and Esther Crawley as being part ofthe experts for the MEGA trial. What is most needed for this potentially important study is the exclusion of the BPS school, alternative recruitment of patients, strict criteria of inclusion which should not include a reference from a psychiatrist.

    Liked by 4 people

  13. In re supporting MEGA: Fool you once, shame on them. Fool you twice, shame on you. 1. Those who may wish to sign ought first to have seen a written account of the MEGA project from earliest concept, including participation by individuals. 2. A serious outline of proposed research paths ought to have been made publicly accessible before any person were asked to lend the project his or her good name. An outline of 10 to 20 pages could offer a tentative idea of what is intended. 3. The promise of Wellcome money should cause fright and flight among PWME due to the Trust’s history with regard to ME. 4. Wrapping up all UK research (due to budget capture as per Invest in ME.) in one large parcel with no disclosed structure or organizational authority would seem to lead (again) to scientific stagnation. Research funding is better done in discrete parcels in order to remain open to advantages of the rapid fire advancement of life sciences, in which Britain plays a disproportionately large role.

    Liked by 4 people

    • Exactly! The only prudent course to take with any of these charlatans is to oppose any ME study they propose to undertake. They’ve burned us on hundreds of studies, probably substantially caused the early death of many many thousands of ME patients and incalculable suffering. This is a human rights issue. NO MORE!!

      Liked by 2 people

  14. People with ME score lower on the Health-Related Quality of Life score than many other conditions, including multiple sclerosis and stroke. There is a dire, urgent need for research into ME that can shed light on the pathophysiology of ME so that there is a better understanding of the disease, and to provide better tools for diagnosis. Research studies need to be scientific, have clear aims, use robust methodology and objective endpoints.

    The proposal to conduct a ‘big data’ genomic study may indeed be the latest trend but, in my opinion, it is not what is needed right now for ME.

    First, we need a better understanding of the pathophysiology of ME. Without it, there is a possibility that a big, expensive genomics study will produce tens or more of risk loci with no understanding of how they are linked to the disease. Given the dire situation that ME research is in, I do not think a genomics study is an appropriate use of funding and is not the most promising line of research.

    Instead, we need research that builds on the studies that have already yielded interesting findings in ME patients in areas such as skeletal muscle dysfunction, the metabolic profile, immune system abnormalities, infection, neuroinflammation and cardiac dysfunction. These are mostly small studies using 50 or fewer subjects and need to be repeated in a larger sample population. This would be a better use of funding, in my opinion.

    A further point is that three of the proposers took part in a campaign organised by the Science Media Centre to smear ME patients. If researchers want support of patients for their research they could start by showing the patients some respect.

    Liked by 3 people

  15. It’s worth mentioning that Stephen Holgate referred to Crawley’s work as high quality research. He is organizing the MEGA study.

    The CBT and GET studies all follow a similar recipe as PACE. I have no confidence in the skills of someone who doesn’t understand why lack of blinding, reliance on subjective outcomes, etc. are problematic.

    I don’t want to see projects led by incompetents take away funding from the good researchers.

    Like

    • I agree. It’s very alarming that Stephen Holgate considers Esther Crawley’s work as high quality. Looking at this section of the protocol for recently and shamefully over-hyped FITNET trial, (itself based on the Dutch study which appears to have similar flaws to PACE) much sounds disturbingly like brain-washing:

      “The modules for participants introduce CBT, present CFS/ME as a multi factorial model, discuss the role of the family and develop treatment goals. The CBT modules focus on cognitive behavioural strategies with instructions on exercises for identifying, challenging and changing cognitive processes.
      Modules 1, 2 and 4 introduce CBT and explain the role of therapists, present CFS/ME as a multifactorial model with predisposing, precipitating and maintaining factors and discuss the role of the family.
      Modules 3 and 5 focus on treatment goals including the goal of full time education. Modules
      6 to 19 focus on cognitive behavioural strategies with instructions on exercises on
      identifying, challenging and changing cognitive processes that contribute to CFS/ME………

      …….After parents complete the psycho-educational sections, they separately complete
      the remaining CBT modules. These explore and address parent’s beliefs and behaviours
      towards their child with CFS/ME.”
      http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0007/170962/PRO-14-192-109.pdf

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  16. Grave concerns about MEGA and some of its personnel are sure to be increased by the very recent Science Media Centre’s highly orchestrated promotion of Esther Crawley’s FITNET trial.
    It is truly a question of history repeating itself – so many of the major flaws in the PACE trial, which were covered up until recently, are glaringly evident in the original trial of FITNET in the Netherlands, as the very admirable citizen scientists Tom Kindlon and Joan Crawford point out in letters to the Lancet:

    “Three of the four thresholds used by Sanne Nijhof and colleagues (April 14, p 1412)1 for their post-hoc definition of recovery from chronic fatigue syndrome are virtually the same as the entry criteria. For example, 40 or more on the fatigue severity subscale of the checklist individual strength 20 (CIS-20) was equivalent to “severe fatigue” at baseline, yet once a participant scored less than 40 (the mean +2 SDs for a healthy population) they could be counted as recovered! The face validity of their other post-hoc recovery definition, listed in the appendix, seems stronger, but it gives a much lower figure for recovery of 36% (rather than 63%).”

    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61324-5/fulltext

    “CFS can have a relapsing-remitting course: some patients self-report recovery, only for the condition to return.3 Further longitudinal data are required to show that the recovered FITNET patients did not subsequently have a return of their symptoms and disability.

    A key feature of CFS is that exertion brings on a range of symptoms;4 those affected tend to engage in little high-intensity activity to avoid such effects.5 Information from actigraphy is essential to ascertain whether the recovered CFS patients are truly well or if they have adapted their lives and are engaging in less high-intensity activity (such as sports and dancing) than their healthy peers.”

    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61325-7/fulltext

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