Early 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.
At 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
“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
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.