MEGA Patient Advisory Group

For better or worse, I found out today I’m on the MEGA patient advisory group. ‘Mixed feelings’ is the best way to describe my reaction. I ‘m pleased that I may have a chance to make a difference to the study but aware that it might not be easy. I will do my best…

In the meantime, if anyone who is reading this has also been accepted onto the group, please get in touch. I only know of two other members so far. It will be very useful for us all to be in contact.


Spreading the Word


Dr Phil Hammond’s latest column in Private Eye is called ‘Trial on Trial’. You may remember he wrote quite a helpful column about ME just recently. This time he writes in response to criticism from a doctor who got in touch to say:

“Every illness has a physical, psychological and social component, and limiting diagnosis or treatment to only one aspect of someone’s illness is likely to lead to a much poorer outcome. This ‘triple diagnosis’ applies to any complaint you care to consider, although obviously in varying proportions. The one exception seems to be CFS/ME, where any suggestion that there might be a psychological or social component leads to criticism. That CBT is the only treatment which has repeatedly been shown to have any benefit is conveniently ignored.”

It does become tiresome having to deal with such ‘arguments’ time and time again. Once upon a time it was ‘yuppie flu’ that popped up in every article about ME. Now, at long last, that is slowly fading away. Yet now we have to deal with this endlessly repeated idea that ME patients have an unreasonable and unsubstantiated resistance to any suggestion that there might be a psychological component to our illness. People with cancer are happy enough to go for CBT, we are told. So what’s our objection?

Sigh. Look, a proportion of people with ME suffer with anxiety or depression due to having our illness, as is the case with any other chronic condition. Some receive CBT to help with this – and also to deal with other aspects of living with our condition, such as coming to terms with the fact that we are ill and the impact this has on our lives.

But CBT is classically used to ‘treat’ ME in a very different way: to try to convince us we’re no longer physically ill and that there is no physical barrier – other than a bit of deconditioning – to us slowly increasing our level of activity till we get back to normal. This was how CBT was applied in the PACE Trial, for instance, yet it is flying in the face of evidence of ongoing pathology and of abnormal response to exercise. It flies in the face of consistent reports from patients of being made to feel worse – sometimes for months or years and sometimes indefinitely – by taking exercise beyond our very limited level of energy.

So unfortunately ME is an exception. It is an exception in the way that CBT is all too often applied to it, and an exception too in this abnormal response to exercise. Put the two together and you get disaster: long-term deterioration and broken lives, with no one to turn to for help – or even apologies. This is why we object so strongly to the psychological label, not because (as is often suggested) we’re scared of the stigma of mental illness, but because it leads to the imposition of such inappropriate, potentially devastating so-called therapies.

Phil Hammond doesn’t make this particular argument in his response to the doctor who wrote in. Perhaps, as he works in Esther Crawley’s clinic, criticising the way CBT is used for ME would be a bit too close to home. But he makes a reasonable argument nonetheless, pointing out “it was doctors who initially dismissed a physical basis for CFS/ME, and as a consequence insufficient attention and resources have been given to doing large scale biological, nutritional, and genetic studies that might provide alternative treatments to the non-drug options currently on offer.”

Too right. It wasn’t patients who started labelling illnesses ‘physical’ or otherwise. It’s been foisted on us unbidden, but every time we try to point out that it’s been misapplied, we get told we’re obsessed with a false dichotomy.

And yes, the popularity (among the medical profession) of the misconceived and unsubstantiated psychogenic theory of ME has held back biological research for decades. For many patients, it has robbed us of any chance of getting well enough to return to normal life.

Dr Hammond also points out that patients are challenging the PACE Trial, the major study which purported to prove the efficacy of CBT and graded exercise therapy (GET). He says: “activists have had to fight to gain access to some of the data which they are re-analysing to find out if claims about the efficacy of CBT and GET have been overstated.” Hence the title of the piece presumably: ‘Trial on Trial’.

Which is all right as far as it goes, but as far as patients are concerned there is no ‘if’ about it. The show’s already over. The lady has already sung. Read David Tuller’s considerable collection of PACE analyses with an open mind and there can be little doubt where the truth lies. There are numerous irregularities in the study, some of them outrageous. Many of them should be enough to condemn the study all on their own, yet they form just a part of a well catalogued portfolio of bad practice.

Internationally, the word is getting around. The PACE  Trial is already being widely referenced as a prime example of bad science, and the ‘retiring’ of the Oxford diagnostic criteria (acknowledged by the US P2P report as being so broad that they include people who don’t have ME) means that the evidence of many studies which had seemed to suggest the effectiveness of CBT and GET (PACE among them) have now been dismissed by the US authorities. The Agency for Healthcare Research and Quality (AHRQ) has therefore concluded that there is now inadequate evidence to support the use of CBT (or GET) for ME.

So when that doctor who wrote in to Private Eye said: “that CBT is the only treatment which has repeatedly been shown to have any benefit (for ME) is conveniently ignored” he himself was ignoring the latest news from America – or as is more likely, he hadn’t read it in the first place, any more than he had read David Tuller’s demolition of the Dutch CBT studies, FITNET included.

ME patients have come a long way in unearthing the ills of the PACE Trial. Some have suffered deteriorating health because of their efforts to expose the shortcomings of those who were supposed to be helping them. If anyone checks the facts of the matter, the evidence to condemn PACE is already out there. So of course it is hard to forgive those journalists who continue to spout nonsense about ME patients just being lazy, but it is also frustrating to see the (now more common) pieces by well-meaning journalists who believe they are taking an even-handed approach, yet giving equal weight to both sides of the argument as though there were simply two opinions and the facts of the matter had yet to be proven.

These writers are perpetuating the current state of confusion because they can’t be bothered – or won’t find the time – to follow the links which patients have doubtless sent them and read the truth for themselves. Patients – and journalist David Tuller who has done so much to help us – are wondering how many times we have to explain the truth, how many more irregularities we have to expose – before what might be best described as ‘the establishment’ will take on board that PACE is a fallacy, CBT & GET are unproven, and ME patients have been not only mistreated but unfairly disparaged for protesting about it.

Dr Hammond has his own ideas about what it will take to get the message about PACE across. He says: “For the PACE researchers to accept (the) reanalysis would require it to be published in a credible, peer-reviewed journal with independent analysis that is free from bias.” I hope he will forgive me for a few moments while I split my sides laughing at that one. PACE itself was peer-reviewed and look what howlers got through that process. The jaw-hanging classic, of course, is that the entry and recovery criteria were set such that patients  could be ill enough to be accepted onto the trial, get worse, yet still be classed as ‘recovered’ at the end. That is a prime example of the nonsense that has been perpetrated but there are many more I could have selected – in PACE and in other studies which David Tuller has exposed, all of them sailing on a breeze through the supposedly ‘free from bias’ peer review process, presumably because the peer circles in a small country such as Britain are so tight knit that everyone knows everyone else and they can’t imagine their mates could possibly get things wrong -not even when patients later point it out to them, citing chapter and verse.

If PACE has proven one thing, it is that the peer review process is in need of some scrutiny itself. However, I understand that an article on the PACE reanalysis has indeed been submitted for publication and I hope that Dr Hammond is right and it will make a difference, at least among disinterested observers. If it doesn’t, then goodness knows what we’re supposed to do about it.

What is really needed, I guess, is for some high profile investigative journalist or broadcaster in the UK to take this issue on. ME patients in this country and throughout the world will be grateful if it can be done. There’s really quite a story to be told: not only about some very wobbly research but also about the (undue) influence of the Science Media Centre, the tendency of lazy journalists to simply repeat what they’re told instead of testing its validity, the shortcomings of peer review, the campaign to portray ME advocates as dangerous sociopaths and even assassins, the seeming inability of those in positions of power and privilege to submit their colleagues to due scrutiny etc etc… Some day it will probably be made into a feature film or a boxed set. All the ingredients are there. It would be a great story for Private Eye to take on, for instance.

Unless of course there’s a conflict of interest…

As for the PACE authors themselves, I doubt that anything will make a difference. They had clearly decided how the trial was going to turn out before they even started it, and I can’t see anything changing their views about it now, whether peer reviewed or otherwise. PACE was not a voyage of discovery. As the godfather of PACE, Sir Simon Wessely, inadvertently revealed, they always knew exactly where they wanted to get to. They simply made whatever adjustments they needed in order to get there. They live in a world where they are right, patients are wrong, and the facts can be changed to support that. I doubt they’re open to any kind of reason.

If you are reading this Dr Hammond – and I know you have found your way to my blog before – then I am grateful for the two articles you have written, but I wish you’d go on and finish the job. You called this latest article ‘Trial on Trial’ but in fact you only mentioned PACE in passing. There is so much more to be said. I really do believe that the whole issue of PACE – and ME in general – would be an excellent subject for a Private Eye expose.  Someone is going to make their mark on history – to say nothing of helping a lot of sick people – by writing it sometime, so it might as well be you. Then maybe you will be able to give up the day job… Which all in all might be for the best.

For your convenience, gathered below are some of the references you’ll need to look at for your article. A glance through previous posts on this blog might also be useful.

Links to David Tuller’s many articles on PACE. Trial by Error (in several parts) is the principal one. This list predates some recent articles, including the following:

Reanalysis by Matthees et al following release of data by Freedom of Information Tribunal

Overview of both reanalyses by Matthees et al and PACE authors

Professor Crawley’s FITNET Trial

FITNET continued including quotes from Crawley’s Radio Bristol interview

Dutch CBT Studies and Esther Crawley’s FITNET Poster

Sense about Statistics Editorial on PACE

Statistical critique of PACE Study Design by Rebecca Goldin

Pathways to Prevention ME/CFS Report

Institutes of Medicine ME/CFS Report

AHRQ Reanalysis of CBT and GET

Abnormal Response to Exercise:

Newton – Muscle Biopsies

VanNess – CPET Test

An Exploration of the Key Clinical Issues by ME Association – contains recent summary for doctors of research evidence regarding ME/CFS

ME Association Survey: Patient Experience of CBT and GET

PACE cited as example of bad science:

“…in no way do the study’s shortcomings rise to the level of fundamental errors of the kind he recently helped expose in the PACE trial…”

“The new analysis revealed what many suspected – that the interventions in the trial had little benefit.”

‘‘PACE trial is a fault line between the way we did medicine (secretive, clubbable) and the way we should do medicine (transparent, shared).’’

Note: Dr Nigel Speight left a comment in response to this post which mentions references for immunoglobulin treatment in ME/CFS. I can’t work out how to attach the documents to the comment but you can find the links here:

Immunoglobulin Treatments – University of York Review

Intravenous Gammaglobulin – Katherine Rowe

Eleven Days of Christmas

Well, in my previous post (a few hours ago), I did say to take a closer look at the MEGA site in case there was something I’d missed – and too right I was. I had failed to read the new MEGA blog post, thinking that it was just about the change of deadline for applications to join the patient advisory group. I hadn’t realised that it also provides a schedule for subsequent weeks. Here it is:

  • 9am 13 December 2016 – Deadline for applications to join the MEGA Patient Advisory Group
  • 13-14 December – Applicants contacted and group members confirmed
  • w/c 19 December – Papers and key information sent out to Patient Advisory Group members
  • 29 or 30 December – Patient Advisory Group teleconference and/or e-group meeting held
  • 4 January 2017 – Back-up call for Patient Advisory Group if needed, to address outstanding issues from December meeting.

So patients are to be given a maximum of eleven days to read the ‘papers and key information’ before discussing it and -presumably – suggesting possible alterations in a teleconference or e-group meeting over the Christmas period! So not only are they expected to do this over Christmas, but the twelve days of Christmas has been shortened to a maximum of eleven. Notice the w/c in there – not meaning ‘toilet’ in this instance (although some might think this an appropriate place to sling the schedule) but ‘week-commencing’, so the papers could theoretically arrive any time that week, which might be as little as six days before the conference.

At least they accept the possible need for a backup call ‘to address outstanding issues’ and also feel that some explanation is due. They say:

The reason that the timescale is so short is because the mainstream funder to whom we want to apply for MEGA funding has an application deadline in early January 2017. This deadline was only recently announced and was different to the timings we expected.


If we miss the deadline for this funder, we will not be able to apply again until 2018.

Even so, to use an old joke from Have I Got News For You, the words piss-up and brewery spring to mind. And of course many will say that they’ve carefully planned it like this to deliberately discourage and marginalise patient involvement. I can fully understand that point of view. If MEGA really want to win back the trust of the patient community, they are not going the right way about it.

Does this make an difference to my decision to apply for the patient advisory group? I’m still processing that one. But I’m getting more and more annoyed. Three more words have sprung to mind: ‘taking the’ and ‘piss’. And it’s not us that’s doing it…

(My normal pristine standard of vocabulary will be resumed in the next post.)

See also this OMEGA post which I should have read yesterday, including pertinent comments by Peter T.

Taking a Closer Look

Regular readers will know that I recently received a response from Professor Holgate to our 200-plus-signature email expressing concerns about the proposed MEGA study. “We are very appreciative of the enthusiasm being shown to pursue an exciting ‘omics-based research project in the field of M.E…” he said, with no mention of the various pressing concerns we raised in our email. You can read the whole of his message in this previous post.

It is a strange response indeed. It is like the shipping line which ran the Titanic writing to bereaved relatives to thank them for their interest in the general principle of oceanic travel. To carry the metaphor further, Professor Holgate is pleased to be in touch with us, but changes the subject whenever we mention icebergs.

I have now received a further response (addressing my response to his response), this one saying so little that I won’t bother printing it here, but once again referring us to the brand new MEGA website, which is indeed up and running at last.

If you’ve seen it, you were probably less than impressed. At first sight, it looks pretty much like the last one, though with the now defunct petition and the opportunity to leave comments both removed.

One thing I did pick up from Holgate’s latest letter, however, is that you can in fact leave comments. You go to the ‘contact us’ page and write in the box. If you leave a comment, it isn’t clear what happens to it, but if you leave a question and it’s one that they feel like answering, they will stick it on the bottom of the question and answer page the next time they update it. It’s not exactly the level of interaction we are used to these days but I guess it’s better than nothing so it’s a pity they don’t explain it properly on the website.

The Q&A section has indeed already been expanded, and down at the bottom there are some questions which seem to have genuinely come from patients. Like this one for instance: Will you define the sample of patients and tests before the study starts or wait till data starts rolling in and then cherry pick the patients and data to best support your hypothesis?

I can’t see Professor Holgate penning that one. I think the world-weary cynicism reveals it as one from a patient or carer. I’m pleased to say that the answer given is reassuring enough: Once we have created the Bioresource, we will apply for funding to do the research. We agree that it is very important that analyses are defined before it is done. It will be a requirement that all scientists who use the MEGA Bioresource will submit an analysis plan prior to using the data or samples.

Here’s another question on the page: Will you ensure that only people with post-exertional malaise are included to ensure this is not a study about people who have unexplained fatigue, many of whom might have had an incorrect diagnosis of ME/CFS? The answer: We agree it is very important that we check that the diagnosis of ME/CFS is correct and will check the diagnosis at several stages during recruitment.

They seem to have side-stepped the mention of PEM there (so maybe Holgate wrote that one – icebergs again…) But no need for dismay. Higher up on the page is this: all patients will need to have post-exertional malaise to be present. That wasn’t on the previous site but it’s definitely on this one. I’ve taken a screenshot as evidence in case they change their minds. It’s heartening to see it there. The patient advisory group needs to ensure it’s enforced.


So it’s worth taking a look through those Q&As rather than assuming you’ve seen it all before. You might spot something I’ve missed. There’s also a ‘why we need MEGA’ overview of the project by Professor Holgate, which looks to be an expansion on his previous piece about the need for a broad definition. Plus, of course, there’s the ‘get involved’ section with instructions for how to apply to be on the adult patient advisory group.

The original deadline for this was six days away  , clearly not long enough considering there’s an important decision to be made and a form to fill in and they’re dealing with people who are either sick or else juggling with their caring duties. Under protest, it has been extended by an extra week. The deadline is now 13th Dec at 9am: about the least they could do really. Six days was patently outrageous.

Which leaves those of us who think we are well enough and interested enough in this whole business in a bit of a quandary. Do we apply to join the advisory group or leave well alone?

Well, I signed the OMEGA petition in good faith and encouraged others to do the same, and with a) the patients coming from the clinics and b) the involvement of Professor Crawley and – especially – c) the juxtaposition of a and b, I’d really rather this thing wasn’t going ahead.

But if we can’t stop it, and that seems unlikely, then it seems to me that the more of us who understand the importance of pushing to get this thing done properly get on the advisory group, the better. Otherwise other people who may be less inclined – or less aware of the need – to stand up to Esther Crawley may end up on it instead.

So my present line of thinking is that I’m going to send in my application form for the group. Your views on this questionable course of action are welcome.

Before I move on, it’s worth observing that volunteers are not being sought to serve on the patient advisory group for the children’s part of the trial. This is because such a group is already established and the word is it’s the same group that is already serving on the FITNET trial. So this is the group that thought it was hunky dory for Professor Crawley to say she’s using the NICE diagnostic criteria when she’s not (having surreptitiously removed the necessity for post exertional malaise to be present) and which also thought it was fine for children in the activity management ‘control’ group to be encouraged to increase their activity by 10 to 20% per week up to 8 hours a day.

So it’s a sobering thought that unless we can persuade the powers that be that a new children’s PAG is needed (and chosen by someone other than Professor Crawley), we’ll have no power to ensure that the children’s trial is run properly, however many informed adults are willing to serve.

This coming Wednesday (7th Dec), Professor Holgate has accepted an invitation from the Countess of Mar to talk about MEGA to the Forward ME Group at the House of Lords. Maybe he will be more inclined to give answers to the Countess of Mar than he has been to us. I’ve sent her a copy of that email of ours and mentioned a few other points. If there’s anything else you think should be brought to her attention, she can be contacted via Forward ME. (I raised with her the issue of ‘recycling’ the children’s PAG but if anyone else would like to mention this, I think it would be no bad thing as I fear it might be overlooked among so many other concerns.)

Someone who knows him well has just described Professor Holgate as ‘a very kind and caring doctor who genuinely wants to get to the bottom of what is causing ME/CFS’ and that may well be true. It may also be that he deserves much more credit from us for bringing together such an impressive team of researchers to work on MEGA. But the trouble is he refuses to see what is right in front of his face, even when we point it out to him.  His heart may be in the right place – and I personally have no evidence either way – but if so, then he makes the mistake of assuming the same is true of all his colleagues, even those of the BPS persuasion.  There is a role for those who are affable hosts but also for those who take resolute action when it is needed and are prepared to tell their colleagues when they’re out of order. Part of the ‘job specification’ for the patient advisory group reads ‘to have a keen interest in critical evaluation and be able to look at a situation as objectively as possible’ and ‘be willing to challenge’. To do this, you have to take off your rose-tinted spectacles first – and it seems wrong that this role has to be left to the patients.

Update: When I wrote this post, I hadn’t noticed the punishing Christmas schedule which the patient group will be required to negotiate. Please take a look at this follow-up post.

FITNET Fiction

Here’s my latest response in the ongoing dialogue with Professor Holgate, CMRC Chair, about the proposed MEGA study:
Dear Professor Holgate
Thank you for your response to our email. I have not been able to consult with all the 218 people who signed the original communication but those whom I have been in touch with have expressed considerable disappointment that you did not attempt to address the specific issues we raised in our letter.
However, I await the new website with interest and hope that the FAQ section will at least deal with the two main issues we mentioned in relation to MEGA:
  •  the recruitment of a representative sample of patients (including the severely affected) who have the cardinal ME symptom of post-exertional malaise, and
  •  the suitability of Professor Crawley to take charge of such recruitment given the highly imprecise nature of her previous work in this field

Many people who signed the previous letter also left relevant comments Continue reading “FITNET Fiction”

More Voices

Many patients and carers left additional comments for Professor Holgate of MEGA when they signed our recent letter. I wasn’t able to carry these over when I transferred the post to its permanent home, so I’m reprinting some of them here.  Sorry I haven’t included them all but I am grateful for all your comments and signatures nevertheless. I shall link to this post when I send the follow-up letter to Prof Holgate (which I hope till be tomorrow). I will post the follow-up letter here on the blog as well.

Here are the comments: Continue reading “More Voices”

Reply from Professor Holgate

Well, here’s Professor Holgate’s response to our recent email. Do I feel heard? No. What about you?

Dear Spoonseeker (I am not sure whether this is the correct title but I hope this reaches you all),

Thank you for your email. We all recognise the concerns that are held about the MEGA Project and value your input. We are very appreciative of the enthusiasm being shown to pursue an exciting ‘omics-based research project in the field of M.E. and  the issues that you have raised. We are soon (next week I hope)  will be issuing a description of what MEGA comprises on a new website and will also have a frequently asked questions (FAQ) page which will be regularly updated. The latter is aimed at addressing the majority of questions that have been raised in your and other emails through the FAQs. Involvement of people with M.E. at the core of MEGA will be essential through an Advisory Group of people with M.E. and their carers.
As yet the first grant outline has not yet been submitted. We will do our very best to create the most competitive application, but even with this there is  certainly no guarantee of funding. Please be assured that we will definitely involve the M.E. community in the proposal. As you will have noted I have brought the very best scientists from across the UK to assemble this application. It will be a real team effort. We need everyone’s support to help with this otherwise it will fail at the first hurdle.

Thank you again for expressing so much interest in our endeavour. Finally, I should add that I am not a CFS/M.E. researcher myself but someone who has realised we must make inroads into the causes of this (these) distressing and serious disorders.

Best Wishes,

Professor Stephen T Holgate CBE, FMedSci
MRC Clinical Professor of Immunopharmacology