More on MEGA

Following on from their original email and Professor Holgate’s response, Leeds ME Network have sent a further email to Prof Holgate of CMRC about concerns regarding the proposed MEGA project:

Many thanks for your swift response to my previous email regarding the MEGA study and for passing our concerns on to those who are preparing the bid for funding…

It is heartening to hear from your email that the inclusion of very severe patients is under discussion by the MEGA team. I notice, however, that you mention ‘financial limitations’ in this context. The reaction of other patients with whom I have shared this issue echoes my own: that severely affected patients should be the priority. People with ME/CFS in general are offered little in the way of treatment but most of the severely affected are abandoned entirely by doctors. They are left to lie in darkened rooms, often unable even to sit up in bed or converse with their loved ones, and without any prospect of medical intervention. I’m sure you know all this. Though I cannot claim to have taken a scientific sample of opinion, the overwhelming impression I get from patients is that if there are financial constraints regarding MEGA then these should apply to the overall number of samples taken rather than be focussed on the severely affected, who are the ones most in need of help. I am reminded of Prof Ron Davis’ observation that data from severely affected patients is the most important ‘because their biology would show the greatest differences compared with healthy controls’. It seems incongruous to be envisaging such an enormous study yet even at this stage, while the grant submission is still being prepared, to be talking about insufficient money for full inclusion in the study of those most in need of help.

A further issue regarding patient selection occurred to me while reading through the ‘questions and answers’ update on the MEGA petition website:

The update says: “The only way to do this is to recruit patients through NHS clinics throughout England.”

As I described in my previous email, taking patients from the clinics alone would produce a sample of patients biased towards the less severely affected. Since that earlier email, I have had chance to listen to Prof Davey Smith’s talk at the CMRC conference and it seems evident that using only the clinics to recruit patients would result in precisely the kind of selection bias he warns against. I’m pleased that plans are now being made to also include the severely affected. However, patients on social media are concerned that we might end up with a sample consisting mainly of mildly affected patients from the clinics along with a small token sample of the severely affected to keep the patient community happy. This will not win patient support. What we need is a fully representative spectrum of patients from mild to severe through moderate. This will require the inclusion of patients from outside the clinics not only to ensure the representation of severe patients but also of those moderately affected, for these would also be underrepresented in a sample which came entirely from the clinics (as I argued in my previous email).

The Q&A update also says with regards to patients from the clinics: “The clinicians will be asked to identify patients they judge from NICE criteria to have CFS/ME” and “Patients will have been examined and a full history taken.”

Speaking to a senior clinician from one of the clinics has confirmed my impression (mentioned in my previous email) that most of the clinics actually consider the NICE criteria to be too broad for use and rely instead on Fukuda and/or their own clinical experience. So a cohort from the clinics will not be a homogenous sample but will have been diagnosed according to the individual expertise of the clinicians involved. As for patients being examined and a full history taken, this seems unlikely to be the norm. Clinicians at triage will usually be nurses or OTs rather than doctors so there is unlikely to have been a full medical examination or a full medical history taken. The emphasis will have been on the symptoms the clinician considers to be typical of ME/CFS. As in some cases these clinicians have little previous experience of the condition and come from a mental health background, this may not necessarily coincide with what experienced doctors – or indeed patients – consider to be ME.

I think the point I am trying to make here is this: The impression is given that one of the main motivations for using the clinics is the belief that a lot of the work of data collection with regard to these patients has already been done. In actual fact, this is unlikely – and certainly not to the uniform standard that reliable research would require. In contrast, the approx. 500 samples in the National Biobank have been rigorously catalogued. Hopefully they will be used as part of the study.

I cannot speak for the whole patient community, of course, but I like to think that the majority of patients would very much support the study if the various issues I’ve described in my two emails (and possibly one two more which may not have occurred to me!) are addressed. If we can reach that stage, I think people with ME would be happy to do whatever they can to help, especially if we can be persuaded there is a genuine desire for a truly representative sample of patients. I mentioned previously that Prof Newton and (especially perhaps) Victoria Strassheim who assisted her in her severely affected project, would be ideal people to ask about reaching patients through social media and the national support groups. Further to which, I feel that local groups like ours could be a source of additional patients – perhaps we could even organise local ‘clinics’ in hired rooms or homes etc to take samples if this would be appropriate. If we can establish trust and work together, we can really make this project into the success we all want to see…

But one last thing… I have tried to stick to issues rather than personalities yet I feel I have to make a final point which unavoidably involves both.

As you well know, precision is vital for any study. But there are one or two people in the MEGA team, and you can probably guess who I mean, who seem to have some very strange ideas about acceptable science. I understand you know all about the damaging misinformation which has been produced by the now largely discredited PACE trial but I should also like to draw your attention to a study on ‘Chronic Fatigue Syndrome at Age 16 Years’.

As the name implies, this study was designed to assess the prevalence of the condition in children at age 16. The authors declared: ‘it is important that the uncertainties regarding the population prevalence of pediatric CFS are resolved.’

However, the children in this study were selected on the basis of no established criteria, but rather:

  1. a parental questionnaire asking if the child had been “feeling tired or felt she/he had no energy” and whether this had affected their education and activities, and
  2. the child’s score of 19 or over on the Chalder Fatigue Questionnaire.

It is worth contrasting this makeshift means of ‘diagnosis’ with Fukuda, which requires four out of eight additional named symptoms in addition to fatigue, and even the NICE criteria (which, as mentioned previously, most clinicians seem to discard as being too broad to actually use) which requires one additional named symptom in addition to post-exertional malaise.

Furthermore, there was no attempt in the ‘age 16’ study to exclude other conditions which might have produced fatigue in these children (with the exception of depression which was again assessed on the strength of only a simple questionnaire enquiry about the children’s feelings). There was no doctor or medical testing involved and no attempt to assess the nature of the fatigue. All that appears to have been identified, therefore, though by no means precisely, were the number of children with ‘generic fatigue’.

In spite of this, Prof Crawley (who was lead author of the study) described these children in the media as having ‘CFS also known as ME’, effectively equating ME with generic fatigue. Yet these are two very different things.

And this was billed as a study helping to ‘resolve uncertainties about prevalence’!

I mention this to help you understand at least some of the reason why patients are so unhappy about Prof Crawley’s involvement with patient selection for MEGA. She has received millions in research funding in recent years yet she produces research like ‘age 16’ which, far from ‘resolving uncertainties’, is so imprecise that it only leads to further misinformation. Patients want quality biomedical research (yes please!) but we do not want another study as poor as PACE which might take us another five years to expose and would soak up all available funding for years to come.

I do not want to make this about personalities but I am anxious for you and your colleagues to be aware of the rational basis of patient concerns, especially with regard to patient selection, for the idea of simply taking all the patients from the clinics seems to us to be little more accurate in terms of patient sample than the makeshift criteria used for ‘age 16’ – and it is hard to avoid the suspicion that both ideas have come from the same source.

I personally am not asking for any personnel to be removed from the MEGA team (as long as there is adequate oversight from patients) but I can fully understand why other patients may be doing so.

P.S. You can read more about the ‘Age 16’ study in this previous post.

Some Response from MEGA

Following yesterday’s emails to Prof Holgate, Chair of the CMRC, and Sonya Chowdhury of Action for ME, Leeds ME Network has received short responses from both of them including a bit of encouraging news.

Prof Holgate said: “The preparation of the initial outline for this grant is very much ongoing. I am sure the applicants will be as inclusive as possible, and I am already aware of a discussion of how to include very severe house-bound patients. Finance will be a limiting factor.” He says he will pass the email on to those involved in preparing the grant outline.

Sonya Chowdhury said she would leave it to Prof Holgate to respond on behalf of MEGA but was able to confirm the following:“There has never been any suggestion that individuals for the patient advisory group will be Action for ME recruited; indeed I believe I have tweeted to this effect. We completely expect the group to be representative and recruited transparently.”

So, two pieces of encouraging news: about the housebound patients and the recruitment of the patient advisory group. I’m a bit concerned, though, about yet another mention of the limitations of finance when the severely affected are mentioned. This is a massive study with 12,000 patients seeking finance in excess of £5m. Surely with so much invested, we can make sure that the severely affected are adequately represented…

Making the Most of MEGA

In an earlier post, I published an email from Leeds ME Network to Sonya Chowdhury, CEO of Action for ME, expressing reservations about the presence of Profs White and Crawley on the team of the proposed MEGA biomedical research project. Here is the latest update from Leeds ME Network:

In response to our letter to Sonya Chowdhury, we have just received what appears to be a standard letter referring to the latest updates on the MEGA petition page at Leeds ME Network have now responded in turn with the following email, slight variations of which will be sent to Ms Chowdhury; Stephen Holgate the CMRC Chair; Dr Charles Shepherd at ME Association; and ME Research UK. Our email follows:

We are grateful to the MEGA team for letting us know about the proposed CFS/ME biomedical research project. We believe it is very important that this study goes ahead but in view of some of the less than helpful research which has taken place in the past (in particular, of course, we are thinking of the PACE trial) we hope you will understand why we patients are keen to voice our concerns about the proposal.

1) The impression has been given that patients for the study group will all be drawn from the NHS Clinics. It seems clear that such a sample would be heavily biased towards less severely affected patients and that the sample would therefore be unrepresentative of the total patient population.

The reasons for this are as follows:

  • Severely affected patients are not well enough to attend the clinics. A few are reached through home visits or telephone/Skype but most do not have this opportunity. If patients come only from the clinics, this very important group will therefore be largely excluded from the study.
  • The clinics select patients with the treatments they have to offer in mind (i.e. GET, GAT, CBT). There is therefore bound to be a selection bias towards patients who they believe will respond well to these therapies. This bias may be unconscious but it will inevitably exist. Once again, this will exclude many of the more severely affected patients.
  • Some patients will not respond well to the therapies so it is likely they will drop out of the programme. Feedback suggests that such patients are often not followed up by the clinics so they are unlikely to appear in the sample. Once again, these missing patients will tend to be the more severely affected.
  • Some patients will have read about the shortcomings and possible dangers of CBT and GET and therefore will not attend the clinics or will refuse their therapies. These patients will therefore not be included if the sample is drawn entirely from the clinics. These are likely to be long term patients and therefore more severely affected.
  • Other patients who have been ill for a long time (and therefore likely to be more severely affected) will often have already been to the clinics some time ago and long since been discharged. The clinics tend to offer a series of so many sessions rather than ongoing support. Patient records are only kept for a maximum of five years.

It is vital that the more severely affected patients (falling into both the severe and moderate categories) are included in the sample, so efforts need to be made to reach additional patients through GPs, through patient support groups and through social media. Prof Newton and her team used many of these avenues to find patients for their own severely affected project so they should be able to provide useful advice. The existing ME biobank, which includes samples from the severely affected, should also be an important source of data and it would seem wasteful to ignore it..

We realise that such measures to obtain a broader sample of patients will entail additional cost but I’m sure you will agree that the study needs to be done properly. It is pointless to spend over £5m on an unrepresentative sample of patients which would only provide further misinformation about this condition.

We have several other important concerns about the MEGA study:

2) How are patients to be selected for the patient advisory groups that are mentioned?

We think it important that:

  • The expertise should be utilised of the many well informed (and often professionally qualified) patients who are active on social media and the Phoenix Rising forum. Contrary to the ‘scare stories’ circulated by the PACE authors (and roundly dismissed by the recent Freedom of Information Tribunal) these are intelligent, reasonable people who have done much to expose the shortcomings of the PACE trial and whose only aim is to encourage high quality scientific research into ME.
  • The confidence of the patient community will not be gained if patient representatives are simply selected by Action for ME, whose credibility among many patients has been severely diminished by their involvement with PACE. (We accept that most of the current leadership of AfME were not in post at the time of PACE but trust once lost can take a long time to regain.)

3) There are numerous references in the 5th Oct ‘questions and answers’ update to the need to limit the amount of data collection if either finances don’t allow or the patient advisory group objects. The issue seems to be overstated and we are concerned that it might be used as an excuse for not developing a Canadian Criteria cohort, which we feel is vital to the success of the study. These fears are amplified by the knowledge that Profs White and Crawley have already made it clear that they consider the Canadian criteria to be ‘not practicable’.

4) The 5th Oct ‘questions and answers’ update reports that patients from the clinics will have been diagnosed with the NICE criteria. However, our information is that at least some of the clinics – possibly more – consider the NICE criteria to be far too broad and they therefore diagnose instead based on their own clinical experience, possibly taking Fukuda into account. So patients from the clinics, though likely to be less severely affected for the numerous reasons given above, will not be a homogeneous sample and this must be taken into account.

5) We believe it is vital, given the nature of the study, to seek out and include patients from families with more than one member affected by the condition.

6) It is also important to include children from more than one source, not just through Prof Crawley who adheres to the now largely discredited BPS model of the condition promoted by PACE.  Tymes Trust and social media etc. are other possible sources of young patients.

7) You will be aware that patients have strong objections to the involvement of Profs White and Crawley with this project. We consider these concerns to be totally reasonable given that Prof White was one of the principal authors of the now largely discredited PACE trial which has done so much to hold back legitimate biomedical research and has led to the use of inappropriate, potentially damaging therapies in Britain and worldwide. Prof Crawley, meanwhile, has been a keen adherent of these therapies for the children in her care. Since many of the MEGA team, though distinguished scientists, are new to the field of ME, we feel there is a danger that they may look upon Profs White and Crawley as ‘experts’ in the field of CFS/ME. We feel it is important they are informed that most patients do not regard Profs White and Crawley as experts in ME, merely in their own simplistic and now effectively discredited attempt to explain it away.

Thank you for reading about our concerns which I hope you will feel free to pass on to other members of the MEGA team as appropriate. Unfortunately we will not at present be recommending our members to sign the petition supporting the MEGA trial, but will change this policy if we can be satisfied that the following measures are to be put in place:

  • an informed and representative patient advisory group
  • a broad, representative sample of patients including the severely affected
  • a cohort assessed by the Canadian Criteria

We believe these measures are necessary for the research to make a worthwhile contribution to the growing body of knowledge about ME. I hope you will agree, and that this important study can move forward with more substantial patient support.

P.S.  As stated in the above email, we are not advising our members to support the MEGA petition until the important changes suggested above have been made. Many people who have already signed have chosen to remove their signatures for the time being. Instructions on how to remove a signature can be found here.

 Naturally other groups and other individual patients will be sending their own communications. While these will have a lot in common, opinion seems to be divided on whether to press for the project to go ahead with changes (as in our own stance) or for it to be abandoned altogether. We understand both points of view but in spite of our reservations it seems wrong to us to pass up on the opportunity of such a potentially powerful biomedical study without doing whatever we can to make it work.

For some, the ousting of Profs White and Crawley from the project will be a ‘make or break’ issue. This is understandable as their presence on the team after all that has happened – especially that of Prof White – is truly outrageous. But from what we can deduce, Prof White’s presence on the team really is only token, while Prof Crawley (unfortunately) appears to be a major driving force behind the project and so is vanishingly unlikely to get kicked off. The latter would be a major cause for concern except that she won’t have control of the lab test results, so as long as the patient advisory group ensures a representative sample of patients, it should be OK.

So we’re holding out for the three issues which we believe are absolutely vital for this project to be worthwhile: a representative sample of patients; a Canadian Criteria cohort; and a strong patient advisory group to ensure that these are achieved. These factors are absolutely necessary to produce a useful and meaningful study so without them MEGA will not have our support.

That’s what we think anyway, though the situation is far from satisfactory. After all that’s happened with PACE, patients really should not be placed in the position of having to make such difficult choices about important future research.

Update: Leeds ME Network received swift replies to the above email from Prof Holgate and Sonya Chowdhury. See the next post for more information.

A Broader Picture

The last draft post I wrote about the MEGA petition was superseded by events before I finished it, so I’ll try and crack on with this one before the same thing happens again. Of course ‘cracking on’ in ME terms is still kind of slow but I’ll see if I can break the tortoise barrier.

So, what’s happened recently?

Well, we’ve been told that Peter White is retiring from research and will only be an ‘advisor’ to MEGA from now on. This perspective appears to be endorsed by the latest list of MEGA personnel, which no longer includes him. I can only give a muted ‘hurrah’ to this one. Advice is dangerous stuff and you can still do a lot of damage with it. His PACE Trial is swiftly becoming a watchword for bad science (see here, here, and here). Is he really the sort of ME ‘expert’ that either we patients or the MEGA team want around to guide this latest project?

It really is astonishing that MEGA apparently do still want him around after all he has done, and that they clearly expect patients to put up with it. It seems to me that if a passing Martian was given a brief course in English and the full facts, then even he (or she) would swiftly understand why we don’t want Prof White anywhere near this project. Why do the MEGA team not get this?

People with ME have  been left on the scrapheap for decades. I myself have been ill for over thirty years. That’s over half my life. I have no children because of it. I lost my job. My life is very limited. Yet I am one of the relatively lucky ones. I can sit and tap at this keyboard – as long as I take plenty of rests to fend off the shoulder and eye pain and overall exhaustion. There are plenty of others who have to spend all their lives in bed, who can’t stand the light, who can’t even talk to their loved ones. We’ve all heard about Whitney Defoe whose birthday it recently was. He is not alone in his suffering. The vast majority of the severely ill are left to fend for themselves as best they can. Rarely do doctors come near them and they wouldn’t know what to do if they did.

And all this time, all these decades, so little research has been done, in large part because of the fairy story dreamed up by the PACE researchers and their associates: the fairy story that Continue reading “A Broader Picture”

Not Looking Good So Far…

A few preliminary thoughts and questions come to mind in response to the latest update on the proposed MEGA Trial.

  • Question: How are patient advisory groups to be recruited?
  • The update says:

How much data we collect will depend on what our patient advisory group says will be acceptable to consenting patients and how much funding we get.

I’m concerned that this will be used as an excuse not to develop the very important Canadian Criteria cohort – Profs White and Crawley have already decided that the Canadian Criteria are not practicable

  • Clinicians who diagnose at the NHS clinics can often be OTs, nurses etc. Some of these may be very good but some have very little experience of ME/CFS. It seems inevitable that they will be focussing on what they believe to be the key symptoms of ME/CFS and not necessarily taking a full and complete history.
  • We know from experience that NHS notes in general can be inaccurate as often as not.
  • What about the severely affected who can’t get to clinics? Some clinics provide a limited home visiting service or skype/telephone consultations  but the vast majority of the severely affected do not receive these services and so will be excluded from the trial. As Prof Ron Davis says, the severely affected provide the most important data.
  • There is circumstantial evidence that many patients are rediagnosed by some of the clinics as having ‘pervasive refusal syndrome’ or ‘illness anxiety’ or some other ‘psychogenic’ condition if they don’t make progress with GET or GAT or if the clinic doesn’t think they will make progress. These patients may be at the more severely affected end of moderate so their elimination will skew the cohort.
  • Similarly, we know that many patients who drop out of therapy are not followed up on. It seems likely that these will not be included in the project, so once again the cohort will be skewed.
  • The update says:

We don’t think we will have the money to do this for everybody or for everything.

This is already sounding a bit half-baked. We’ve had enough such research. Isn’t it better to set out to do less and do it properly?

  • The clinics in general subscribe to the biopsychosoial model of the illness. Given what has happened with the now largely discredited PACE Trial, it is understandable that informed patients  will be mistrustful of a study which has the NHS Clinics at its heart. In its presently proposed form and on first reading, this project seems to me to be unlikely to obtain the support of the whole ME/CFS community.  This is unfortunate and I hope that another way of proceeding can be found.

MEGA Update

Here’s the latest from the MEGA petition site:

3 Oct 2016 — Two members of the Alliance have retired from the group: Simon Collins, University of Bristol, will be changing universities; Prof Peter White, Queen Mary University, London, is retiring from research at the end of this year and will have an advisory role.

We will be launching a series of blogs this week from MEGA members outlining why they joined MEGA and what their expertise and field/discipline has to offer.

Which doesn’t seem to me to make a whole lot of difference unfortunately. It does make you wonder why, after the PACE trial, anyone running a research study would want to take advice from Peter White… And Esther Crawley remains involved. The other day, at the CMRC conference, she was seeking to justify her use of GET on children by saying there is ‘good evidence that it works for adults’. It doesn’t seem like she’s paying much attention to the recent slippage in the reputation of PACE.

Previous posts related to MEGA:

MEGA Petition




Over the past 48 hours, many patients have been expressing concern about the involvement of Prof Peter White in the proposed MEGA biomedical ‘big data’ study of ME/CFS. It seems extraordinary that someone who believes in the simplistic ‘fear-avoidance’ model of ME/CFS should even wish to be involved in this study. Of what relevance is psychiatry to genomics?

Then, yesterday, came a timely reminder of why we can’t allow Prof White anywhere near this project. His Guardian article in defence of PACE was an extraordinary illustration of a) his refusal to accept the truth about his fatally flawed research and b) his determination to say whatever it takes to try to defend the trial, however much deceit this may involve.

It has long been obvious to those who have studied PACE that the trial involved blatant trickery, juggling outcome measures to produce the results they wanted, but these deceits were not always obvious to those unschooled in statistics and/or without the time to sit down and read through the details. Just recently, however, as the whole PACE edifice comes closer to collapse, the lies seem to be getting both more desperate and more transparent. Yesterday’s article contains a real transparent whopper, but I’ll work through the piece in order, saving the whopper for last:

  • White dismissively mentions an earlier post which claimed that sexism was part of the cause of ME patients’ mistreatment. He must surely be aware, however, that McEvedy and Beard, the two psychiatrists who first claimed ME to be a ‘hysterical’ condition cited ‘the high attack rate in females compared with males’ as part of their argument. Sexism therefore certainly played a part in the emergence of the PACE authors’ view of the condition.
  • White goes on to make several mentions of ‘fear’ among patients. “The idea of exercise was scary for some patients” he writes, though he seems to have forgotten his own 2005 study which demonstrated that “CFS patients without a comorbid psychiatric disorder do not have an exercise phobia”.
  • White speaks disparagingly of the newspaper articles which followed the various PACE announcements, accepting that headlines such as “just get out and exercise, say scientists” were harmful and misleading. At the time, however, he and his fellow PACE authors did little or nothing to try to correct such coverage. Furthermore, these very articles were written by journalists who had been briefed by the Science Media Centre, the shadowy organisation purporting to support “balance” in science reporting, which in turn was briefed by the PACE authors themselves and their associates.
  • White continues to quote his figure of 22% for ‘recovery’ in patients receiving GET or CBT, making clear that by ‘recovery’ he really means ‘remission’. (This was another sleight of hand. White and his fellow authors failed to correct media reports which – not unreasonably – assumed that ‘recovery’ meant ‘recovery’). Yet those of us who have been following the PACE saga know that the 22% result no longer stands. Alem Matthees, Tom Kindlon and their colleagues have shown in their reanalysis that the true result is only 7% for CBT and 4% for GET, a statistically insignificant outcome, being scarcely above the 3% figure for standard medical care which everyone on the trial received anyway (including those on CBT and GET.)

This leads on to the whopper, for White gives the impression in the Guardian article that Matthees and his team got their result by playing around with the figures. The implication is that this was a fiddle. In actual fact, of course, Matthees used the original trial protocol which White and his colleagues had said they would use but changed when (we can only assume) it failed to give them the results they wanted. Yes, there was fiddling going on, but it wasn’t Matthees that was doing it.

White must know that Matthees was using the original protocol. This was explicitly why Matthees requested the data – because White and his team had protested they didn’t have time to do the calculations themselves. White must have sat through – or at least paid close attention to – the Freedom of Information Tribunal which issued the order to release the data. It can’t have escaped his attention that it had been requested specifically to reanalyse the figures according to the PACE authors’ own original protocol. Yet in the Guardian article, White gave the impression that Matthees and his team had simply been making random tweaks to fiddle the figures. The only possible explanation for why he wrote it like that was to deliberately mislead Guardian readers. He must have known better. He did know better. He was telling a barefaced lie to try to save his reputation.

I’m sorry. A man who will do something like that is not to be trusted. It is totally unreasonable for the ME organisations who are supposed to be protecting patients’ interests to think it is OK for him to be involved in an important piece of biomedical research into this illness. Why they even talk to him any longer is beyond me. It is high time we move on from PACE – and move on from Peter White. We’re really suffering here. We deserve better.

 Note: I’ve been asked to include details of ‘unsigning’ in case you previously signed the MEGA petition and wish to un-sign pending further information about the study. I covered it here