New MEGA study website (30 November 2016)

[Countrygirl]

I'd like to see the above printed out and stapled to every telegraph pole between Southampton and Bristol.

Love it!

If only!!

 

[Jo Best]

Patients are being told that it’s better to be inside the ‘big tent’ of the CMRC and have been urged to apply to join the MEGA Patient Advisory Group.

Our advice to MEGA is – disband. We have no trust in the board of the CMRC or thus the MEGA project. Now is the time for any serious biomedical researchers to cut loose and exit the CMRC tent to join the world-class UK biomedical research into ME/CFS being done right now outside. There is still time to do this. You have not yet embedded yourself in this morass but time is running out as the deadline for funding application looms ever nearer. At that point your reputation will forever be linked with the sham research that is PACE. Unless you put clear blue water between yourselves and the PACE trial, you are risking your own reputation and that of your university by association. From - https://opposingmega.wordpress.com/2016/12/14/highly-misleading/

 

[Jo Best]

I'd like to see the above printed out and stapled to every telegraph pole between Southampton and Bristol.

OPPOSING MEGA PETITION UPDATE 15 DEC 2016 —
https://www.change.org/p/opposing-m...idence-in-mega-research-for-me-cfs/u/18796154

 

[A.B.]

It is in Esther Crawley's interests to keep the BPS myth going for as long as possible, and tie up funds for biomedical research in a huge project that for the present only promises to collect samples and questionnaire data, with vague promised for future -omics when 12000 patients have been found.

It is also in her interests that the biobank they set up uses a definition of CFS and a sampling method not recognised anywhere else in the world so that no international researchers will want to use it, and savvy UK biomedical researchers who do their homework will not want to use it either.

Now imagine if they make up their own definition of a phenomenon such as PEM, one that fits into a narrative of excessive worries about health, rather than a measurable reduction in function. We would not be able to tell who actually has something resembling PEM and who doesn't. We would not be able to link any biological parameters to the symptoms of PEM. This is how easy it is for them to sabotage this project.

Even worse, outsiders could be misled into thinking the MEGA PEM is actually the PEM referred to by international research. This could influence future reviews that thanks to this confusion may conclude that data relating to PEM is contradictory.

 

[user9876]

Now imagine if they make up their own definition of a phenomenon such as PEM, one that fits into a narrative of excessive worries about health, rather than a measurable reduction in function. We would not be able to tell who actually has something resembling PEM and who doesn't. We would not be able to link any biological parameters to the symptoms of PEM. This is how easy it is for them to sabotage this project. Even worse, outsiders could be misled into thinking the MEGA PEM is actually the PEM referred to by international research.

Its not just about definitions but also about how they operationalise them.

 

[A.B.]

The more I see of communications coming out of the CMRC and MEGA team the clearer it is to me that they have no real idea what they are doing other than trying to secure money for certain researchers. The token involvement of a patient group at a point in time when one assumes the first grant application has already been written and submitted to local administrative offices is a farce.

Just to make sure I understand: a grant application being sent out would imply that the MEGA team has already decided what they want to do and how they will do it, and that patients are being involved at a point in time where they no longer get to have any meaningful influence on the design and planning of the study. Is that correct?

 

[Gijs]

Is this BPS/CBT research ever going to stop? All this bullshit keeps on and on... i really get tired of them... and angry too... There are a lot of lives being destroyed not only by this disease but also by people like Crawley, White, Chalder, Wessely, Blijenberg, Knoops e.a. but they don't care if their paychecks are comming in. These people do have a very bad karma. One day they will pay for it.

 

[rosamary]

Is this BPS/CBT research ever going to stop? All this bullshit keeps on and on... i really get tired of them... and angry too... There are a lot of lives being destroyed not only by this disease but also by people like Crawley, White, Chalder, Wessely, Blijenberg, Knoops e.a. but they don't care if their paychecks are comming in. These people do have a very bad karma. One day they will pay for it.

No they won't. They'll all retire happily and live off BIG pensions. What happened to all the psyches and other medics who were so cruel to people with MS not so many decades back? Nothing.

Sorry. They make my blood boil. But that's the way I see it.

 

[slysaint]

No they won't. They'll all retire happily and live off BIG pensions. What happened to all the psyches and other medics who were so cruel to people with MS not so many decades back? Nothing.

Sorry. They make my blood boil. But that's the way I see it.

quote from a history of MS (sounds too familiar):
"
Clinical charisma and
the exploitation of frightened vulnerable patients and
their relatives litter the historical highways and by-
ways of therapeutic endeavour in multiple sclerosis.
It has not been a golden road."

 

[Barry53]

No they won't. They'll all retire happily and live off BIG pensions. What happened to all the psyches and other medics who were so cruel to people with MS not so many decades back? Nothing.

Sorry. They make my blood boil. But that's the way I see it.

There is a big difference now, and we are part of it. Not so long back it was much easier for researchers to hide bad science (and no doubt some did). But modern social media technology is becoming their undoing - they have simply not caught up with the idea yet, but it will start to dawn on them one of these days.

 

[Jonathan Edwards]

Just to make sure I understand: a grant application being sent out would imply that the MEGA team has already decided what they want to do and how they will do it, and that patients are being involved at a point in time where they no longer get to have any meaningful influence on the design and planning of the study. Is that correct?

It is normally essential to have a grant written at leat three weeks before the deadline in order to get local admin signatures and letters of support etc. So, yes, if the PAG is meeting on 30th December presumably the project will already be written by then. There is no possibility of the PAG influencing what is being submitted. The only thing they can do that would make any difference would be to come to a decision that the current proposal is counterproductive and should not be submitted.

 

[Peter Trewhitt]

As already discussed above, the MEGA website does not allow public comments, rather people must send messages, and they aim to update their question and answer section in response every two weeks or so. Again as discussed above, this question and answer section has recently been updated.

I had contacted them about various issues, as I am sure many others have. Much of what I have raised has been addressed in their recent amendments, with the notable exception of issues relating to PACE, MAGENTA and FITNET. This is relevant given that their Team member Prof Esther Crawley is still actively pursing ME related research based on the discredited PACE model and as another Team member, Prof Paul Little, is involved in a large scale study using an at least superficially similar methodology looking at use of CBT in treating IBS based on a psychosocial illness model.

(see http://eprints.soton.ac.uk/379324/1/e008622.full.pdf . His research protocol's title is "Assessing Cognitive Behavioural Therapy in Irritable Bowel (ACTIB): protocol for a randomised controlled trial of clinical-effectiveness and cost-effectiveness of therapist delivered cognitive behavioural therapy and web-based self-management in irritable bowel syndrome in adults" and contains the following statement "The CBT content of the two treatments is the same and is based on an empirical cognitive behavioural model of IBS.The model specifies that factors such as stress and/or gastric infection trigger the symptoms of IBS, which are then maintained by patients’ cognitive, behavioural and emotional responses to the symptoms ". The CBT content also contains emphasis on the value of physical exercise.)

It would be interesting to have an idea of how many others have contacted them on this issue or on other issues not addressed in their questions and answers, in order to evaluate how selective MEGA are being in what they respond to.

 

[Peter Trewhitt]

It is normally essential to have a grant written at leat three weeks before the deadline in order to get local admin signatures and letters of support etc. So, yes, if the PAG is meeting on 30th December presumably the project will already be written by then. There is no possibility of the PAG influencing what is being submitted. The only thing they can do that would make any difference would be to come to a decision that the current proposal is counterproductive and should not be submitted.

Given the PAG will need to establish how they will organise themselves, including the issue of whether their names are publicly released as discussed above, it will be difficult to see how they can be particularly proactive at this stage. Obviously things will depend on the individuals involved, but the timetable seems to be suggesting that the MEGA team envisage very much setting the agenda and the patient advisors only able to react or comment. There is a risk that this will set the tone for a very passive or disempowered group. It will require strong personalities, who are also able to instantaneously develop effective group dynamics if they are going to achieve anything constructive. This is before you also consider that pacing may be required for group members with ME and the complications of video conferencing.

 

[Dx Revision Watch]

FORWARD ME GROUP:

Minutes for the meeting held at the House of Lords on December 7th 2016

Meeting included a presentation from Professor Stephen Holgate on the MEGA research study which was followed by questions.

Minutes December 7, 2016

http://www.forward-me.org.uk/7th December 2016.htm

Present:

Countess of Mar (Chairman)
Janice Kent (reMEmber)
Bill Kent (reMEmber)
Hannah Clifton (ME Trust)
Jane Colby (TYMES Trust)
Christine Harrison (BRAME)
Clare Ogden (AFME)
Dr Charles Shepherd (ME Association)
Sue Waddle (ME Research UK)

1. Apologies had been received from Sonya Chowdhury (AFME), Dr Paul Worthley (ME Trust) and Cath Ross (25% Group)

2. Professor Stephen Holgate, Chairman of UK CFS/ME Research Collaborative (CMRC)

2.1 The Chairman welcomed Professor Holgate. She said that there was concern by many people about the Collaborative’s MEGA study and that we would like to hear all about the study from him.

2.2 The Professor explained that he did not represent any ME organisation. He chaired the Collaborative – that was all. Some people who had posted comments on the internet seemed to think that he was a funder or represented a charity, or was a ME researcher. Some seemed to think that he was influential in the Medical Research Council (MRC). However, none of those things applied. Some people seemed to be confused about the role of the CMRC although he was sure that did not apply to those present. The reason he wanted to set up the CMRC was because he was appalled at the difficult situation many ME patients found themselves in and ashamed that so little was being done to research the illness and help those patients.

2.3 The collaborative exists, he explained, to bring together people with an interest in researching CFS/ME. It is made up mainly of scientists and the ME charities, and its purpose is to generate collaboration across the field. At last year’s Newcastle conference he had set out what he called “the grand challenge” – to scrub out what had been done before and to start again. This is called the “hypothesis-free” approach; to look at the way the condition presents itself and try to determine what is “driving” it. This is a method that has been very successful in researching illnesses such as epilepsy and arthritis.

2.4 The method involves collecting together large numbers of patients who show different “expressions” of the disease in question (such as different degrees of severity, different times of onset). You then examine them and perform various measurements within those groups, use standard clinical tests and then enter all the data into a computer programme to identify sub-types. This is called “cluster analysis”. The method makes no assumption about existing criteria such as Fukuda or Canada – although a number of participants in the study will conform to those criteria, but others will not. This lack of restraint had been very successful with migraine recently. It was very important, he said, that we respect heterogeneity.

2.5 Once the data had been analysed, Prof Holgate said, we should end up with about 12 to 15 clusters within which there will be certain characteristics – age groups, degrees of severity etc. All this data will be anonymised. They would then move on to the second part of the study which was to collect biological samples such as blood, urine and saliva which were fairly easy to collect. These samples must be kept carefully to ensure that protein didn’t break down or that DNA was not damaged. They would then be sent to a biobank (which is similar to the UK Biobank) where each sample would be annotated with a code to indicate the cluster from which it came. Otherwise each sample would be anonymised, so that the name or address of the donor is not known.

2.6 The next stage, Prof Holgate said, was the really exciting part. This was the “omics” – looking at hundreds of thousands of molecules to sequence the genome of each participant (they hope to have about 10,000 participants). They will look at mutations in the DNA and see how these relate to the patient’s symptoms. What they hope to find is multiple patients having similar associations.

2.7 Epigenetics. The professor said we can tell whether the genome is switched “on” or “off” by looking at the methylation. We can look at the protein wrapped around the DNA which can also affect genes being switched on or off. This enables us to identify what environmental factors are influencing the expression of the genetic part of the disease (viruses, air pollution, chemicals etc). The third level of epigenetics is to look at the proteome, where you take the serum or plasma and look at the many proteins in it which may help to identify the sub-groups. The final bit is the metabalome, where you take the plasma and from that identify what pathways are activated in the metabolism. Those are the different levels of epigenetics. There might be another if funding can be obtained. It’s called the Microbiome. In the human body there is much more bacterial and fungal DNA than human DNA and that could affect the condition.

2.8 Finally, Professor Holgate said, there is the need to bring all of this together; an enormous job, which is why he had contacted the Farr Informatics Centre and the Alan Turing Centre about analysing these complex datasets with their sophisticated computers. He had tried to put all this in a nutshell but inevitably it was complicated and took time to explain. They had tried to encapsulate it all on their new website www.megaresearch.me.uk. There will be a page on it enabling you to put questions to the MEGA team. (see: www.megaresearch.me.uk) They are also convening a Patient Advisory Group (PAG), and members of Forward-ME might wish to join it. The requirements and an application form are on the website. The closing date for applications is December 13th.


3. Discussion and questions

3.1 The Chairman said she had received a number of enquiries about MEGA and asked Prof Holgate if he could answer such questions at this meeting. He said he would try, but some might be best put to the MEGA team.

3.2 Christine Harrison asked for clarification of the PAG. Prof Holgate said the Advisory Group was a hugely important one. They needed to take account of the very strong feelings held by some patients and groups. The Chairman said it would be necessary for patients and their carers/families to have complete trust in this project. Their trust had been undermined by the PACE trial and other exercises. Prof Holgate assured the meeting that MEGA had nothing to do with the PACE trial etc.

3.3 Janice Kent asked whether representatives of the ME charities who were sceptical about NICE could join the PAG. Prof Holgate assured her they could. Janice said she would certainly apply, then, because she thought it was a brilliant project.

3.4 The Chairman expressed concern about the very short time scale. The Professor agreed the time was short but it would all be done via the website. The team would be working on it over Christmas after which there would be more time for deep discussion and refining the application. Dr Charles Shepherd said he understood the application scheduled to go in on 17th January was very much an outline, and didn’t get down to the “nitty gritty” of how patients will be selected including the severely affected. Prof Holgate explained that the selection of patients would not be looked into until the PAG had been convened which would be after the New Year.

3.5 For the benefit of the Group, Charles Shepherd asked what would be required of the PAG selection panel. Prof Holgate said the qualifications for PAG members were on the website. Sue Waddle said MERUK did not know what was expected of PAG members. Prof Holgate said there was information on the website. Clare added that AFME could help and asked Sue to send her an e-mail.

3.6 Jane Colby referred to the requirement for 10,000 patients. Were they to be recruited from the ME/CFS clinics? If so, what about those who were too unwell to attend them? Prof Holgate said recruitment would not be restricted to those clinics. Patients with ME attended many clinics – such as neurology, rheumatology and pain clinics, so it would not just draw from ME/CFS clinics. MEGA would need to approach all organisations who deal with ME sufferers. Some of the severely affected might need to be visited at home, and MEGA might have to apply for special funding to employ nurses for that purpose. Dr Charles Shepherd said the information on the MEGA website ought to be amended to make these points clear.

3.7 In response to Christine Harrison and the Chairman, Prof Holgate gave an assurance that recruitment would not be confined to clinics that were “signed up to” NICE. He added that the PAG would need to get together with the MEGA team to resolve the many queries that surrounded the condition of ME/CFS patients. He could not answer these himself as he was not a ME/CFS clinician. Jane Colby suggested it might be helpful to put the words “Chronic Fatigue” into the title to indicate the breadth of the study. Prof Holgate said they could consider that, but MEGA should not be constrained by historic descriptors which had not been established scientifically.

3.8 The professor confirmed that MEGA would not be looking at fatigue per se because that could attend all sorts of conditions. They would be guided by broad definitions of symptoms. He confirmed that it would not be mandatory for patients to take part in this study, and indeed no conditions for participation had been set yet. In response to Jane and the Chairman he said they could suggest to MEGA that consideration be given to the name of the study to more accurately reflect the condition of the participants.

3.9 Sue Waddle said ME Research UK was already getting many queries about the study which she was struggling to answer. For example, what definitions of the illness were to be used for the purposes of this study? Prof Holgate said there were none; to establish them was an important purpose of the study. The research was likely to show a number of “clusters” each of which could then be investigated separately. This had happened in other conditions that had been researched in this way. In lung cancer, for example, it was now known that there were seventeen different clusters each with its own characteristics and for which different treatments were appropriate. In the same way it was necessary to “drill down” into ME/CFS to discover the causative mechanisms. At the moment none of us know what those are.

3.10 Christine Harrison asked what would be the PAG’s method of working. She referred to the experience of the patient reference group of the CMO’S Working Group on CFS/ME. The professor said that would be a matter for the PAG to decide. Each patient representative would be an equal of every other member of the MEGA team. Clare Ogden confirmed that this would be the case. Prof Holgate added that MEGA would be quite different from the CMO’s group which had basically looked at the lack of provision for ME/CFS patients. The work of MEGA was more akin to astro-physics. Think about discovering black holes in space. He said this was probably why some people had difficulty with the concept.

3.11 Sue Waddle said she was concerned that the study should include the full spectrum of patients. Prof Holgate said he was signed up to that, and it was a discussion the patient representatives would need to have with the scientists. Jane Colby asked what software the study would be using. Prof Holgate explained that the equipment in question was far beyond software; they would be using the resources of the Turing Centre, the Farr Informatics Centre and five other centres across the UK, all full of informaticists, physicists and computer engineers who can put together enormous databases that can analyse the sort of complex data this study is likely to generate. That is what they did with astro-physics. This is a field in which the UK is in the lead

3.12 Patient selection. Dr Charles Shepherd said this was a matter of great concern to many patients. He said although he had many criticisms of the NICE Guidance he thought the diagnostic descriptor was a useful starting point for considering the diagnosis of ME/CFS. It was important to include post-exertional malaise. Prof Holgate said the wider the spectrum the better and noted the importance of including post-exertional malaise, but it would be for the PAG to decide. There should be a basic minimum diagnostic requirement.

3.13 The Chairman thanked Professor Holgate for being so helpful, and asked to whom we should send questions. The Professor said we should send them to the website. Clare Ogden added that she was collating questions, so they could be sent to her.

[ Ed: For Agenda Items 4 to 10 see copy of full Minutes for the December 7th meeting at http://www.forward-me.org.uk/7th December 2016.htm ]​

10. The meeting concluded with some general discussion about MEGA and the PAG. The Chairman thanked all members Date of next meeting to be announced. The meeting ended at 3.20 pm

 

[Jan]

No mention of the elephant then

 

[Peter Trewhitt]

No mention of the elephant then

Prof Holgate does repeat the assertion that MEGA is totally unconnected with the PACE trial:

"3.2 Christine Harrison asked for clarification of the PAG. Prof Holgate said the Advisory Group was a hugely important one. They needed to take account of the very strong feelings held by some patients and groups. The Chairman said it would be necessary for patients and their carers/families to have complete trust in this project. Their trust had been undermined by the PACE trial and other exercises. Prof Holgate assured the meeting that MEGA had nothing to do with the PACE trial etc."

This is factually true, but is potentially disingenuous given the involvement of the MEGA team member, Prof Crawley, in various PACE derived research trials including the latest, FITNET.

Further Prof Holgate is on record as describing the PACE based FITNET project as "quality research", and is presumably happy with the use of "the children and young people’s advisory group, which is an existing group working with the University of Bristol" that is also advising on FITNET.

Also at least one other member of the MEGA team, Prof Little, is involved is research on use of CBT using a psychosocial model of IBS with a methodology paralleling the FITNET trial ("Assessing Cognitive Behavioural Therapy in Irritable Bowel (ACTIB): protocol for a randomised controlled trial of clinical-effectiveness and cost-effectiveness of therapist delivered cognitive behavioural therapy and web-based self-management in irritable bowel syndrome in adults" See http://eprints.soton.ac.uk/379324/1/e008622.full.pdf )

For the patient community to have confidence that the MEGA project will live up to its laudable aims it is important they clearly indicate an understanding of the failings of PACE and the ongoing PACE based ME/CFS trials and distance themselves from these ongoing trials despite the overlap in the research interests of at least two of the MEGA team.

 

[Hutan]

Prof Holgate added ..... The work of MEGA was more akin to astro-physics. Think about discovering black holes in space. He said this was probably why some people had difficulty with the concept.

Oh, that clarifies things greatly thanks.

So the MEGA project is like a finding a black hole in space. A black hole, sucking in UK ME/CFS research funding and effort and shedding no light perhaps?

Prof Holgate, it's not the broad concept of MEGA that us ungrateful patients have a problem understanding or even accepting and supporting. The main problem is our lack of trust that those managing the project are competent and unbiased. If the people driving MEGA can't identify and acknowledge clear, major flaws in past and current ME/CFS research then research funds need to go to more competent people.

 

[Hip]

For me the fixation on NICE criteria is an issue in U.K. How much do the respected American scientists and ME & CFS drs e.g. aDavis, Peterson, Montoya and Jason recognise it or value it in relation to ME? Americans, when it comes to Oxford CFS seem to think it's irrelevant and should be scrapped as an impediment to proper ME & CFS research, how does NICE stand on the world CFS stage?

The Oxford criteria and the NICE criteria are not the same. The NICE criteria are in fact very similar to the CDC criteria.

@MEMum wrote: .'The amount of criticism, verging on abuse, that Dr Shepherd gets on this thread, could be a huge deterrent to any PAG member liaising with this patient forum.'

Provide examples of what you class as 'abuse' on this thread. Actual examples. And the names of the so-called 'abusers'.

"Abuse" may not be the right term, though "interrogation" might be.




My question is: people here are worried that Prof Esther Crawley will bring in BPS views of ME/CFS into the MEGA project (a valid concern). However, it seems that her responsibility is going to be setting up a biobank, which seems to be about as for as you can get from psychology; you would use a biobank to do biomedical research. Does anyone have any views on this?

 

[trishrhymes]

'it is important that we respect heterogeneity' according to Holgate.

But he does not seem to recognise that by listening to the likes of Wessely, White and Crawley he seems to have formed a misconception of what ME is, and to completely ignore progress made Internationally in defining the difference between fatigue and ME.

Heterogeneity already exists within well defined (CCC / ICC) cohorts. Widening the definition as he proposes is likely to bring in so much heterogeneity as to be indistinguishable from the healthy population, I suggest (which is exactly what the psychobabblers want).

He will not even be pinned down to insisting on PEM as essential.

I don't understand how someone so apparently proudly and willfully ignorant about the nature of an illness can think he's the right person to determine the direction of research. A massive genetics and epidemiology based study may not be the best starting point. Especially one deliberately designed to include anything anyone chooses to define as ME/CFS.

It would be a bit like someone ignorant of his field of asthma deciding they should be in charge of the direction of asthma research, and saying a mega study should be set up including everyone who has breathlessness problems. And then being bemused when asthma sufferers complain.

I still think it would be much better for smaller studies based on the existing biobank to be the focus if they want to make real progress quickly. All those other -omics could start now using that resource. He has said anyway that these parts of MEGA would be done on a much smaller subset of the MEGA sample. So why not bypass mega altogether and get on with them.

 

[TiredSam]

My question is: people here are worried that Prof Esther Crawley will bring in BPS views of ME/CFS into the MEGA project (a valid concern). However, it seems that her responsibility is going to be setting up a biobank, which seems to be about as for as you can get from psychology; you would use a biobank to do biomedical research.

Why are they getting a psychologist to set up the biobank if it's about as far away as you can get from her day job? Why not get a proper biobank upsetter? Oh, hang on ...

This sounds like the argument used when patients objected to Wallit - he won't be allowed near anything important, he can't influence anything. Next thing we know he's got Shorter in there spouting drivel. When has the BPS brigade ever tried to stop meddling and interfering anywhere and everywhere they can to the patients' detriment? The only way I would even think of supporting MEGA would be if the door was slammed very firmly in their faces. That's the trouble with a tent-flap, it doesn't slam very well.