New MEGA study website (30 November 2016)

[user9876]

Professor Holgate is very well aware of these concerns, criticisms and objections and the reasons why they are being made by the ME patient community

But membership of the MEGA planning group was not discussed in any detail at this meeting

If he is aware of the criticisms of things like FITNET why did he describe it as a good trial. It suggests that he either isn't aware of the criticism, he has bad judgement or he is naive about the methodological flaws.

 

[user9876]

You are making a very valid point

A meaningful number of people with severe ME/CFS must be included in this study

So the MEGA ream will have to accept that there will be additional costs involved if people are going to be clinically assessed, examined and blood and urine samples taken in their own homes

Depending on what is being looked at results could be skewed by the exertion in getting to blood taking centers.

 

[Jonathan Edwards]

Do the MEGA team support her statements that PACE was a great trial. Do they support the methodology of her previous and ongoing work. If no statement is made on this, the assumption must be that they do, and that is not acceptable.

I am well aware that this is a key issue in relation to the patient community

It is an issue for the scientific community, Charles. Judging by the minutes I have received there will be no attempt to address it.

As far as I can establish, at least for the present, 'MEGA' consists of a bid by Dr Crawley to duplicate the existing ME/CFS Biobank, with no specification about what will be done with the samples. We are told that there is a lot of costing work to do before January but this costing work was done long ago and put into practice at LSHTM. There appears to be a lack of demand for samples even from the existing Biobank, although hopefully that will change. One or two 'leading scientists' are already making use of the Biobank material as I understand it, with funding from sources including the NIH. As has been pointed out there do not appear to be any named adult ME/CFS physicians associated with Dr Crawley's proposal. I find it very hard to see how this project makes sense.

My concern is that if there are two Biobanks, the second of which is likely to take at least three years to collect enough material to use for research, resources will be wasted and there is a considerable risk that both will eventually fizzle out. Surely the priority at this point in time is to make the maximum use of the existing Biobank. The cohort is already being documented in terms of immune function. Metabolic studies would not require very large cohorts and probably need post exercise functional studies anyway and genomic studies can be done once the cohort has been enlarged further.

I have no personal vested interest in any of this. I am on the steering committee of the Biobank and I am a CMRC member (if an inactive one). As an independent scientific opinion it seems to me that political interests are getting in the way of doing science for the patients.

 

[JoanDublin]

It is an issue for the scientific community, Charles.

Thank you

 

[trishrhymes]

Thank you @Jonathan Edwards. I agree with everything you say here.

Take Crawley out of the picture and the 'need' for a new biobank evaporates. All the effort should go into expanding and making good use of the existing one.

I would go further and speculate that MEGA could be seen as a deliberate attempt to undermine the existing biobank by setting up a bigger better funded one where Crawley and the BPS crowd have control and where they use their own fatigue based diagnostic criteria.

Any biological research done on these samples would, because of the hugely broadened definition, be likely to be so confusing as to be uninterpretable because it would mash together samples from such a wide range of conditions.

Which is exactly what the BPS people want - for the biological picture to remain obscure so they can go on playing with their questionnaires and with our lives.

 

[docsimsim]

Professor Stephen Holgate was with us for about an hour at the House of Lords yesterday afternoon - during which he gave a detailed overview of the MEGA Study and then answered a number of questions relating to the various concerns and uncertainties that are being expressed here and elsewhere about both the MEGA Study and the Patient Advisory Group

As Margaret says, we are aiming to produce the Minutes for this meeting as soon as possible

This will not be a word by word transcript of the session with Professor Holgate but it should provide a very comprehensive account of everything that was discussed and said

We normally pass the draft minutes to invited speakers to make sure that there are no inaccuracies present - so the turnaround is likely to take a week or so

I don't recall anything being said by Professor Holgate that was' not for minuting' - so there should not be any omissions

Please note that the group does not have any staff or money - so all the administrative work is done by members of the group on a voluntary basis

Forward ME Group website:
http://www.forward-me.org.uk

Dr Charles Shepherd

Look forward to hearing what he thinks E

You are making a very valid point

A meaningful number of people with severe ME/CFS must be included in this study

So the MEGA ream will have to accept that there will be additional costs involved if people are going to be clinically assessed, examined and blood and urine samples taken in their own homes

We know that 25% of ME/CFS sufferers are house/bedbound and they are readily available for MEGA to tap into (if the inclination is there which I'm not convinced it is) via the patient advocacy groups set up for severe sufferers.

So, meaningful numbers, if the study is to be scientifically valid would means 3000 (25% of the total 12,000). I don't get the impression that MEGA is prepared to do that?

 

[docsimsim]

Yes MEGA from day 1 seemed to be an attempt to set up a rival biobank, filled with genral fatigue patients, to further conflate fatigue and ME/CFS. In other words businsss as usual as it's been since 1988

Thank you @Jonathan Edwards. I agree with everything you say here.

Take Crawley out of the picture and the 'need' for a new biobank evaporates. All the effort should go into expanding and making good use of the existing one.

I would go further and speculate that MEGA could be seen as a deliberate attempt to undermine the existing biobank by setting up a bigger better funded one where Crawley and the BPS crowd have control and where they use their own fatigue based diagnostic criteria.

Any biological research done on these samples would, because of the hugely broadened definition, be likely to be so confusing as to be uninterpretable because it would mash together samples from such a wide range of conditions.

Which is exactly what the BPS people want - for the biological picture to remain obscure so they can go on playing with their questionnaires and with our lives.

s

 

[Jo Best]

Aside from the issues of research conduct and quality around PACE, SMILE, MAGENTA, FITNET etc. I would have more respect for MEGA if they were openly planning to study the symptom of chronic fatigue, instead of masquerading under the name of ME/CFS. I am heartily sick of ME/CFS being used and abused by researchers in this way, and when public funds for ME/CFS are so scarce and have been so hard won by patients and families.

 

[docsimsim]

It is an issue for the scientific community, Charles. Judging by the minutes I have received there will be no attempt to address it.

As far as I can establish, at least for the present, 'MEGA' consists of a bid by Dr Crawley to duplicate the existing ME/CFS Biobank, with no specification about what will be done with the samples. We are told that there is a lot of costing work to do before January but this costing work was done long ago and put into practice at LSHTM. There appears to be a lack of demand for samples even from the existing Biobank, although hopefully that will change. One or two 'leading scientists' are already making use of the Biobank material as I understand it, with funding from sources including the NIH. As has been pointed out there do not appear to be any named adult ME/CFS physicians associated with Dr Crawley's proposal. I find it very hard to see how this project makes sense.

My concern is that if there are two Biobanks, the second of which is likely to take at least three years to collect enough material to use for research, resources will be wasted and there is a considerable risk that both will eventually fizzle out. Surely the priority at this point in time is to make the maximum use of the existing Biobank. The cohort is already being documented in terms of immune function. Metabolic studies would not require very large cohorts and probably need post exercise functional studies anyway and genomic studies can be done once the cohort has been enlarged further.

I have no personal vested interest in any of this. I am on the steering committee of the Biobank and I am a CMRC member (if an inactive one). As an independent scientific opinion it seems to me that political interests are getting in the way of doing science for the patients.

@

It is an issue for the scientific community, Charles. Judging by the minutes I have received there will be no attempt to address it.

As far as I can establish, at least for the present, 'MEGA' consists of a bid by Dr Crawley to duplicate the existing ME/CFS Biobank, with no specification about what will be done with the samples. We are told that there is a lot of costing work to do before January but this costing work was done long ago and put into practice at LSHTM. There appears to be a lack of demand for samples even from the existing Biobank, although hopefully that will change. One or two 'leading scientists' are already making use of the Biobank material as I understand it, with funding from sources including the NIH. As has been pointed out there do not appear to be any named adult ME/CFS physicians associated with Dr Crawley's proposal. I find it very hard to see how this project makes sense.

My concern is that if there are two Biobanks, the second of which is likely to take at least three years to collect enough material to use for research, resources will be wasted and there is a considerable risk that both will eventually fizzle out. Surely the priority at this point in time is to make the maximum use of the existing Biobank. The cohort is already being documented in terms of immune function. Metabolic studies would not require very large cohorts and probably need post exercise functional studies anyway and genomic studies can be done once the cohort has been enlarged further.

I have no personal vested interest in any of this. I am on the steering committee of the Biobank and I am a CMRC member (if an inactive one). As an independent scientific opinion it seems to me that political interests are getting in the way of doing science for the patients.

@Jonathan Edwards, Is it not possible for the more reasonable CMRC members like your good self, MEA and MERUK to call for postponement of the funding application? We can't build a credible study on such faulty foundations, surely.

Last month MEGA were at the stage of asking patients for endorsement of what appeared to be just proposals and there was no mention of putting in the application form in early Jan 2017. I was one of the 3000 people who signed the OMEGA petition and gave solid reasons for our objections to MEGA (as it was/is). Some of us also wrote to Prof Holgate and CC'd in other CMRC members. Most of our concerns remained ignored in the reply emails we received, most significantly, the subject of Esther Crawley's involvement and her continued support of the discredited PACE.

The leap from the appearance of the MEGA 'petition' last month to where we are now (with PAG selections/decision making being so hastily arranged), has been gynomous as we patients had the latest bombshell dropped on us.

There's a strong sense that the agenda was set behind closed doors long before the public petition was released and that we patients have been presented with a fait accompli, and the rushed manner in which this funding application is being done further signifies the terrible sense of inevitably.

Why did the CMRC members (not all of whom are the BPS cabal) let all this happen?

 

[Jo Best]

Last month MEGA were at the stage of asking patients for endorsement of what appeared to be just proposals and there was no mention of putting in the application form in early Jan 2017.

I fully support the wording of the Opposing MEGA counter-petition (so I'm by no means making excuses for MEGA) but they did state back in April/May 2016 -

We anticipate applying for funding at the end of 2016. If successful, data and sample collection will start late in 2017. Work is now being undertaken to further develop the collaboration and application. A study of this scale will require considerable funding and may need a two-phase approach.

Source - http://forums.phoenixrising.me/index.php?threads/me-cfs-grand-challenge-mega.44637/
Then the petition that they posted on Change.org on 28th Sept. stated -

MEGA is working on putting together an application to mainstream funders to take this project forward. The first application will be submitted in January 2017 as an outline application. For this to have a high chance of success, we need evidence that patients support MEGA.

Their covering letter for the petition is as follows -

Letter to
Mainstream research funders in support of our biomedical M.E./CFS research project.
MEGA is working on putting together an application to mainstream funders to take this project forward. The first application will be submitted in January 2017 as an outline application, and we will post updates as we have them.

That's all assuming they didn't update the content from 28th Sept., as it is possible to edit the content of a petition on Change.org, but also suggests they didn't anticipate too much involvement from patients in this first stage of funding application, unless they've been doing that by consulting with patient representative members of the CMRC/MEGA.

ETA link to the MEGA petition as source - https://www.change.org/p/support-th...-its-application-to-major-uk-research-funders

 

[charles shepherd]

Having previously worked in both primary care (general practice) and various specialities in hospital medicine (including psychiatry) I know that chronic fatigue is an extremely common symptom in the general population.

Chronic fatigue can be a key symptom in both existing physical and psychological/psychiatric illnesses as well as resulting from a combination of less well defined physical, psychological and social components.

But in many cases a simple neat cause/explanation for chronic fatigue just cannot be given.

So there are obviously many different causes of chronic fatigue and whilst we can debate, criticise and question the way in which the MEGA study is going to be carried out (which is to be encouraged and should be part of the scientific process), MEGA is not going to be a study that is going to try and sort out clusters involving the huge numbers of patients who have some form of chronic fatigue.

Rightly or wrongly, and this again is being debated, the MEGA study is going to be looking at a much smaller but still very heterogenous group of patients who meet one of the 20+ clinical or research definitions of ME, CFS or ME/CFS - Canadian, Fukuda, IoM, International Consensus, Ramsay ME, London ME, NICE etc - where there is no general agreement as to which is the most accurate or helpful and where we do not have any consistent and robust associations between symptoms and pathological abnormalities.

In other words, a situation which is very messy to say the least.

The prime intention of MEGA (and I am again open to opinions as to whether this is the most effective way of doing this) is to investigate a large group of patients that meet with one of more of these definitions of ME, CFS, ME/CFS to see (as is the case in asthma and a growing number of other conditions) whether there are symptoms and/or abnormalities as identified by the new technologies that will be used (genomics, epigenomics, metabolomics, proteomics etc) that form clusters that could then help with both sub-grouping under the ME/CFS umbrella, as well as helping us to move away from the dreadful 'one size fits all' approach to management with CBT and GET for everyone who comes under the ME/CFS umbrella that is applied by NICE in particular here in the UK.

This is why I am willing to support the AIMS of the MEGA study, am willing to take part in the discussions on how the study will be designed, and at the same time listen to critical and opposing views from both people with ME/CFS and researchers such as Jonathan.

At the conclusion of this process the MEA will again be consulting with its members.

We will then be making a decision as to whether the charity is going to support a research grant proposal for the protocol that has been decided.

The MEGA study is also on the Agenda for a meeting of the ME Biobank Steering Group (which I chair) on Wednesday next week - which will give us an opportunity to discuss this particular aspect of the MEGA study.

 

[charles shepherd]

The above posting will probably have to be my last comment here on PR on the MEGA website today because we have just reached our target of £50,000 - well in advance of the deadline - for the microbiome research study appeal and I need to concentrate on this right now

So a big thank you to everyone who has donated to this MEA appeal to set up the first UK ME/CFS research study involving metabolomics

We have decided to keep the Appeal open in the run up to Christmas and I am discussing with Karl Morten and the team at Oxford how any extra funding could be used to increase the value of the existing proposal

MEA Just Giving page:

https://www.justgiving.com/campaigns/charity/meassociation/makemebetter

 

[user9876]

As far as I can establish, at least for the present, 'MEGA' consists of a bid by Dr Crawley to duplicate the existing ME/CFS Biobank, with no specification about what will be done with the samples.

Wouldn't any proposal to duplicate an under used resource simply get rejected by any funding body. I would have thought that they would need to provide a very clear reason why this is different and necessary to be taken seriously as a group. Otherwise wouldn't reviewers just reject the proposal out of hand. I think that would happen in my subject area.

 

[Jo Best]

I should think most people on PR will be aware how common a symptom is chronic fatigue and how wide-ranging the causes, but the fact remains that this is the primary symptom used to give a diagnosis of CFS/ME in UK.

One of my own objections to the MEGA proposal is precisely this -

Rightly or wrongly, and this again is being debated, the MEGA study is going to be looking at a much smaller but still very heterogenous group of patients who meet one of the 20+ clinical or research definitions of ME, CFS or ME/CFS - Canadian, Fukuda, IoM, International Consensus, Ramsay ME, London ME, NICE etc - where there is no general agreement as to which is the most accurate or helpful and where we do not have any consistent and robust associations between symptoms and pathological abnormalities.

What an inordinate waste of money, researcher time and people's lives.

There is an international expert consensus on criteria - 'Canadian' ME/CFS and 'International ME'. Matching patients to different criteria, some of which have never been operationalised, won't necessarily help in identifyng sub-groups or phenotypes. The plan sounds set to make everything more messy, not less.

There is a way to

move away from the dreadful 'one size fits all' approach to management with CBT and GET for everyone who comes under the ME/CFS umbrella that is applied by NICE in particular here in the UK.

It's for NICE to accept there's no evidence to support that CBT or GET help even a sub-group of patients.

I needn't comment on consultation with MEA members as I'm not a member of the MEA.

 

[docsimsim]

I fully support the wording of the Opposing MEGA counter-petition (so I'm by no means making excuses for MEGA) but they did state back in April/May 2016 - Source - http://forums.phoenixrising.me/index.php?threads/me-cfs-grand-challenge-mega.44637/
Then the petition that they posted on Change.org on 28th Sept. stated -
Their covering letter for the petition is as follows -

That's all assuming they didn't update the content from 28th Sept., as it is possible to edit the content of a petition on Change.org, but also suggests they didn't anticipate too much involvement from patients in this first stage of funding application, unless they've been doing that by consulting with patient representative members of the CMRC/MEGA.

ETA link to the MEGA petition as source - https://www.change.org/p/support-th...-its-application-to-major-uk-research-funders

It's CMRC that's the root of the problem. I never thought it was a good idea for patient organisations such as MEA and MERUK to join a group that included the likes of Peter White and Esther Crawley. No good can ever come out of collaborating with those who consider ME a somatisation disorder. We should know after 30 years of fatigue/ME conflation

I fully support the wording of the Opposing MEGA counter-petition (so I'm by no means making excuses for MEGA) but they did state back in April/May 2016 - Source - http://forums.phoenixrising.me/index.php?threads/me-cfs-grand-challenge-mega.44637/
Then the petition that they posted on Change.org on 28th Sept. stated -
Their covering letter for the petition is as follows -

That's all assuming they didn't update the content from 28th Sept., as it is possible to edit the content of a petition on Change.org, but also suggests they didn't anticipate too much involvement from patients in this first stage of funding application, unless they've been doing that by consulting with patient representative members of the CMRC/MEGA.

ETA link to the MEGA petition as source - https://www.change.org/p/support-th...-its-application-to-major-uk-research-funders

The trouble is that the BPS and PACE proponents have had the upper hand in the CMRC since day 1. Question remains whether MEA, MERUK and other genuine individuals like Prof Edwards can have any influence on its direction. Must admit I find it very difficult to hold any such hopes given the fiasco occurring last month where we had prominent members of the CMRC who have extremely close links to the Science media centre (SMC) wholesale blitzing the U.K. media on FITNET (which was hailed a succes in treating young people with ME, even before the trial has commenced!!). This was done with other members of the CMRC (including one of our main national charities MEA and their medical advisor dr Shepherd kept in the dark by the SMC). That was the last straw that drove many of us to sign the OMEGA petition.

 

[slysaint]

suggests they didn't anticipate too much involvement from patients in this first stage of funding application

You'd have thought they would have organised recruitment of the PAG much earlier.
"This will include establishing two patient advisory groups, one for adults and one for children and young people with M.E./CFS."

ME/CFS umbrella that is applied by NICE in particular

I seem to remember reading on a couple of threads that the diagnostic criteria at the fatigue clinics and those used by EC are even broader/vaguer. So much more akin to "chronic fatigue" than ME. Would it not be better to filter these out at the offset, or are they just to make up the numbers, thus diluting the sample.

eta: I'm still dead against MEGA BTW

 

[Jo Best]

It's CMRC that's the root of the problem. I never thought it was a good idea for patient organisations such as MEA and MERUK to join a group that included the likes of Peter White and Esther Crawley. No good can ever come out of colanorating with those who consider ME a somatisation disorder.

Presumably that's why The 25% M.E. Group, The Young ME Sufferers Trust and Invest in ME Research decided to stay out of the CMRC from the start. I thought they were right then and so nothing surprises me coming from the CMRC and I'd not have bothered about MEGA if they hadn't posted that dreadful petition. The petition was a patient-relations mistake but, like any political party, they just plough on regardless.

This was done with other members of the CMRC (including one of our main national charities MEA and their medical advisor dr Shepherd kept in the dark by the SMC).

On the same theme that for medical doctors they make good politicians, perhaps keeping Charles Shepherd in the dark was to save him any embarrassment that may be caused by contradicting Stephen Holgate's opinion of FITNET, as Charles' comments always suggest to me that he holds Stephen Holgate in high regard.

ETA - also, to be fair, it would have been better for another (or two other) non-CMRC representative to have been interviewed alongside Jane Colby (as there was Stephen Holgate, Esther Crawley, and Mary-Jane Willows representing support for FITNET).

 

[Cinders66]

NICE criteria aren't like the other ME ones though which is why Crawley quotes much higher prevalence rates than say LSTMH do. The PEM in NICE is interchangeable with PEF and only require 1 symptom other than being tired. I'm not against these wider, less burdensome fatigue syndromes getting research money but I am against those of us with severe classic ME, which is generally multi-symptom/multi-system, high burden illness not getting at the same time high injections of cash into specific needy avenues relating to the cutting edge worldwide ME/CFS effort (using stricter criteria) and more done to stimulate research into what's going wrong and what treatment can be found.
From what @Jonathon Edwards said this massive, expensive, wider syndrome biobank, phase 1 of MEGA, could take years to set up And uk will say we can't recognise or research Ramsey or ICC ME until all this is done?. Frankly it ain't gonna really help me, in bed, for years is it? Yet nothing else is being spoken of...

 

[Jonathan Edwards]

Wouldn't any proposal to duplicate an under used resource simply get rejected by any funding body. I would have thought that they would need to provide a very clear reason why this is different and necessary to be taken seriously as a group. Otherwise wouldn't reviewers just reject the proposal out of hand. I think that would happen in my subject area.

I am afraid that my experience of the funding mechanisms in biomedical science do not lead me to be so confident.

 

[Skippa]

PACE TEAM: jeez that was close, I think we got away with it.

PACE SUPPORTERS: don't be so sure, what if they find out that ME/CFS really is biological? And NICE is reviewing next year too.

PACE TEAM: yikes, we need to delay that. And what can we do about them finding out ME/CFS is biological?

PACE SUPPORTERS: why not set up a biobank of sleepy people, make them dig around for a needle in a haystack trying to find a common denominator.

PACE TEAM: yes! And if we drag our heels about it, we can force NICE to delay their review too.

ALL: perfect!