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MEGA Questions and Answers: Latest Petition update

JohnCB

Immoderate
Messages
351
Location
England
But I have just had one email from a PR MEA member expressing concerns!

I'll identify this as me. I wrote back channel as I included personal information. Also I was too poorly to write more than single sentence at that time.

My position is that I do share many of the concerns expressed by PR members. On the other hand I regard Dr Shepherd as the most knowledgeable person in the UK on medical ME.

I am concerned that the BPS brigade seems to be in a position of influence on CMRC. I remember that this same crew destroyed and distorted the work of CMO report 10 or 15 years ago and did us a lot of damage.

I think Stephen Holgate wants to do his best but I am not sure that he is free of manipulaion having seen the infamous email with SW re CMRC representation. I don't think SH understands how awful things have been over the years nor how much the BPS brigade hates people with ME and what they are prepared to do..

I am confident that Charles Shepherd has no illusions about the BPS brigade. I have heard CS talk and I spoke with him for a few minutes in the interval, years ago when I could still get to such events. I was impressed by him. I saw the afwul look on CS face when SW was mentioned. I can tell you there is no love lost there whatsoever.

So I am in a dilemma. I do share the concerns that have been expressed here on PR, but I also trust Charles Shepherd to do his best on our behalf. I can see also that over the years CS has had to do a lot in the background without publicity, quiet diplomacy if you will. It's easy for self-styled advocates to shout abuse but this often achieves little

I really do not know what to make of the petition raised by MEGA. It seems weird and we are being asked to support a pig in a poke.
 

Cinders66

Senior Member
Messages
494
Why do you think Fukuda is so superior to NICE? AFAIK, there's precious little data on NICE cohorts, but I'd be interested.

I'm not sure there are many that would 'love' to do so, that's the whole problem. And people like Stehen Holgate have worked had to bring in new talent. I'm not keen on driving them away by making their lives really difficult.

I'd say we need large scale biomed research precisely to find out what's really causing our illness, and end the influence of the BPS model. That's a major reasonn I'm keen to see such an important study go eahead.

OK, but if that's the case you can forget all the VO2 max exercise studies (who's patients are generally the mildest patients), the cytokine work from Lipkin and Hornig, all the NK cell findings, the latest Naviaux metabolomics findings: pretty much every published finding to date. There may well be a stronger signal from severe patients, and I'm keeen they are studied. But one complication is that inactivity due to bedrest is likely to cause a strong biological signal itself (while not in any way causing the disease), making such studies harder to interpret.

A very large study is well place to detect smaller effects from more typical patients.

Why I think fukuda superior to NICE -
To me fukuda try to select a sick cohort beyond th e idiopathic fatigue that USA have as the chronically fatigued. So you need 4 symptoms on top of fatigue which cover a reasonable spectrum of key add ons - immune, pain ,sleep and concentration and PEM. And you need 4. I have read in British journals that they see the fukuda as born out of assumptions of physical /immune illness.
NICE in my view comes from the fatigue spectrum angle, not as fatigue vague as Oxford but not much better. I may be wrong but I thought using them a CFS diagnosis could be given via them for a presentation of fatigue, PEF (not PEM) and sleep issues, that's it. Given sleep issues will make you tired and youd expect to also feel a bit more so if pushed, it seems pretty weak and quite away from the complex multisysytem & multi symptom presentation we were supposed to be trying to get recognition for.

I thought post IOM the move now was to have complex multi system disease recognised, PEM as a global exacerbation recognised and the NICE guidelines scrapped , not that weak criteria and fatigue spectrum idea further perpetuated

Also Esther Crawley uses NICE and believes millions meet that criteria, I don't think millions have fukuda CFS or ME.
 

charles shepherd

Senior Member
Messages
2,239
I'll identify this as me. I wrote back channel as I included personal information. Also I was too poorly to write more than single sentence at that time.

My position is that I do share many of the concerns expressed by PR members. On the other hand I regard Dr Shepherd as the most knowledgeable person in the UK on medical ME.

I am concerned that the BPS brigade seems to be in a position of influence on CMRC. I remember that this same crew destroyed and distorted the work of CMO report 10 or 15 years ago and did us a lot of damage.

I think Stephen Holgate wants to do his best but I am not sure that he is free of manipulaion having seen the infamous email with SW re CMRC representation. I don't think SH understands how awful things have been over the years nor how much the BPS brigade hates people with ME and what they are prepared to do..

I am confident that Charles Shepherd has no illusions about the BPS brigade. I have heard CS talk and I spoke with him for a few minutes in the interval, years ago when I could still get to such events. I was impressed by him. I saw the afwul look on CS face when SW was mentioned. I can tell you there is no love lost there whatsoever.

So I am in a dilemma. I do share the concerns that have been expressed here on PR, but I also trust Charles Shepherd to do his best on our behalf. I can see also that over the years CS has had to do a lot in the background without publicity, quiet diplomacy if you will. It's easy for self-styled advocates to shout abuse but this often achieves little

I really do not know what to make of the petition raised by MEGA. It seems weird and we are being asked to support a pig in a poke.

Thanks John

For the sake of accuracy, Gill phoned me from the MEA office at lunchtime to say that two members have now stated that they do not want to endorse the MEGA study in its current format
 

Jan

Senior Member
Messages
458
Location
Devon UK
.
@charles shepherd

you wrote: "In addition, there are other people out there who would support this trial - provided certain conditions were met - but they will not join in internet discussions when they feel that their views are not going to be listened t,o or are going to be opposed by a very vocal group"


How do you know there are other people out there who would support the MEGA Trial but dare not say so on the internet due to some mythical "vocal group" ? ....
.

Please don't characterise the many who have valid concerns about this study, and who make their points cogently, as some minority 'vocal group'.... We have heard that phrase used before, but always in the context of negatively mis-characterising informed patients. The claim that only a minority vocal group opposed PACE was proved to be unfounded.
.
.
Agree, I actively have been on PR for only a short time, I have not come across this here or on your Fb page or anywhere else. If people don't agree then they may not 'like' the post, or may ignore the comment, which is fine. I see no intimidation of posters here or elsewhere. I am a member of the MEA.
 

JohnCB

Immoderate
Messages
351
Location
England
Thanks John

For the sake of accuracy, Gill phoned me from the MEA office at lunchtime to say that two members have now stated that they do not want to endorse the MEGA study in its current format

Thank you, Charles, for taking the time and effort that is involved in keeping up with this discussion. I am aware that you do so much if this on a voluntary basis. Others should take note of this too, and remember that you are doing a huge amount for PwME and the ME Association and its members.
 

Simon

Senior Member
Messages
3,789
Location
Monmouth, UK
Also Esther Crawley uses NICE and believes millions meet that criteria, I don't think millions have fukuda CFS or ME.
If you mean her recent paper claiming a 3% prevalence rate for adolescent CFS, that was based on parental-reported fatigue (I know, bizarre). The paper cited the NICE criteria, but regrettably did not use them to calculate a prevalence rate - so that study tells us nothing about prevalence with NICE criteria.

To me fukuda try to select a sick cohort beyond th e idiopathic fatigue that USA have as the chronically fatigued. So you need 4 symptoms on top of fatigue which cover a reasonable spectrum of key add ons - immune, pain ,sleep and concentration and PEM. And you need 4. I have read in British journals that they see the fukuda as born out of assumptions of physical /immune illness.
Thanks. I'd certainly not read that about Fukuda assumin a physical basis. But I see what you mean: Fukuda is fatigue + 4, NICE is fatigue + 2, though I'm not sure how much difference that would make in practice (I suspect many NICE patients would have more than 2 symptoms, even though only are required). There's a lack of hard data with NICE criteria.

Note that Fukuda doesn't require PEM or even the delayed and long-lasting fatigue in response to exertion. And I'm not sure if people realise that Canadian crtieria have the same post exertional malaise OR fatigue criterion as NICE i.e. PEM is not mandatory.

The second mandatory NICE symptom could be sleep, but could be a lot of other things too:
NICE said:
1.2.1.2 Healthcare professionals should consider the possibility of CFS/ME if a person has:
  • fatigue with all of the following features:
    new or had a specific onset (that is, it is not lifelong)
    • persistent and/or recurrent

    • unexplained by other conditions

    • has resulted in a substantial reduction in activity level

    • characterised by post-exertional malaise and/or fatigue (typically delayed, for example by at least 24 hours, with slow recovery over several days)

      and
  • one or more of the following symptoms:
    • difficulty with sleeping, such as insomnia, hypersomnia, unrefreshing sleep, a disturbed sleep–wake cycle

    • muscle and/or joint pain that is multi-site and without evidence of inflammation

    • headaches

    • painful lymph nodes without pathological enlargement

    • sore throat

    • cognitive dysfunction, such as difficulty thinking, inability to concentrate, impairment of short-term memory, and difficulties with word-finding, planning/organising thoughts and information processing

    • physical or mental exertion makes symptoms worse

    • general malaise or 'flu-like' symptoms

    • dizziness and/or nausea

    • palpitations in the absence of identified cardiac pathology.
 

user9876

Senior Member
Messages
4,556
Note that Fukuda doesn't require PEM or even the delayed and long-lasting fatigue in response to exertion. And I'm not sure if people realise that Canadian crtieria have the same post exertional malaise OR fatigue criterion as NICE i.e. PEM is not mandatory.

The second mandatory NICE symptom could be sleep, but could be a lot of other things too:

I don't think the NICE diagnostic guidelines are too bad but they are designed for a clinical situation, hence they are inclusive and don't exclude all other things. From a clinical perspective it is important not to disclude corner cases from getting a diagnosis.

However, they are not intended to be used for research. Here there may need to be some tightening up particularly around co-morbid disease.

In general terms I think it is worth having a list of all the symptoms from all the different criteria and using them to see which are met.

The other complexity comes from how the criteria are implemented in a quick way so they can be done on such a large number of people. I think Jason has done work in this area and that may form a better starting point?
 

Cinders66

Senior Member
Messages
494
Interestingly just found this on BMJ Best practice page

http://bestpractice.bmj.com/best-practice/monograph/277/diagnosis/criteria.html

A complicating factor in chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is the presence of 9 sets of subjective clinical criteria. The 1994 US Centers for Disease Control and Prevention (CDC) 'Fukuda' criteria are most widely used. [5] The preeminence of post-exertional malaise (PEM) is central to the Canadian consensus ('Carruthers') criteria [84] [85] and the 2015 US Institute of Medicine (IOM) criteria. [4] The term 'systemic exertion intolerance disease' (SEID) has been proposed by the IOM as an alternative term for CFS/ME. The Oxford criteria [89] and the UK National Institute of Health and Care Excellence (NICE) criteria [90] are not recommended, due in part to their inclusion of mental dysfunction and overlap with psychiatric disease. [91] Caution should be used when interpreting CFS/ME studies using the Oxford criteria. [94] [92] [93] [95] The US National Institutes of Health (NIH) Pathways to Prevention working group has also suggested that the Oxford criteria should be 'retired' as it may impair progress and cause harm. [96] Overall, the Canadian consensus criteria are most widely accepted. [84] [85]
 
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Messages
60
As far as public opinion and the MEA is concerned, I think we now need to consult our membership (through our magazine as well as the internet) to see what they feel about this trial - which will have to be on the basis of where we are now, or where we are in two weeks time

Charles, As I wrote in my email, I am one of those who would like to be able to support MEGA but will not do so unless significant changes are made. These include the exclusion of Peter White and Esther Crawley from any involvement and the inclusion of severely affected patients and patients who do not attend CFS clinics.

As I'm sure you appreciate, how your members respond may be heavily influenced by how the information is presented to them. Can you tell us, as a member of CMRC, is MEA permitted to inform its member about what it considers to be the valid criticisms that have been raised about MEGA on PR and elsewhere? For instance, would you be able to inform them that many people have expressed concern about the involvement of Peter White (still an advisor) and Esther Crawley due to their promotion of and involvement with PACE, GET, BPS etc? And if you are permitted, is it something you intend to do?

Thanks again for all the time you have spent on this, and for all the work you do.
 

Simon

Senior Member
Messages
3,789
Location
Monmouth, UK
The other complexity comes from how the criteria are implemented in a quick way so they can be done on such a large number of people. I think Jason has done work in this area and that may form a better starting point?
I would have thought the Jason questionnaires were well worth considering, and I very much hope MEGA willl reach out to US researchers who alsoo have more experience of using Canadian criteria in research.

The preeminence of post-exertional malaise (PEM) is central to the Canadian consensus ('Carruthers') criteria [84] [85]
The BMJ best practics article is misinformed:
Carruthers 2003 said:
DIAGNOSTIC PROTOCOL
2. Post-Exertional Malaise and/or Fatigue: There is an inappropriate
loss of physical and mental stamina, rapid muscular and cognitive
fatigability, post exertional malaise and/or fatigue and/or pain and
a tendency for other associated symptoms within the patient's cluster
of symptoms to worsen. There is a pathologically slow recovery
period–usually 24 hours or longer

The Oxford criteria [89] and the UK National Institute of Health and Care Excellence (NICE) criteria [90] are not recommended, due in part to their inclusion of mental dysfunction and overlap with psychiatric disease. [91]
Do you know what that's based on? Oxford criteria allow depression as the primary cause of fatigue; I don't think NICE does (in any event, MEGA specify that depression can't be the primary cause of fatigue, if so it excludes a CFS diagnosis).
 

Cinders66

Senior Member
Messages
494
If you mean her recent paper claiming a 3% prevalence rate for adolescent CFS, that was based on parental-reported fatigue (I know, bizarre). The paper cited the NICE criteria, but regrettably did not use them to calculate a prevalence rate - so that study tells us nothing about prevalence with NICE criteria.


Thanks. I'd certainly not read that about Fukuda assumin a physical basis. But I see what you mean: Fukuda is fatigue + 4, NICE is fatigue + 2, though I'm not sure how much difference that would make in practice (I suspect many NICE patients would have more than 2 symptoms, even though only are required). There's a lack of hard data with NICE criteria.

Note that Fukuda doesn't require PEM or even the delayed and long-lasting fatigue in response to exertion. And I'm not sure if people realise that Canadian crtieria have the same post exertional malaise OR fatigue criterion as NICE i.e. PEM is not mandatory.

The second mandatory NICE symptom could be sleep, but could be a lot of other things too:


It was in the BMJ 2010 learning module I think. Written by a psychiatrist (the other module is EC & SW) I think the other criteria suggested was Oxford at the time which presumably he felt made more assumption as to there being no physical disease or significant immune problems, contrasting with Fukuda. Both the BMJ CFS training modules for Drs are listed under psychiatry. Perhaps Prof Hugh Parry could raise that as another reason biological Drs aren't interested
 

Glycon

World's Most Dangerous Hand Puppet
Messages
299
Location
ON, Canada
I'm still not clear what that purpose of such a role would be in this study. The focus of the study is supposed to be omics in ME/CFS. The fact some might actually not have ME/CFS doesn't mean they therefore have a psychiatric illness of course, but I accept a number might - but so what? Unless there is a need for a psychiatrist to identify those who do so their omics profile can be compares to other subgroups, I just don't see what a psychiatrist specialism is supposed to offer the study. If it is that then I suppose that might be useful, but I haven't heard any suggestion that MEGA is thinking in that way.

Have you heard any suggestion that they are definitely NOT going to do something like that? Here is a hint that MEGA researchers could be thinking along the right lines after all:
We will collect sufficient information on each patient to be able to say whether they have CFS/ME using other research diagnoses (for example, the CDC [Fukuda 1994] diagnostic criteria, the IACFS criteria, Canadian criteria and so on). This is in addition to the diagnoses of CFS/ME that patients will get following NICE guidance.

And you are definitely on the right track. I have suggested elsewhere that one of the ways of thinking (for research purposes) about certain subsets of the patient population identified by PACE is as a "deeper" control group.

It is important to look at the omics of those who fit the NICE criteria and also fit criteria for some psychiatric illness. Within those, it is important to look at those who fit CCC, say, versus those who do not.

Regardless of the failures of PACE, it is important to look at the omics of those who saw improvement (under one set of standards or another) versus those who did not.

All of this can only help the search for tests and treatments for what is almost certainly - and this must be stressed in contexts such as this one! - an etiologically heterogenous, multifactorial disease.
 
Messages
2,391
Location
UK
Besides why would they need to collect data on depression and anxiety?
A suggestion: When there is a contentious problem to solve, and different factions argue the cause (for example) is a, b or c, it is best to gather good objective data for all the possibilities. Without gathering data for something, it can be much harder to prove it is not the cause, and so exclude it. But it would be absolutely crucial they gather adequate data, and design the trial well, so they could identify where people's ME/CFS suffering had maybe triggered a degree of depression/anxiety, and not try to put the cart before the horse, and erroneously blame people's ME/CFS on their depression/anxiety. But without the data - good well thought through data - you cannot prove anything.
 
Messages
2,391
Location
UK
So if MEGA is recruiting solely from NHS clinics then it won't learn anything about me and people in a similar condition.

That is an extremely valid point, and highlights what a farce the NHS approach is to ME/CFS. There needs to be much better trial design effort put in, so that the all the right data is gathered, else the trial's integrity will be doomed from the start. In engineering design there is a well known maxim: "cr*p in equals cr*p out".
 
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Messages
2,391
Location
UK
Except the problem is not the involvement of psychiatrists, but the involvement of specific psychiatrists associated with discredited, probably dangerous, and possibly fraudulent research into ME/CFS.

White and and Crawley must go for me personally to take this project seriously.

I would be fine with any relevant, dedicated, high integrity medical professional, whatever their discipline. Which excludes anyone involved in the PACE trial by definition, so far as I am concerned.
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
People really need to stop equating psychiatry with the psychological approach to ME or the advocacy of CBT as a cure for it.

Such kneejerk myopia just makes some of you look like the caricatures drawn by the very people you oppose.

A doctor who dismisses out of hand the possibility of any and all psychogenetic explanations of the symptoms of ME/CFS is just as misguided and irresponsible as the doctor who assumes that these are the only possible explanations.

(First thing I insisted on when my symptoms began is a psychiatric evaluation. Not only did it help save everyone time, but it also helps keep other specialists on the right track.)

drs saw no need at all to send me to a psych for my symptoms before I was diagnosed with CFS as no psychological illness could cause all the symptoms I had eg actual fevers often high even now when I go to hospital the hospital often says Im running a fever, sore throats (very red) with very swollen glands etc etc. It was quite obvious my illness wasnt in my head.

If you dont have testable abnormalities which help point to ME I can understand then people may want a psych evaluation but one certainly isnt necessary for many who have ME.
 

eafw

Senior Member
Messages
936
Location
UK
OK, but if that's the case you can forget all the VO2 max exercise studies (who's patients are generally the mildest patients), the cytokine work from Lipkin and Hornig, all the NK cell findings, the latest Naviaux metabolomics findings: pretty much every published finding to date. There may well be a stronger signal from severe patients, and I'm keeen they are studied. But one complication is that inactivity due to bedrest is likely to cause a strong biological signal itself (while not in any way causing the disease), making such studies harder to interpret.

A very large study is well place to detect smaller effects from more typical patients.

First, I think we are using different definitions of "severe". I don't mean the totally bedbound/24hr care people - "very severe" - I mean those who function independently, but only just. Mostly housebound, usually long term sufferers, and almost constant PEM.

MEGA claims: "We are trying to understand more about the biology of the chronic neurological condition, Myalgic Encephalomyelitis (M.E., often diagnosed within the NHS as chronic fatigue syndrome or M.E./CFS)".

Then they need to study the people who have ME, and the researchers need to realise (or at least be honest about the fact) that there are many people who have have no contact with the NHS clinics precisely because they are a typical ME patient that won't be picked up (or helped in any way) in the clinics, and these patients form an important subgroup that must be included.

Big data will not magically fix a failure to look at a significant cohort like that, and neither is it an excuse to throw out previously targetted studies on smaller groups either.
 

Simon

Senior Member
Messages
3,789
Location
Monmouth, UK
From what I have read, the London biobank is reaching out to severe ME patients to collect samples. Is that true and has MEGA implemented a strategy for this?
Apologies, I missed your long post yesterday - there seem to be several different threads on this topic, and I'm struggling to keep up!

Yes, the biobank has samples from 50 severely-affected mecfs patients (out of 300 patients). MEGA has not mentioned this yet - my guess is this is because they are recruiting from clinics and clinics don't see severely affected patients (yup the only illness where the worse you are, the less attention you get from the NHS). I think this is well worth raising with MEGA, maybe via the open letter thread discussion.

To what extent do the clinics exclude patients from a diagnosis of NICE CFS who have evidence of e..g. neurological or immunological impairment?..

The CDC CFS website used to say that a diagnosis by CCC was not the same as a diagnosis of CFS since CCC included neurological symptoms that were considered exclusionary for CFS
I've not heard that of the UK at all. known neurological conditions such as MS and autoimmune ones such as rheumatoid arthritis are exclusionary, but I've seen nothing to suggest the neuoroligcal symptoms like those in CCC or immunological issues would exclude patients.

NIH has announced a focus group to collect information on PEM which will be used as interview tool for assessing post-exertional malaise in its intramural study. (Patient selection will be key there as well and ideally, the outcome will be compared to the DePaul questionnaire.)
Hey, I'd missed that. And I think a focus group, where patients can discuss the subtleties of PEM, is EXACTLY what's needed. It will be interesting to see how the outcomes compare with a questionnaire - my issue with questionnaires generally is that patients don't have enough input into deciding what the questions should be.

NIH consenst form said:
For this study, questions about post-exertional malaise will be asked to all the members of the group, who are then free to discuss their answers with each other. The information collected as part of this focus group will be used to develop an interview tool for assessing post-exertional malaise. This tool will be used in an NIH study of post-infectious ME/CFS
It's a phone group so more severely-affected patients will be able to attend.

While I appreciate the value of common data elements, I wonder how well we will be able to harness the future evidence base if every published study continues to use the same disease label for all these different definitions. Assuming I got it right, I think that's one of the things the London biobank is doing right - samples that meet only Fukuda and not CCC are labeled differently than those that meet CCC.
MEGA wouuld be just the same in labelling. And the idea is that if you want to compare new results from MEGA (or the MEGA biorepository) you select from the data the subgroups that match eg select data for CCC patient to compare results with a published study that used CCC.

. I've read the NICE criteria but I can't tell whether PEM is mandatory or not and how its assessed. Based on concerns raised here, it sounds like NICE's focus, like Oxford and Fukuda, is still on medically unexplained chronic fatigue. Is that true?
As posted here, NICE uses PEM or post-exertional fatigue - which is precisely what CCC do (here). I wouldn't agree NICE, or even Fukuda, is as broad s Oxford. Oxford is purely unexplained fatigue, with no other symptoms required, and also accepts depression as the main cause of fatigue, which NICE and Fukuda do not.

So why not start with a research definition that requires the hallmark symptoms of ME? If one of the goals is to compare the underlying biology of ME patients to fatigued patients who do not have ME, what about including some patients with medically explained fatigue, like MS
I'm not in favour of using just medically unexplained fatigue, as above. I wouldn't want to use just CCC either, because a) I doubt it's exactly right, consensus definitions in general tend not to be - we need to find the biology to get really good case definitions - and b) because with a slightly wider definition you should be able to find boundaries: where one subgroup begins and another ends. So, for instance, would PEF(fatigue- but-not-PEM patients be different from PEM patients? Id love to see the data on that (equally, I'd be most PEF patients were also PEM). I'd prefer, like you, to select on PEM, but I can live with some PEF patients, not least because I think they'd be very useful

As for medically explained patients aka sick controls, as I understand it, there is a ton of omics data sitting in databases that will allow comparisons with these other groups. Though I think that would be another good Q to put to MEGA.

It may be necessary, but this seems like an expensive and time-consuming way to solve that problem especially given all the reports and science that have come out in the last 2-3 years.
Solve which problem? I'm not sure reports over the last few years have really given us clear answers yet. Clues, yes, but not answers. We still don't have any biomarkers, and still haven't shown bioabnormalities are speciific to mecfs. I wish that wasn't the case, but it is where we are.
 

Cinders66

Senior Member
Messages
494
Apologies, I missed your long post yesterday - there seem to be several different threads on this topic, and I'm struggling to keep up!

Yes, the biobank has samples from 50 severely-affected mecfs patients (out of 300 patients). MEGA has not mentioned this yet - my guess is this is because they are recruiting from clinics and clinics don't see severely affected patients (yup the only illness where the worse you are, the less attention you get from the NHS). I think this is well worth raising with MEGA, maybe via the open letter thread discussion.

I've not heard that of the UK at all. known neurological conditions such as MS and autoimmune ones such as rheumatoid arthritis are exclusionary, but I've seen nothing to suggest the neuoroligcal symptoms like those in CCC or immunological issues would exclude patients.


Hey, I'd missed that. And I think a focus group, where patients can discuss the subtleties of PEM, is EXACTLY what's needed. It will be interesting to see how the outcomes compare with a questionnaire - my issue with questionnaires generally is that patients don't have enough input into deciding what the questions should be.

It's a phone group so more severely-affected patients will be able to attend.

MEGA wouuld be just the same in labelling. And the idea is that if you want to compare new results from MEGA (or the MEGA biorepository) you select from the data the subgroups that match eg select data for CCC patient to compare results with a published study that used CCC.

As posted here, NICE uses PEM or post-exertional fatigue - which is precisely what CCC do (here). I wouldn't agree NICE, or even Fukuda, is as broad s Oxford. Oxford is purely unexplained fatigue, with no other symptoms required, and also accepts depression as the main cause of fatigue, which NICE and Fukuda do not.

I'm not in favour of using just medically unexplained fatigue, as above. I wouldn't want to use just CCC either, because a) I doubt it's exactly right, consensus definitions in general tend not to be - we need to find the biology to get really good case definitions - and b) because with a slightly wider definition you should be able to find boundaries: where one subgroup begins and another ends. So, for instance, would PEF(fatigue- but-not-PEM patients be different from PEM patients? Id love to see the data on that (equally, I'd be most PEF patients were also PEM). I'd prefer, like you, to select on PEM, but I can live with some PEF patients, not least because I think they'd be very useful

As for medically explained patients aka sick controls, as I understand it, there is a ton of omics data sitting in databases that will allow comparisons with these other groups. Though I think that would be another good Q to put to MEGA.

Solve which problem? I'm not sure reports over the last few years have really given us clear answers yet. Clues, yes, but not answers. We still don't have any biomarkers, and still haven't shown bioabnormalities are speciific to mecfs. I wish that wasn't the case, but it is where we are.



CCC is still a much better ME definition than NICE as it required more sickness symptoms getting away from fatigue and most people with ME & severe ME 25% are concerned how much if any specific attention ME will get in research terms and clinical care whilst the MRC says it's subgrouping its crs umbrella.

CCC isn't even patients/researchers criteria of choice now , it was superseded by the ICC , I can't remember the details but I'm guessing dumping the CFS name and possibly refining the PEM definition were the reason why? it's just been harder to get universal acceptance of the newer ICC when people were trying to get fukuda dumped for being too broad and unspecific on PEM. SEID has happened in the meantime too

Ultimately U.K. Probably does need to subgroup its self imposed CFS umbrella and as it has refused to go so in any other way I guess this study will happen. Am I anticipating the prospect of getting Good severe ME care, recognition and well funded well rounded research projects happening concurrently though , no, do I think we should, yes. Do I think the uk should have done this years back (as tech allowed) yes, do i support uk CFS /fatigue umbrella approach and ME burial no. Do I think the CMRC & ME EXPERT group have focused enough on the severe, no so am I likely to cheerlead this 1 project in my state with the general uk failings, still abounding , no.