MEGA 'Why broad definition should be used as a starting point - by Prof Stephen Holgate'

[AndyPR]

Well, in her most recent study, Crawley, the MEGA ME 'expert', used this definition "Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has a prevalence of 0.4–2.4% and is defined as ‘generalised disabling fatigue persisting after routine tests and investigations have failed to identify an obvious underlying cause’."

So all they need to do is rename it FEGA, problem is though that doesn't sound so cool

 

[Jan]

Oh, I'm so bloody furious!! The UK can't, or won't diagnose ME correctly, so we have to spend millions of pounds to sort out the mess, that's all this study is. We are so far behind other countries we are probably a laughing stock, especially having a BPS person in charge who claims to be an expert but can't even diagnose it. How the hell can we have a person involved who uses PACE to treat children, now PACE has thoroughly discredited? They should be ashamed to have her as part of it.

It's time to own up Crawley, admit you were/are wrong and go away and leave ME patients alone instead of trying to bully them into doing exercise which has the potential to ruin the rest of their lives.

 

[Jan]

To quote Professor Malcolm Hooper http://www.margaretwilliams.me/2016/response-to-professor-fred-friedberg.pdf

''Behavioural researchers who for over 30 years have shown disregard for the scientific process
should have no influence on future research.
Patients with ME/CFS do not need “behavioural” guidance from a pr
ofession which has visited such
harm upon them.
To spell it out: directive CBT does not work for patients with ME/CFS and it is time that those
psychologists and psychiatrists who insist that it does returned to reality.''

 

[rosieness]

Dialogue has always got to be good but I don’t think the fact that SH is communicating with patients over the details of the study means anything if MEGA hasn’t looked at and dealt with the history of ME/CFS research in the UK and how it has negatively impacted patients lives. You can even discuss how you might include patients with severe and very severe ME in a study, but it doesn’t mean that they’re going to be comfortable or happy being a part of this research.

I don’t think that patients’ feelings and huge mistrust following PACE is something that can be ignored. To create research proposals that patients feel able to put their trust in, that are inclusive of people with severe and very severe ME, I think the MEGA team have to start being honest in their communications about where they are and what exactly they are struggling with, and it seems to me that they want to do something that isn’t that. Perhaps because that’s the hardest thing to do.

Perhaps this research is not designed for people with severe and very severe ME, but if this research is to work for patients, including patients with severe and very severe ME, I think it is also the most critical thing to do for any meaningful dialogue between the MEGA team and patients to happen.

The USA NIH Pathways to Prevention Workshop deal with this honestly when they say:

“Unfortunately, ME/CFS is an area where the research and health care community has frustrated its constituents, by failing to appropriately assess and treat the disease and by allowing patients to be stigmatised”

Without this being properly addressed I cannot go forward with trust and feel able to engage with this research.

This is the elephant in the room. Shouldn’t patients and the UK ME/CFS Charities be asking whether the CMRC and MEGA are open to a truly honest dialogue on this?

 

[Simon]

The point of the picture is that we keep having "broadness" used as an explanation as to why they can claim to be studying the disease but "broad study" is not an adequate response to the questions around patient selection from NHS clinics - and all the data they will be missing if the majority that they pick up are short term, mild, recent, and mixed in with those who have some other fatiguing condition

I agree that "broadness" is way too vague a term and we need clarity on patient diagnosis and representativeness.

Re short term, the PACE clinic recruited from NHS clinics and the average duration was 2.5 years, with 25% with a duration of over 5.6 years. That 25% might be enough. Certainly duration shouldn't matter too much for the genetic study, given the depressingly low natural recovery rates (it's only the genomic study that needs the very large numbers, and once you have the illness you tend to stay ill, so it's genes that predict illness itself that are of interest). For the other omics work you need much smaller samples so could easily select samples that had 50% who were ill for five years or more.

Re mild: I'm not sure if we know they are mainly mild, or a mix of mild and moderate, though clearly not severe.
The PACE trial also has a mean SF36 baseline score of around 35/100, which I would have said was moderate. I suspect thre wouuld be a good mix of mild and moderate cases.

Ironically, by using NHS patients from clinics rooted in the NICE/BPS school of thought they are narrowing the field in the way George Davey Smith highlights as a problem in his paper here:

I was thinkig of the 'collider bias' issue he cited, but it's the same problem that clinics might well be unrepresentative, and certainly are as far as severe cases go.

Re 50% misdiagnosis
That was 50% misdiagnosis by GPs referring patients to clinics, not misdiagnosis at the clinics themselves. Also, I think almost all the errors were down to known medical/psychiatric exclusionary causes of fatigue. 13% of diagnostic errors were cases of unexplained fatigue that didn't have enough symptoms to qualify for (FUkuda) CFS.


The Newcastle NHS Chronic Fatigue Syndrome Service: not all fatigue is the same. - PubMed - NCBI

.. This service evaluation examined the proportion of those referred to a specialist CFS service fulfilling the Fukuda diagnostic criteria for CFS and the alternative fatigue-associated diagnoses. The CFS database was interrogated to include every patient referred to the Newcastle service from November 2008 to December 2009. All medical notes were reviewed and the diagnosis, sex and age recorded. Data were compared to a previous service evaluation (2005-07).

In 2008-09, 260 subjects were referred: 19 referrals per month (260/14), compared with 17 referrals per month in 2005-07 (375/24). The proportion of patients diagnosed with CFS increased significantly compared with 2007 (36% [20/56] vs 60% [157/260]; p < 0.0001).

Of the 40% of patients subsequently found not to have CFS the most common diagnosis was fatigue associated with a chronic disease (47% of all alternative diagnoses); 20% had primary sleep disorders, 15% psychological/psychiatric illnesses and 4% a cardiovascular disorder. Thirteen per cent remained unexplained (5.2% of the total referrals).

This study found a significant increase in the proportion of patients referred to National Health Service (NHS) CFS services diagnosed with CFS. A large proportion of patients presenting with fatigue are not eligible for referral to the Department of Health specialist fatigue services, which represents an unmet need in terms of symptom management in current NHS services.

GP diagnostic accuracy improved substantially (the 50% was a combined figure for the two periods, I think)

The proportion of patients diagnosed with CFS by the Newcastle service has increased significantly compared with the results of our previous audit in 2007 (36% [20/56] vs 60% [157/260]; F p<0.0001).

Added: looking at a strongly BPS clinic, this (less thorough) study by Peter White also comes up with a 50% figure, but again these cases were excluded so wouldn't be part of a MEGA-like cohort.
Alternative diagnoses to chronic fatigue syndrome in referrals to a specialist service: service evaluation survey

Anyway, putting all that together it seems likely they clinics are bringing in, after diagnosis:
- moderate and mild cases (but no severe ones)
- around a quarter who've been ill for five years or more.
- not many cases of 'unexplained fatigue'

 

[Barry53]

Not replying to any particular post - just musing.

It occurs to me there is a parallel between the very high tech big data MEGA (if it were to be run properly, big IF of course), and the work John Snow did in London in the 19th century, discovering the source of cholera epidemics. There was much controversy at the time about how people caught cholera, the establishment view being it was air borne; Snow believed it was water borne.

A link to one description of his work: http://www.ph.ucla.edu/epi/snow/snowcricketarticle.html.

Worth noting that Snow discovered the causal mechanism, and how to avoid it, before the biology was properly understood. Unsurprisingly the medical establishment of the time took a very long time to be convinced.

ME is a hugely more complex problem, but in Snow's time, with much less science and technology available to him, his challenge was also massive. For ME it is nothing like so straightforwards as plotting occurrences on a geographical map; when the answer is eventually found (as it will be), there will likely be the modern equivalents of Snow's map, but buried deep within masses of complex data, and maybe only discoverable using big data analytics. The odds are no one yet knows what such a map might even be a map of, let alone what it might look like, or what it might reveal.

A few quotes from the above link:-

Dr. Snow worked around the clock to track down information from hospital and public records on when the outbreak began and whether the victims drank water from the Broad Street pump. Snow suspected that those who lived or worked near the pump were the most likely to use the pump and thus, contract cholera. His pioneering medical research paid off. By using a geographical grid to chart deaths from the outbreak and investigating each case to determine access to the pump water, Snow developed what he considered positive proof the pump was the source of the epidemic.

Might not have worked so well if he excluded the more severely affected.

Snow also investigated groups of people who did not get cholera and tracked down whether they drank pump water. That information was important because it helped Snow rule out other possible sources of the epidemic besides pump water.

I believe the same fundamental principle still applies, which is why I am OK with people being included in the study, provided it is all done properly.

On 7 September 1854, Snow took his research to the town officials and convinced them to take the handle off the pump, making it impossible to draw water. The officials were reluctant to believe him, but took the handle off as a trial only to find the outbreak of cholera almost immediately trickled to a stop.

EDIT: When I wrote this I did not realise @SilverbladeTE had already noted this bit of medical history, in post #7 at http://forums.phoenixrising.me/inde...-differently-to-us-says-nice-spokesman.47568/.

 

[slysaint]

For the other omics work you need much smaller samples so could easily select samples that had 50% who were ill for five years or more.

So why not start with these. Use the Biobank samples. Continue adding to the Biobank with people who have been ill for for than 5 years so you are more likely to be using ME sufferers data.
Leave the Genomics on the back burner.
Then you will be less likely to get bogged down with diagnosis criteria,(all you need to know is what diagnosis was made, when, and by whom eg GP, clinic,specialist); leave the massive questionnaires and the whole huge recruitment thing that will take years and probably use up most, if not all of the funding and largely be of interest by a select few of the 'researchers'.
Get to the real science first.