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

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Unfortunately @worldbackwards I feel strongly that this work could be amazing but only if done properly and I'm loosing all faith now that it will be and that patients will have sincere input in development. That's aside from Crawely White concerns I mean. How can you have any confidence in them listening if they go about things this way. I'm done with hope right now. The insightless from them just seems either ignorant or arrogant I don't know which at this point.
I've given up on the UK. Why waste energy getting worked up, they'll do as they please anyway.
 

trishrhymes

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In my earlier comment I listed 3 subgroups who might or might not be included in this study.

I've had another think.

Here's my next version, with a question for Stephen Holgate - which of these would you want to include in your study?
(I hope he'll be invited to read this thread).

1. Severe and very severe ME (with PEM) - housebound and/or bedbound.
2. Mild and moderate ME (with PEM) - long term illness
3. Mild and moderate ME (with PEM) - recent onset

4. Mild and moderate chronic fatigue (no PEM) - with physiological cause not yet known to medicine

5. Mild and moderate fatigue (no PEM) with physiological cause, diagnosis missed by clinic tests (eg sleep apnea)
6. Mild and moderate fatigue (no PEM) - psychological cause diagnosis missed by clinician (eg depression, burnout)
7. Mild and moderate fatigue(no PEM) - 'lifestyle' cause missed by clinician (eg dietary deficiency, bad sleep habits)
8. Mild and moderate fatigue (no PEM) - false illness beliefs and de-conditioning (if such people exist).

I think the most likely people to turn up at CFS clinics are from groups 3 to 8 (if 8 exists!)

The biopsychosocial model lumps all groups into group 8, and could easily diagnose all groups as fitting the Fukuda criteria as I explained before.

I assume the groups you actually want to study are groups 1 to 4.

I am afraid that, since most people running CFS clinics offering GET and CBT assume that everyone belongs to group 8, the study will include a lot of people from groups 5 to 8, thus contaminating the data so much that it becomes meaningless.

As an example of how clinicians can get diagnosis wrong- I was referred by GP to a fibromyalgia clinic run by rheumatology department who had asked for patients to include in a group. Diagnosed was by OT who ran the group teaching pilates which she claimed had 'cured' her. 7 patients in group -we compared notes - 2 had ME, 2 had arthritis, one was depressed and sleeping badly, 2 probably had fibro. She needed people to fill her group, so her diagnosis was very sketchy - asked a few questions (I do have a lot of muscle pain, made worse by exercise), poked hard at a few pressure points... She wanted to run a group and needed people to fill it - bingo, 7 fibro diagnoses. My health crashed (PEM for a couple of weeks), I gave up after 3 sessions. Probably put down as treatment resistant.
 

AndyPR

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Guiding the lifeboats to safer waters.
Blog post that ties in with what is being discussed here

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

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

We are grateful to the MEGA team for letting us know about the proposed CFS/ME biomedical research project. We believe it is very important that this study goes ahead but in view of some of the less than helpful research which has taken place in the past (in particular, of course, we are thinking of the PACE trial) we hope you will understand why we patients are keen to voice our concerns about the proposal.
.....
https://spoonseeker.com/2016/10/14/making-the-most-of-mega/
 

Jan

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I seriously doubt that the fatigue clinics have access to anywhere near 12,000 patients.

As a perfect example, straight from the horse's mouth (Esther Crawley)

'However, approximately 90% of children in the UK cannot have treatment because they live too far away from specialist services.'

http://www.nets.nihr.ac.uk/projects/hta/14192109

That means that her studies to date have only been focused on a tiny percentage of patients, as the 10% will also include all the patients too ill to take part in exercise therapy.

How many patient per year are seen at these clinics please, both children and adults?

I think it's clear that recruiting 12,000 from these clinics is going to be impossible.

How are you going to recruit the severe patients?

How are you going to recruit the long term moderate/severe patients?

Edited to change quantity of patients to 12000
 
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Countrygirl

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I think it is crucial that SH confirms that they are prepared to visit the severely ill at home. If they refuse to do this then I don't believe we can support the study as the people who are bedbound are the most important category and it does need to involve a very significant percentage of the total number of trial participants. I would suggest at least 25% of the total. MEGA cannot claim to be including those in the severe category if they only study those who attend the fatigue clinics.

Dr Nigel Speight could provide a number of children who are in the severe category.
 

slysaint

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Other observations on the presentations;
SC was more or less given credit for the Missing Millions protests.
Although SC mentioned that most research funding in the UK had gone to two particular researchers, she didn't name them (we know who they are but did they, her audience?).
Prof. Davey Smith openly admitted that at the last conference he knew nothing about CFS, and then admitted that he still knew nothing; this doesn't exactly inspire you with confidence of his commitment, and although epidemiology sounds impressive I'm really not sure how it fits into the ME scenario(?) Based on this

General Dichotomies in Epidemiological Studies
When designing epidemiologic studies, choices must be made about the role of the investigator, the purpose of the study, the hypothesis regarding exposure and the unit of analysis. Here are some examples:

Role of investigator:
  • Observational – The investigator does not manipulate exposure of participants to risk factors. Most epidemiological studiesare observational OR
  • Experimental - According to the study design, the investigator manipulates the exposure of participants to some factor. Clinical trials and intervention studies are examples of such experiments. If the study participants themselves act to change their exposure to an influence, a natural experiment may occur. For example, a study of persone who have migrated from one environment to another could constitute a natural experiment.
Purpose of the study:
  • Descriptive - describes distribution of disease by time, place, person; used to generate hypotheses of disease causation or for health planning OR
  • Analytic - measures and tests the association between a hypothesized risk factor and a disease
Hypothesized Effect of Exposure
  • Harmful - exposure increases risk or presence of disease OR
  • Beneficial - exposure reduces risk or presence of disease
Unit of Analysis
  • Individual - the individual (e.g., person, animal) is the unit of analysis; potential to ignore the impact of the community or group effect on individual risk OR
  • Community - the community (e.g., county, hospital) is unit of analysis. There is potential for ecological fallacy in such studies. Lacking individual data, assuming that individuals perform similar to the average of the group may not be true.
The only scientist who really talked sense was the Canadian early on (can't remember his name), who made a point of saying that for research to be succesful you had to 'Back the Winning horses' (ie bits of research that show the most promise). He mentioned Naviaux's and other biological studies. But it appeared to fall on deaf ears.
:depressed:

EDIT: there is also this 'Dr Esther Crawley, a consultant paediatrician at Bristol University and AYME's lead medical advisor, is one of the country's leading experts on the epidemiology and treatment of CFS/ME.'
I would like to see what Prof Davey Smith makes of the PACE trials and MAGENTA
 
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Gijs

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It is not about 'severe' in definition Oxford, Fukuda, ICC and IOM but we are talking probably about totally different diseases. Fatique is not a disease but a common symptom. Is he really a professor?
 

eafw

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Holgate is showing us with these responses just how unwilling he/they are to genuinely engage with patients. Here he is giving us another explanation of the "big data" idea - as in previous correspondence where he said how it was an ever-so-complicated concept and therefore that must be what we need telling about.

What they are sidestepping, and it seems very deliberate, is that if you claim to be studying a disease, say diabetes, then you don't just turn up at the local weightwatchers and recruit those who one time felt a bit funny after eating too much cake. Especially not while ignoring all those suffering hypos, at risk of going blind, kidney failure etc etc (who in the case of diabetes would be under the care of a proper clinic, but in the case of ME are sent away and left to rot)

The NHS "CFS" clinics are the equivalent of weight-management clubs, maybe in a "broad" study you take some people from there and would catch a few of your intended targets - but that cannot be your sole place of recruitment. "Broadness" does not fix this.
 
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I wonder if it is not more productive to subgroup. At least you will get for sure some significant data then widen the criteria with the data for sure that identifies the soubgroup.
Lets say we study all people that in the 2 day exercise test gets worst on second test (proven / measureable PEM).
Get lets say a gene study or metabolites -= you find abnormal gene 1,2,3.
Lets say you broaden criteria and find = 1,2,4

You are sure CFS people have 1,2 so 3 and 4 are under question but it will give you something to go by. Not like now that we have 0.
 

alex3619

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My fear is that the sample, however large, will be so 'contaminated' by group 3 that any evidence will be diluted into insignificance and a great deal of money and time will be wasted, and the biopsychosocial model will be apparently strengthened.
I actually do not see this as a problem. The point of this kind of in depth analysis is to identify subgroups. That kind of group will separate out. So will ME patients. So this kind of study might well validate ME as a separate disease. However the recruitment issue with respect to severe patients is not answered. Its been evaded. It needs to be specifically addressed, with specific mechanisms to ensure that severe patients are sufficiently represented.
 

Barry53

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I will just make one short point on entry criteria - if you want to do an epigenetics study looking at biological mechanisms of illness - I'd head straight for the sickest patients with the least chance of mis-diagnosis - ie long standing clear ME/CFS with no other explanation.
This sounds a bit like in engineering sometimes. It can be helpful to look at the extremes of a spectrum initially, to get some baseline references that are least ambiguous. Then you have something to help make more sense of the stuff in between, which by definition almost, is less clear cut.
 

Barry53

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Here's the symptom list for these multitudes:

Tired all the time,
concentration problems at school or work
muscle or joint pain from poor posture,
headaches - (from tension, posture, poor sleep, poor diet)
unrefreshing sleep.

BIngo, CFS diagnosed by Fukuda criteria.

And busy GP's may be tempted to refer them to a fatigue clinic rather than having the time or knowledge to do differential diagnosis. I doubt most GP's have even heard of post-exertional malaise, or understand it as it applies to ME.
Looking at the Fukuda criteria, the above symptoms list would not automatically fit, albeit many GPs might mistakenly think so. If the GP investigate a bit further, they should realise the fatigue in such cases was not "unexplained" and would in fact be "substantially alleviated by rest", so Fukuda would exclude. And without the GP understanding and investigating the PEM issue, would not realise Fukuda excludes on that basis either.