Petition: Opposing MEGA

[charles shepherd]

Via Twitter:

I think this information re NIH relates to the IACFS conference currently taking place - which I am not attending this time

Vicky Whittemore of the NIH:

“Would be interested in looking at grants for U.K. Mega study if approached.

No approach yet.”

Collaboration with NIH on the MEGA study could be very helpful……..

 

[Jo Best]

Reposting part of a comment I just made on another thread as it's relevant to the Opposing MEGA petition (https://www.change.org/p/opposing-mega-a-vote-of-no-confidence-in-mega-research-for-me-cfs). The point may have been made above, but hopefuly ok to repeat that it's possible NICE will be guided to keep the clinical guideline for ME/CFS on the static list pending the MEGA study, in the same way they previously delayed review to await publication of the PACE trial. As the MEGA study would take years to yield evidence to warrant updating the NICE guideline, that would do nicely. These are just thoughts based on what's gone before with NICE.

 

[Jo Best]

Via Twitter:

I think this information re NIH relates to the IACFS conference currently taking place - which I am not attending this time

Vicky Whittemore of the NIH:

“Would be interested in looking at grants for U.K. Mega study if approached.

No approach yet.”

Collaboration with NIH on the MEGA study could be very helpful……..

Presumably, she knows that NIH contributed $1m to the London Biobank and assumes the MEGA study would be properly conducted.

 

[Sasha]

Nope - somebody said 'oh was that the one with White and all that?'

 

[jodie100]

@Jonathan Edwards If the Mega study is going to try and subgroup the CFS patients selected, would it matter even if one subgroup turned out to have a genetic marker for hypochondriasis ( although in that case they would have been misdiagnosed and not have CFS)? Would this not result in being able to distinguish between the two groups of people - those with an actual M.E./CFS illness v. healthy hypochondriacs i.e it would be a win-win situation as some people could be unequivocally diagnosed with hypochondria based on a biomarker and those who are not positive for this marker would then be a purer sample to do further CFS research on in the future so there would still be research progress?

 

[A.B.]

If the Mega study is going to try and subgroup the CFS patients selected, would it matter even if one subgroup turned out to have a genetic marker for hypochondriasis ( although in that case they would have been misdiagnosed and not have CFS)?

Such a genetic marker would perfectly fit the concept of CFS that the BPS authors want to promote. Crawley is rumored to rediagnose CFS patients with pervasive refusal syndrome when they don't respond to CBT, which is nothing more than reassurance, some common sense tips, and motivational intervention to do more.

I have some doubts that linking a gene to a vague human concept such as hypochondriasis, or any personality trait, is going to happen. Genes encode proteins. There isn't going to be a polymorphism that corresponds to either normal worry about health, or exaggerated worry about health.

 

[charles shepherd]

Reposting part of a comment I just made on another thread as it's relevant to the Opposing MEGA petition (https://www.change.org/p/opposing-mega-a-vote-of-no-confidence-in-mega-research-for-me-cfs). The point may have been made above, but hopefuly ok to repeat that it's possible NICE will be guided to keep the clinical guideline for ME/CFS on the static list pending the MEGA study, in the same way they previously delayed review to await publication of the PACE trial. As the MEGA study would take years to yield evidence to warrant updating the NICE guideline, that would do nicely. These are just thoughts based on what's gone before with NICE.

Jo - I don't think the MEGA study will have any role in the decision making process at NICE regarding the survellience review in early 2007 and any decision regarding an update or proper review of the ME/CFS guideline later in the year

As you probably know, NICE are only really interested in research that is directly related to the management of an illness - because NICE guidelines are there to guide doctors on how to manage the conditions they deal with

So decisions on updates and reviews to NICE guidelines are very much determined by whether there have been any significant developments in the management or treatment of a condition - not research which is looking at causation or underlying biomedical abnormalities

In the case of ME/CFS, NICE has therefore justified the decision to basically do nothing for almost 10 years because (1) there haven't been any significant developments in treatment of ME/CFS and (2) the PACE trial, as well as some other trials involving CBT and GET have (as far as NICE is concerned) confirmed that their recommendations re CBT and GET are safe and sound

 

[lilpink]

The problem is not CBT per se, but the absence of a biomarker.

To bring this discussion back to MEGA/OMEGA, I’m not sure that EC is at all interested in finding biomarkers from the MEGA project. If we look at what she apparently said in 2010 - From https://meagenda.wordpress.com/2010...presentation-the-future-of-research-in-cfsme/ - we get a better understanding of what she wants to use the genomic data for.

“What we’re interested in doing is finding risk factors that we can change. So that’s either going to be drug treatments or other risk factors that we can change.” She later lists the risk factors –


“Slide 32: Risk Factors

• Known: Older age; female; lower SE class; heritable component; infection

• Trauma: Heim ’09 Retrospective case – control [*1 see below]

• Ethnicity: Dinos ’09: meta analysis – ↑Native Americans OR 1.5 (CI1.08 – 56.4)

• Mood: Harvey ’08 “Psychiatric illness” in adults [*2 see below]

• Systematic review: Hempel 2007: none replicated [*3 see below]

Hempel 07; Katz 09; Heim 06 & 09; Kerr 08

[she continues -] These are the known risk factors for chronic fatigue syndrome. We’ve already talked about heritability, lower socio-economic class, older age, female and infection. For a long time, we’ve known that infection was a trigger for chronic fatigue syndrome. All these other ones have not been reproduced.

OK, so people talk about it, not been reproduced, don’t know if they’re true or not.”

(End of Excerpt of transcript)


It seems that these other ‘risk factors’ are actually what she is interested in researching, not biomarkers. How many of them are biomedical and how many psychosocial? You decide. To help here are the references –


*1 https://www.ncbi.nlm.nih.gov/pubmed/19124690

Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction

RESULTS - Individuals with CFS reported significantly higher levels of childhood trauma and psychopathological symptoms than control subjects. Exposure to childhood trauma was associated with a 6-fold increased risk of CFS. Sexual abuse, emotional abuse, and emotional neglect were most effective in discriminating CFS cases from controls. There was a graded relationship between exposure level and CFS risk. The risk of CFS conveyed by childhood trauma further increased with the presence of posttraumatic stress disorder symptoms. Only individuals with CFS and with childhood trauma exposure, but not individuals with CFS without exposure, exhibited decreased salivary cortisol concentrations after awakening compared with control subjects.

CONCLUSIONS:
Our results confirm childhood trauma as an important risk factor of CFS. In addition, neuroendocrine dysfunction, a hallmark feature of CFS, appears to be associated with childhood trauma.


*2 https://www.ncbi.nlm.nih.gov/pubmed/17976252]

The relationship between prior psychiatric disorder and chronic fatigue: evidence from a national birth cohort study. Harvey SB1, Wadsworth M, Wessely S, Hotopf M.

CONCLUSIONS:
This temporal, dose-response relationship suggests that psychiatric disorders, or shared risk factors for psychiatric disorders, are likely to have an aetiological role in some cases of CFS/ME.


*3 https://www.ncbi.nlm.nih.gov/pubmed/17892624

Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies.

CONCLUSIONS:
Various potential risk factors for the development of CFS/ME have been assessed but definitive evidence that appears meaningful for clinicians is lacking.




Incidentally she also remarked in this talk that “we must include the severely affected and children.”

 

[Wildcat]

.
@jodie100 ... Thanks, the first laugh of the day ... though pretty black humour.
.

 

[Jo Best]

Jo - I don't think the MEGA study will have any role in the decision making process at NICE regarding the survellience review in early 2007 and any decision regarding an update or proper review of the ME/CFS guideline later in the year

As you probably know, NICE are only really interested in research that is directly related to the management of an illness - because NICE guidelines are there to guide doctors on how to manage the conditions they deal with

So decisions on updates and reviews to NICE guidelines are very much determined by whether there have been any significant developments in the management or treatment of a condition - not research which is looking at causation or underlying biomedical abnormalities

In the case of ME/CFS, NICE has therefore justified the decision to basically do nothing for almost 10 years because (1) there haven't been any significant developments in treatment of ME/CFS and (2) the PACE trial, as well as some other trials involving CBT and GET have (as far as NICE is concerned) confirmed that their recommendations re CBT and GET are safe and sound

@charles shepherd - from the MEGA petition -

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). If we do this, we think we may be able to develop new treatments. We also think we may be able to target treatments more effectively for those that will benefit.

 

[Simon]

Thanks for the thoughtful discussion.

I am going to be very up front and that may feel uncomfortable for some although I suspect we are all aware of the reality.

Wow, I see what you mean (below)

When I talk to colleagues who look after people with ME/CFS many of them say that some patients obviously have an unexplained physical illness and some have 'other issues'. In ordinary parlance this second group are hypochondriacs, or people with inappropriate illness beliefs

If we consider that we almost certainly have two groups of patients, the question is which one will be most regularly attending CFS outpatient clinics. I think the answer is group 2, because hypochondriacs like seeing doctors. So it may be that the psychiatrists are right - the people they see may be 80% hypochondriacs. Clearly it is not that simple but it is a major issue.

One might argue that one would do no better with a population based cohort. However, my instinct is that it would be significantly richer in people without inappropriate illness beliefs and at least it would reduce the risk of referral bias.

I'd like to offer (one) patient perspective on this. While I'm sure that, by definition, hypochondriacs like seeing doctors, the issue is to what extent the non-hypochondriacs are willing/keen to do so. Maybe for a lot of ailments the worried well will dominate consultations. But mecfs is different (demonstrably) because of the severity of the illness and the impact on our lives - it's functional impact is substantially worse, on average, than MS and RA in both clinical and population samples. Peope who have lost their livelihood (or are struggling to keep it), their social life, maybe their marriage too, are very likely to seek medical help, and press for whatever further help is going in a desperate attempt to recover some of their life. That makes the 80% figure, or anything like it, hard to understand in my view.

You could also argue that the same problem would taint most research done to date: hypochondriacs dominating (or at least being well-represented) in private and public clinics, not 'real' patients. If that's the case, we have serious problems.

 

[charles shepherd]

@charles shepherd - from the MEGA petition -

Yes, that's true and it is possible that some new treatment leads could follow on from a good -omic study

But the time frame here is years away

There are all kinds of other ME/CFS research studies in progress (e.g. the mitochondrial dysfunction studies) that could also lead to new treatments being assessed or developed

There always are!

So I don't think this type of research information has any effect on NICE

 

[AndyPR]

Peope who have lost their livelihood (or are struggling to keep it), their social life, maybe their marriage too, are very likely to seek medical help, and press for whatever further help is going in a desperate attempt to recover some of their life.

And when they don't receive any medical help how many repeatedly go back in the vain hope that, this time, they will get the help they need? Or do they accept that nothing has changed, as far as they can see nothing will change in their lifetime, and stop going, and by doing this, they stop the drain on their energy of getting to the doctors, of vainly attempting to explain how badly their lives are affected, and the disappointment of being rejected, yet again. My experience is of the latter.

 

[Countrygirl]

To bring this discussion back to MEGA/OMEGA, I’m not sure that EC is at all interested in finding biomarkers from the MEGA project.



Incidentally she also remarked in this talk that “we must include the severely affected and children.”

Interesting comment as she claims to believe that ME cannot be severe.

Having read the transcript of her talk, she would have made a very good primary school teacher.. She has missed her vocation

Edited because I stated the exact opposite of what I intended thanks to a stray 'not'.

 

[Countrygirl]

Thanks for the thoughtful discussion.


Wow, I see what you mean (below)

You could also argue that the same problem would taint most research done to date: hypochondriacs dominating (or at least being well-represented) in private and public clinics, not 'real' patients. If that's the case, we have serious problems.

Reminds me of a relevant comment made by an A&E doctor to me as I was lying on a hospital trolley a few weeks ago: paraphrasing 'We only give a diagnosis of ME to people who are mentally ill, so keep quiet about your diagnosis as you won't be treated kindly here if my colleagues become aware of it' Another told me (he was asking me for information as he feared he might have developed the illness) 'My colleagues regard ME with even more contempt than they do people with depression' (!)

Given such a view of ME by at least our docs here, is it likely they would take care to refer only people with ME to the clinics? Hardly!

 

[slysaint]

comment made by an A&E doctor

A few years ago I found myself in A and E (kidney stones); in the 9 hours I was there I was seen by 3 doctors when I told them I had ME the first just smiled as he handed me a sample pot and told me to go and find the loos, the second said 'what's that?', I didn't bother telling the 3rd one as I was still in agony and exhausted and just wanted to go home.

 

[batteredoldbook]

CS:
>I think this is the current list of esearch scientists
>who are currently involved in planning the MEGA study:
>
>* Genomics – Prof George Davey-Smith (Bristol),
> Prof Chris Ponting (Edinburgh),
> Prof Colin Smith (Brighton)
>* Epigenetics – Prof Caroline Relton (Bristol)
>* Proteomics – Mr Tony Bartlett (Somalogic)
>* Metabolomics – Dr Rick Dunn (Birmingham)
>* Routinely collected data – Prof Andrew Morris (Edinburgh)
> Prof David Ford (Swansea)
>* Infection – Prof Paul Moss (Birmingham)
>* Sleep – Prof Jim Horne (Loughborough)
>* Pain – Prof Maria Fitzgerald (UCL)
>* Autonomic dysfunction - Prof Julia Newton (Newcastle)

Patients have expressed a reasonable doubt over whether UK medical research is following the scientific method.

Let that sink in a moment. If your jaw's not on the floor then re-read it.

On this basis I ask all researchers involved with the proposed MEGA study the fair question below. Further I ask all those involved in MEGA to ensure that each researcher has been made aware of it.

"Is the PACE trial good science & can research & treatment be safely founded upon it?"

@batteredoldbook
16:27 27/10/2016

 

[Jo Best]

Yes, that's true and it is possible that some new treatment leads could follow on from a good -omic study

That's why the timing is wrong for a large fishing expedition - we have leads - we need more focus.

But the time frame here is years away

Exactly. That would suit those pulling the strings of NICE. The time frame of the project at this stage on the scene of international ME/CFS research is a reason some people give for Opposing MEGA.

There are all kinds of other ME/CFS research studies in progress (e.g. the mitochondrial dysfunction studies) that could also lead to new treatments being assessed or developed

Yes and the UK B-cell and gut research and in the light of the Norwegian Phase III Rituximab probably to be published in 2018 I think, though of course, we know that NICE won't be guided by foreign research.

So I don't think this type of research information has any effect on NICE

We'll have to wait and see.

 

[lilpink]

Or do they accept that nothing has changed, as far as they can see nothing will change in their lifetime, and stop going, and by doing this, they stop the drain on their energy of getting to the doctors, of vainly attempting to explain how badly their lives are affected, and the disappointment of being rejected, yet again. My experience is of the latter.

Yes I am in the latter camp also. I'm also conscious that with 'minor issues' which others might take to their GP I conversely avoid such contact on the basis that I'm very aware that 'over consultation' is deemed an expression of psychosomatic illness. So too if you attend with more than two symptoms etc etc. Thus I'd argue that most people with authentic ME stay away from their primary practitioners unless or until something so dire occurs that they have no choice. Personally, when that happens, I now avail myself of the benefit of good advice from friends who happen to be sympathetic medics so I can attend my GP properly armed with an idea of what is needed. Of course that in itself is a red flag of psychosomatic illness, I realise that.. but having learned the hard way I prefer to have my ducks in a row ahead of time.

 

[Jo Best]

And when they don't receive any medical help how many repeatedly go back in the vain hope that, this time, they will get the help they need? Or do they accept that nothing has changed, as far as they can see nothing will change in their lifetime, and stop going, and by doing this, they stop the drain on their energy of getting to the doctors, of vainly attempting to explain how badly their lives are affected, and the disappointment of being rejected, yet again. My experience is of the latter.

Yes, I think there's a timeline of sorts whereby patients and maybe their GPs (depending, they're not all thick) are looking for answers so there may be a few referrals initially, e.g. to neurology or rheumatology or endocrinology, and then only to a fatigue clinic if nothing else shows up, then in the latter case, once the patient has gone through the 'specialist' 'treatment' hoops that's it then bar visits to A and E and maybe GP when new symptoms arise. It's such a sad state of affairs and seems to be to much worse since NICE CG53 and the fatigue clinics.