Independent advisory group for the full update of the Cochrane review on exercise therapy and ME/CFS (2020), led by Hilda Bastian

Perfect Trish -thank you! I was thinking yesterday about the diagnostic criteria issue which has got a bit lost in all the discussion on subjective outcomes. An empty review with a detailed explanation of why it's empty could be a very powerful document.

 

Also important: always ask what is missing.

As far as I know, there is no study that has shown that exercise therapy leads to a sustainable increase in daily activity levels of ME/CFS patients.

 

Even if confirmed by school records this would still occupy an uncertain position on the spectrum between what we are labeling subjective and objective.

School attendance can be measured in such a way to be a matter of objective fact, but is also the end result of actions performed by individuals who can be influenced in various ways to achieve certain desired outcome measures - so this measure is both objective in the sense of being factual and subjective in the sense of being open to rather massive bias.

>>When it comes to these spectrummy measures in unblinded trials I think we have to look at the case made as a whole too see whether there good reason to believe in a real improvement. Some combination of positive results for multiple outcomes / massive improvement in an outcome would help build the positive case.

For example, we all know a child with CFS who attends more school after treatment could simply be pushing themselves in this one way at the implied or explicit behest of researchers/doctors/parents, while truly being no better. Even if they are confirmed to have improved attendance for years, this evidence alone leaves quite a lot of reasonable doubt given the psychology of the situation.

If you factually measure that a child who was mostly homebound from CFS and not attending school is now walking 5,000 steps/day and is going to the majority of classes, I'd say there is pretty good reason to think they are truly significantly improved (though likely not 'cured' by any common-sense standard) if this is sustained for, lets say, a year.

If you factually measure that they are running 6 miles/day, I think that would pretty much close the case on there being a 'real' improvement even if you only tracked activity for, like, two consecutive days. Other measures would not even be needed. (Of course people can relapse so you'd want to follow for longer.)

So I guess the thesis is that factual ≠ objective in terms of what we are talking about, but there is some potential value in verifiable facts in terms of building a case for positive outcome. Factually verifiable measures, despite also being open to possibly massive bias, can potentially build a case of absurdity against the null that non-factual subjective outcomes cannot (in unblinded trials).

 

Another issue which Hilda mentioned in her blog about protocols was the mandatory section on "How the intervention might work". This is one of the reasons I am unsure about the idea of a new review on exercise for ME/CFS, as opposed to maybe splitting it into two: 1. ME and 2. Idiopathic (non-ME) chronic fatigue. Or widening the scope to include pharma and non-pharma treatments. In the latter case the section “how the interventions might work” could include other hypotheses other than the BPS one. The overview might still be empty if the diagnostic criteria limited participants to those with ME and not other fatiguing conditions, and the selection of outcomes were also tightened up. Even without any/many included studies, it would be a useful overview of the state of research in this area, for all proposed treatments, and could give a clearer idea of what needs to change to move forward.

 

Thank you. That would be very helpful, and is what I was hoping for when I asked for clarification above.

I agree, but God help us if that led anyone to conclude that we need more GET studies. I’m not even sure how an ME GET study could get ethical approval.

I think the general issue of the uninterpretability of unblinded trials which rely on subjective outcome measures is hugely important but, if there is disagreement about exactly where the line should be drawn, it may be pragmatic to start with examining the specific issues of subjective outcome measures in trials of GET for ME/CFS.

I suspect that the general issue may be part of the reason why there is so much resistance to acknowledging the problems, as it could mean reclassifying a great deal of published research for all sorts of conditions as worthless, and make a lot of important people look rather stupid.

On the specific issue of the use of subjective outcome measures for trials of GET, my recollection is that at least one of the prominent investigators (not sure if it was a PACE author) once specifically stated the primary objective of GET was to increase the activity levels of patients. (Can someone find the reference I’m thinking of?) If that was the objective then surely the primary outcome measure needs to be something which accurately measures activity over a prolonged period of time, ie actigraphy. As @strategist says above, “As far as I know, there is no study that has shown that exercise therapy leads to a sustainable increase in daily activity levels of ME/CFS patients.” To which I would add: despite a great deal of time and money being spent trying to prove that it does.

 

One more question for @Hilda Bastian:

Jonathan is one of the very few independent experts who has got involved with the issues under review. Out of interest, will the IAG be consulting any other truly independent scientists with relevant experience of designing and conducting clinical trials?

To my mind, nobody with from the field of ME/CFS or psychological medicine could be considered independent. Neither could anybody with a vested interest in defending the use of unblinded trials which rely on subjective outcome measures.

 

I have been identified by Reuters, BMJ, the Guardian and most recently Dagbladet as some combination of blogger/activist/journalist with no mention of my academic position at Berkeley and the fact that my investigation of this research is my Berkeley project. The assumption has been that if I am agreeing with patients in this domain I am obviously an activist or advocate and not a professional with expertise. After 100+ scientists, academics, clinicians etc signed a letter castigating the PACE study's flaws to The Lancet, Professor Sharpe stated somewhere something to the effect that none of them had expertise in clinical trials.

 

Thanks for your reply.
Would I be right in saying you meant "sticking your neck out on social media"

If so, I understand what you meant.
Its important to clarify because social media and the real world are very different to a lot of people.

Accusing people of prolific agressive behaviour is something QMUL tried to do when appealling against PACE trial data release. Thankfully the judge dismissed their claims but its a slur that has been very common from the side of the PACE trial in an effort to dismiss all scientific arguments against PACE.

My original question was actually based on a concern that you felt you were sticking your neck out against the establishment.

I'd wager most patients and most people here couldn't care less about a few angry people on twitter and are more than happy to see proper scientific methods being followed.

 

Yes, we will have independent methodological experts (both for trials and systematic reviews) as members of the IAG, and we'll consult other independent experts of various types (eg statistics) in several ways. Same goes for people with content expertise.

 

No, that's not what I meant: I meant making my position public. Social media is a big part of my day and integral to a major part of my work, so it is my real world. Emails are also a big part of my day, and integral to my work, and I explicitly included that. If you're a communication professional, media (social and other) is your real world. Even just "a few angry people on twitter" can suck up a huge amount of time, but it's more than a few - I think that what a lot of other people (including me) regard as a heightened level of aggression has been normalized in this discourse. I'd place the bar for I'd call "aggressive" at a very difference place to many here, so it's not a just few people that I'd be muting/directing to spam. On the other hand, it's nowhere near as bad as many of your opponents say it is: I've been extremely critical of the demonization of ME/CFS activists, publicly and privately, and will continue to be. I believe it is their demonization that has resulted in deterring people from ME/CFS research, not the actual behavior of activists (which is actually mild in comparison to many other topics) - and that they have actually publicly campaigned with a message that translates to stay out of ME/CFS research is unconscionable.

No, I stick my neck out against the establishment all the time, and have for decades.

 

Do you have people that will look for misleading research practices like outcome switching, not reporting outcomes as planned, altering diagostic criteria (and then making claims involving diagnostic criteria) or absurd definitions of recovery? Are these things taken into account?

The CBT/GET reseach is filled with these and they often require good domain knowledge and time to spot them. @dave30th has been documenting a lot of these.

 

We will have that expertise and (b) ...

....That material I talk about above is full of references and links to the discussion you mean. There will be multiple opportunities along the way for people to let us know, in a variety of ways, what we have failed to consider.

 

I think the main reasons for lack of research is the illness model proposed by CBT/GET proponents. According to this model the chronicity of ME/CFS is due to abnormal thoughts and behaviours of patients, not due to an underlying organic disease. The symptoms experienced by patients would be caused by deconditioning, which patients erroneously attribute to the disease they believe they have. Patients also believe that their disease can worsen with exertion but they are again misinterpreting ordinary bodily sensations (eg. delayed muscle soreness), and so they limit their activities and perpetuate their deconditioning.

For more information, see The ‘cognitive behavioural model’ of chronic fatigue syndrome: Critique of a flawed model

CBT isn't any CBT, but it's meant to challenge the patient's illness beliefs.
GET isn't normal exercise, it's meant to help patients overcome their fear of increasing activity.

The apparent success of CBT/GET and in particular the claims of recovery creates the impression that the aforementioned model accurately describes the mechanism involved in maintaining the illness. If one accepts these results as true, then logically there is little reason to do biomedical research.

The media campaign that demonized patients critical of these claims came after decades of neglect so it cannot possibly explain the neglect. In contrast, the CBT/GET model of ME/CFS was first proposed by Wessely and Chalder in 1989 (without any evidence I might add).

Essentially my argument is that society's response to ME/CFS is so inadequate and often harmful because the CBT/GET research has for 30 years acted like a misinformation campaign that gave people all the wrong ideas. It doesn't take much to see that a lack of biomedical research might be the logical consequence of people vigorously insisting that patients have no organic disease.

 

(Good post.)

Generally, "interpretating" sensations is a complex concept.

Which sensations in my soul pop up I have no influence on:

If there are sensations in my eye, I may interpret them and say "This is a car." And logically this makes sense, as it may explain why such a perception can be false or true. But the sensation itself cannot be false or true, it is there or it is not there.

Now if we take pain, it is clear that pain cannot be false or true, it is there or it is not there. Pain is also not an object like a car, which would be the goal of the interpretation. Only an interpretation then, like "This is pain in my foot." can be false or true.

So if there now comes a theory that - in fact - states that sensations are a result of mental acts, it may please explain of which basis this is, logically or at least empirically.

Logically, sensations are a basis of interpretations, not the result.

If you just claim there are these cases, it´s nothing than a claim, and by no means any empirical evidence. One may please give any examples where pain or other sensations have by any means shown to be a result of an interpretation.

This consideration relies on the normal sense of words, and even if some consequences may look strange it must be considered as agreeing with common sense. This is not the cases with the concept we are faced with, it is at least in a first approach against common sense, and asks therefore for detailed enough explanation (which is lacking).


This must not be confused with the interpretation of ones own abilities, which can be cultured. This is another subject, right?

 

I wanted to clarify what I mean with "all the wrong ideas". The CBT/GET proponents have a model and they selectively acknowledge and report information so that it conforms to their model. They omit other important things, ignore inconsistencies and contradictory evidence, inflate the importance of personality and so on. They also manipulate their studies so that they obtain the desired results. This distortion happens to such a degree that the resulting description of the illness is often unrecognizable by patients, but unfortunately it will appear credible and science-based to people without special knowledge of the topic.

For example, the deconditioning hypothesis has been rejected by other scientists because it fits so poorly with available evidence (including the US National Academies of Medicine who published a report on the illness). There is a whole line of research into postexertional malaise because it's an unsual response to exercise, not an ordinary one like the CBT/GET people claim.

In my opinion patients and some biomedically oriented doctors are also guilty of promoting unreliable ideas about the illness in a similar manner. There is definitely a problem with low standards of evidence, zombie hypotheses and dubious claims of being able to treat ME/CFS. This is one of the reasons there is so much enthusiasm for simply rejecting unblinded subjective clinical trials. I hope I'm able to explain this well enough: if we weigh the benefits and harms caused by allowing low quality standards in research against benefits and harms caused by setting the bar very high, it seems very much preferable to set the bar high.