Protocol for studying ME/CFS and Long Covid

[ScoutB]

Could you expand on this or point me to somewhere that does?

Some good discussion around this happened recently in this thread: Should we initiate development of a new, short questionnaire to identify PEM (to aid diagnosis)?

I'm having a hard time trying to understand what you mean by this. Doesn't making someone fitter by definition resolve their deconditioning?

I think this was meant in the context of a disease. As in, the patient has a disease (one that may make it harder to exercise) and they are deconditioned. An exercise intervention is performed, and the researchers report that (eureka!) they managed to make the patient fitter (e.g. the patient can walk more steps in 5 minutes by the end of the trial). The fact that this may not really mean anything for the underlying disease, and may have come at the cost of other activities, is typically overlooked. We've seen a fair number of these sorts of trials and are a bit jaded..

 

[Jonathan Edwards]

Could you expand on this or point me to somewhere that does? Does it mean you don't think it is a good idea to call PEM "the hallmark feature of ME/CFS"?

Pretty much yes. ME/CFS is an agreed syndrome, which means that it is a clinical pattern that we have reason to think reflects some underlying shared mechanism. But we do not know if it it does or what that shared mechanism is. So we do not know if PEM is the best pointed to that mechanism.

Everything here is much less certain than a lot of people would like to believe. I have a personal view on what clinical pattern seems to point to a shared mechanism in ME/CFS. It may be quite well reflected by the existence of 'PEM' but I am not sure that PEM is the best way to define it. And all we have are these personal views of physicians, who sort of agree. There is nothing more to get hold of yet.

I'm having a hard time trying to understand what you mean by this. Doesn't making someone fitter by definition resolve their deconditioning?

Yes, but if symptoms weren't due to the deconditioning then you have someone who is fitter but just as miserable and ill. When I reviewed the trials of GET for ME and CFS I found one or two trials that showed an increase in physical fitness reasonably well. But that was no indiction that the illness had improved. Being fatigued is not being deconditioned. I know of no evidence for deconditioned people being more fatigued than anyone else. In terms of normal fatigue they will be less so because they do't do much.

 

[wallfish]

Some good discussion around this happened recently in this thread: Should we initiate development of a new, short questionnaire to identify PEM (to aid diagnosis)?

Pretty much yes. ME/CFS is an agreed syndrome, which means that it is a clinical pattern that we have reason to think reflects some underlying shared mechanism. But we do not know if it it does or what that shared mechanism is. So we do not know if PEM is the best pointed to that mechanism.

That's quite a discussion in that tread. Thanks for the discussion here, too. I was not aware of some views on the relevance of PEM in ME/CFS criteria.

 

[rvallee]

If the intervention is only effective for one subgroup, doing a study with a population that also includes other subgroups might obscure the real effect on the first subgroup. An exaggerated example is that a trial of radiation therapy for a group of patients that are coughing would get a negative result even if the therapy is effective for the subgroup that has lung cancer.

Meaning that a null result in isolation might not mean that it doesn’t work for some. Although you can’t claim that it works for some unless you get a positive result in a subsequent trial that only includes the subgroup of interest.

At the same time, if the intervention actually doesn’t work for anyone in the larger group, by definition it won’t work for anyone in the subgroups.

Something especially absurd about this idea of sub-groups is that it's been tried (well, mostly asserted) for both trials and observational studies, and not a single sub-group has ever been found. If at the very least it could be said that observational studies did find well-defined sub-groups, but that they didn't workout in trials, it would be one thing, but it has been tried from opposite ends and failed equally. No one has ever identified anything that isn't more vague and generic than what a coin toss would produce. And we can be sure of this because it should technically look better with more generic groupings, and it just doesn't, it's clearly random noise.

There very likely are sub-groups, but they aren't defined by any of the standard biopsychosocial factors that are mindlessly asserted to be very significant. Frankly things would be entirely equivalent if those made-up sub-groups had been asserted to be on purely physical features, such as height or eye color.

Medicine seems to have simply abandoned the idea that explanations in reality have to account for tangible things. Medicine is a purely biological discipline, the rest is essentially of no importance. It's not a weakness, there is nothing wrong with that. It's not much different than how AI is also limited by physical factors, in terms of energy and heat. The universe and its rules are not a negotiable thing.

 

[rvallee]

The problem with invoking indirectness is that it provides a tacit recognition that CBT and GET might be useful for some other people. We have no reason to think that. It also makes people focus on PEM as a discriminator and I don't personally see that as robust. You end up going off on tangents.

Yeah this is something we need to move in the right direction. All the arguments about indirectness are irrelevant when the most generic definitions have failed just as much as the tightest sub-groupings. If anything, this whole ideology has effectively proven to have zero applicability in the real world, and it makes zero difference whether the target population is tightly defined or fully generic. Everything's been tried already, we have 10x more evidence than is needed to shut this all down.

That was the main lesson out of PACE: it doesn't matter what criteria are used for this treatment model, because the treatment model is a universal failure, simply has no meaningful application in the real world. This idea about requiring PEM is still around, but that's already been completely invalidated. Trials have essentially burned the candle at both ends (in a different application of the metaphor) in that observational studies have shown that the only risk factor for having symptoms is having symptoms, and that symptoms are the only relevant factor in who has symptoms, whether before, during or after a treatment.

Which is entirely expected with treatments that don't work and a model that isn't based in reality. And is the most frustrating thing out of this: literally every damn bit of data over the last few decades is 100% consistent with the psychobehavioral model being completely, comically even, wrong. If one were to make a list of all the features that should exist if it were wrong, it's very obvious that every single one of those is not only met, but to perfection.

 

[rvallee]

These arguments are new to me and conflict with my current understanding. @Jonathan Edwards, is your opinion that CBT does not work for depression?

Actually, I don't even remember a recent study of CBT for depression. There might be a couple in the last decade, but it's clearly not seen as a target application. Which is odd, because along with addiction it's basically the most tailored application of this treatment model.

For depression instead it's all the typical exercise and 'activation' stuff. Maybe it's because CBT for depression is simply assumed to work, that no one questions it, but the evidence simply isn't there. It's not really better for exercise, actually the evidence has gotten worse over time, it's all over the place.

 

[poetinsf]

If the intervention is only effective for one subgroup, doing a study with a population that also includes other subgroups might obscure the real effect on the first subgroup.

This would be true if there are indeed such subgroups divisible by the treatment. But we don't know that. At this point, all we can say is that Oxford definition casts wider net than CCC. One may draw the line with PEM as we often do here, which I think is reasonable btw, but we don't know for sure either if those without pronounced PEM is in fact not an edge case of MECFS. (My case for example is looking more and more like an idiopathic chronic fatigue as time goes on).

There are lots of a priori assumption about subgroups or subtypes without much evidence. I think such assumption could do more damage than wider inclusion. (Not to mention being used as an excuse for failed study). If you look at severe cases only, for example, MECFS resembles infection. And moderate cases look like muscle/energy production problem. Too narrow a focus could miss the whole picture and mislead the search towards a wrong direction.

edit: added ""which I think is reasonable" to avoid impression that I'm against PEM as a litmus test.

 

[poetinsf]

If this has already been discussed

This might be somewhat related: https://s4me.info/threads/making-a-charter-for-ethical-me-cfs-research.37592/

 

[Utsikt]

So you’re saying that the probability that the subset has the same properties as the whole set with regards to the intervention that was tested, is by default greater than the probability of the opposite being true?

That is the basis of all medicine based on trials. Every patient is that 'subset' when it comes to their treatment plan.

That’s a very obvious point now that you’ve spelled it out!

I’ve now realised that the properties of the whole group is that you have a probability X of having a response Y from doing Z, and that it’s not «the treatment works or not».

Thank you!