Clinical trial outcome measures of improvement and recovery in ME/CFS - which ones are useful? Discussion thread

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

Leaving some notes here regarding caveats when critiquing most common features of some researchers' claims about trial methodology and alleged benefits from therapist-delivered treatments for ME/CFS.

- Objective outcomes:

It's true that objectivity with regard to outcome measures is always a 'spectrum'.

And even an indisputably objective outcome like death needs to be interpreted: Is it caused / delayed due to the investigated treatment or due to an other cause?

So, there is a hierarchy of robustness with regards to objective outcome measures and those outcomes need to be analyzed properly, but on the other hand, there are subjective outcomes that clearly are subjective, and only subjective -- both subjectively reported and only subjectively assessable.

The point that certain objective outcomes are not entirely objective is not valid with regard to differentiating between subjective and objective outcomes in the context of reliable trial methodology.

- Improvement versus recovery

This point is somewhat related to objective outcomes like going back to work or school.

It there is no cure, of course every relevant improvement should also be counted as benefit, even if it doesn't lead to restored working ability.

I think that needs to be taken into account when evaluating treatment trials that claim to have found evidence for improvement of symptoms but not for restoring working ability.

If there were any reliably measurable, relevant improvements, that actually would be better than nothing. But behavorial treatment and physiotherapy ME/CFS trials I'm aware of didn't show evidence of improvement beyond a short-term placebo effect in a minority of patients.

I think though that selling placebo as evidenced-based treatment could be counter-productive to coping with a life-altering illness and could cause long term mental suffering and other harm.

Perhaps it would be worthwhile to discuss what people with ME see as relevant improvements if they can't go back to work or school?

 

An absolutely excellent idea. I have been criticized for suggesting both the return to work or return to school outcomes for over-simplifying and discriminating against people who volunteer, are retired, or who may have or want to take on caring responsibilities. And also against those who may not improve enough to be able to do these things, but still improve. And I fully accept that criticism. I agree it should be people with ME who decide what defines meaningful improvement.

 

Totally agree with you Trish. Being able to do more is what my daughter longs for.
She would be happy with more physical or cognitive function.

There are some cognitive tests that are useful. @Joan Crawford would know more.

I know that Graham was trialling a type of Stroop test and using it in ways to test fatiguability.

This is the kind of work we need doing/funding for. Great to have this thread

 

I was once told that as there is no cure, no effective management treatment and no underlying pathology I should force myself to return to work part time to acclimatise myself to a working life with symptoms because I would always have symptoms anyway.

I don't think it's entirely unreasonable to have return to work or school as a measure of recovery if that's the normal function for a particular age group. Someone might choose to do something different but that's a matter of choice rather than capability.

I think first and foremost is the capacity for self care.

Whatever the measure used for me the most important thing is that they do not become a stick to beat people with. That's the really tricky thing.

 

What about the tests for cognitive performance, in particular reaction speed, that were used in the trial discussed here?

 

I think any measure of changes in physical activity should be accompanied by measures of diverse features of cognitive performance (with respect to both time and quality).

We repeatedly discussed that in mild to moderate ME people can do certain activities at cost of other activities. To a certain extent, people who are not on the severe spectrum can chose between rest and activity and also different kinds of activity, and influence their symptoms that way. That decision can influence objective measures like activity trackers.

If people are only mildly affected or if they have sufficient support, perhaps some people choose not to do more physically but cognitively?

I consider myself in the moderate spectrum and it seems to me that if I reduce my physical activities I have more capacities for cognitive activities in addition to the time saved by refraining from physical activies.

In addition, if I break down cognitive activities into very short time spans and rest in between, my concentration, reading speed and other features of cognitive performance benefit (at least I think they do).

(A part of that post is copied from a post in another thread.)

Edited for clarity.

 

A PSP question ..... ?

 

(Just leaving some thoughts here before I try to have a bit of a forum break. So apologies if this is somewhat out of context.)

What perhaps also needs to be considered is how structural/ systemic bias can impact even objective outcomes.

Health care usage, for instance. If doctors have nothing to offer but ignore patients' disabilities and health care needs, why should patients turn up at a clinic or their doctor's office? Patients will try to survive by other means, often this might imply a serious 'psychosocial' deterioration: financial loss; if people still are able to work somehow they might work part-time, earn less but still have to give up social activities, will lose friends, can't afford to keep their home in a good condition etc.

Also, if people's disabilities aren't properly assessed and they won't get a disability certificate, their disability won't show up in objective records.

If people find other means for existing, live from their savings, receive support from their family etc. they aren't even eligible for unemployment benefit or social benefits, and again, their status won't show up in any objective records.

So that seems to be an example that rather shows that under certain conditions some objective outcomes can be misleading and need to be collated with other data, including perhaps subjective outcomes?

 

Political censuses have often been weaponized in history, counting the number of people as they are, now just certain people, is a reliable way to oppress people. If we're not counted when we exist, we sure as hell won't be counted when we die.

This is a continuation of the same, just as this BPS dystopian nightmare is a continuation of the horrible abuses psychiatry committed in institutionalized systems, just without the walls or paperwork. There are differences but fundamentally it's the same thing playing out. Not counting people is the most effective way to get them to disappear. This is even evident in the number of physicians who oddly proclaim that "chronic fatigue" is not really a thing anymore. It's not counted so in a sense they're right. Millions disappeared on purpose, in plain sight.

Usually it's governments abusing their power that do this, however. That medicine is doing something notoriously political is several layers of worse.

 

Apologies for only guessing -- I still lack some basic understanding of statistics and trial methodology.

I think return to work and school attendance are still meaningful outcomes for a large group of PWME. I just wanted to suggest that, in unblinded trials, they shouldn't be the only objective outcomes to corroborate the subjective outcomes?

However, if, in a randomized trial, there were improvements in subjective outcomes but those improvements aren't reflected in return to work or school, those objective findings are still an important and valid means to cast doubt on the significance of the reported improvement in subjective outcomes.

I also think employment status is an important point in epidemiological studies, but it's important to not confuse different types of studies with regard to how the corresponding data are collected and used? (Epidemiological studies that are representative in socioeconomic respects for a 'natural' population versus clinical trials that I think can't be representative in those respects for a global or even regional patient community?)

Edit: wording, e.g. added "reported improvement" in subjective outcomes in 3rd paragraph.

 

Another point I'm thinking about is how to make sure that trial participants report objective outcomes in a reliable way if they can't be collected otherwise than by self-report.

I think the risk of bias in reporting employment status is very low as this nowadays won't fluctuate much short term.

It's more difficult to report how many days/ hours a week you were able to work (including non-paid work) or could attend school if you don't have to record these data daily.

So any questionnaires to be filled in retrospectively to report fluctuating data for a longer period of time seem to me to be problematic.