Is there a need for patient stratification in ME/CFS studies or trials, and if so what should it be?

[Andy]

I'm starting to see this come up some what regularly, mostly off-forum, as a suggestion and feel that a discussion of the idea here would be useful. I suppose at the end of the day the answer is that it depends on the situation, but exploration of when it would be useful and when it wouldn't would be worthwhile.

So is there a need for patient stratification in ME/CFS studies or trials, and if so what should it be?

 

[Deanne NZ]

I cannot give you a scientific rationale, but my mother’s hunch is that there is merit in looking a males with early teen onset as a specific patient group.

 

[Kitty]

males with early teen onset as a specific patient group.

Yes. And in young females, what is the time relationship between menarche and onset? I don't think I've ever been asked that.

Another is separating people who've never experienced severe illness (e.g., being bedbound 90% of the time for at least 12 months), and those who've never experienced mild illness (e.g., being able to carry on with some work / study / exercise / caring for others for at least 12 months).

Maybe also people who've experienced remissions where they recovered normal or almost-normal function for at least 12 months.


Another aspect of stratification is inclusion. For instance, should all Phase III treatment trials be made accessible to a severely ill cohort, unless there are drug safety concerns specific to that group?

 

[BrightCandle]

Every time stratification seems to come up its in relation to a trial where some people seemed to improve and most didn't. There was no way from the trial data to identify what that stratification for a future study might be. It doesn't seem to go along lines of what we can currently see like severity or anything the study captured. The one exception to that was the Daratumumab study on NK cell count.

Where studies have been done with appropriate follow up and control group they show no positive result but there is always a number in the control and receivers groups that improve. To me this means that the disease has a variable level of severity over time and studies are capturing those positive upswings. It is not a signal above the general noise of severity in the diseases normal course however. Which is a good argument for ensuring sufficient size, follow up time and appropriate control as a necessity in all ME/CFS trials. It is not yet a good argument for stratification, much better studies would be needed to determine that.

 

[Creekside]

IMO, there already is stratification. The various criterias for ME are based on best guesses, rather than absolute measurable factors, so there's probably some number of people with the ME mechanism that are not included in studies because the criterias are wrong in some way.

I think stratification--inclusion criteria--should be left to the researchers. They know what their goals are, and which subgroups might drown out the signal they're looking for. It's up to people reading those studies to judge whether a finding is predetermined by inclusion criteria. This forum has plenty of people who look for flaws in studies, and are quite vocal about them.