Trial design for drug trials for ME/CFS - discussion thread

has there ever been a good trial - or is it the same as homeopathy - loads of trials on just about any condition, but all badly designed/biased? Zalewski's point was that with this approach seeming to have potential, should not knowing why prevent trials happening? Could a rigorous trial be done, in a practical and safe a way as possible, before we know why it works/doesn't make people worse, even if we don't know why it works/doesn't make people worse?

 

Back in the 90s (?), after years in bed and having to have my food cut up for me, I had a spectacular improvement after several weeks of a cold-water therapy that consisted of immersing yourself in an increasingly cold bath for longer and longer. I'd read about it in the Daily Mail - a Professor Kakkar (this guy, I think) had published a protocol for readers with ME to follow and IIRC was claiming to have got results and was promising a clinical trial (which never appeared, AFAIK).

I went from bedbound to walking four miles a day, pretty quickly, without slowly grading up. Then seemed to catch another bug and the improvement disappeared and never came back, even though I persisted with the horrible baths for ages.

I think this situation - weird treatment, no obvious mechanism, spectacular N=1 anecdote that might have been coincidence - raises some interesting questions about the value (or otherwise) of anecdotes, such as:

• I think you're now positing that ME/CFS might be caused by something that medical science doesn't yet know about. If that's the case, should the lack of a meaningful background hypothesis based on current knowledge matter (or even be a good thing)?

• We know that whatever preceded one PwME's spectacular remission rarely (though maybe sometimes) helps other PwME but could this be an interesting indication of subgroups? If we could identify PwME for whom a particular intervention seems to have worked, could we identify what else distinguishes them from other PwME (genetics, microbiome, etc.) and move our knowledge forward that way? Could this be a follow-up project with DecodeME's data?

• Anecdotes on their own are dodgy but surely they're often also sometimes massive signposts to research-worthy interventions, like the serendipitous observations with rituximab that led to the Fluge and Mella trial. Is there a more powerful and systematic way of taking advantage of anecdotal improvements in PwME following some sort of intervention?