2024: Call for a Research Case Definition Consensus Statement for ME/CFS

Looking at the paper from February, something very ambitious was proposed there:

What I am not entirely certain of is whether that is still the intention & whether this statement is definitely part of the same effort - it mentions the same people. An international conference full of government officials and "key gatekeepers" and historians and social scientists is quite a thought & would be a massive undertaking.

 

Sounds a bit like 6 blind men arranging to meet with a virtual white elephant to me.
I wouldn't discourage trying to get more agreement on criteria but I doubt I shall be jetting off to feel the pachyderm in the room myself.

 

I agree that research criteria may be different and that researchers need to select research criteria to meet the needs of their studies.

The problem is we still have researchers using Fukuda to select ME/CFS participants even though it doesn't require PEM. In fact, NIH's Common Data Elements (CDE) for ME/CFS still explicitly state that researchers can use any criteria they wish, including Fukuda and presumably anything else, as long as they collect common data. The idea was that researchers needed the freedom to decide how to select cases to meet their particular needs and eventually, the collected data would allow researchers to sort it all out. CDC's Unger for one was adamant that PEM should not be required in "ME/CFS" research. I don't know if the CDE group intends to change that in any new iteration of the CDE effort.

As the least, I'd think researchers studying ME/CFS need to start with the ME/CFS criteria and then add additional criteria as needed for their specific purposes. If they can just ignore core features like PEM in selecting ME/CFS cases but then go on to label them as "ME/CFS" in publications, we won't be able to make sense of either the data or the publication. If they don't even require PEM, for instance, what entity are they studying?

Edited to add: Speaking to the same point as @Hutan made in the previous post

 

This!

 

That's the one thing that needs saying.

A consensus might be easier to achieve if it states that, at minimum, delayed-onset PEM is required for a definition of ME/CFS, and (as @Hutan points out) researchers should be clear how they determined its presence.

 

@ME/CFS Skeptic I see you’ve signed the statement. What are your thoughts on the discussion above?

 

I interpreted the statement as highlighting current problems with ME/CFS case definitions, so more a starting point for discussion than a specific proposal on how things should be.

I think the required impairment for ME/CFS diagnosis, definition of PEM, and exclusionary conditions are good examples of where there is a lack of guidance on how this should be assessed. We may not have enough new evidence to tighten things but some consensus and minimal requirements would be useful so that we are comparing like with like.

 

This is basically it. The intention is to ultimately have a set of minimum standards, such as mandated PEM and proper exclusions. The exclusions would have to be driven by individual cases, obviously, but there have been trials where IOM has been used without any exclusions, so patients with bipolar or other major psychiatric conditions have been included in the cohort. That wouldn't stop anyone looking at ME + bipolar in a trial set up to do that, but you ideally don't want that on every trial of ME either.

Someone mentioned the conference upthread, and that's indeed an aim. We've spoken to a couple of parties who are interested in funding such a thing (and hosting it in the UK), but the bulk of the funding will require proof of need. The conference would precede any final set of guidelines.

We were thinking the final guideline might be something like "x, y and z are fine; Oxford isn't," etc. Really, the only things we thought would probably be an absolute were PEM, minimum exclusionary testing of some kind (not a prescriptive list but guidelines for how to generally go about this), and ensuring the severity/chronicity of symptoms.

The idea is to aim for some kind of consistency. Admittedly, when we began this effort (over a year ago), it was because people were getting frustrated with apparently huge sums of COVID research cash going on poor quality studies. We're hoping to avoid that.

The next stage probably wouldn't be handled by us. We've been speaking to potential researchers who might be interested in convening the conference. We've got someone great in mind but we'll see how it pans out.

 

Honest question (I don't know the answer): would that matter in every study?

I've variously shared houses and worked closely with people with bipolar disorder, schizophrenia and severe depression, and their symptoms couldn't seriously be confused with ME/CFS. I'm not sure why they'd always have to be excluded, when people with other long term conditions that have fatigue as an element aren't.

 

I think it is less so about confusing the symptoms and rather ensuring that the result you are obtaining are a result of ME/CFS rather than something else and that will always depend on the study setup.

If you're studying cognitive problems in ME/CFS you want to exclude people with Dementia or MS. If you're studying coagulation you will want to exlude patients that have a known condition that includes problems related to coagulation. If you're studying "effort preference" you might want to exclude certain groups with known psychiatric illnesses. A mouse model transferring autoantibodies of patients to mice might want to exclude patients with a known autoimmune disease.

I think the intramural study may have shown that most studies probably had insufficient exclusionary criteria, so I think a tightening there is very adaquate. It may however mean that we'll end up with many underpowered studies. I think the most obvious solution to this problem is that every ME/CFS patient should have access to a specialist once a year where they can undergo a thorough investigation to rule out problems which might have occured over time, but I don't see anybody tackling this problem.

That might all seem pretty obvious, but I think we've seen that most studies don't adhere to such principles and in the case of Long-Covid, out of the several thousand studies published only less than a handful actually looked at their cohort selection with any rigor at all. Now one might argue that the researchers that are making these mistakes are clearly not bright enough to give us valuable clues to solving ME/CFS or Long-Covid in the first place, so whether or not one now enforces certain principles upon them is anyways irrelevant.

However, there is the additional problem that you might have a strong researcher who is aware of all of these problems, but this researcher cannot get access to any "meaningful" patient data because all of the clinicians he can work with and all the databses that exist are not aware of these problems. So enforcing a set of minimally required conditions in ME/CFS research might force the clinicans to start thinking more clearly. But what exactly such a set of minimally required conditions would look like seems to be the key and I suspect that progress will be rather hard as such criteria will fundamentally depend on the type of study you're conducting. In one study excluding people with a certain condition might for example be rather irrelevant whilst matching to controls by gender or age might be more important. In a study on viral persistence you might want to look at date of last known infection (which of the hundreds of studies on LC viral persistence not a single study has done). So whilst enforcing anything doesn't necessarily seem really fruitful to me, I can definitely see how there is a massive necessity for some form of guideline/code of conduct that is well thought out and is also able to go into more details for specific study setups. Which is essentially what I understand @Hutan to be saying as well. I wouldn't be surprised if there is an abundance of doctors recruiting patients for ME/CFS studies, who have however never heard of ME/CFS before. I can see a sort of Code of Conduct being especially useful there.

In regards to the specifics that the paper mentions like using DePaul etc I also agree with others that it doesn't seem very well thought out yet.

Generally speaking I think one probably doesn't have to enforce much because smart researchers tend to usually figure these things out and those will then flock together and those that don't, don't matter much, however especially when it comes to Long-Covid research I am not convinced anybody is commited to figuring even the most basic things out. At least it seems that even the smart ones have no problem deluding themselves into thinking they have found a singular "biomarker for Long-Covid" albeit their patient cohort consisting of a heterogeneous set of patients where one suffers from anosmia, one had a stroke, the other had acute lung damage, the other had PICS, the other had 4 weeks of diarrhoea, whilst another had ME/CFS and them not even having any idea about whether they are actually studying "Long-Covid" or what that is even supposed to mean.

 

I agree that because Long COVID is even more broadly defined than ME was historically, the issue of heterogeneity there is going to be especially daunting for the reasons you describe.

However, I'm not so optimistic about what is happening or has happened with ME. The 2015 IOM initiative was an attempt to reach consensus for a clinical case definition but that was originally not intended for research. Post IOM, NIH and CDC decided the field was not ready to address the research case definition and instead took the formal position noted above that researchers could use any definition they want. Some of those researchers have continued to use Fukuda because e.g. they always used Fukuda and wanted to compare their new studies to their old studies. Or the researcher was really more interested in studying the general problem of fatigue than ME itself so Fukuda worked for him.

 

If there is to be consistency in case definitions, that needs to include nomenclature. I noticed that the google doc page where you can add your signature to the consensus statement refers to ME/CFS, but the statement itself refers to ME. My preference is to use ME/CFS for the reason's Jonathan explains in The Concept of ME (Thread here: https://www.s4me.info/threads/the-concept-of-me-cfs-2024-edwards.40979/) but there seem to be many in the community who disagree.

 

Well, while I understand the appeal of ME, I for one believe that the way forward is with ME/CFS, for what it is worth.

 

The current situation is that formal mentions tend to be ME/CFS and informal mention tend to be CFS. (except in very informed or activist groups where that moves to ME).

Hopefully, the best case scenario for me is formally ME/CFS and informally ME, so there’s none of that “chronic fatigue” confusion without, some neurologist spending their speech at every ME related conference saying the name ME is wrong and we must switch to CFS.