Anomalies in the review process and interpretation of the evidence in the NICE guideline for (CFS & ME), 2023, White et al

You are right! There is no treatment for ME!

 

tHANKS

 

they keep moving all the PACE stuff
Trying to keep the latest link up to date on this thread
https://www.s4me.info/threads/the-pace-trial.22088/

eta: recently found that this link redirects you to current location of all PACE trial docs. www.pacetrial.org

 

A tangent to this thread, but did anyone ever manage to access the PACE data from the sharing platform where it was supposedly accessible.

[added - see our thread on the PACE trial data https://www.s4me.info/threads/pace-trial-data.2337/page-9#post-483591 though it seems no one has reported successfully accessing the data there either.]

 

I recall independent researchers such as Nick (?) Brown being turned down. I posted about it on I think the main PACE Trial thread (or one of them). Huge hurdles were put in their way.

 

Well done to Dr Shepherd of the ME Association for his e-letter on the BMJ website

https://www.bmj.com/content/382/bmj.p1621/rapid-responses

 

minor point but they should get someone to check things like this
"as a result. off receiving harmful advice on activity mansagement."

 

Nice touch.

 

I've seen someone say in a private conversation that e-letters to the Journal of Neurology, Neurosurgery & Psychiatry should be kept under 600 words because this is a BMJ Journal. That's not correct. See for example the second last e-letter published https://jnnp.bmj.com/content/early/...-revision-to-functional-neurological-disorder. The BMJ itself does have a 600-word limit. But different BMJ journals have their own rules as can be seen by submission guidelines in general.

 

I think the “off” is a remnant from his first draft, where he was telling the authors what they could do.

 

This seems to be another sentence that sounds like a logical argument is being made but then falls apart when examined more closely.

White cited this to argue against PEM being considered a required symptom for diagnosing ME/CFS.

One would assume that White cited it because it contains data on the diagnostic sensitivity and specificity of PEM. But the study examined whether certain symptoms in people with a CFS-like illness predicted a later diagnosis of CFS. This is what the sensitivity specificity values refer to (unless I've misunderstood). It says nothing at all about how important PEM is in people that have ME/CFS. All it seems to say is that having PEM and a CFS-like illness is a poor indicator that the person will meet CFS diagnostic criteria 10 years later.

One could dig deeper into this study to see how PEM was defined and assessed and whether that was good enough. The study author was L. Jason who I consider to be a person that favors somewhat unspecific definitions of PEM. But there's no need to dig deeper.

A description of the study (copied from NICE documents):

Edit: should have said "it says nothing at all about whether PEM is core symptom of ME/CFS. People that don't yet have ME/CFS, unsurprisingly, don't yet have all of the symptoms. And people who had ME/CFS can improve over time and no longer meet diagnostic criteria."

 

Hopefully there will be lots of e-letters picking the commentary apart. Some of the authors might feel some embarrassment for trusting Peter White and being a co-author of the piece.

People could send in more than one as I have done with e-letters in the past.

 

Actual quote from NICE: https://www.nice.org.uk/guidance/ng206/evidence/d-identifying-and-diagnosing-mecfs-pdf-9265183025

White et al. agrees with NICE so far.

A bit later NICE says

So let's look at how NICE rated the quality of various diagnostic criteria. According to Google, AGREE II is widely used guideline appraisal tool.

The IOM and NICE 2007 criteria were rated as having "serious limitations". All other criteria had "very serious limitations".

Looking at bit closer, the IOM criteria "met" or partially met" slightly more quality criteria but this didn't result in a higher final grade than NICE 2007.

How the decision was made:

So in summary White et al seem to agree with NICE that there is no gold standard for determining which diagnsotic criteria is most accurate, but it's presented as if it were an argument against NICE's decision. White et al seem to say nothing about the quality grading of the diagnostic criteria (presumably because they do not see a weak spot, but maybe they say something elsewhere in the article. The Fukuda criteria seem clearly outdated: the committee opinion agrees with the AGREE II guideline grading tool.

 

A different Peter White has explained in this thread how there was a post-exertional symptom requirement in the 2007 NICE guidelines, that that is not a new requirement:

 

The treatment for ME is consideration.

I've been bed bound since 2013. My severity is due to Consequential Progression / Deteriorative Progression, years of inappropriate housing, lack of care, and an inappropriate sectioning in 2014 where they starved me until I walked to the canteen. If I was treated differently and shown consideration I would only be house bound and still able to talk.

 

A lot of this seems of little relevance. The important parts are: the "participants with PEM" treshold for clinical trials, and the question of whether clinical trial outcomes between participants with PEM and without PEM are different. If they are different this would support the decision to require PEM as symptom. If it makes no difference this would argue against it, but it would not be only factor to be considered.

NICE called this the "PEM reanalysis" and says that in the original analysis they excluded all clinical trials where PEM was not a required symptom. After stakeholder consultation, they performed another analysis with slightly less stringent rules that allowed clinical trials where ≥95% of participants met certain, slightly more flexible criteria intended to ensure they had PEM (I'm skipping the uninteresting details). This reanalysis didn't change the conclusions.

Why is White et al criticizing the less stringest PEM reanalysis but not the original plan where it was decided to exclude clinical trials where PEM was not required? I'm unable to find discussions that explain the precise rationale for that original plan by the NICE team.

Sounds interesting but I'm exhausted now and can't look. This sensitivity analysis was probably discussed extensively already by forum members.

 

Yes, of course the quote as a whole is totally non sequitur.
The last sentence is fine. But it in no way justifies the first, which is a bogus justification of criminal negligence.

 

There's also the FINE trial that is getting a bit forgotten in this, especially as it has formed the basis for NHS training despite showing null results.

"You're fine, there's nothing wrong with you, this is the moment where you push", etc.

 

None of it is of the slightest relevance because there are no trials that give reliable evidence for a cost effective treatment regardless of whatever diagnostic criteria are used!

 

That prevalence of PEM varies according to its definition could also mean that there is a need for more stringent diagnostic criteria and clearer definitions of PEM.

If PEM is seen in other conditions, that means it's not unique to ME/CFS. That does not contradict the idea that PEM is a hallmark symptom of ME/CFS.

Also, the 4 studies cited as evidence PEM is found in "many conditions" don't seem particularly convincing at first glance. They seem more like White defining PEM as equivalent to postexertional fatigue and then concluding that PEM is a common symptom in patients with fatigue. But I admit that I haven't looked at them in detail because I'm exhausted.