2025: The 2019/24 Cochrane Larun review Exercise Therapy for CFS - including IAG, campaign, petition, comments and articles

That's ironic, because every time I use voice recognition software, it turns rude words into polite ones.

 

Thank you for dealing with all of my questions!

Wouldn’t the likelihood depend on the selection method, the number of participants, and the distribution of humans in the pool of animals that the participants were selected from? I.e. doesn’t the the number and ratio of humans affect the likelihood that the results apply to that subset?

 

You've just described in your last paragraph exactly my 6 week experience of CBT and Activity management in a clinic, diagnosed under the 2007 NICE guideline and PACE trial results in 2011. My form filling was worse on fatigue but I felt better on everything else. I had been given tools to help me manage my illness going forward, or so I thought. A week after the end I collapsed and been severe ever since. A six month following SF36 was sent to me, but I wasn't well enough to complete it. That was it, lost to follow up, but hey, on the subjective forms they held I was a success and have been for the last 13 years!

Added: The review is causing harm at treatment level globally.

What I haven't seen in the review, unless I've missed it, is the outcome measures reviews which Crawley and Crawley and White did in 2013 on 5 and 6 treatment centres respectively in the UK, showing deterioration in a proportion of patients.

Hence the new PROMS?

Also, regarding criteria, I noticed a couple of months back that the Review had been cited in at least two US trials concerning GWI. What's included in that criteria? Because in the UK, last time I checked, that illness was on 'watch and wait'.

Been trying to catch up with the last 2 days of post on here and failing miserably, so apologies if this is a replication.

 

Yes, it could be useful to study "different sorts of asthmatics..." The key there is they all have asthma.

But we are talking about a group of "different sorts of chronic fatigue". IMO, that is no longer - and I think never was - an appropriate group to stuff ME/CFS into. Especially with what we know about PEM. Continuing to claim that studies with Oxford for instance can appropriately be used to

I completely agree that a poor trial design with respect to outcomes and controls is a disaster.

BUT a poor trial design with regards to patient selection is also a disaster when a trial selects one group of patients who have not been demonstrated to have the condition for which the intervention is being evaluated don't actually have that condition.

Yes, it may be legitimate to generalize from a wider cohort to a narrower one. But when the wider cohort selection criteria are so broad as to be effectively meaningless from a clinical perspective - e.g. nonspecific medically unexplained chronic fatigue of any kind - then one has to question the appropriateness of generalizing from that wide cohort to ALL the clinical populations that might be stuffed into it.

 

Just to clarify, this is what I’ve been trying to say. Medfeb said it a lot better. @Jonathan Edwards

I don’t know if it’s correct, but it’s my current understanding.

 

There are a whole lot of different likelihoods to consider here so it gets complicated. The first thing is the likelihood that the results of a trial can be taken as showing that it is more probable than not that at least some people treated in the future will benefit. Subsets do not come into that much. There is a similar estimation of likelihood of harm.

But a likelihood of 95% that at least some will benefit may go along with a likelihood of benefit for an individual of only 30%, or even less. That likelihood may well be affected by features of the individual that put them in a subset - like PEM. But the PACE trial selection criteria are justified on the basis that if it gave a positive result with 95% confidence that would be a starting point for treating anyone with the criteria if there were no obvious eta features.

The problem then is what features one thinks can legitimately be used to change one's assessment of likelihood of benefit. Say a trial shows that a particular dose of methotrexate shows a good risk/benefit ratio in treating rheumatoid arthritis. Should one then say that this cannot be applied to people with red hair or who are Japanese because there was only one person in the study with red hair and no Japanese.

The answer is quite interesting because we have no reason to think people with red hair would be different and after decades of usage we still don't, but we had no reason to think Japanese people would be different but after decades of use we have discovered that the drug is much more likely to be toxic because Japanese people have different liver enzymes.

If we come to exercise intolerance we might say that (if PACE had had a positive result) an intelligent doctor would be less confident of a good result in someone with PEM from GET, since they are exercise intolerant. That still leaves the PACE trial as legitimate but allows for intelligent interpretation, which is always going to be needed. (You tend not to use injection therapies for people with needle phobias.)

But, interestingly, if you follow the PACE authors' logic, people with PEM ought to be more likely to benefit, because the idea was to desensitise them to exercise intolerance and a reconditioning cycle. People without exercise intolerance shouldn't benefit.

The bottom line is that the choice of entry criteria for PACE was entirely legitimate. Whether PACE could be used as evidence for likely benefit for people with PEM is more debatable but it is and unknown and as such you cannot throw out PACE on that basis. But what you can do is throw out PACE because there were no eggs in the box after all.

 

I don't buy it. Remember that Simon Wessely said that yes there are very ill disabled people who he loved to look after with chronic fatigue syndrome but they are different from people who think they have ME because having ME is just thinking you have ME. Admittedly, the logic starts to fall apart if you treat people with chronic fatigue syndrome as if they have unhelpful beliefs and a reconditioning cycle, but from listening to Peter White and other psychiatrists talk I am fairly sure that most of their patients had ME/CFS.

Most people who are bad enough to need to see a specialist - unable to work, housebound or whatever - with long term fatigue type symptoms probably have ME/CFS I suspect. I am very suspicious of the suggestion circulating in the ME/CFS advocacy community that there are masses of people around with just chronic fatigue who are likely to do fine on GET and shouldn't gum up research into ME (usually without the CFS). I see no evidence for that.

And if you are going to argue that people with ME/CFS do not fall under the wide umbrella of Oxford or Fukuda it needs to be clear why. As far as I know most people with ME/CFS do fall under Oxford and Fukuda. The do not fall under criteria for asthma or rheumatoid arthritis, so we can't say these criteria are meaningless. They do not overlap with any other medical conditions much. (The other conditions require other specific features.)

For all their faults I suspect that people like Peter Denton White spent years doing their best to look after people with ME/CFS. It is just that they did not apply clear reasoning and got stuck with doing things that don't work. It doesn't help if ME/CFS advocates try to counter this with equally poor reasoning.

 

I still don’t understand how you can use a CF study to say something in general about ME/CFS unless you’ve 1) proven that you have a representative sample of the CF population, and 2) the ME/CFS subset is large enough to have the required statistical power.

The fact that I don’t understand doesn’t mean that I disagree. I don’t have an opinion yet, I’m just struggling to understand. Maybe we should just leave it here.

That might say more about the suitability of GET for CF than the ratio of disabling non-ME/CFS CF to ME/CFS.

For all I know, the X-factor(s) for ME/CFS might also be responsible for some non-PEM CF.

 

Statistical power does not come into the extrapolation from the wider set to the narrower one because there is nothing to do statistics on in this situation. Other than what the PACE authors did, which was a post-hoc sub analysis that showed no difference between people with PEM and others. But if only one person in PACE had red hair there are no statistics that tell you how legitimate or otherwise it is to apply the overall result to people with red hair.

You aren't looking for confidence limits. You are looking for balance of probabilities and that is a different analysis.

 

Notable that since this follows, this has been Garner's most recent promotional tour. Out of some trial on LC that doesn't actually say that, but he's been making this claim loudly, that those with PEM benefit the most, for a few months.

 

This is not just my opinion. The IOM and NICE both require PEM for a diagnosis of ME/CFS.

Yes, it may be useful to compare people with chronic fatigue (as in the example you gave) to people with ME/CFS. But the problem is when all of those people, regardless of what they have, are labelled ME/CFS. That creates a body of evidence that can't be interpreted.

We are just going to have to agree to disagree.

Edited to put the end quote in the right place

 

There are a couple of studies that looked at people referred to specialist centres with a suspicion of ME/CFS and around 50% did not meet ME/CFS criteria (it did not seem like solely a problem of the criteria). The non-ME/CFS group included conditions like depression, sleep disorders, overtraining syndrome, burnout etc.

Newton JL, Mabillard H, Scott A, Hoad A, Spickett G. The Newcastle NHS Chronic Fatigue Syndrome Service: not all fatigue is the same. J R Coll Physicians Edinb. 2010 Dec;40(4):304-7.

Devasahayam A, Lawn T, Murphy M, White PD. Alternative diagnoses to chronic fatigue syndrome in referrals to a specialist service: service evaluation survey. JRSM Short Rep. 2012 Jan;3(1):4.

Darbishire L, Ridsdale L, Seed PT. Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care. Br J Gen Pract. 2003 Jun; 53(491): 441–445.

Mariman A, Delesie L, Tobback E, Hanoulle I, Sermijn E, Vermeir P, Pevernagie D, Vogelaers D. Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome. J Psychosom Res. 2013 Nov;75(5):491-6.

Johnston SC, Staines DR, Marshall-Gradisnik SM. Epidemiological characteristics of chronic fatigue syndrome/myalgic encephalomyelitis in Australian patients. Clin Epidemiol. 2016 May 17;8:97-107.

 

and the obvious conclusion to that being that when we die, we really did bring it upon ourselves through behaviour and chronic deconditioning, as the current 2024 (re-dated 2019 review) implies, because the therapy causes no harms at all, and that's why there'd be no need for a reporting mechanism.

In the same way that patients are not allowed to see their mental health records, so there's no requirement to publicly explain all that. All one needs to do is republish with the date 16 December 2024 and stay silent.

 

Iirc, the studies that have looked self-reported ME/CFS status in combination with a symptoms survey, about 50 % of the self reported patients do not fulfill the criteria.

The main causes are probably a poor understanding of what ME/CFS actually is, from either the patients or their doctors.

 

I completely agree that poor trial design is a huge problem. But for me, patient selection is a critical part of trial design - that's exactly what defines "the group of people you are looking at."

At this point, PEM is mandatory for a diagnosis of ME/CFS and using selection criteria that do not require PEM to study people who are claimed to have ME/CFS is unscientific. Any review that does not grapple with that fact - in addition to addressing the issues with subjective outcomes in unblinded trials, failure to evaluate PEM as a hard, failure to address the impact of outcome switching, etc - can not be relied on as the basis of recommendations specifically for people with ME/CFS.

IMO, its not just any one of those issues. It's all of them. I accept you feel differently