Systematic review of randomized controlled trials for (CFS/ME) - Do-Young Kim et al Jan 2020

[Sly Saint]

Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)

Abstract
Background

Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date.

Methods
RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes.

Results
Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%). Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I)Poly(C12U) and CoQ10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility.

Conclusions
This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.

full paper
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-02196-9

 

[wdb]

Contrary to the positive outcomes in the 1990s and 2000s, more recent CBT trials have failed to show consistent benefits in patients with CFS/ME: 5 of 7 RCTs of CBT did not show significant effects...

In our data, 4 of 5 RCTs with graded-exercise-related therapies presented positive outcomes; however, the clinical usefulness of GET is highly controversial [88]. One survey reported that 79% of CFS/ME participants felt that GET worsened their health status [89]. Furthermore, GET was criticized due to the conflict with PEM, a particularly essential symptom of CFS/ME according to the IOM diagnostic criteria [90]. Both CBT and GET have limitations and have received criticism more recently because they are based on psychiatric views, which is contrary to the fact that CFS/ME is a physical illness based on accumulated evidence from scientists as well as patients and physicians [1].

 

[Amw66]

How many of these are actually randomized and controlled trials?

 

[Mithriel]

There is no value in this sort of review. There have not been enough (any!) proper Rcts to do a systematic review.

It is the wrong place to look for any interesting data and looks like something made up to get a grant rather than anything done for the benefit of patients.

 

[Esther12]

There is no value in this sort of review. There have not been enough (any!) proper Rcts to do a systematic review.

I've not read this paper yet, but a careful systematic review pointing out all the problems with the research in this area would be valuable.

Systematic reviews have real political power and leaving them to just those trying to promote CBT/GET would do real harm.

 

[Marky]

I've not read this paper yet, but a careful systematic review pointing out all the problems with the research in this area would be valuable.

Systematic reviews have real political power and leaving them to just those trying to promote CBT/GET would do real harm.

I agree, seems like exactly the kind of systematic reviews that are needed. I agree with Mithriel however that its pointless to investigate intervention efficacy (when its not criticism)

 

[rvallee]

I don't see the point of restricting to trials that focused only on fatigue, this obsessive focus over the one symptom is a major part of the problem. There is also the problem of pretending many of those trials are controlled, when only the drug tests were controlled and many weren't because the side-effects are too obvious. Giving the label of RCT to non-controlled trials is itself extremely problematic. They're open label randomized trials, say it. Giving credibility to P values is frankly a bit insulting, like giving guesstimates 5 significant decimals, should not be taken as reliable, psychometric questionnaires are not at all reliable.

Even PACE describes itself as a randomized trial, basically the only thing it can be credited for. And actually, looking at the table of non-pharma interventions, it looks like PACE was excluded. Which is fair, though all the other non-pharma trials are not controlled either so that's weird. Would have been nice to look at trial pre-registration and how common it is to deviate from.

I think this is the reason PACE was excluded:

The Jadad scale is a five-point scale in which descriptions of randomization, double-blinding, or withdrawals and drop-outs receive one point each

But none of the non-pharma ones actually meet that threshold without being over-generous.

But overall it's a fine review in that the reliability of evidence is extremely poor and so conclusions over this evidence cannot be better than what goes in. The simple truth is that there is nothing reliable after 3 decades of "research" and 2 decades in practice. This alone should upend everything, it's madness that medicine continues to pretend there is anything there. But it would upend the BPS model and expose many institutions' failure in protecting a vulnerable population.

At least this is a much more honest review than the Cochrane ones. Much less biased as well, by the simple fact that primary researchers in some of those trials were not involved in the review. Without the layer of varnish, a polished turd is just that, a turd, and the body of evidence is generally a giant pile of that.

 

[ME/CFS Skeptic]

So there have been more RCT's on non-pharmacological interventions than on pharmacological interventions (even though the latter includes nutrients and homeopathy).

And the most common type of pharmacological intervention tested is psychiatric drugs. Another five trials looked at the stress hormone cortisol. Both interventions don't help in treating ME/CFS.

Some immunomodulators were tested but these trials are old. With the exception of the rituximab trial, there have been so little RCT's in recent years that tried to treat this illness. Practically none, really.

The result is that in 2020 there's no treatment for ME/CFS, nothing that relieves the constant exhaustion or disability that tortures millions of patients. I myself have been severely disabled because of ME/CFS for more than 10 years and there's nothing doctors can do to relieve the suffering, not even a little bit.

I can't help but think that a focus on a psychiatric aetiology and the fear-avoidance model has wasted precious time and resources to get a to treatment for ME/CFS that actually works.

 

[Ravn]

Some immunomodulators were tested but these trials are old.

And were any of those old pharmacological treatment trials ever replicated? A couple of them had at least somewhat positive findings.

On a less serious note, I looked up the reference for the Tuina study because I wanted to know what Tuina was - an unpleasant sounding abdominal massage, apparently. But it got better: that Tuina paper then referred to something called "intelligent-turtle massage"! Now, due to my complete ignorance on the topic I have no opinion of any sort about traditional Chinese medicine but it sure has more linguistic creativity than Western medicine.

 

[Sly Saint]

Correction to: Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)

Correction to: J Transl Med (2020) 18:7. https://doi.org/10.1186/s12967-019-02196-9
Following publication of the original article [1], the authors noted that one study (PACE trial) [2] had been missed in the captured data. Accordingly, some corrections were made in multiple sections, including the addition of the reference information for the PACE trial in the reference list. The updated sections are given in this Correction, and the changes have been highlighted in bold typeface. The original article [1] has been corrected.

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02603-6

 

[Jonathan Edwards]

Except is wasn't a controlled trial.

Wonder how this came about!

 

[rvallee]

Even more so many of the trials in this review are not controlled, not just PACE. Only the drug trials are. The behavioral ones are all clearly not controlled and PACE itself even acknowledges it. There is ambiguity in the use of RCT throughout the article but the title clearly says controlled. How is such careless disregard for important terms acceptable?

Way way weirder still is that PACE has been added to the table of interventions under... drum roll... adaptive pacing. Seriously. It's even listed under Others even though there is a Rehabilitation group. PACE was very much all about rehabilitation. Although that may be because PACE was a mish-mash of things. In the same category as Distant healing, which is about right. Although to some credit it's marked as statistically not significant. Which is interesting.

FINE is marked as not significant. It is the literal basis for NHS training programmes. Neat. And GETSET too is not significant. So all the big ones. But frankly the table is a bit weird as it lists FITNET as the intervention, even though the actual intervention is CBT. There is already an item for iCBT so it should have been used. So bit of a mess here, frankly.

Ultimately, the only relevant part is the very last sentence:

An exploration of the pathophysiology of CFS/ME and better development of treatments are needed.

So there's at least that. PACE changes nothing to that.