2025: Survey on the draft protocol for the cancelled update of the 2019 Cochrane ME/CFS Exercise Review

Midnattsol

Midnattsol

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Todd Davenport and Mary Dimmock, two of the author panel of the now-cancelled update of the 2019 Cochrane ME/CFS Exercise Review, posted an open letter to the ME/CFS community March 11 2025 including the draft protocol that was developed to update the review and an opportunity to comment on said draft protocol.

Links to the draft protocol, survey, and FAQs:
● The draft protocol:
● The survey to provide comments: https://pacific.qualtrics.com/jfe/form/SV_0wRPgjuYlVVZa6i
● FAQs on the draft protocol and survey:

The letter can be read in full below:
To: The ME/CFS Community

Subject: Cochrane ME/CFS Exercise Review
Date: March 11, 2025

We are writing this letter to the ME/CFS community as two of the original eight members of the author panel convened by Cochrane in 2020 to produce a full update of their review of Exercise Therapy for Chronic Fatigue Syndrome by Larun et al (1,2). When Cochrane disbanded this initiative in December 2024, they told the authors they retained the rights to use the contents of the draft protocol elsewhere. The other authors have relinquished their rights and moved on. As the remaining authors, we have decided to release the final draft protocol, as submitted to Cochrane in February 2023, and to solicit public comment. We have also sent an open letter to Cochrane calling on them to withdraw the review by Larun et al (3).

As background, in October 2019, Cochrane committed to a full update of this review. They did this because of continued serious concerns, despite amendments made by the authors to the last update in 2019 (1, 2). To that end, Cochrane established an Independent Advisory Group (IAG) and a new author panel (4). Both groups included individuals with lived experience of ME/CFS; the author panel also included two ME/CFS clinician/researchers.

The author panel met regularly from October 2020 until February 2023. During that time, we analyzed the documentation of concerns with Larun et al provided by the IAG (5), considered the findings of UK’s NICE review of ME/CFS exercise studies, and drafted four successive draft protocols for review and feedback by Cochrane Central Editorial Services. We incorporated their feedback, which played a critical role in improving the draft protocol. The fourth and final version was submitted in February 2023, with the expectation that it would be distributed to peer reviewers and IAG members and then for public consultation (4). In May 2023, the Executive Director of Cochrane Central Editorial Services informed the authors by email that they were awaiting clarity on next steps in that process (6).

Cochrane did not communicate with the author panel again until December 16, 2024, when the Office of the Editor in Chief emailed all of us that the initiative had been disbanded. Cochrane’s brief explanation was that “producing a meaningful update of this review is not a priority based on insufficient new research in the field and the available organizational resources to oversee this work (7).” But Cochrane’s original decision to undertake this review was never predicated solely on the emergence of new studies; it was to address concerns with Larun et al (1, 4). The explanation about resources was also confusing as Cochrane Central Editorial Service had been actively involved for two years in shaping the successive drafts of the protocol. And a change in priority at Cochrane would be equally befuddling, given the dramatic increase in the prevalence of ME/CFS in the wake of the coronavirus pandemic (8).

When Cochrane Central Editorial Service informed the authors that they retained the rights to use the content of the withdrawn protocol elsewhere, they also noted that Cochrane retained the rights to the elements developed by Cochrane, such as the search strategy, as well as the right to publish a new Cochrane ME/CFS exercise review, using “potentially, an entirely new author team” (9). Cochrane did not provide further explanation on their future intent.

The most disturbing aspect of Cochrane’s decision to abandon the planned update is that it simultaneously decided to leave Larun et al in place (10,11,12). As the IAG had documented and as Cochrane’s own statements and actions had acknowledged, Larun et al has serious methodological deficiencies in how it assessed both the efficacy and safety of exercise in ME/CFS (1,4,5). This includes Larun et al’s failure to adequately address the harms associated with post-exertional malaise (PEM), an adverse reaction to exercise and other forms of exertion that is the hallmark of ME/CFS (13).

This failure creates a significant risk of harm for people with ME/CFS, including the millions who have developed ME/CFS following COVID (8). This risk of harm is compounded by Cochrane’s decision to revise the date of Larun et al from October 2019 (2) to December 2024 (14), despite the only change being the addition of an editorial note announcing the cancellation of the update. Many, if not most, readers will undoubtedly make the unwarranted assumption that the review itself has been substantially updated and that any criticisms raised in the posted comments relate to previous versions. This risk of harm can only be rectified by Cochrane fully withdrawing Larun et al, as we and others have requested (3,10).

As the remaining two authors, we are considering next steps. In the meantime, we are releasing the final version of the draft protocol submitted to Cochrane to provide transparency about its contents and to provide the opportunity for public consultation as originally promised (4).

Links to the final version of the draft protocol, to a survey for comments on the protocol, and an FAQ on both are provided below. Please provide your comments by May 15, 2025. We will review those comments and provide a summary.

If you have any questions, you can submit them to mecfsexercisereview@proton.me. We may not be able to reply directly to each individual email, but we will add the answers to the FAQ.

We recognize there are opportunities to improve this draft protocol. We look forward to your feedback.

Dr. Todd E. Davenport, Researcher author
Mary Dimmock, Consumer author

Links to the draft protocol, survey, and FAQs:
● The draft protocol:
● The survey to provide comments: https://pacific.qualtrics.com/jfe/form/SV_0wRPgjuYlVVZa6i
● FAQs on the draft protocol and survey:

References
1) Cochrane announcement regarding its plans for a full update of its review of Exercise Therapy for Chronic Fatigue Syndrome by Larun et al. October 2019. https://community.cochrane.org/.../publication-cochrane...
2) Larun et al. Exercise therapy for chronic fatigue syndrome. Cochrane. October 2019 https://www.cochranelibrary.com/.../14651858.../full
3) Davenport, T, Dimmock, M. Open letter to Cochrane. March 11, 2025. https://drive.google.com/.../12.../view...
4) Cochrane announcement on stakeholder engagement in the update to the ME/CFS exercise review. March 2020. Discusses the approach to be taken in the review, including the IAG and new author panel https://web.archive.org/.../stakeholder-engagement-high...
5) Bastian, Hilda. Cochrane Exercise and ME/CFS Review Update: May 2021. https://web.archive.org/.../stakeholder-engagement-high...
6) Email to the authors from Helen Wakeford, Executive Editor, Cochrane Central Editorial Service. May 26, 2023
7) Unsigned email to the authors from the Office of the Editor in Chief, December 16, 2024.
8) COVID-19 Infection Associated With Nearly Eightfold Increase in Chronic Fatigue Syndrome. University of Utah. January 14, 2025. https://healthcare.utah.edu/.../covid-19-infection...
9) Unsigned email to the authors from Cochrane Central Editorial Service, December 16, 2024
10) March 17, 2024 letter from Science for ME to Cochrane calling for withdrawal of Larun et al because of risk of harms https://www.s4me.info/.../s4me-2023-open-letter.../page-2...
a) Cochrane’s response, February 14, 2025 https://www.s4me.info/.../s4me-2023-open-letter.../page-3...
11) Thousands demand withdrawal of review article recommending exercise therapy for chronic fatigue syndrome. Retraction Watch. January 23, 2025. https://retractionwatch.com/.../thousands-demand.../
12) Rücker, M. ME/CFS: New dispute over potentially harmful activation therapy shakes Cochrane network. January 30, 2025. https://www.riffreporter.de/.../mecfs-cochrane...
a) Cochrane told Rücker "Cochrane stands by its decision to have published this review in 2019" and that the decision was made at the Governing Board, the highest group in Cochrane in September 2024.
13) Vink M, Vink-Niese F. Graded exercise therapy does not restore the ability to work in ME/CFS – Rethinking of a Cochrane review. Mooney A, ed. WOR. 2020;66(2):283-308. doi:10.3233/WOR-203174 https://pubmed.ncbi.nlm.nih.gov/32568149/
14) Larun et al. Exercise therapy for chronic fatigue syndrome. Cochrane. December 2024 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003200.pub9/full
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In case anybody wants to be able to copy and paste the links to the draft protocol and to the FAQs.

Draft protocol
Code: 
https://drive.google.com/file/d/1bJzQ7C6Gr2sCFQ37vZ0fSiObkSmqc22T/view

FAQs
Code: 
https://drive.google.com/file/d/1Njn0o98LMoU9nyJmd_AXmQNqIV_3e4xV/view
 
Was only able to briefly skim the protocol but I think it looks good and addresses most of the problems raised with the Larun et al. 2019 version. For example, it includes objective outcomes and reports of harm from non-randomized studies.

A (minor) point of critique is that it overstates the evidence for post-exercise abnormalities in ME/CFS, for example here:
Studies have demonstrated responses to even singular sessions of exercise in people with ME/CFS can be abnormal and have shown to be associated with exacerbated symptoms and decreased functioning (Snell 2013). Objective changes following exercise in people with ME/CFS have also shown deterioration of oxygen consumption and workload measures, and abnormalities in gene expression, metabolism, microbiome, neurological functioning, the immune and vascular systems, and redox
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Most are these are from small unreplicated studies.

It also intends to split up ME and CFS, which I think will mostly cause confusion:
For the purpose of this review we distinguish between the term "myalgic encephalomyelitis (ME)", which will be used when post-exertional malaise (PEM) is a cardinal feature and is present in addition to other core symptoms, and the term "chronic fatigue syndrome (CFS)” which will be used when PEM is an optional feature of the diagnostic criteria. All analyses will be performed separately for these two diagnoses.
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So if I understand correctly inclusion using the IOM-criteria or 2007 NICE criteria will be called ME even though these are quite vague and usually not considered diagnostic criteria for ME.

It might be easier to just do a subgroup analysis for studies that did require PEM or downgrade studies that did not require PEM for indirectness as the NICE committee did.
 
ME/CFS Skeptic said:
It also intends to split up ME and CFS, which I think will mostly cause confusion:
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Andy said:
<groan> Yep, that is exactly what it will do, as it always does when people try to make them into different things. Better to describe them as "ME/CFS with PEM" and "ME/CFS without PEM".
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Strongly agree. The same issue is discussed on the thread about the Irish HSE guidelines for ME/CFS here: https://www.s4me.info/threads/hse-c...c-fatigue-syndrome-ireland.42810/#post-590220


ME/CFS Skeptic said:
A (minor) point of critique is that it overstates the evidence for post-exercise abnormalities in ME/CFS, for example here
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Again I agree, although I think it is more than a minor point. As we have learnt from repeated experience, overstating the evidence of physiological abnormalities is invariably counterproductive as it can be used to undermine the credibility of valid arguments. We don’t need evidence of physiological abnormalities to show that GET doesn’t work and causes harm, so better to err on the side of understating what is know or leave it out.
 
I haven't found the time or energy to go through this in detail or respond to the survey.

I note from the letter:

Please provide your comments by May 15, 2025. We will review those comments and provide a summary.

That's only one week from now. I guess I'd better try to at least skim the protocol and respond. I would like Todd and Mary to find a way of publishing something useful based on all the work that went into the protocol.
 
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