Trial By Error: Cochrane CFS Exercise Review “May Not Apply” to Patients Diagnosed with Newer ME/CFS Definitions, Per Lead Author

By David Tuller, DrPH

It’s hard to keep up with everything going on in this field these days. So I missed the fact that Lillebeth Larun, the lead author behind the deeply flawed Cochrane review of exercise therapies for what the organization then called chronic fatigue syndrome (CFS) has concocted yet another unconvincing defense of her work. (Larun is a researcher and associate professor at the Norwegian Institute for Public Health.)

The content of the review was last updated in 2019. At that time, Cochrane acknowledged that it needed to be completely redone, starting with an updated protocol, since the review was based on one written in 2002. In addition to appointing a team of authors for the new protocol and review, the organization designated Hilda Bastian, a consumer health advocate and longtime Cochrane insider, to lead an Independent Advisory Group (IAG) that would help oversee the project.

Last December, Cochrane abruptly reversed itself, pulling the plug on the update while providing specious reasons for the decision. At the same time, in a blatant and remarkably cynical contradiction of its prior position, it endorsed the 2019 review as perfectly adequate. Cochrane added an editorial note explaining the situation–then re-published it with a 2024 date, creating the false impression that the review itself was updated. This pre-Christmas “fuck you” from Cochrane hit the ME/CFS patient and advocacy community hard, causing dismay, anger and despair.

In January, Bastian publicly broke with her former colleagues and criticized Cochrane’s actions in a blistering post on her blog, Absolutely Maybe, published on the PLoS platform. In March, Cochrane appended to the review a comment from Bastian, on behalf of herself and the other members of the IAG, headlined “Outdated and misleading content; review unsuitable for clinical decisions.” In June, Cochrane posted Larun’s response. In July, Bastian posted yet another critique on Absolutely Maybe about what Cochrane’s failure to adequately address this situation reveals about the organization. (I wrote about the Cochrane mess for The Sick Times in February.)

Here’s the opening of Bastian’s and the IAG’s March comment on the review:

“This review states that treatment guidelines recommend exercise therapy for people with CFS. This is reflected in a statement in the Plain Language Summary that implicitly encourages use of the intervention: “Exercise therapy is recommended by treatment guidelines and often used as treatment for people with chronic fatigue syndrome.

“This is outdated and misleading.

“In support of these statements, the authors cite a NICE guideline for people with ME/CFS that was published in 2007. The NICE guideline was updated in 2021. It no longer recommends exercise as a therapy, and stresses the possibility of harm.”

Another section noted that current definitions of ME/CFS, unlike those used in the trials included in the 2019 review, require the presence of post-exertional malaise (PEM):

“Furthermore, the participants included in this review’s included trials do not reflect the current population of people diagnosed with ME/CFS, as following the publication of a report by the US Institute of Medicine in 2015, post-exertional malaise has been recognised as the hallmark symptom of the condition.”

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Misunderstanding or willful misstatement?

In her response, Larun appears to misunderstand or willfully misstate the first point, and then responds to her own misstatement.

For example, she writes:

“You state that the review is misleading because the 2022 (sic) Nice guidelines do not recommend exercise therapy. This is a circular argument, as the aim of a Cochrane review is to evaluate the evidence independently, not to ensure the findings of a review are consistent with a particular professional group, guideline group, or advocacy group. “

This response is absurd. Larun completely misrepresents what Bastian wrote. Bastian did not argue that the review was “misleading” because it contradicts the updated NICE guidelines. Bastian’s point was that the review’s claim that “exercise therapy is recommended by treatment guidelines” was “outdated and misleading” because it relied on 2007 NICE guidelines for “CFS/ME” that were superceded in 2021 by the new ME/CFS guidelines.

In other words, the situation has changed since 2019. The blanket statement in the review that “exercise therapy is recommended by treatment guidelines” is self-evidently “outdated and misleading.”

Regarding the concern about changes in definitions, Larun appears to concede—I assume inadvertently—what critics have been noting all along. She writes the following:

“It is unclear if you are suggesting that (i) the spectrum of CFS/ME has changed or (ii) the definition of CFS/ME has changed? As no evidence of the first was supplied, we assume it is the second issue. If so, then the current review does apply to patients with *some* form of chronic fatigue but may or may not apply to all subgroups including those falling within more recent narrower definitions. Whatever definition is accepted, clinicians will need evidence on what is helpful for all patients with some form of (idiopathic) chronic fatigue – that is likely a much broader group.”

Her response illustrates what has been a problem in this field for 30+ years—the conflation of chronic fatigue syndrome, as a distinct clinical entity, with the symptom of unexplained or “idiopathic” chronic fatigue. Of course the latter is a much larger group—the ME/CFS community has been making that point for decades. And of course clinicians need evidence on what is helpful for patients with idiopathic chronic fatigue. But they do not need that evidence to be presented in a document that is purportedly about the illness referred to as CFS/ME.

The 2019 review presumed that those with idiopathic chronic fatigue and those with CFS/ME can be offered exactly the same treatments–as if it makes no difference what condition they have. But if these two groups are different in fundamental ways, as they clearly are, that presumption is unwarranted and potentially harmful.

Larun likely doesn’t realize that her own statement renders her defense of the review incoherent. As its title indicates, the review claims to be about CFS/ME—not about idiopathic chronic fatigue. Larun now acknowledges that the review includes the latter and “may not apply” to subgroups defined with ME/CFS under “narrower” definitions—that is, definitions that require post-exertional malaise.

So that’s clear. Despite the assertion that the 2019 review is about CFS/ME, or what is now generally referred to as ME/CFS, it is also clearly about idiopathic chronic fatigue as well. That seems like a pretty good argument for an updated ME/CFs review.