"Why the Cochrane review on exercise therapy ... is still misleading"

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Why the Cochrane review on exercise therapy for chronic fatigue syndrome is still misleading
ME/CFS skeptic 20 oktober 2019 Laat een reactie achterop

On Wednesday, October 2, Cochrane published a long-awaited amendment to its review of exercise therapy for chronic fatigue syndrome (CFS) [1] following a formal complaint to Cochrane’s Editor in Chief. Unfortunately, the published amendment does not address the main flaws of the review and continues to overestimate the evidence for exercise therapy in CFS.

In this blog post, I will argue that treatment effects found in the review are (1) small and lower than some estimates of the minimal clinically important difference (2) no longer statistically significant at follow-up and (3) contradicted by objective measurements. I will argue that there is currently no plausible mechanism for the effectiveness of exercise therapy in CFS and that the treatment effects found are better explained as bias due to a lack of blinding. Finally, I will explain how patient surveys suggest that some CFS patients deteriorate following exercise therapy.


A major flaw of the Cochrane review is that it did not report on objective outcomes (the sole exception is service use). Given that none of the trials were blinded, one would expect that reviewers focus on objective outcomes as these are less influenced by the hopes and expectations of trial participants. The largest study to date on bias in randomized trials, the BRANDO project, gave the following recommendation:

“Our results suggest that, as far as possible, clinical and policy decisions should not be based on trials in which blinding is not feasible and outcome measures are subjectively assessed. Therefore, trials in which blinding is not feasible should focus as far as possible on objectively measured outcomes, and should aim to blind outcome assessors.” [8]​
Unfortunately, the authors of the Cochrane review did just the opposite: they focused on the subjective outcomes and ignored the objective outcomes. The 8 randomized trials had data on employment [9], disability benefits [10], activity levels [11] and fitness tests [12-13] that were not presented in the Cochrane review. These showed no significant difference between the exercise group and the passive control group. [14]

No plausible mechanism
The lack of improvement on objective measures of fitness is puzzling given that the rationale for exercise therapy was to recondition CFS patients. [15] Nonetheless, the results are clear and consistent: the four trials [12-13, 16-17] that conducted a mediation analysis all found that self-reported improvements in fatigue or physical function are not mediated by objective measures of fitness. In CFS, exercise therapy does not work by increasing physical fitness, which is contrary to the offered treatment rationale. [15] This means that exercise therapy currently lacks a plausible mechanism for improvement.



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