Rethinking the treatment of chronic fatigue syndrome-a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT

Abstract

Background: The PACE trial was a well-powered randomised trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome. Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence.

Methods: Here, we present results based on the original protocol-specified procedures. Data from a recent Freedom of Information request enabled us to closely approximate these procedures. We also evaluate the conclusions from the trial as a whole.

Results: On the original protocol-specified primary outcome measure - overall improvement rates - there was a significant effect of treatment group. However, the groups receiving CBT or GET did not significantly outperform the Control group after correcting for the number of comparisons specified in the trial protocol. Also, rates of recovery were consistently low and not significantly different across treatment groups. Finally, on secondary measures, significant effects were almost entirely confined to self-report measures. These effects did not endure beyond two years.

Conclusions: These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.

Keywords: Chronic fatigue syndrome; Cognitive behavioral therapy; Graded exercise therapy; Myalgic encephalomyelitis.

Fig. 1

Intent-to-treat means for fatigue and physical function ratings, the two measures that contributed to the criterion for improvement specified in the published protocol (Definition A in Table 1). Estimates of healthy performance for the fatigue and physical function measures are based on previously published samples that further excluded the elderly (over 60), and those with a significant medical condition (95% CI bands = upper and lower bounds of 95% confidence interval). The relevant normative data for the Chalder Fatigue Questionnaire were obtained from [48], and those for the SF-36 physical function scale were obtained from [49]. In the case of the SF-36 scale, the healthy sample was highly negatively skewed, so medians are reported. The median score for this sample was 100 (95% confidence intervals: 100,100)