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Pressure grows on Lancet to review “flawed” PACE trial

BMJ 2018; 362 doi: (Published 22 August 2018) Cite this as: BMJ 2018;362:k3621

Rapid Response:

Please do not misunderstand patient views

This editorial stated "On its publication patients expressed anger because they thought that it suggested that ME/CFS was all in the mind".

In anticipation of any future comments about this, I'd like to point out that this is a mischaraterisation of patient views. I have communicated with a quite a number of patients who are critical of the trial in question and none of them were angry because "it suggested thats ME/CFS was all in the mind". I don't know where this view comes from, but it seems to be a misunderstanding of patient views.

Patients were angry that the results of the trial were excessively spun, and that much of the outcome measures specified in the protocol were not reported in the manuscript published in The Lancet. In particular, the thresholds for "positive outcome" and "recovery" were heavily watered down such that they were no longer meaningful.

One of the major criticisms by patients was that the "recovery" (remission) criteria as described in the protocol was not used and in its place, a highly questionable and misleading criteria for "normal" function was used instead. This criteria was used to imply recovery in one of the associated editorials published at the time of the original manuscript.

The criteria for "normal" functioning in the trial was defined as a SF-36 physical function score above 60. A SF-36 physical function score of 60 is less than the 15th percentile of the overall population of men/women that were of the median age enrolled in this study. The median and mode for mostly healthy western women of this age is somewhere around 95/100. Since patients were screened for other conditions that would affect their physical functioning, one would expect far higher scores to be considered recovered. The most strange aspect however was the entry criteria required a score lower than 70/100. Which is to say according to the thresholds used in the PACE trial, you could simultaneously be considered ill enough to participate and well enough to be considered recovered with the same score of 60/100.

The reanalysis by Wilshire et al. analysed the data as close as possible to the original protocol, given the data they had access to. they discovered that on the contrary to claims made by the authors, there was no difference in recovery rates between the randomised groups. This lack of recovery from such treatments is much more in line with patient community experiences with these treatments. Namely that they might be useful for a minority of patients to manage living with a chronic illness more effectively, but that they should not be considered primary treatments that lead to remission.

This example is potentially a textbook example of how pre-publishing clinical protocols is important and how deviation from that protocol is used in an attempt to exaggerate the efficacy of an intervention in a clinical trial.


White, PD, Sharpe, M, Chalder, T, DeCesare, JC, Walwyn, R, the PACE trial group "Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy" BMC Neurology 2007 7:6

Wilshire C, Kindlon T, Matthees A, McGrath S. "Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial." Fatigue 2017;5:43-56.

Competing interests: No competing interests

22 August 2018
Andrew J Kewley
South Australia