Following on from requests in comments here for missing data [1,2], and McCrone commenting that he would attempt to find a way to publish this information, I thought I would also draw attention to another omission from this cost-effectiveness paper, as well as important deviations from the PACE trial's protocol which have led to inaccurate claims about the efficacy of the interventions available for CFS.

The PACE trial's statistical analysis plan stated: "The estimated costs of APT, GET and CBT will be increased and decreased by 50% to see how sensitive the costs, cost-effectiveness and cost-utility findings are to these variables" [3], yet the results of this analysis have not been reported.

Current figures from the Maudsley Chronic Fatigue Service report the cost per hour of CBT/GET as being £176. This is 76% more than the £100 figure used by McCrone et al for GET, and 60% more than the £110 figure used for CBT [4] . The Maudsley document also makes a number of references to the potential of these interventions leading to return to work, despite the evidence reported reported by McCrone et al. that CBT and GET do not lead to increased rates of return to work.

The Maudsley document actually promotes the efficacy of their service by citing research indicating that results for CBT were poorer outside of randomized controlled trials [5], and a comparison between the results from PACE and the results reported as part of the CFS/ME National Outcomes database [6] would seem to confirm this finding. If the results from the PACE trial are seen as reason to expand the provision of CBT/GET to a wider range of patients diagnosed with CFS, then there is an increasing risk that any expected benefits will diminish further, while costs continue to rise.
As with all unblinded trials which rely upon subjective self-report measures as outcome measures, there is a danger that potential biases (eg: response bias) will lead to researchers making unduly positive claims about the impact of the treatments examined. In the case of the PACE trial, this danger is increased by the nature of the therapies being assessed, and the specific claims made to patients about efficacy as part of these interventions [7-10].

Reporting of results could be biased further as a result of the numerous deviations made from the trial's published protocol [11], a number of which were post-hoc and seem to have been justified by inaccurate claims about population norms, and have since gone on to be further exaggerated by other researchers [12]. The number of misleading claims within the medical literature about PACE's findings on recovery following treatment with CBT and GET mean that it is of particular importance that results for the recovery criteria laid out in the trial's published protocol are released.

Given the high cost of the PACE trial and the problems with misleading claims, distrust and controversy in this area, it is important that every effort is made to release data for all of the outcomes laid out in the trial's published protocol and statistical analysis plan.


[1] http://www.plosone.org/an...
[2] http://www.plosone.org/an...
[3] 1. Walwyn R, Potts L, McCrone P, Johnson AL, DeCesare JC, Baber H, Goldsmith K, Sharpe M, Chalder T, White PD. A randomised trial of adaptive pacing therapy, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome (PACE): statistical analysis plan. Trials. 2013 Nov 13;14:386. doi: 10.1186/1745-6215-14-386
[4] https://www.national.slam...
[5] Quarmby, L., Rimes, K. A., Deale, A., Wessely, S., & Chalder, T. (2007).
Cognitive–behaviour therapy for chronic fatigue syndrome: Comparison
of outcomes within and outside the confines of a randomized controlled
trial.
Behaviour Research and Therapy, 45
(6), 1085–109
[6] Crawley E, Collin SM, White PD, Rimes K, Sterne JA, May MT; CFS/ME National Outcomes Database. (2013) Treatment outcome in adults with chronic fatigue syndrome: a prospective study in England based on the CFS/ME National Outcomes Database. QJM. 106:555-65.
[7] PACE CBT treatment manual: http://www.pacetrial.org/...
[8] PACE CBT participant manual: http://www.pacetrial.org/...
[9] PACE GET treatment manual: http://www.pacetrial.org/...
[10] PACE GET participant manual: http://www.pacetrial.org/...
[11] White PD, Sharpe MC, Chalder T, DeCesare JC, Walyin R: Protocol for the PACE trial: a randomised controlled trial of adaptative 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 Neurol 2007, 7:6
[12] Dan Clarke. It is wrong to prevent patients from making informed decisions about their medical care. http://www.bmj.com/conten...