The PACE trial in chronic fatigue syndrome

Abstract

The findings of the PACE trial1White PD Goldsmith KA Johnson AL et al.on behalf of the PACE trial management groupComparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.Lancet. 2011; 377: 823-836Summary Full Text Full Text PDF PubMed Scopus (620) Google Scholar seem impressive, but the discrepancy between the definitions of improvement in the protocol2White PD Sharpe MC Chalder T et al.on behalf of the PACE trial groupProtocol 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 Neurol. 2007; 7: 6Crossref PubMed Scopus (113) Google Scholar and paper requires an explanation. In the paper “clinically useful differences” were defined as 0·5 SD changes in fatigue or physical functioning compared with baseline. However, the criteria for improvement published in the trial protocol were much more demanding (table).2White PD Sharpe MC Chalder T et al.on behalf of the PACE trial groupProtocol 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 Neurol. 2007; 7: 6Crossref PubMed Scopus (113) Google Scholar Use of a cut-off score of 75 on the short-form 36 physical functioning subscale, as originally proposed, would halve the number of “recovered” patients.TableDefinition of positive outcome/improvement in the trial protocol and the final publicationTrial protocolFinal publicationFatigue (bimodal Chalder scale)50% reduction or score ≤37% reduction*Clinically useful difference of 2 points (0·5 SD) and mean baseline Likert score of 28·2. or score ≤4†Likert score of ≤18 used by the authors implies bimodal score of ≤4.Physical functioning (SF-36 subscale)50% increase or score ≥7521% increase‡Clinically useful difference of 8 points (0·5 SD) and mean baseline short-form 36 (SF-36) physical function subscale score of 38·0. or score ≥60* Clinically useful difference of 2 points (0·5 SD) and mean baseline Likert score of 28·2.† Likert score of ≤18 used by the authors implies bimodal score of ≤4.‡ Clinically useful difference of 8 points (0·5 SD) and mean baseline short-form 36 (SF-36) physical function subscale score of 38·0. Open table in a new tab Moreover, consulting the normative data for the scale reveals that the mean score of 58 after both cognitive behaviour therapy and graded exercise improved a patient's physical functioning to the level of someone 40 years older than himself.3Bowling A Bond M Jenkinson C Lamping DL Short form 36 (SF-36) health survey questionnaire: which normative data should be used? Comparisons between the norms provided by the Omnibus Survey in Britain, the Health Survey for England and the Oxford Healthy Life Survey.J Public Health Med. 1999; 21: 255-270Crossref PubMed Scopus (236) Google Scholar Is this a case of “outcome reporting bias”?4Smyth RMD Kirkham JJ Jacoby A Altman DG Gamble C Williamson PR Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists.BMJ. 2011; 342: c7153Crossref PubMed Scopus (126) Google Scholar We declare that we have no conflicts of interest. Patients' power and PACEOnce every few years, we publish a paper that elicits an outpouring of consternation and condemnation from individuals or groups outside our usual reach. The latest topic to have caused such a reaction is chronic fatigue syndrome (CFS), and—more specifically—Peter White and colleagues' randomised PACE trial published on March 5, this year. Full-Text PDF The PACE trial in chronic fatigue syndrome – Authors' replyThe PACE trial for patients with chronic fatigue syndrome (CFS) found that supplementation of specialist medical care with either cognitive behaviour therapy or graded exercise therapy was more effective in reducing fatigue and physical disability than was supplementation of specialist medical care with adaptive pacing therapy or specialist medical care alone. We chose patient-rated measures of fatigue and physical function as primary outcomes because this is how the disorder is defined. Full-Text PDF