Publications from the PACE trial

[Woolie]

Publications from the PACE trial
(**= key article, read this first) ​

The PACE trial assessed the effectiveness of CBT and GET as treatments for CFS. Over 600 patients diagnosed with CFS according to the Oxford criteria (in which fatigue is the only required symptom) were allocated to four groups. One group received a few sessions with a doctor, and symptomatic treatments for pain and sleep. The other groups were also offered these sessions, but in addition, they received a programme of CBT, GET or Adaptive Pacing therapy (a new intervention which encouraged patients to strictly limit their activity). One year later, patients who received CBT and GET reported lower levels of fatigue, one average, and better physical function than those in the medical control group, or in the adaptive pacing group. There were improvements on several other self-report measures, but not on most objective measures (e.g., fitness level, lost employment hours, receipt of disability benefits). Below is a list of some of the main reports of the trial. Various critiques of the trial – and of other similar trials - can be found here.

Published protocol:
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.
White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R.
BMC Neurol. 2007;7:1.
link to article
In this paper, the PACE researchers set out the design of their trial, and what outcomes they will measure. More specifically, they set our what measure they will treat as their primary outcome (the one which will be used to decide whether treatment was effective or not). The primary outcome measure was the number of participants that met a specific definition of improvement.

** Primary results paper (2011), published in the Lancet:
Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.
White PD, Goldsmith KA, Johnson AL, Potts L et al.
Lancet. 2011; 377(9768):823-36.
link to article
This paper presents the primary findings from the trial. However, just prior to this publication, the researchers changed the primary outcome: instead of reporting the number of patients that improved, they reported average self-rated fatigue and physical function. On these two measures, participants in the CBT and GET groups improvement to a great extent than those in the Control (medical care only) and Adaptive Pacing therapy groups.

** Paper on recovery rates:
Recovery from chronic fatigue syndrome after treatments given in the PACE trial.
White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M.
Psychol Med. 2013;43(10):2227-35.
link to article
This paper assessed how many people recovered in each of the treatment groups. The definition of recovery that was used here was not the same as that specified in the trial protocol. It was a lot looser, allowing the researchers to classify more patients as 'recovered'. Using this new definition, they were able to show that over a fifth of patients recovered following CBT and GET, and this number was statistically higher than in the other two groups A critique of this paper can be found here.

Cost-effectiveness paper (also includes employment and disability benefits outcomes):
Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: A cost-effectiveness analysis.
McCrone P, Sharpe M, Chalder T, Knapp M, Johnson AL, Goldsmith KA, White PD.
PLoS One. 2012;7:e40808.
link to article
This paper focuses on whether the therapies offered in PACE were worth the cost, in terms of reducing subsequent health care/disability support costs, and increasing employment hours. It reports for the first time that patients receiving CBT or GET were not different to controls in the hours of employment they were able to work after treatment, or in the amount of health-related benefits/income support they received.

Paper on adverse events:
Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome.
Dougall D, Johnson A, Goldsmith K, Sharpe M, Angus B, Chalder T, White P.
J Psychosom Res. 2014;77(1):20-6.
link to article

Mediation analysis paper (also includes fitness/step-test results):
Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial.
Chalder T, Goldsmith KA, White PD, Sharpe M, Pickles AR.
Lancet Psychiatry. 2015;2(2):141-52.
link to article
This paper examines whether CBT and GET 'worked' by reducing people's fears about exercise.There are some major flaws with the way the analysis was done, which make it impossible to confirm whether reduced fears of exercise caused the improvements in self-reported health, or whether the improvements led to reduced fears of exercise. The most valuable aspects of the paper is that it reports the fitness results for the study. At the end of the trial were no differences in fitness levels amongst any of the treatment groups. Even the GET group, who were supposed to have systematically increased their activity over the course of the trial, were not fitter than the other groups at the end of the study.

Long-term follow up paper:
Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial.
Sharpe M, Goldsmith KA, Johnson AL, Chalder T, Walker J, White PD
Lancet Psychiatry. 2015;2(12):1067-74.
link to article
This study followed up the PACE participants at least two years after the start of the trial. Participants completed the same self-report questionnaires about fatigue and physical function they had completed during the trial. About 75% of participants completed the questionnaires. At this time, the Control and adaptive pacing groups had caught up to the other groups, and there were no overall group differences.

Other material published about PACE by the trial authors:
Statistical analysis plan (2013) link to article
Press release from King’s College London: CBT for chronic fatigue syndrome. link to article
Unpublished article that presented results based the original primary outcome measure (this was released the day after the FOI ruling). link to article
Other materials by the PACE authors that aim to address key criticisms:

White et al 2015 commentary in response to critics link to article
PACE trial authors' answers to FAQs link to web page ​

A list of other published papers from the PACE trial. link to list of articles
PACE treatment manuals and participants’ newsletters: link to list of articles