1 White PD

Goldsmith KA

Johnson AL

et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. The open-label PACE trialwas designed to compare efficacy of cognitive behavioural therapy (CBT), graded exercise therapy (GET), and adaptive pacing therapy (APT), when added to a standardised intervention resembling usual care (specialist medical care) as treatments for chronic fatigue syndrome.

2 Bavinton J

Darbishire L

White PD PACE manual for therapists; graded exercise therapy for CFS/ME. 1 White PD

Goldsmith KA

Johnson AL

et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. , 2 Bavinton J

Darbishire L

White PD PACE manual for therapists; graded exercise therapy for CFS/ME. CBT and GET were based on a hypothetical model of chronic fatigue syndrome whereby symptoms and disability are assumed to be primarily perpetuated by a fear of symptoms and activity, avoidance of activity, and associated deconditioning (lack of fitness). CBT and GET were intended to address these assumed perpetuating factors and to “reverse”the illness, leading to “an increase in activity capacity” and ultimately a recovery. CBT mainly focused on addressing fear and avoidance, and GET on reversing deconditioning. The trial's manual for therapists explains the model of illness for GET: “Participants are encouraged to see symptoms as temporary and reversible, as a result of their current physical weakness, and not as signs of progressive pathology”.

3 Chalder T

Goldsmith KA

White PD

Sharpe M

Pickles AR Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. 3 Chalder T

Goldsmith KA

White PD

Sharpe M

Pickles AR Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. In the latest analysis of the PACE trial in The Lancet Psychiatry (February, 2015),Trudie Chalder and colleagues explain that CBT and GET did not improve the assumed lack of fitness, as assessed via a step test, and that “fitness measures do not appear to mediate the effects of either treatment”. Chalder and colleagues acknowledge that the trial outcomes do not support the hypothetical deconditioning model of GET for chronic fatigue syndrome.

1 White PD

Goldsmith KA

Johnson AL

et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. , 3 Chalder T

Goldsmith KA

White PD

Sharpe M

Pickles AR Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. 1 White PD

Goldsmith KA

Johnson AL

et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. , 3 Chalder T

Goldsmith KA

White PD

Sharpe M

Pickles AR Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. The PACE trial had two objective measures of physical capacityfor which data have been published: a step test and a 6 min walking test. CBT did not significantly improve either measure. Chalder and colleagues arguethat their mediation analysis strengthens the validity of the hypothetical fear-avoidance model of CBT; however, the failure of CBT to significantly improve either of the trial's objective measures of physical capacity suggests that CBT failed to reverse the illness or lead to an increase in activity capacity. The objective outcomes do not support the fear-avoidance model of CBT.

1 White PD

Goldsmith KA

Johnson AL

et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. 4 Kindlon TP Objective measures found a lack of improvement for CBT & GET in the PACE Trial: subjective improvements may simply represent response biases or placebo effects in this non-blinded trial. , 5 Wilshire CE Re: Tackling fears about exercise is important for ME treatment, analysis indicates. 2 Bavinton J

Darbishire L

White PD PACE manual for therapists; graded exercise therapy for CFS/ME. For the trial's self-report primary outcome measures (fatigue and physical function), a moderate effect size was reported for CBT and GET, and (an additional) 11–15% of participants clinically responded to treatment when CBT or GET were added to specialist medical care.However, as the PACE trial was open-label, we cannot know if some or all of the reported improvements reflect issues with the trial's methodology and are a result of biases, such as response bias and a placebo effect.For example, unlike the specialist medical care and APT groups, participants receiving CBT and GET were told that the therapies were highly effective and were encouraged to see symptoms as temporary and reversible, possibly leading to differing expectations across the various trial groups.

The PACE trial is to our knowledge the largest investigation of CBT and GET for chronic fatigue syndrome to date. The deconditioning hypothesis was not supported, and the fear-avoidance hypothesis was not supported by the trial's objective outcomes. These factors, along with the disappointing self-report clinical response rates for CBT and GET in an open-label trial, cast substantial doubt over the validity of the fear-avoidance and deconditioning hypothesis for chronic fatigue syndrome.

I declare no competing interests.