Summary of findings 2. Exercise therapy versus psychological treatment for chronic fatigue syndrome.

Exercise therapy versus psychological treatment for chronic fatigue syndrome
Patient or population: men and women aged over 18 years with chronic fatigue syndrome Intervention: exercise therapy Comparison: cognitive‐behaviour therapy (CBT) Setting: outpatient/primary care
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	CBT	Exercise
Fatigue Measured at end of treatment, 24 weeks Measured with Chalder Fatigue Scale, 0‐33 points Low score means less fatigue	Mean fatigue score in the CBT group was 21.5 points	Mean fatigue score in the exercise group was 0.20 higher (1.49 lower to 1.89 higher)		298 (1 study)	⊕⊕⊝⊝ Lowa,b	Exercise therapy may make little or no difference to fatigue after 24 weeks
Fatigue Measured after 52 weeks Measured with Chalder Fatigue Scales (0‐33 points) or Fatigue Severity Scale (1‐7 points) Low score means less fatigue	See comment	SMD 0.07 higher (0.13 lower to 0.28 higher)		351 (2 studies)	⊕⊕⊕⊝ Moderatea	Exercise therapy probably makes little or no difference to fatigue after 52 weeks Estimate expressed in standardised units (SMD)c. SMD of 0.07 corresponds to MD of 0.5 points when re‐expressed on the Chalder Fatigue Scale (0‐33 points)
Participants with serious adverse reactions Measured after 52 weeks Measured according to European Union Clinical Trials Directive by recording the number of serious reactions	Study population		RR 0.67 (0.11 to 3.96)	321 (1 study)	⊕⊕⊝⊝ Very lowd,e,f	The impact of exercise therapy on serious adverse reactions is uncertain
	19 per 1000	13 per 1000 (2 to 75)
Pain intensity End of treatment	‐	‐	‐	‐	‐	No studies looked at pain at end of treatment
Pain intensity Measured after 52 weeks Measured with the Brief Pain Inventory subscale, 0‐10 Low score means less pain	Mean pain score in the CBT group was 3.56 points	Mean pain score in the exercise group was 0.07 points higher (1.52 lower to 1.66 higher)		43 (1 study)	⊕⊝⊝⊝ Very lowg,h	The effect of exercise therapy on pain intensity after 52 weeks is uncertain
Physical functioning Measured at end of treatment, 24 weeks Measured with SF‐36 physical functioning subscale, 0‐100 points High score means better physical functioning	Mean physical functioning score in the CBT group was 54.2 points	Mean physical functioning score in the exercise group was 1.20 points higher (3.90 lower to 6.30 higher)		298 (1 study)	⊕⊕⊝⊝ Lowa,b	Exercise therapy may make little or no difference to physical functioning after 24 weeks
Physical functioning Measured after 52 weeks Measured with SF‐36 physical functioning subscale, 0‐100 points High score means better physical functioning	Mean physical functioning score in the CBT group was 58.2 points	Mean physical functioning score in the exercise group was 7.92 points higher (9.79 lower to 25.63 higher)		348 (2 studies)	⊕⊝⊝⊝ Very lowa,i	The effect of exercise therapy on physical functioning after 52 weeks is uncertain
Quality of Life (QoL)	‐	‐	‐	‐	‐	No studies looked at QoL at end of treatment
Quality of Life (QoL) Measured after 52 weeks Measured on the Quality of Life Scale, 16‐112 points High score means better quality of life	Mean QOL score in the CBT group was 69 points	Mean QOL score in the exercise group was 6.10 points lower (15.87 lower to 3.67 higher)		44 (1 study)	⊕⊝⊝⊝ Very lowb,g	The effect of exercise therapy on quality of life after 52 weeks is uncertain
Depression	‐	‐	‐	‐	‐	No studies looked at depression at end of treatment
Depression Measured after 52 weeks HADS depression score (0‐21 points) or Beck Depression Inventory‐II (0‐63 points) Low score means fewer symptoms	See comment	SMD0.01 higher (0.21 lower to 0.22 higher)		331 (2 studies)	⊕⊕⊕⊝ Moderatea	Exercise therapy probably makes little or no difference to depression after 52 weeks Estimate expressed in standardised units (SMD). SMD of 0.01 corresponds to MD of 0.4 points when re‐expressed on HADS Depression (0‐21 points)
Sleep	‐	‐	‐	‐	‐	No studies looked at this outcome at end of treatment
Sleep Measured after 52 weeks Jenkins Sleep Scale, 0‐20 points Low score means better sleep	Mean sleep score in CBT group was 9.9 points.	Mean sleep score in the exercise group was 0.9 points lower (2.07 lower to 0.27 higher)		287 (1 study)	⊕⊕⊝⊝ Lowa,b	Exercise therapy may make little or no difference to sleep after 52 weeks
*The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HADS: Hospital Anxiety and Depression Scale; QoL: quality of life; RR: risk ratio; SF‐36: Short Form 36; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^aRisk of bias (certainty downgraded by ‐1): all studies were at risk of performance bias, as they were unblinded.
^bImprecision (certainty downgraded by ‐1): single study and/or limited number of participants.
^cRe‐expressed standardised mean difference: less than 0.41 = small; between 0.40 and 0.70 = moderate and over 0.70 = large effect size.
^dRisk of bias (certainty not downgraded): this outcome is unlikely to have been affected by detection or performance bias.
^eImprecision (certainty downgraded by ‐2): low numbers of events and wide confidence intervals.
^fThe only available trial was not powered to detect differences this outcome.
^gRisk of bias (certainty downgraded by ‐2): unblinded study with large baseline differences between groups.
^hImprecision (certainty downgraded by ‐2): single study with very few participants and confidence interval ranging from a positive effect to little or no difference.
ⁱImprecision/inconsistency (certainty downgraded by ‐2): heterogeneity between the two available studies causes a confidence interval that ranges from a benefit of exercise to a large benefit in favour of cognitive behavioural therapy.