Wearden 2010

Methods	RCT, 3 parallel arms
Participants	Diagnostic criteria: Oxford (31% fulfilled London ME criteria) Number of participants: N = 296 Gender: 230 (78%) female Age, mean (SD): 44.6 (11.4) years Earlier treatment: 264 (89%) reported medication during the past 6 months with antidepressant (n = 160) or analgesic (n = 79) Co‐morbidity, N (%): 53 (18) had a depression diagnosis, 160 (54) were prescribed antidepressants the last 6 months Illness duration (M): 7 (range from 0.5 to 51.7) years Work and employment status: not stated Setting: primary care Country: UK
Interventions	Group 1: pragmatic rehabilitation, 10 sessions over an 18‐week period; graded return to activity designed collaboratively by the participant and the therapist, also focusing on sleep patterns and relaxation exercises to address somatic symptoms of anxiety (n = 95) Group 2: supportive listening, 10 sessions over an 18‐week period; listening therapy in which the therapist aims to provide an empathic and validating environment in which patients can freely discuss their prioritised concerns (n = 101) Group 3: general practitioner treatment as usual; GPs were asked to manage their cases as they saw fit, but to not refer participants for systematic psychological therapies for CFS/ME during the 18‐week treatment period (n = 100)
Outcomes	Physical functioning (SF‐36 physical functioning subscale, percentage score in which higher scores indicate better outcomes) Fatigue (Fatigue Scale, FS; 11 items; each item was scored dichotomously on a 4‐point scale (0, 0, 1 or 1); total scores of 4 or more designated significant levels of fatigue. Lower scores indicated better outcomes) Anxiety and depression (Hospital Anxiety and Depression Scale (HADS), depression and anxiety scale; lower scores indicate better outcomes) Sleep (Jenkins Sleep Scale; 4 items; lower scores indicate better outcomes) Outcomes assessed at 20 weeks (end of treatment) and at 70 weeks (follow‐up)
Notes	Economic evaluation of the relative cost‐effectiveness of pragmatic rehabilitation and supportive listening when compared with treatment as usual, results of which will be reported separately
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Individual patients were randomly allocated to one of the three treatment arms using computer generated randomised permuted blocks (with randomly varying block sizes of 9, 12, 15, and 18), after stratification on the basis of whether the patient was non‐ambulatory (used a mobility aid on most days) and whether the patient fulfilled London ME criteria"
Allocation concealment (selection bias)	Low risk	Quote: "The random allocation was emailed to the trial manager, who assigned each patient a unique study number and notified the designated nurse therapist if the patient had been allocated to a therapy arm"
Blinding (performance bias and detection bias) of participants and personnel?	High risk	Not possible to blind participants or personnel (supervisors) to treatment allocation
Blinding (performance bias and detection bias) of outcome assessors?	High risk	Blinding not possible for self‐reported measurements (e.g. FS, SF‐36)
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Number of drop‐outs (did not complete treatment): 18/95 (group 1), 17/101 (group 2). Reasons for drop‐out: unhappy with randomisation (n = 8), lost contact (n = 8), too busy (n = 7), not benefiting or feeling worse (n = 5), nurse therapist safety concern (n = 2), misdiagnosis (n = 1), received different treatment (n = 1) Loss to follow‐up at 20 weeks: 10/95 (group 1), 4/101 (group 2), 8/100 (group 3) Loss to follow‐up at 70 weeks: 14/95 (group 1), 11/101 (group 2), 14/100 (group 3)
Selective reporting (reporting bias)	Low risk	All relevant outcomes are reported in accordance with the protocol
Other bias	Low risk	We do not suspect other types of bias