Wiles 2016.

Methods	RCT, parallel group (CoBalT trial)
Participants	Recruited from GP practices Location: UK Criteria for depression: ICD‐10 criteria for depression and at least 14 on the Beck Depression Inventory (BDI‐II) Age: range 18 to 75 years (mean age 49.2 years for CBT group, 50.0 years for usual care group) 469 participants in total (n = 339 (72%) female) Baseline BDI score: CBT + TAU = 31.8; TAU = 31.8
Interventions	Group I: cognitive‐behavioural therapy plus usual care Participants received a course of 12 sessions of CBT, with (up to) 6 additional sessions if deemed necessary by the therapist. Eleven trained and supervised therapists were representative of NHS psychological therapy services. Sessions typically lasted 50 to 60 minutes. At 12 months, the median number of sessions received was 12 (IQR 6 to 17). Group II: usual care Investigators applied no restrictions on treatment options for participants randomised to be managed as usual by their GP. Participants could be referred for counselling or for secondary care (including for CBT). Both groups continued antidepressant medication as part of usual care.
Outcomes	Depressive symptoms were measured by (1) Beck Depression Inventory (BDI‐II) ‐ mean scores, response (reduction in BDI of at least 50% compared with baseline), and remission (BDI‐II score < 10); and (2) Patient Health Questionnaire (PHQ‐9). Measures of anxiety (Generalised Anxiety Disorder Assessment (GAD‐7)) and panic (Brief PHQ) Quality of life (QOL): SF mental and SF physical scales of the SF‐12 version 2 and the EuroQOL (EQ‐5D) Economic outcomes: primary and secondary care resource use, direct costs to NHS and Personal Social Services, and participants' out‐of‐pocket personal expenses and indirect costs such as travel
Definition of TRD	Non‐response to at least 6 weeks of antidepressant treatment at British National Formulary (BNF) recommended doses
Notes	A predefined analysis plan was agreed upon with the Trial Steering Committee. The primary outcome for the main trial (measured at 6 months post randomisation) was a dichotomous outcome of response (defined as at least a 50% reduction in depressive symptoms compared with baseline), but for long‐term follow‐up (on average, 46 months post randomisation), the primary outcome was specified as a continuous outcome (BDI‐II score) to maximise power. This change was made at the time the request for additional funding was submitted to the funder (6 November 2012).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomisation was by means of a computer‐generated code....Allocation was stratified by centre and minimised (with a probability weighting of 0.80) according to baseline BDI score (14–19, 20–28, ≥ 29); whether the general practice had a counsellor (yes or no); previous treatment with antidepressants (yes or no); and duration of present episode of depression (< 1 year, 1–2 years, ≥ 2 years)."
Allocation concealment (selection bias)	Low risk	Quote: "randomisation...from a remote automated telephone randomisation service, which thus ensured that the treatment allocation was concealed from the recruiting researcher"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Because of the nature of the intervention, it was not possible to mask participants, general practitioners, CBT therapists, or researchers to the treatment allocation."
Blinding of outcome assessment (detection bias) Patient reported depressive symptoms	High risk	Quote: "Because of the nature of the intervention, it was not possible to mask participants, general practitioners, CBT therapists, or researchers to the treatment allocation."
Blinding of outcome assessment (detection bias) Observer rated depressive symptoms	Low risk	Not applicable ‐ no observer‐rated scales
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT done with and without imputation for missing data with similar results Quote: "Trial dealt with any missing data at an individual item level by adopting the following rule. If > 10% of the items were incomplete, then the data collected on that measure for that participant were disregarded. However, if < 10% of items on a particular measure were missing, missing item(s) were imputed using the mean of the remaining items (rounded to an integer). Sensitivity analyses were conducted using the method of multiple imputation by chained equation (MICE) to examine the impact of missing data on the main findings."
Selective reporting (reporting bias)	Low risk	Protocol is available. Depression outcomes and main QOL measures (SF‐12) are reported fully for all time points described. Additional QOL measures collected for the economic analyses (EQ‐5D‐3L, SF‐6D) are not reported separately but were used to derive QALYs.
Other bias	Low risk	No differential attrition, baseline differences, nor selective follow‐up apparent

BDI: Beck Depression Inventory.

BNF: British National Formulary.

CBT: cognitive‐behavioural therapy.

CGI‐S: Clinical Global Impressions Scale.

DBT: dialectical behaviour therapy.

DSM: Diagnostic and Statistical Manual of Mental Disorders.

EQ‐5D: EuroQOL Group Quality of Life Questionnaire based on five dimensions.

EQ‐5D‐3L: EuroQOL Group Quality of Life Questionnaire based on a three‐level scale.

EuroQOL: EuroQOL Group Quality of Life Questionnaire.

GAD: generalised anxiety disorder.

GP: general practice.

HAMD: Hamilton Depression Rating Scale.

ICD: International Classification of Diseases.

IPT: interpersonal therapy.

IQR: interquartile range.

ISTDP: intensive short‐term dynamic psychotherapy.

ITT: intention‐to‐treat.

MICE: multiple imputation by chained equation.

mg: milligram.

NHS: National Health Service.

PHQ: Patient Health Questionnaire.

QALY: quality‐adjusted life‐year.

QOL: quality of life.

RCT: randomised controlled trial.

SCID: Structured Clinical Interview for DSM‐IV diagnoses.

SD: standard deviation.

SF: Short Form.

TAU: treatment as usual.