TORCH

Methods	RCT, parallel group design. Trial duration: 156 weeks. Baseline characteristics: comparable. Intention‐to‐treat analysis: stated.
Participants	Setting: 444 centres in North America, Central America and Asia Pacific. Participants randomised: 3088 (FPS: 1546; salmeterol: 1542). Baseline characteristics: 65 years; Male: 76%. Inclusion criteria: M/F 40‐80 years of age; diagnosis of COPD (ERS); <10% reversibility of predicted FEV1; FEV1/FVC ratio <70%; FEV1< 60% predicted; ≥10 pack year smoking history. Exclusion criteria: Asthma or respiratory diseases other than COPD; LVRS/lung transplant; requirement for >12hrs/day LTOT; long‐term OCS therapy; 'serious uncontrolled disease likely to interfere with medication/cause death in next three years'.
Interventions	Run‐in: 2 weeks. All maintenance treatment with ICS and LABA ceased. FPS combination 500/50 mcg BID. salmeterol 50 mcg BID. Additional treatment groups not covered in this review fluticasone 500 mcg BID placebo. Inhaler device: DPI.
Outcomes	All cause mortality; change in SGRQ; exacerbations (requiring antibiotics, steroids, hospitalisation or combination of these); lung function; withdrawals; adverse events.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated scheme. Permuted block randomisation with stratification for smoking status and country.
Allocation concealment (selection bias)	Low risk	Centralised randomisation scheme.
Blinding (performance bias and detection bias) All outcomes	Low risk	Identical inhaler devices.
Incomplete outcome data (attrition bias) Mortality	Low risk	Mortality was the primary outcome and vital status was checked in those who withdrew.
Incomplete outcome data (attrition bias) All other outcomes	High risk	36.9% withdrew on salmeterol and 34.1% on FPS.
Selective reporting (reporting bias)	High risk	Does not contribute data to analysis of exacerbations as dichotomous data.