Methods	Study design: a randomised, double-blind, double-dummy, multicentre, parallel-group study over 24 weeks from November 2001 to January 2003 at 178 centres in 18 European countries. Run-in 2 weeks
Participants	Population: 1397 adults (18 to 91) years with patients with moderate-to-severe asthma Baseline characteristics: mean age 46 years. FEV1 78.6% predicted. Concomitant inhaled corticosteroids used by 100% of participants. Run-in on previous dose of ICS alone; LABA (if previously used) was withdrawn during the run-in period Inclusion criteria: aged 18 years or over, with a documented clinical history of asthma of at least 6 months and receiving 1000 to 2000 μg/day of beclomethasone dipropionate or equivalent. Combination therapy, if used, was discontinued and replaced with ICS alone, at least 4 weeks prior to study start (screening visit). Bronchodilator reversibility by an increase of at least 12% in FEV1 15 min after inhaling salbutamol 200 to 400 μg. For the randomised treatment period (baseline), bronchodilator reversibility by an increase of at least 12% in FEV1 (and > 200 mL), 15 min after inhaling salbutamol 200 to 400 μg, and an asthma symptom score (day and night combined) of at least 2 (2 or more episodes of symptoms during the day/night) on at least 4 of the last 7 evaluable days of the run-in period. Exclusion criteria: suffered an upper or lower respiratory tract infection or an acute asthma exacerbation (requiring emergency treatment or hospitalisation) within 4 weeks of Visit 1; used oral corticosteroids within 4 weeks or depot steroids within 12 weeks of Visit 1; a pre-bronchodilator FEV1 % predicted of less than 50%, smoking history of 10 pack-years or more
Interventions	1. Salmeterol/fluticasone 50/250 μg bdx 1DPI 2. Formoterol/budesonide 6/200 μg bdx 2DPI
Outcomes	The primary efficacy measure was the number of exacerbations, expressed as a rate over the 24-week treatment period SAE data described in paper only as “No deaths in the study and only a small proportion of patients reported serious AEs” SAE data obtained from sponsors website
Notes	Sponsored by GSK
Risk of bias
Bias	Authors’ judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were assigned to study treatment in accordance with the randomisation schedule from the Interactive Voice Recognition System, which was part of the GSK System for the Central Allocation of Medication
Allocation concealment (selection bias)	Low risk	Blinded study medication was packed and supplied by GlaxoSmithKline (GSK). All treatment packs contained both Diskus/Accuhaler and Turbuhaler devices (either active Diskus/Accuhaler + placebo Turbuhaler, or active Turbuhaler + placebo Diskus/Accuhaler) and looked identical
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double-blind, double-dummy
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double-blind, double-dummy
Incomplete outcome data (attrition bias) All outcomes	Low risk	1258/1397 (90%) completed the study
Selective reporting (reporting bias)	Low risk	SAE data found on website
Independent Outcome Assessment Asthma-related serious adverse events	High risk	No independent outcome assessment