Kerwin 2011

Methods	A 52‐week, randomised, double‐blind, parallel‐group study of fluticasone propionate/salmeterol combination product (fluticasone propionate/salmeterol) 250/50 μg twice daily and fluticasone propionate Diskus 250 twice daily in treatment of people with asthma, at 76 centres in North and South America, Canada, and the Philippines, from May 2007 to April 2009
Participants	Population: 628 adults and adolescents (12+ years) with asthma that was not controlled on ICS at low dose (with or without LABA), or at medium dose without LABA; clinical diagnosis of asthma, defined by the ATS, for ≥ 6 months before screening Baseline characteristics: mean age 40 years; FEV₁ 74% predicted Concomitant ICS used by 100% of participants   Inclusion criteria: required to have received treatment with a low to medium dose of ICS or combination inhaled corticosteroid/long‐acting beta₂–agonist (ICS/LABA) controller medications, if ICS was at a low dose, for ≥ 4 weeks before screening; must have reported being symptomatic while taking fluticasone propionate/salmeterol Diskus 100 μg twice daily in the 4 weeks before screening Exclusion criteria: life‐threatening asthma in the 12 months before screening; seasonal or exercise‐induced asthma without other manifestations of persistent asthma, concurrent respiratory disease, or any other significant concurrent condition/disease; patients were excluded if they had worsening asthma in the 4 weeks before screening including an emergency room visit, hospitalisation, or use of oral/ parenteral corticosteroid. Concurrent use of medications that could have affected the course of asthma or interacted with study medication was prohibited
Interventions	• Fluticasone propionate and salmeterol 250/50 μg twice daily • Fluticasone 250 μg twice daily Delivery device Diskus
Outcomes	Primary outcome: FEV₁ over a 52‐treatment‐week period; SAE data fully reported in the published paper and in the GlaxoSmithKline Web report (ADA109057)
Notes	Sponsored by GSK. ClinicalTrials.gov identifier NCT00452348 (identical in design to Katial 2011)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	"Double‐blind therapy"
Independent Assessment of causation (detection bias) Asthma‐related events	High risk	Causation of SAEs not independently assessed
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	79/310 on fluticasone propionate/salmeterol and 84/318 on fluticasone withdrew, but withdrawals were balanced for adverse events and lack of efficacy
Selective reporting (reporting bias)	Low risk	Full SAE data reported in paper and in the GlaxoSmithKline Web report