Pearlman 2004

Methods	A randomised, double‐blind, active‐controlled, parallel‐group study over 12 weeks, at 36 centres in the USA and 1 centre in Puerto Rico
Participants	N = 360. Fluticasone propionate/salmeterol arm n = 92, fluticasone propionate arm n = 89 Population: males and females 12 years of age or older with a diagnosis of asthma, using the ATS definition, were screened. All patients were required to have FEV₁ 40% to 85% predicted normal and > 15% reversibility following 2 puffs of ventolin at screening. Study population was stratified according to whether or not participants were treated with ICS or inhaled beta₂‐agonists at screening (salmeterol or short‐acting beta₂‐agonists only). Patients treated with ICS must have been treated for at least 3 months before visit 1 and must have been receiving a daily dose of 252 to 336 μg beclomethasone dipropionate, 600 to 800 μg triamcinolone acetonide, 1000 μg flunisolide, 400 to 600 μg budesonide, 176 μg fluticasone propionate inhalation aerosol, or 200 μg fluticasone propionate inhalation powder for at least 1 month before visit 1 with no change in regimen. Eligible patients using only as‐needed short‐acting beta‐agonist therapy were required to have received treatment for at least 1 week before visit 1 with a 7‐day total symptom score > 7 for the 7 days before visit 2. Eligible patients using salmeterol at baseline were required to have received only salmeterol and as‐needed, short‐acting beta₂‐agonists for at least 1 week before visit 1. No details were provided on distribution between groups. Participants were described as symptomatic. Baseline medication included prn SABA alone ‐ 142; salmeterol ‐ 84; and ICS ‐ 134 (37%)
Interventions	• Fluticasone propionate and salmeterol 100/50 μg twice daily • Fluticasone 100 μg twice daily The other treatment arms were not used for this review
Outcomes	Paper reports no serious drug‐related adverse events Website: SAS3003. No fatal SAEs in the fluticasone propionate/salmeterol or fluticasone propionate group. One tachyarrhythmia on fluticasone propionate
Notes	Sponsored by GSK
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind
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	279/360 (77%) completed the study
Selective reporting (reporting bias)	Low risk	Data on GSK website