SAM40065

Methods	A randomised, double‐blind, double‐dummy, multi‐centre, parallel‐group study for 40 weeks from January 2003 to October 2004, at 44 centres (United States (39), Brazil (3), Bulgaria (2)). Run‐in 2 weeks Comparison of asthma control using bronchial hyperresponsiveness as an additional guide to long‐term treatment in adolescents and adults receiving fluticasone propionate/salmeterol Diskus twice daily or fluticasone propionate Diskus twice daily (or placebo twice daily if asymptomatic)
Participants	Population: 449 adults (12+ years) with asthma  Baseline characteristics: mean age 34 years; FEV₁ not reported % predicted Concomitant ICS used by 100% of participants   Inclusion criteria: 12 years of age or older with diagnosis of asthma, as defined by the ATS, for at least 3 months before visit 1; must have been treated with a SABA, an anticholinergic, or an allowed ICS at a fixed dosing regimen (within an allowed total daily dose) for at least 4 weeks before the screening visit; FEV₁ % predicted between 60% and 95%; bronchodilator reversibility by an increase ≥ 12% in FEV₁ over baseline within 30 minutes following 2 puffs of albuterol inhalation aerosol at the screening visit. Documentation of historical reversibility within 24 months was allowed  Exclusion criteria: history of life‐threatening asthma; current unstable asthma; current respiratory tract infection or clinically significant concurrent disease that would put the patient at risk during the study if the condition was exacerbated
Interventions	• Fluticasone propionate and salmeterol 100/50, 250/50, or 500/50 μg twice daily • Fluticasone propionate 100, 250, or 500 μg twice daily (BHR strategy) • Fluticasone propionate 100, 250, or 500 μg  twice daily (reference strategy) Delivery was Diskus device (third arm not used in this review)
Outcomes	Primary efficacy endpoint: average ICS treatment dose over the treatment period; SAE data included run‐in
Notes	Sponsored by GSK
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Not reported
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	Low risk	322/449 (72%) completed the study
Selective reporting (reporting bias)	Low risk	Data on GSK website