Nelson 2003

Methods	A randomised, double‐blind, active‐controlled, parallel‐group study over 12 weeks, at 33 centres in the USA. Run‐in 2 weeks (run‐in was single‐blind placebo)
Participants	Population: 283 adolescents and adults  (12 to 77 years) with asthma   Baseline characteristics: mean age 32 years; FEV₁ 66% predicted Concomitant ICS used by 0% of participants  Inclusion criteria: at least 12 years old with medical history of asthma (as defined by the ATS) requiring asthma pharmacotherapy for at least 6 months; FEV₁ % predicted between 40% and 85%; bronchodilator reversibility by an increase ≥ 15% in FEV₁ over baseline within 30 minutes after 2 inhalations of inhaled albuterol (180 μg)   Exclusion criteria: history of life‐threatening asthma; hypersensitivity reaction to sympathomimetic drugs or corticosteroids; smoking within previous year or history of > 10 pack‐years; use of oral, inhaled, or injectable corticosteroid therapy within previous month; use of intranasal corticosteroid therapy except for Flonase (GlaxoWellcome Inc.); use of daily oral corticosteroid treatment within previous 6 months; use of any other prescription or over‐the‐counter medication that could have affected the course of asthma or interacted with sympathomimetic amines; abnormal chest x‐ray films; clinically significant abnormal 12‐lead electrocardiograms (ECGs); or history of significant concurrent disease (e.g. glaucoma, diabetes, hypertension)
Interventions	• Fluticasone propionate and salmeterol 100/50 μg HFA twice daily • Fluticasone propionate 100 μg CFC twice daily • Salmeterol 502 μg CFC twice daily (not considered in this review) Delivery was MDI
Outcomes	Primary efficacy measures: area under the serial FEV₁ curve for 12 hours following administration of study medication; change from baseline at endpoint in morning pre‐dose  FEV₁ The paper reports: "no serious drug related adverse events"
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	257/283 (91%) completed the study
Selective reporting (reporting bias)	Low risk	Full data on GSK website