Malone 2005

Methods	A randomised, double‐blind, active‐controlled, multi‐centre, parallel‐group study over 12 weeks from April 2002 to January 2003, at 79 centres (66 in the USA and 13 in Canada). Run‐in 2 weeks
Participants	Population: 203 children (4 to 11 years) with persistent asthma Baseline characteristics: mean age 8 years; FEV₁ mean 80% predicted (6 to 11 years); PEF mean 87% predicted (4 to 5 years) Concomitant ICS used by 100% of participants   Inclusion criteria: 4 to 11 years of age with diagnosis of asthma (ATS definition), who required physician‐prescribed treatment for at least 2 months and were taking an inhaled corticosteroid for asthma for at least 1 month before visit 1; FEV₁ % predicted between 50% and 95% (6 to 11 years), AM PEF % predicted between 50% and 95% (4 to 5 years). Bronchodilator reversibility by an increase ≥ 12% in FEV₁ (6 to 11 years) or AM PEF (4 to 5 years) over baseline within 30 minutes of 2 to 4 actuations of albuterol (180 to 360 μg), or with historical documentation of ≥ 12% reversibility within the previous year  Exclusion criteria: history of life‐threatening asthma; hospitalisation due to asthma twice or more often in the previous year; significant concurrent disease (e.g. cystic fibrosis, malignancy, immunological compromise); recent upper or lower respiratory tract infection; current chickenpox or recent exposure to chickenpox in a non‐immune patient; severe milk protein allergy; hypersensitivity to beta₂‐agonist, sympathomimetic, or corticosteroid therapy; clinically significant abnormal laboratory test results
Interventions	• Fluticasone propionate and salmeterol 100/50 μg twice daily • Fluticasone propionate 100 μg twice daily Delivery was Diskus device.
Outcomes	This was a safety study, and no primary efficacy endpoint was identified No SAEs occurred in this study
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	168/203 (83%) completed the study
Selective reporting (reporting bias)	Low risk	Full data on GSK website