GOAL 2004

Methods	A randomised, double‐blind, multi‐centre, stratified, parallel‐group study over 12 months from December 2000 to December 2002, at 326 centres in Europe, North America, Latin America, and Asia Pacific. Run‐in 4 weeks
Participants	Population: 3416 adolescents and adults (9 to 83 years) with uncontrolled asthma   Baseline characteristics: mean age 40 years; FEV₁ 77% predicted; concomitant ICS not previously used in stratum 1, low dose in stratum 2, and medium to high dose in stratum 3 at baseline  Inclusion criteria: 12 years old or older but younger than 80 years, with at least a 6‐month history of asthma, bronchodilator reversibility by an increase of at least 15%  in FEV₁ over baseline (and 200 mL) based on FEV₁ measured pre‐ and post‐inhalation of any short‐acting beta₂‐agonist within last 6 months or to demonstrate reversibility at visit 1, at visit 2, or between visit 1 and visit 2 using 200 to 400 μg of salbutamol/albuterol  Eligible for stratum 1 of the study if had not received ICS for at least 6 months before visit 1; for stratum 2, if receiving ≤ 500 μg BDP or equivalent daily; for stratum 3, if receiving > 500 and ≤ 1000 μg BDP or equivalent daily During 2 or more of the 4 weeks before visit 2, participants should have failed to achieve the criteria for 'well‐controlled' asthma  Exclusion criteria: assessed as having well‐controlled asthma on more than 3 of the 4 weeks during run‐in; change in regular asthma medication; emergency visits due to asthma; treatment with systemic corticosteroids; respiratory tract infection; more than 3 days of morning PEF < 50% predicted; non‐compliance with diary record card
Interventions	• Fluticasone propionate and salmeterol 100/50, 250/50, or 500/50 μg twice daily (by strata) • Fluticasone propionate 100, 250, or 500 μg twice daily (by strata) Delivery was Diskus device
Outcomes	Primary efficacy variable: proportion of participants who achieved 'well‐controlled' asthma with the fluticasone propionate/salmeterol combination compared with fluticasone propionate alone during phase 1 of the study Paper states: "Serious adverse events were observed during the double‐blind period in 4% and 3% of patients in the salmeterol/fluticasone and fluticasone arms, respectively" Web report gives the numbers of participants (67 and 53, respectively) Website reports 2 deaths on fluticasone propionate (both myocardial infarction) and 3 deaths on fluticasone propionate/salmeterol (2 myocardial infarction and 1 pneumonia). No asthma‐related deaths were reported
Notes	Sponsored by GSK
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was done telephonically from a computer‐generated allocation schedule balanced per stratum and per country
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	2890/3416 (85%) completed the study
Selective reporting (reporting bias)	Low risk	Full data on GlaxoSmithKline website