Methods	Parallel-group, multicentre study (39 centres in North America, Europe and South Africa) Jadad quality score = 5
Participants	Symptomatic asthmatic patients % ELIGIBLE OF SCREENED POPULATION: Not reported % RUN-IN PARTICIPANTS RANDOMISED: 80 RANDOMISED: 349 (FP/SAL: 176; BUD: 173) WITHDRAWALS: FP/SAL: 23; BUD: 15 AGE mean (years): 36 GENDER (% male): 43 SEVERITY: moderate BASELINE % PREDICTED FEV1: 77 BASELINE DOSE OF ICS: mean in mcg (note: 19% of Sal FP group and 40% of BUD group on no corticosteroids before randomisation): FP 375; BUD 400; BDP 500 ASTHMA DURATION: Not reported ATOPY (%): Not reported SMOKING STATUS: Not reported ELIGIBILITY CRITERIA (including run-in criteria for randomisation): Mild to moderate asthma; symptomatic patients determined either by use of rescue salbutamol (on more than 2 occasions per 24 hours) or symptoms (total daytime and nighttime diary card symptom score of >= 2) on at least 4 of the last 7 days of the run-in period EXCLUSION CRITERIA: If patients had changed their regular asthma medication or received any long-acting or slow-release bronchodilators within the previous 2 weeks, had had a lower respiratory tract infection within the previous 4 weeks, or were smokers with a history of 10 pack years or more; if in the previous 4 weeks patients had had an asthma exacerbation requiring hospitalisation and/or treatment with oral, parenteral or depot corticosteroids; patients with serious uncontrolled diseases likely to interfere with the study or who showed evidence of alcohol or drug abuse; pregnant or lactating females, or those likely to become pregnant
Interventions	LABA + ICS versus INCREASED dose of ICS OUTCOMES: Reported at 12 weeks RUN-IN PERIOD: 2 weeks DOSE OF ICS DURING RUN-IN: Usual ICS DOSE OPTIMISATION PERIOD: None INTERVENTION PERIOD: 12 weeks TEST GROUP: Combination fluticasone/salmeterol 100/50 mcg bid CONTROL GROUP: Budesonide 400 mcg bid DEVICE: FP/SAL: Diskus, BUD: Turbuhaler NUMBER OF DEVICES: 1 COMPLIANCE: Not reported CO-TREATMENT: prn SABA (use of stable asthma medications permitted)
Outcomes	PULMONARY FUNCTION TEST: am PEF*; pm PEF; diurnal variation in PEF post-treatment in each group SYMPTOM SCORES: % days and nights when symptom score < 2 (daytime 0 to 5; nighttime 0 to 4) FUNCTIONAL STATUS: Rescue medication use; symptom-free days/nights INFLAMMATORY MARKERS: Not reported ADVERSE EFFECTS: Reported WITHDRAWALS: Reported Primary outcome measure*
Notes	Full-text publication Funded by GlaxoSmithKline Confirmation of methodology and data extraction: Not obtained User defined number: 400 (800-400)
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	See Appendix 3
Allocation concealment?	Yes	See Appendix 3
Blinding? All outcomes	Yes	Use of identical placebo
Incomplete outcome data addressed? All outcomes	Unclear	“The Intent-to-Treat (ITT) population was defined as all patients who entered the study, were randomised, and received at least one dose of study treatment: it was used for assessment of safety data as well as for all efficacy analyses.”
Free of selective reporting?	Yes	OCS-treated exacerbations available on request from study sponsor