Methods	Parallel-group, multicentre study (246 centres in 22 countries). Three treatment groups: BUD; BUD/F and BUD/F (with BUD/F also as reliever) Jadad quality score: 4
Participants	Symptomatic asthmatic adults and children % ELIGIBLE OF SCREENED POPULATION: Not reported % RUN-IN PARTICIPANTS RANDOMISED: 85 RANDOMISED: 1835 (BUD: 926; BUD/F: 909) WITHDRAWALS: BUD/F: 148; BUD: 142 AGE mean (range): 35 (4 to 79) GENDER (% male): 44 SEVERITY: Moderate BASELINE % PREDICTED FEV1 (mean): 73 BASELINE DOSE OF ICS: 615 mcg/d ASTHMA DURATION: 9 years ATOPY (%): Not reported ELIGIBILITY CRITERIA: 4 to 80 years; treatment with 400 to 1000 mcg/d ICS (200 to 500 mcg/d for participants aged 4 to 11 years) for 3 or more months; FEV1 predicted 60% to 100%; 12 or more inhalations during last 10 days of run-in (8 for participants aged 4 to 11 years) EXCLUSION CRITERIA: Participants using 10 or more inhalations on one day during run-in (7 or more for participants aged 4 to 11 years); participants experiencing an exacerbation of asthma during run-in period
Interventions	LABA + ICS versus INCREASED dose ICS OUTCOMES: TIMING 12 months RUN-IN: 14 to 18 days DOSE OF ICS DURING RUN-IN: Same as pre-study ICS dose (+ terbutaline) INTERVENTION PERIOD: 12 months TEST GROUP: Combination budesonide and formoterol (100/6 mcg) bid CONTROL GROUP: Budesonide 400 mcg bid (plus as needed terbutaline) DEVICE: Turbohaler NUMBER OF DEVICES: 1 COMPLIANCE: Self-reported compliance on 84% of days; self-reported non-compliance on 3% of days; incomplete records on 13% of days CO-TREATMENT: prn SABA
Outcomes	PULMONARY FUNCTION TEST: FEV1; am PEF; pm PEF SYMPTOM SCORES: Daytime scores; nighttime scores; % symptom-free days FUNCTIONAL STATUS: Exacerbations (treated with oral steroids, hospitalisation or ED visit)*; rescue medication use; night awakenings INFLAMMATORY MARKERS: Not reported ADVERSE EFFECTS: Reported WITHDRAWALS: Reported Primary outcome measure*
Notes	Full-text publication Source of funding Astra Zeneca Confirmation of methodology and data: Requested, obtained for adults. Data on children were requested directly from the study sponsors concurrently. The data for OCS-treated exacerbations for children were not available User defined number: 800
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	Computer-generated randomisation scheme
Allocation concealment?	Unclear	Eligible patients were randomised in balanced blocks by allocating patient numbers in consecutive order
Blinding? All outcomes	Yes	Double-blind; identical inhaler devices used
Incomplete outcome data addressed? All outcomes	Unclear	“All analyses were performed on an intention-to-treat basis.” Additional information on the composition of the ITT population was not provided
Free of selective reporting?	Yes	Data on OCS-treated exacerbations reported as composite with ED visits/hospitalisations, PEF falls and requirement for medical intervention. Separate data for OCS-treated exacerbations and hospital admission received. Data on adults were received from study sponsors directly. We requested data for children from the study sponsors concurrently but these were not available