Methods	Parallel-group, multicentre study. Four treatment groups of which 2 considered for this review, namely: BUD 200 + F12 bid and BUD 400 bid Jadad quality score: 4
Participants	Symptomatic asthmatic teenagers >= 12 years and adults % ELIGIBLE OF SCREENED POPULATION: Not reported % RUN-IN PARTICIPANTS RANDOMISED: Not reported RANDOMISED: 634 (BUD200 + F: 323; BUD400: 312) WITHDRAWALS: Not reported by subgroup AGE mean: 37 GENDER (% male): 43.6 SEVERITY: Mild BASELINE % PREDICTED FEV1: 87 BASELINE DOSE OF ICS : <= 400 mcg/d BUD ASTHMA DURATION: Not reported ATOPY(%): Not reported ELIGIBILITY CRITERIA: >= 12 years of age with mild asthma; taking <= 400 mcg/daily of inhaled budesonide or its equivalent for >= 3 months; FEV1 >= 70% predicted normal after terbutaline EXCLUSION CRITERIA: Experience 3 severe exacerbations during the initial 6 months or 5 exacerbations in total; 2 poorly controlled asthma days, defined as days with morning PEF values >= 2 above baseline, or with asthma awakening CRITERIA FOR RANDOMISATION DURING RUN-IN: Randomised patients demonstrated a need for 2 or more inhalations per week of rescue medication during the last 2 weeks of run-in, a >= 15% variability in peak expiratory flows, or a >= 12% increase in FEV1 after terbutaline
Interventions	LABA + ICS vs INCREASED dose ICS OUTCOMES reported at 52 weeks RUN-IN PERIOD: 4 weeks DOSE OF ICS DURING RUN-IN: BUD 100 bid DOSE OPTIMISATION PERIOD: None INTERVENTION PERIOD: 52 weeks TEST GROUP: Budesonide 100 mcg bid + formoterol 12 mcg bid CONTROL GROUP: Budesonide 200 mcg bid DEVICE: Turbuhaler NUMBER OF DEVICES: 2 COMPLIANCE: Not reported CO-TREATMENT: prn SABA
Outcomes	PULMONARY FUNCTION TEST: am PEF; FEV1 SYMPTOM SCORES: Not reported FUNCTIONAL STATUS: Asthma symptom days; nocturnal awakenings; rescue medication use; exacerbations INFLAMMATORY MARKERS: Not reported ADVERSE EFFECTS: Not reported WITHDRAWAL: Not reported *Primary outcome: time to the first severe asthma exacerbation defined as need for treatment with oral corticosteroids or hospital admission or emergency treatment for worsening asthma or a decrease in morning PEF > 25% from baseline
Notes	Full-text publication Funded by AstraZeneca Confirmation of methodology obtained User-defined number: 200
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	Computer-generated random numbers
Allocation concealment?	Yes	Opaque consecutive numbered envelopes containing assignment
Blinding? All outcomes	Yes	Use of identical placebo
Incomplete outcome data addressed? All outcomes	Unclear	Intention-to-treat analysis stated, but explicit description of its composition not available
Free of selective reporting?	Yes	Primary outcome data available from study publication