Methods	Parallel-group, multicentre trial (16 centres) Jadad quality score: 4
Participants	Symptomatic asthmatic adults % ELIGIBLE OF SCREENED POPULATION: Not reported % RUN-IN PARTICIPANTS RANDOMISED: 203/274 (74%) RANDOMISED: 203 (BDP/F: 102; BDP: 101) WITHDRAWALS: BDP/F: 7; BDP: 12 AGE mean: 43.9 GENDER (% males): 44.6 SEVERITY: Moderate to severe BASELINE % PREDICTED FEV1 mean: 72 BASELINE DOSE OF ICS: Not reported ASTHMA DURATION mean: 27 years ATOPY (%): Not reported SMOKING STATUS: Current smokers: 8%; previous smokers: 40 ELIGIBILITY CRITERIA: Aged 18 years or more; moderate to severe asthma; FEV1 >= of predicted and increased by 15% or more within 30 minutes after beta2 agonists or historical evidence of reversibility; had to have received Rx with ICS (metered dose inhaler) at a constant daily dose of 1000 mcg beclomethasone dipropionate or 800 mcg budesonide for at least 1 month before screening EXCLUSION CRITERIA: Change in daily dose of ICS in the previous month; use of a LABA or having received a course of oral corticosteroid in the month before the screening; problems using the Aeroliser (R) despite proper instruction CRITERIA FOR RANDOMISATION DURING RUN-IN: Presence of at least 2 of the following on at least 2 of the last 7 days of the run-in period: waking at least once/night because of asthma; asthma interfering with daily activities on at least 1 day; at least 4 puffs of salbutamol rescue medication a day; diurnal variation in PEF of at least 15%
Interventions	LABA + ICS vs INCREASED dose ICS OUTCOMES: measured at 4, 8 and 12 weeks RUN-IN PERIOD: 2 to 4 weeks DOSE OF ICS DURING RUN-IN: 500 BDP bid DOSE OPTIMISATION PERIOD: Not reported INTERVENTION PERIOD: 12 weeks TEST GROUP: (BDP/F) beclomethasone 500 mcg bid and formoterol 12 mcg bid CONTROL GROUP: (BDP) beclomethasone 1000 mcg bid and placebo INHALER DEVICE: Formoterol: Aerolizer; BDP: dry powder inhaler NUMBER OF DEVICES: 2 COMPLIANCE: Not reported CO-TREATMENT: prn SABA
Outcomes	PULMONARY FUNCTION TEST: am PEF*; FEV1 SYMPTOM SCORES: Score of 0 to 4 (day and night ) FUNCTIONAL STATUS: Rescue medication use; exacerbations INFLAMMATORY MARKERS: None ADVERSE EFFECTS: Reported WITHDRAWALS: Described *Primary outcome measure
Notes	Full-text publication Funded by Novartis Pharmaceutical Australia Pty Ltd Confirmation of methodology and data: not obtained User-defined number: 1000
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Unclear	Described as randomised; no other information available
Allocation concealment?	Unclear	Information not available
Blinding? All outcomes	Yes	Double-dummy design
Incomplete outcome data addressed? All outcomes	Unclear	“The analysis of efficacy was carried out in the intention-to-treat analysis and, in addition, a confirmatory analysis was carried out on the mean morning pre-medication PEF measured during the last 7 days of treatment in the patients who had completed the whole treatment period.”
Free of selective reporting?	Unclear	Moderate exacerbations included OCS exacerbations; added as additional study to sensitivity analysis (see Analysis 3.1)