Methods	Parallel-group, multicentre study (50 centres). Three groups of which 2 considered here, namely: FP 250 bid; FP 100 + SL 50 bid Jadad quality score = 5
Participants	Symptomatic asthmatic children >= 12 years and adults % ELIGIBLE OF SCREENED POPULATION: Not reported % RUN-IN PARTICIPANTS RANDOMISED: Not reported RANDOMISED: 454 (FP100 + Salm50: 231; FP250: 223) WITHDRAWALS: FP100 + Salm50: 16; FP250: 13 AGE: mean (range): 41 (12 to 79) GENDER (% male): 40 SEVERITY: Moderate BASELINE % PREDICTED FEV1: 63.1 BASELINE DOSE OF ICS (start of run-in): Not reported ASTHMA DURATION: Not reported ATOPY (%): Not reported ELIGIBILITY CRITERIA: Non-smokers; >= 12 years of age who had asthma defined in accordance with American Thoracic Society criteria; low dose of beclomethasone dipropionate or fluticasone for at least 3 months preceding the study; the daily dosing schedule for the inhaled corticosteroid had to be constant for the 14-day run-in period prior to the study; FEV1 of 40% to 85% of predicted normal values for age, gender and height; reversibility of airway obstruction was demonstrated by >= 15% increase in FEV1 within 30 minutes after 2 puffs of albuterol EXCLUSION CRITERIA: Pregnant/lactating mothers; use of methotrexate, gold, cyclosporine or azathioprine for control of asthma within 30 days prior to study; use of inhaled cromolyn or inhaled nedocromil within weeks prior to the study; use of oral or injectable corticosteroids within 4 weeks prior to the study; significant concomitant illness or concurrent use of any other prescription or over-the-counter medication that might affect the course of asthma or interact with sympathomimetic amines CRITERIA FOR RANDOMISATION DURING RUN-IN: FEV1 between 40% to 65%, if FEV1 65.1% to 85% had to have asthma symptoms; demonstrate compliance and complete diary cards; not to have experienced clinical exacerbation during screening period
Interventions	LABA + ICS versus INCREASED dose of ICS OUTCOMES: Reported at 1, 2, 4, 6, 8 and 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: (FP 100 + Salm 50) fluticasone 100 mcg bid + salmeterol 50 mcg bid CONTROL GROUP: (FP 250) fluticasone 250 mcg bid DEVICE: MDI NUMBER OF DEVICES: 2 COMPLIANCE: Assessed CO-TREATMENT: prn SABA and theophylline as needed
Outcomes	PULMONARY FUNCTION TEST: FEV1*; am PEF; pm PEF SYMPTOM SCORES: Symptom scores (score of 0 to 5) FUNCTIONAL STATUS: Rescue medication use; nocturnal awakenings; symptom-free days; physician global assessment INFLAMMATORY MARKERS: Not described ADVERSE EFFECTS: Described WITHDRAWALS: Described Primary outcome measure*
Notes	Full-text publication Funded by Glaxo Wellcome Confirmation of methodology and data obtained User-defined number: 1000
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	Computer-generated random numbers
Allocation concealment?	Yes	Numbered coded inhalers supplied by pharmacy
Blinding? All outcomes	Yes	Double-dummy design; use of identical placebo
Incomplete outcome data addressed? All outcomes	Unclear	“Analyses were based on data from the intent-to-treat population, consisting of all patients exposed to the study drug.”
Free of selective reporting?	Yes	Data available for meta-analysis