Methods	Parallel-group, multicentre study (11 centres). Six treatment groups of which 2 are considered for this review, namely: FP 100 bid + SL 50 bid; FP250 bid + placebo Jadad quality score = 5
Participants	Symptomatic asthmatic adults % ELIGIBLE OF SCREENED POPULATION: Not reported % RUN-IN PARTICIPANTS RANDOMISED: Not reported RANDOMISED: 48 (FP/Sal: 25; FP: 23) WITHDRAWALS: FP/Sal: 2; FP: 2 AGE: mean (range): 32 (14 to 61) GENDER (% male): 48 SEVERITY: Moderate BASELINE % PREDICTED FEV1: 66 BASELINE DOSE OF ICS (SE): Steroid-naive for at least 30 days prior to study onset ASTHMA DURATION: >= 6 months and < 1 year: 0; >= 1 year and < 5 years: 8; >= 5 years and < 10 years: 5; >= 10 years and < 15 years: 6; >= 15 years: 29 ATOPY(%): Not recorded ELIGIBILITY CRITERIA: >= 12 years; FEV1 between 50% and 80% of predicted value for age, sex, height and race; medical history of asthma of at least 6 months requiring pharmacotherapy; >= 15% increase in FEV1 15 minutes after 2 puffs of inhaled albuterol; being treated with daily or as-needed short-acting beta-sympathomimetic bronchodilators; females had negative pregnancy tests, or be surgically sterile, or postmenopausal for at least 1 year, or using acceptable birth control for at least 1 month prior to participation EXCLUSION CRITERIA: History of life-threatening asthma; hypersensitivity reaction to sympathomimetic drugs or corticosteroids; smoking within the previous year or a history of > 10 pack-years; use of oral, inhaled, injectable, or intranasal corticosteroid therapy within the previous month; use of daily oral corticosteroid treatment within the previous 6 months; use of any other prescription or over-the-counter medication that may affect the course of asthma or interact with sympathomimetic amines; abnormal chest X-rays; clinically significant abnormal 12-lead electrocardiograms; history of significant concurrent disease CRITERIA FOR RANDOMISATION DURING RUN-IN: Completion of daily diary cards and report medication compliance; patients were not eligible for inclusion if they used 12 or more puffs of albuterol daily for more than 2 days or if they had more than 2 nighttime awakenings due to asthma requiring treatment with albuterol during the 7 days immediately preceding the randomisation period; FEV 1 had to be between 50% and 80% of the predicted value and within 15% of the FEV1 obtained at the beginning of the screening period
Interventions	LABA + ICS vs INCREASED dose ICS OUTCOMES reported at 2 and 4 weeks RUN-IN PERIOD: 2 weeks DOSE OF ICS DURING RUN-IN: Same as usual DOSE OPTIMISATION PERIOD: None INTERVENTION PERIOD: 4 weeks TEST GROUP: (SL50 + FP100) salmeterol 50 mg bid + fluticasone propionate 100 mg bid CONTROL GROUP: (FP 250) fluticasone propionate 250 mg bid DEVICE: Metered-dose inhaler NUMBER OF DEVICES: 2 COMPLIANCE: Evaluated CO-TREATMENT: prn SABA
Outcomes	PULMONARY FUNCTION TEST: FEV1; am PEF SYMPTOM SCORE: Score of 0 to 4 mean change from baseline FUNCTIONAL STATUS: Rescue medication use; mean change in % nights with no awakenings; episode-free days INFLAMMATORY MARKERS: Not measured ADVERSE EFFECTS: Reported WITHDRAWALS: Reported Primary outcome measure: Not reported
Notes	Full-text publication Funded by Glaxo Wellcome Confirmation of methodology and data confirmed User defined number: 600
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 (double-dummy design)
Incomplete outcome data addressed? All outcomes	Unclear	Intention-to-treat population defined as “all randomised subjects exposed to the study drug”. Handling of withdrawals not explicit
Free of selective reporting?	Yes	Exacerbations not assessed