Sorkness 2007.

Methods	DESIGN: randomised, double‐blind, multi‐centre, parallel‐group study
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 190 ANALYSED: N = 190 INTERVENTION: ICS (fluticasone/salmeterol 100/50 μg/d): 96 CONTROL: ICS (fluticasone 200 μg/d): 94 WITHDRAWALS: reported AGE: mean (SD) years INTERVENTION: ICS (fluticasone/salmeterol 100/50 μg/d): 9.8(2.2) CONTROL: ICS (fluticasone 200 μg/d): 10.3 (2.1) GENDER: male N (%) INTERVENTION: ICS (fluticasone/salmeterol(100/50 μg/d): 96 CONTROL: ICS (fluticasone 200 μg/d): 94 ASTHMA SEVERITY: mild to moderate persistent asthma ASTHMA DURATION: mean (range) years INTERVENTION: ICS (fluticasone/salmeterol 100/50 μg/d): 96 CONTROL: ICS (fluticasone 200 μg/d): 94 MEAN (± SD) β2‐AGONIST USE (puffs/d): DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: ATOPY (% of participants): 78% ELIGIBILITY CRITERIA Physician‐diagnosed asthma, age 6 to younger than 14 years Ability to perform reproducible spirometry FEV1 (measured more than 4 hours since the most recent use of a bronchodilator) 80% predicted normal at screening and 70% predicted normal at randomisation Methacholine FEV1 PC20 12.5 mg/mL. All children had mild to moderate persistent asthma, as defined by diary‐reported symptoms or beta‐agonist use (not including pre‐exercise) or peak flows < 80% calculated from the mean of morning and evening peak flows obtained during the final week of the run‐in period, on average at least 3 times per week EXCLUSION CRITERIA Other lung diseases; respiratory tract infection, asthma exacerbation or systemic corticosteroid use within 4 weeks 2 or more asthma hospitalisations in the past year History of a life‐threatening asthma exacerbation 4 courses of systemic corticosteroids in the past year Cigarette smoking within the past year Pregnancy or lactation Failure to practice abstinence or to use a medically acceptable birth control method History of adverse reactions to the PACT medications
Interventions	PROTOCOL DURATION Run‐in = 2 to 4 weeks Intervention = 48 weeks (1 year) DEVICE: Diskus (GlaxoSmithKline, Research Triangle Park, NC) DOSE OF ICS INTERVENTION: fluticasone 100 + salmeterol 50 μg/d CONTROL: fluticasone 200 μg/d CRITERIA FOR WITHDRAWAL FROM STUDY:
Outcomes	ANALYSIS: Primary analysis of asthma control days consisted of the 3 pair‐wise comparisons by ANOVA with post hoc pair‐wise comparisons of group means OUTCOMES GROWTH MEASUREMENT TECHNIQUE: Height was measured using the calibrated stadiometer PULMONARY FUNCTION TESTS Percentage predicted FEV1 FEV1/FVC Pre‐BD AM PEFR, % predicted Pre‐BD PM PEFR, % predicted Methacholine FEV1 PC20 Maximum bronchodilator response FUNCTIONAL STATUS Percentage of asthma control days Growth Failureto respond to treatment ACQ Monthly asthma control days Monthly episode‐free days BIOMARKERS eNO ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (2007) FUNDING: grants from National Heart, Lung and Blood Institute, USA CONFIRMATION OF METHODOLOGY: not received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A stratified randomisation scheme was applied on the basis of bronchodilator response (< 12% or 12% change in FEV1), race (white or non‐white) and methacholine FEV1 PC20 (< 2 or 2 mg/mL)
Allocation concealment (selection bias)	Low risk	Matching placebo was provided by sponsor
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Well‐balanced withdrawal in comparison groups. No missing outcome data. Primary and secondary outcomes specified
Selective reporting (reporting bias)	Low risk	Protocol available. All analyses performed under the intent‐to‐treat paradigm
Other bias	Low risk	Study apparently free of other sources of bias