Shapiro 1998.

Methods	DESIGN: randomised, double‐blind, placebo‐controlled, parallel‐group, multi‐centre study
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 202 ANALYSED: N = 74 INTERVENTION: ICS (budesonide 100 μg/d): 102 CONTROL: ICS (budesonide 200 μg/d): 100 WITHDRAWALS: reported AGE: mean (range) years INTERVENTION: ICS (budesonide 100 μg/d): 11.8 (6‐18) CONTROL: ICS (budesonide 200 μg/d): 12.1 (6‐18) GENDER: male N (%) INTERVENTION: ICS (budesonide 100 μg/d): 76 (74.5) CONTROL: ICS (budesonide 200 μg/d): 76 (76) ASTHMA SEVERITY: moderate to severe persistent asthma ASTHMA DURATION: duration of ICS‐dependent asthma: mean (range) years INTERVENTION: ICS (budesonide 100 μg/d): 2.8 (0.5‐11) CONTROL: ICS (budesonide 200 μg/d): 2.5 (0.5‐13) MEAN (± SD) β2‐AGONIST USE (puffs/d): INTERVENTION: ICS (budesonide 100 μg/d): 2.8 CONTROL: ICS (budesonide 200 μg/day): 3.1 DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: Participants discontinued their previous ICS at randomisation ATOPY (% of participants): not reported ELIGIBILITY CRITERIA Aged 6 to 18 years Reversible airway obstruction at the screening visit, defined by a 15% increase in forced expiratory volume in 1 second after inhalation of 180 or 360 mg of the beta2‐agonist FEV1 of 50% or greater, and 85% or less of predicted value Ability to use a peak flow meter Use of a minimum of 2 asthma medications every day during the previous 6 months, 1 of which must have been an ICS Female patients of childbearing potential must have had a negative result on a serum pregnancy test EXCLUSION CRITERIA History of carcinoma, diabetes, significant chest infection or any other major disorder
Interventions	PROTOCOL DURATION Run‐in = 2 weeks Intervention = 12 weeks DEVICE: dry powder inhaler DOSE OF ICS INTERVENTION: budesonide 100 μg/d CONTROL: budesonide 200 μg/d CRITERIA FOR WITHDRAWAL FROM STUDY: reported
Outcomes	ANALYSIS: done by analysis of variance. Poportion of patients who discontinued enrolment in the study was compared between treatment groups by using the Cochran‐Mantel‐Haenszel statistic OUTCOMES GROWTH MEASUREMENT TECHNIQUE: not reported PULMONARY FUNCTION TESTS Mean change from baseline FEV1 (percentage of predicted value) throughout the treatment period (from baseline to week 12) Mean change from baseline in morning PEFR by treatment week and as average value throughout 12‐week treatment period (weeks 0 to 12) FUNCTIONAL STATUS Daytime and nighttime asthma symptom scores BIOMARKERS: before randomisation and after 12 weeks of treatment Blood samples for cortisol measurements Cosyntropin stimulation test ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (1998) FUNDING: supported by a grant from Astra, USA CONFIRMATION OF METHODOLOGY: data received from Symbicort and Established Respiratory Brands, AstraZeneca R&D, Mölndal, Sweden
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information on sequence generation
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of participants and key study personnel ensured
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding of participants and key study personnel ensured
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data
Selective reporting (reporting bias)	Low risk	Study protocol not available but published reports include all expected outcomes, including those that were prespecified
Other bias	Low risk	Study apparently free of other sources of bias