Allen 1998.

Methods	DESIGN: prospective, randomised, double‐blind, parallel‐group trial; in 19 clinical centres
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 219 ANALYSED PARTICIPANTS: N = 219 INTERVENTION: ICS (fluticasone propionate 100 μg/d): 85 CONTROL: ICS (fluticasone propionate 200 μg/d): 96 WITHDRAWALS: reported AGE: mean (years) (range): INTERVENTION: ICS (fluticasone propionate 100 μg/d): 8.1 ± 0.2 (4.5‐11.9) CONTROL: ICS (fluticasone propionate 200 μg/d): 7.9 ± 0.2 (4.0‐11.6) GENDER: N (male %): INTERVENTION: ICS (fluticasone propionate 100 μg/d): 62 (73) CONTROL: ICS (fluticasone propionate 200 μg/d): 72 (75) ASTHMA SEVERITY: persistent asthma for at least 3 months ASTHMA DURATION: not reported MEAN (± SD) β2‐AGONIST USE (puffs/d): not reported DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: Participants taking ICS or other antiasthma medications (e.g. β2‐agonists, theophylline, cromolyn) were allowed to continue taking these medications as needed during the run‐in period ATOPY (% of participants): not reported ELIGIBILITY CRITERIA Children aged 4 to 11 years with persistent asthma of all severity diagnosed ≥ 3 months as defined in the American Thoracic Society criteria Normal growth rates as defined by height measurements between the 5th and 95th centiles and growth velocity between the 10th and 97th centiles Prepubescent as defined by a sexual maturity rating of 1 in any Tanner classification On maintenance dose of ICS and required to maintain a fixed dosage regimen for at least 3 months before screening Previous systemic corticosteroid use limited to a total of 60 days within the 2 years before study entry EXCLUSION CRITERIA Patients who have received systemic, intranasal or ophthalmic corticosteroids within the month before study entry, or who had cataracts, glaucoma or any other significant concurrent disease or condition
Interventions	PROTOCOL DURATION Run‐in = 2 weeks Intervention = 52 weeks DEVICE: Diskhaler (Glaxo Wellcome, Eureaux, France) DOSE OF ICS INTERVENTION: fluticasone propionate 100 μg/d CONTROL: fluticasone propionate 200 μg/d CRITERIA FOR WITHDRAWAL FROM STUDY: reported
Outcomes	ANALYSIS: Comparisons between treatment groups for nonparametric variables were based on the Cochran‐Mantel‐Haenszel test, controlling for investigators; comparisons for parametric variables were based on an analysis of variance F test, controlling for investigator. Traditional safety analyses were based on data from the intent‐to‐treat population, comprising all participants exposed to the study drug, whereas growth analyses were based on the same population minus participants who achieved pubescence during the study OUTCOMES: reported at 52 weeks GROWTH: Outcomes were measured at the beginning and at the end of the run‐in period; after the first, second and fourth weeks of the treatment period; and then every 4 weeks throughout the 52‐week treatment period Mean height increases from baseline to 52 weeks Mean growth velocity at the end of treatment Mean change from baseline in skeletal age: bone age of the left hand and wrist was performed at baseline and at 24 and 52 weeks GROWTH MEASUREMENT TECHNIQUE: All height measurements were taken using identical wall‐mounted Harpenden stadiometers (manufactured by Holtain, Crymmych, Wales) PULMONARY FUNCTION TESTS: not reported FUNCTIONAL STATUS: not reported BIOMARKERS: not reported ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (1998) FUNDING: sponsored by a grant from Glaxo Wellcome Inc. CONFIRMATION OF METHODOLOGY: not received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using a computer random number generator: “At the end of the run‐in period, eligible patients were stratified according to ICS use at study entry and randomly allocated to receive fluticasone propionate 50 μg or 100 μg, or matching placebo, twice daily via a Diskhaler”
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