Wasserman 2006.

Methods	Design: multi‐centre, randomised, double‐blind, parallel‐group, controlled trial Sponsor: GlaxoSmithKline Inc
Participants	Setting: 77 study sites in the USA Eligible: 493 Randomly assigned: 111 (CFC‐fluticasone 50 μg); 108 (CFC‐fluticasone 100 μg); 113 (placebo) Analysed: 111 (CFC‐fluticasone 50 μg); 108 (CFC‐fluticasone 100 μg); 113 (placebo) Gender (male): 61.3% Age, months, mean (range): 35.6 (24–47) Inclusion criteria: children 24‐47 months of age; at least 2 exacerbations in the year before screening; regular maintenance therapy for asthma required during the 6 weeks before screening and/or short‐acting β‐agonist therapy for relief of respiratory symptoms at least twice weekly during the 3 weeks before screening Exclusion criteria: history of life‐threatening asthma; upper or lower respiratory tract infection; systemic or moderate to high doses of inhaled corticosteroids within 8 weeks; more than 2 courses of systemic corticosteroids during the previous 6 months; an investigational drug within 30 days of screening Previous regular use of ICS: 24% in the fluticasone 50 group; 29% in the fluticasone 100 group; 35% in the placebo group
Interventions	Test group: CFC‐fluticasone propionate, 100 μg/d CFC‐fluticasone propionate, 200 μg/d Control group: matching placebo All drugs were given twice daily via CFC‐MDI with a valved holding chamber. Treatment duration was 12 weeks
Outcomes	Asthma symptom score Time to first asthma exacerbation Percentage of symptom‐free days Morning and evening PEF Change in height over time (mm) Height was measured in triplicate at approximately the same time of day using a calibrated stadiometer at each visit
Notes	Treatment compliance was not mentioned
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was stratified by age
Allocation concealment (selection bias)	Unclear risk	No details provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Use of matching placebo
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Use of matching placebo
Incomplete outcome data (attrition bias) All outcomes	Low risk	Withdrawal rate was 18/219 (8.2%) in the fluticasone group and 18/113 (15.9%) in the placebo group
Selective reporting (reporting bias)	Low risk	Study protocol is not available, but the published reports include all expected outcomes, including those that were pre‐specified
Other bias	Low risk	Study appears to be free of other sources of bias

BDP: budesonide dipropionate.

BUD: budesonide.

CFC: chlorofluorocarbon.

CIC: ciclesonide.

DPI: dry powder inhaler.

DSCG: disodium cromoglycate

DXA: dual‐energy x‐ray absorptiometry.

FENO: fractional exhaled nitric oxide.

FEV₁: forced expiratory volume in one second.

FP: fluticasone propionate.

HFA: hydrofluoroalkane.

HPA: hypothalamic‐pituitary‐adrenal.

ICS: inhaled corticosteroids.

MDI: metered‐dose inhaler.

PC20: 20%.

PEF: peak expiratory flow.

SCG: sodium cromoglycate.

SD: standard deviation.

SDS: standard deviation score.

SE: standard error.