STAY ‐ Children.

Methods	Study Design: Randomised, double‐blind, parallel group study over a 12‐month period in 41 centres in 12 countries (between Jan 2001 and Jan 2003). In the 14‐18 day run‐in patients used pre‐study ICS with terbutaline for symptom relief (LABA had to be discontinued at least 3 days before run‐in).
Participants	Children in Study: 341 asthmatic children aged 4‐11 years with asthma uncontrolled on ICS (200‐500 µg/day) and a history of at least one "clinically important" exacerbation in the past year. 224 children were in arms considered in this review. Mean age: 8 years. Mean morning PEF: 220 L/min. FEV176% predicted pre bronchodilator. Mean ICS dose at enrolment 315 µg/day. Hospital admission for asthma in the past year: unknown proportion. Course of oral steroids for asthma in past year: unknown proportion. Inclusion Criteria: Aged 4‐11 years, with a constant dose of ICS (200‐500 µg/day) at least 3 months. Prebronchodilator FEV1 of 60‐100% predicted normal value and at least 12% reversibility following terbutaline. To be included patients had to need at least 8 rescue inhalations in the last 10 days of run‐in.  Children using seven or more rescue inhalations in a single day or with an exacerbation during run‐in were not randomised.
Interventions	1.       Budesonide 100 µg (80 µg delivered dose) and Formoterol  4.5 µg in the evening  and as‐needed (one maintenance and one relief Turbuhaler) 2.       Budesonide 100 µg (80 µg delivered dose) and Formoterol  4.5 µg in the evening  and terbutaline as‐needed (one maintenance and one relief Turbuhaler) 3.       Budesonide 400 µg (320 µg delivered dose) in the evening  and terbutaline as‐needed (one maintenance and one relief Turbuhaler)
Outcomes	Primary outcome Time to first severe exacerbations Secondary outcomes Number of severe exacerbations Time to mild exacerbations Number of mild exacerbations Symptom‐free days QOL scores No particular variable was chosen to assess safety. Exacerbation Definition: Severe ‐ Deterioration in asthma requiring hospital or emergency room treatment, or oral steroids (or an increase in ICS or other additional treatment) or morning PEF 70% or less of baseline on two consecutive days. Severe exacerbations requiring medical intervention were analysed separately . Mild exacerbation day ‐ PEF 80% or less of baseline, relief medication 2 or more inhalations above baseline, or awakenings due to asthma. Mild exacerbation defined as 2 consecutive mild exacerbation days using the same criteria. Additional Data Data on file from AstraZeneca indicate that 0/118 children under the age of 12 years had at least one asthma related SAE on SMART and 2/106 on Pulmicort. Data on children given a course of oral corticosteroids have not been obtained.
Notes	Adverse Events: SAE data given (2,16,5) of these (0,7,2) were related to asthma. Change from baseline nights with awakenings were the same in both groups, P value in the paper not used as it related to post treatment levels not changes. No SD data published in the paper with respect to growth comparing budesonide/formoterol to terbutaline as reliever, so SD calculated from the other comparisons presented.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	See STAY ‐ Adults
Allocation concealment (selection bias)	Unclear risk	See STAY ‐ Adults
Blinding (performance bias and detection bias) All outcomes	Low risk	See STAY ‐ Adults
Incomplete outcome data (attrition bias) All outcomes	Low risk	See STAY ‐ Adults
Selective reporting (reporting bias)	High risk	Data on children given a course of oral corticosteroids have not been reported.