STEAM.

Methods	The study was double‐blind, randomised, active‐controlled, multicentre and multinational with a parallel group design comparing the efficacy and safety of Symbicort 80/4.5 µg/inhalation, 2 inhalations once daily plus Symbicort 80/4.5 µg/inhalation as‐needed (Symbicort SiT) with that of Pulmicort 160 µg/inhalation, 2 inhalations once daily plus Bricanyl 0.4 mg/dose as‐needed when given to adults and adolescents (12‐80 years) for a period of 6 months in the treatment of asthma. This was a multicentre study with 77 centres participating from the following countries: Argentina (5 centres), Brazil (7 centres), China (4 centres), Denmark (15 centres), Indonesia (6 centres), Norway (10 centres), The Philippines (10 centres), Spain (9 centres), and Sweden (11 centres).
Participants	Population: Male and female participants (n = 696), 12 to 80 years with asthma, previously treated with 200‐500 µg per day of IGCS. They had to have a FEV1 of 60% to 100% of predicted normal at Visit 1 and a reversibility in FEV1 from baseline of at least 12% at Visit 1 or 2, or a PEF variability of at least 12% on at least 3 out of the last 10 days of the run‐in. During the last 10 days of the run‐in period the participants also had to have used at least 7 inhalations of the as‐needed medication. Run‐in was on Budesonide 100µg bd with terbutaline prn (this represents around half the previous dose of ICS and LABA was withdrawn from the 20% participants who were taking LABA previously). Baseline Characteristics: Mean age:  38 years. FEV175% predicted. Mean ICS dose at enrolment 348 µg/day and 20% were also on LABA. Hospital admission for asthma in the past year: unknown. Course of oral steroids for asthma in past year: unknown. Previous exacerbation not required for eligibility.
Interventions	1.       Budesonide/formoterol  100/6 µgtwo inhalation in the evening  [200 µgbudesonide/day], with additional doses as‐needed as reliever 2.       Budesonide 200 µg two inhalations once daily [400 µgbudesonide/day], with terbutaline reliever *200 µg actuator dose is described as 160 µg delivered dose in the paper.
Outcomes	Primary outcome: Morning PEF.   Secondary outcomes Number of severe exacerbations FEV1 Evening PEF Asthma symptom score As‐needed medication Nights with awakenings due to asthma Asthma‐control days Number of mild and severe exacerbation days As‐needed free days Symptom‐free days were added as outcomes before the data was unblinded. Exacerbation Definition: Severe ‐ Deterioration in asthma requiring hospital or emergency room treatment, or oral steroids , or at least 30% fall in PEF from baseline on two consecutive days. If prednisone was needed beyond 10 days this was counted as a second exacerbation. Mild exacerbation day ‐ defined in other studies as PEF 80% or less of baseline(average of last 10 days of run‐in), relief medication 2 or more inhalations above baseline, or a night with awakenings due to asthma. No report of definition in trial report. Additional Data Data on file from AstraZeneca indicate 12/354 patients with at least one course of oral steroids on SMART and 31/342 on Pulmicort. For asthma‐aggravated SAE the figures were 0/1 and for hospitalisation or ER visits 1/9 (which suggests that most of these were ER visits as hospitalisation for asthma is a mandatory category for asthma SAE).
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details
Allocation concealment (selection bias)	Unclear risk	No details
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	639/697 (92%) completed the study
Selective reporting (reporting bias)	Low risk	Data have been obtained for all primary outcome measures