MONO.

Methods	This was a randomised, open‐label, parallel‐group, multicentre study in 1900 patients (planned number) with persistent asthma. Patients were treated with either Symbicort® SMART (i.e. Symbicort® Turbuhaler® (budesonide/formoterol) 160/4.5 μg (delivered dose), 1 inhalation b.i.d. plus as‐needed), or conventional best practice according to the investigator’s judgement, following GINA guidelines (Ref: Global Initiative for Asthma 2002). The treatment period lasted for 26 weeks, with no mention of any run‐in period. This study was conducted in Denmark (123 centres), Finland (69 centres) and Norway (83 centres) between September 2004 and October 2006.
Participants	1854 patients were randomised, 1835 took at least one treatment and contributed to the analysis, and 1667 completed the study. 75% were taking LABA and daily ICS dose was 1035 µg/day (BDP equivalence). Male and female patients, > 12 years of age, with persistent asthma who were currently treated with inhaled glucocorticosteroids (IGCSs) and LABA.
Interventions	Investigational product was Symbicort® Turbuhaler®, 160/4.5 μg/dose budesonide/formoterol (delivered dose), 1 inhalation b.i.d. as maintenance treatment plus as‐needed, in response to symptoms. Comparator products were any conventional best practice treatments, except Symbicort® SMART and/or maintenance with oral glucocorticosteroids prescribed at the discretion of the investigator according to GINA treatment guidelines Ref: Global Initiative for Asthma 2002).
Outcomes	Primary variable Time to first severe asthma exacerbation Secondary variables Total number of severe asthma exacerbations Mean use of as‐needed medication Prescribed asthma medications Patient reported outcomes (PRO) Change in Asthma Control Questionnaire (ACQ) score Safety Only information regarding SAEs and discontinuations due to AE (DAEs) were collected in this study. Definition of severe exacerbation Not specified Additional Data Data on file from AstraZeneca indicated 51/64 patients with at least one course of oral steroids and 5/7 with at least one hospitalisation on single inhaler therapy/current best practice (921/914)
Notes	One (1) death was reported in the study in the SiT group in Denmark. The patient contacted the investigator 16 August due to asthma deterioration. The patient discontinued the study and study medication on 9 September 2005 due to “Subject not willing to continue study” and experienced asthma exacerbation on 30 September 2005. The event was considered serious due to hospitalisation, and the patient died the same day. The events pneumonia and in compensatio cordis led to death and not the event of asthma exacerbation. The investigator considered the event to be unrelated to the study therapy.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization code assigned from a computer generated randomisation schedule" Demoly 2009
Allocation concealment (selection bias)	Low risk	"Patients were randomised, strictly sequentially...using coded envelopes. When a patient had been randomised, the envelope was opened and the code was revealed." Demoly 2009
Blinding (performance bias and detection bias) All outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias) All outcomes	Low risk	90% of randomised patients completed the study and analyses was ITT
Selective reporting (reporting bias)	Low risk	Data have been obtained for all primary outcome measures