Papi 2007.

Methods	Design: 6 month, double blind, double dummy, parallel group randomised controlled trial Setting: Multinational, multicenter in 25 centres Date of study: August 2002 to September 2004
Participants	Participants: n = 466 (124 received as‐needed combination therapy: 119 received as‐needed albuterol therapy) Baseline characteristics: mean age (intermittent ICS: 36.8 years, placebo 40.6 years; recruitment of patients between ages of 18‐65 years); gender ‐ male (intermittent ICS 50%, placebo 49%); mean % predicted FEV1 (intermittent ICS 88.5%, placebo 88.9%); mean asthma history (not stated); mean daily dose of inhaled corticosteroids (intermittent ICS 458.8 μg of beclomethasone equivalent, placebo 468.6 μg); rescue medication (intermittent ICS 0.4, placebo 0.5 puffs/day). Diagnostic criteria: National Asthma Education and Prevention Program guidelines Asthma severity: mild persistent asthma Inclusion criteria: History of mild persistent asthma for at least 6 months, prebronchodilator FEV1 >75% associated with ≥ 12% reversibility or positive methacholine challenge. Exclusion criteria: Current or ex‐smoker, diagnosis of COPD, or history of near‐fatal asthma and/or admission to emergency room/intensive care unit because of asthma, 3 or more courses of oral corticosteroids or hospitalisation for asthma during the previous year, or regular treatment for > 6 months with ≥ 500 μg/day of beclomethasone or equivalent.
Interventions	Run‐in period: 250 μg of inhaled beclomethasone dipropionate twice daily and albuterol on an as‐needed basis for the relief of symptoms Interventions: Patients were not given a written plan of action to guide the as‐needed use of study drugs but were simply instructed orally to use them any time they were needed for relief of symptoms. 1. placebo twice daily plus 250 μg of beclomethasone and 100 μg of albuterol in a single inhaler as‐needed (as‐needed combination therapy) 2. placebo twice daily plus 100 μg of albuterol as needed (as‐needed albuterol therapy) Concomitant medication Nil
Outcomes	Primary outcome(s): mean rate of morning peak expiratory flow during weeks 23 and 24. Secondary outcome(s): 1. other functional variables; 2. symptom scores; 3. number and severity of exacerbations. "A mild exacerbation was defined as awakening at night owing to asthma or as a decrease in the morning peak expiratory flow rate to more than 20% below the baseline value, the use of more than three additional puffs per day of rescue medication (either albuterol or beclomethasone and albuterol) as compared with during the baseline period (the last week of the run‐in period) for 2 or more consecutive days, or both. Single, isolated days on which mild exacerbation occurred were not counted. A severe exacerbation was defined as a decrease in the morning peak expiratory flow rate to more than 30% below the baseline value on 2 consecutive days or more than eight puffs per day of rescue medication for 3 consecutive days or the need for treatment with oral corticosteroids, as judged by the investigator. Days on which severe exacerbations occurred were excluded from the count of days with mild exacerbations".
Notes	Funding: this study was funded by Chiesi Farmaceutici Clinicaltrials.gov study code NCT00382889
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was prepared with the use of a random‐number generator and a balanced‐block design stratified according to centre
Allocation concealment (selection bias)	Unclear risk	No details reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, double‐dummy
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind, double‐dummy
Incomplete outcome data (attrition bias) All outcomes	Low risk	Well balanced attrition rate. Reasons for withdrawals were reported per group. Intention to treat analysis
Selective reporting (reporting bias)	Low risk	No apparent risk of bias noted
Other bias	Low risk	No apparent risk of bias noted