Tashkin 2012.

Methods	Design: randomised, double‐blind, placebo‐controlled trial Duration: 6 months (+ 2 weeks run‐in period) Location: 131 centres located in South America, Asia, Africa, Europe and North America
Participants	Population: 1055 participants were randomised to formoterol (209), mometasone (210), two doses of formoterol/mometasone combination (217 and 207), and placebo (212) Baseline characteristics Age (mean years): form 59.6, mom 59.8, form/mom400 59.7, form/mom200 60.9, pbo 58.8 % Male: form 72.7, mom 78.1, form/mom400 78.8, form/mom200 77.8, pbo 80.2 % FEV1 predicted: not reported Pack‐years (mean): form 40.3, mom 40.0, form/mom400 39.7, form/mom200 41.7, pbo 40.3 Inclusion criteria: males and females aged 40 and older; history of at least 10 pack‐years; moderate to severe COPD for at least 2 years; predicted FEV1 between 25% and 60% normal Exclusion criteria: exacerbation in the four weeks before randomisation; significant medical illness; diagnosis of asthma, lung cancer or alpha1‐antitrypsin deficiency, lobectomy, pneumonectomy, lung volume reduction surgery or ocular problems
Interventions	1. Formoterol 10 bid (LABA) 2. Mometasone 400 bid (ICS) 3. Formoterol/mometasone 10/400 bid (LABA/ICS) 4. Formoterol/mometasone 10/200 bid (LABA/ICS) 5. Placebo (PBO) Inhaler device: metered dose Allowed co‐medications: Participants were given open‐label, short‐acting beta2‐agonist (SABA)/short‐acting anticholinergic fixed‐dose combination to use as relief medication throughout the study. All long‐acting COPD treatments (LABA, ICS, LABA/ICS FDC or long‐acting anticholinergics), supplemental oxygen and beta‐blocking agents were not allowed during the study period
Outcomes	St George's Respiratory Questionnaire (SQRQ), reported as both final scores and the number of people experiencing a MCID (improvement or worsening by 4 units), COPD exacerbations, serial FEV1 post‐dose, standardised FEV1 area under the curve, systemic and ocular effects
Notes	Funding: Merck & Co/Schering‐Plough Identifier(s): NCT00383435
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The sponsor’s statistician produced a computer‐generated randomisation schedule with treatment codes in blocks using SAS. Randomisation was stratified according to the subject’s smoking status at the time of randomisation.
Allocation concealment (selection bias)	Low risk	Randomized treatment assignment was provided to the investigative site by means of an interactive voice response system at the time subjects were randomized.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Protocol describes the study masking as double‐blind (subject, investigator)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Protocol describes the study masking as double‐blind (subject, investigator)
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Withdrawal rates 17.7% in formoterol and 25% in the placebo group, unclear methods of imputation for some outcomes
Selective reporting (reporting bias)	High risk	Can't extract FEV1 (table 3), other outcomes poorly reported for the comparison used in this review