Donohue 2010.

Methods	Design: 26‐week, randomised, partly‐blind, placebo‐controlled, parallel‐group study Setting: unclear Date of study: April 2007 to August 2008
Participants	Participants: n = 1683 (tiotropium: 420, indacaterol 150 µg: 420, indacaterol 300 µg: 418) Baseline characteristics: mean age (tiotropium: 64.0 years, indacaterol 150 µg: 63.4 years, indacaterol 300 µg: 63.3 years); gender (tiotropium 65% male, indacaterol 150 µg 62% male, indacaterol 300 µg 63%); mean % predicted FEV1 (tiotropium 53.9%, indacaterol 150 µg 56.1%, indacaterol 300 µg 56.3%); mean smoking pack year history (tiotropium 50.0 years, indacaterol 150 µg 48.3 years, indacaterol 300 µg 50.8 years) Diagnostic criteria: GOLD guideline definition COPD severity: moderate to severe Inclusion criteria: patients who were ≥ 40 years of age at COPD onset, with a cigarette smoking history of ≥ 20 pack years, and a clinical diagnosis of moderate‐to‐severe COPD. Entry criteria included post‐bronchodilator (within 30 min of inhaling albuterol 360 μg) FEV1 < 80% and ≥ 30% predicted and FEV1/FVC < 70%. Exclusion criteria: patients with a history of asthma were excluded
Interventions	Run‐in period: 14‐day run‐in to check eligibility and record baseline assessments Interventions: 1. Tiotropium, 18 µg once daily via the HandiHaler device; or 2a. Indacaterol 150 µg via single‐dose dry powder inhaler taken once daily 2b. Indacaterol 300 µg via single‐dose dry powder inhaler taken once daily Concomitant medication Short‐acting anticholingeric: no Short‐acting beta2‐agonist: yes Inhaled corticosteroid: yes Long‐acting beta2‐agonist: no Other: unclear “Patients could continue inhaled corticosteroid (ICS) monotherapy if stable for 1 month before screening; dose and regimen were to remain stable throughout the study. Before the start of the run‐in period, treatment with anticholinergic bronchodilators or with beta2‐agonists was discontinued with appropriate washout, and patients receiving fixed‐combination beta2‐agonist /ICS were switched to ICS monotherapy at an equivalent dose. All patients were supplied with albuterol for use as needed".
Outcomes	Primary outcome(s): 24 hours post‐dose (trough) FEV1 (mean of 23 h 10 min and 23 h 45 min post‐dose measurements) at Week 12 Secondary outcome(s): to demonstrate non‐inferiority of at least one indacaterol dose to tiotropium for trough FEV1 at week 12 (and, if met, to demonstrate superiority)
Notes	Funding: this study was funded by Novartis Pharma AG Data pooled for continuous and dichotomous data for indacaterol 150 µg and indacaterol 300 µg subgroups Novartis study code CQAB149B2335s Clinicaltrials.gov study code NCT00463567
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was performed using an automated interactive voice response system (IVRS), and was stratified by smoking status (current or ex‐smoker)
Allocation concealment (selection bias)	Low risk	The randomisation numbers were linked to different treatment groups, which in turn were linked to medication numbers. A separate medication list was produced using a validated system that automated the random assignment of medication numbers to medication packs.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinded tiotropium was not available, but personnel involved in the continuing clinical study (stage 2) remained blinded for the remainder of the study, as to whom were on indacaterol and placebo. The blinding of indacaterol and placebo continued until the study database was locked at the end of stage 2.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	The withdrawal rates were relatively even between the treatment groups but they were also relatively large (tiotropium 21%, indacaterol 150 µg 23% and indacaterol 300 µg 18%)
Selective reporting (reporting bias)	Low risk	All collected data reported