Magnussen 2008.

Methods	Design: randomised, double‐blind, placebo‐controlled study with 12 weeks treatment duration, conducted at 67 centres distributed within Belgium, Canada, Germany, Denmark, France, Italy, the Netherlands, and South Africa
Participants	Population: 472 patients with COPD, as defined by GOLD guidelines, were randomised to tiotropium (228) and placebo (244) Baseline Characteristics: mean age 60 years, 61% male, mean FEV1 1.5 L, mean FEV1 predicted 53%, 34 pack‐years smoking history Inclusion Criteria: patients were required to have a physician‐diagnosis of asthma (before the age of 30 years), a diagnosis of COPD, post‐bronchodilator FEV1 < 80% predicted normal and a post‐bronchodilator ratio of FEV1/FVC < 70%. Other inclusion criteria were: smoking history > 10 pack‐years, age ≥ 40 years, treatment with ICS for ≥ 1 year prior to study entry, and an acute bronchodilator response ≥ 200 ml and ≥ 12% of pre‐bronchodilator FEV1 at the screening visit or documented during the past five years in the patient clinic records
Interventions	1. Tiotropium 18 mcg once daily 2. Placebo once daily Inhaler device: dry powder inhaler Co‐medication: patients were allowed to continue treatment with inhaled LABAs, ICS, oral steroids (≤ 10 mg/day prednisone or equivalent), theophyllines, leukotriene antagonists, and cromones as concomitant medication. Salbutamol was provided for as‐needed acute symptom relief. Patients were not allowed to take anticholinergic therapy other than study drug during the randomisation period
Outcomes	Spirometry: FEV1 and FVC area under the curve (AUC) 0‐6h, PEFR, symptom relief: rescue medication use
Notes	Funding: Boehringer Ingelheim Study number: Boehringer Ingelheim 205.301, ClinicalTrials.gov NCT00152984 Definitions: an exacerbation of COPD and asthma was defined as an adverse event which was a worsening of disease meeting the criteria for an serious adverse event, or led to treatment discontinuation, or required changed concomitant medication, or was an unexpected deterioration from baseline
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation list was generated by Boehringer Ingelheim using a validated system, which involved a pseudo‐random number generator so that the resulting treatment sequence was both reproducible and non‐predictable
Allocation concealment (selection bias)	Low risk	All investigational medication for each patient was identified by a unique medication number. Each eligible patient was assigned the lowest medication number available to the investigator at the time of randomisation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Boehringer Ingelheim was responsible for preparing and coding study medication in a blinded fashion (Boehringer Ingelheim study drug and control were indistinguishable). Patients, investigators and study personnel remained blinded with regard to the treatment assignments up to database lock
Blinding of outcome assessment (detection bias) All outcomes	Low risk	In all studies, a selection of standard respiratory endpoints like pulmonary function, SGRQ, TDI, treadmill, exacerbations, etc. were used. Outcome assessors remained blinded with regard to the treatment assignments up to database lock
Incomplete outcome data (attrition bias) All outcomes	Low risk	Withdrawal rates were low (tiotropium 2.2%, placebo 4.5%)
Selective reporting (reporting bias)	Low risk	Results for all specified outcomes were reported