Tashkin 1996.

Methods	RCT: 85 day (two arm) parallel group inhalation solution study. Randomisation: computer generated Blinding: double blind Excluded: not described. Withdrawals: described. Baseline characteristics: comparable Power calculation: not given. Intention to treat analysis not stated. Jadad Score:5
Participants	Setting: USA, multi‐centre (8) study. 213 stable subjects with COPD. mean age: 60.6 years male : female= 67% : 33% mean baseline FEV1: 1.07 Litres or 37.4% predicted. range:0.36‐2.37 litres or 13‐64% predicted. Inclusion criteria: > or = 40 years of age, > or =10 year pack history of smoking, stable disease, FEV1 < or = 65% predicted, FEV1/FVC < or =70 %. Exclusion criteria: history of asthma, allergic rhinitis or atopy, total blood eosinophil count >500/mm3, recent MI (< 1 year), other significant disease, recent respiratory tract infection, narrow angle.
Interventions	1) 0.5 mg ipratropium 0.167% inhalation solution (0.3 ml), plus 15 mg metaproterenol 0.6% inhalation solution (2.5 ml), three times daily. 2) placebo (0.3 ml diluent) plus 15 mg metaproterenol 0.6% inhalation solution (2.5 ml), three times daily. Medication was delivered by nebuliser, for 85 days.
Outcomes	Outcomes measured on Days 1, 43 and 85: 1) pulmonary function i.e. Test Day baseline FEV1, FVC. 2) peak change in FEV1, FVC from test day baseline. 3) % change in FEV1, FVC from test day baseline. 4) FEV1, FVC AUC (0‐8 hr). 5) HRQL: Chronic Respiratory Disease Questionnaire (CRQ). Recorded in a daily diary card during run‐in period and study: 6) daily morning and evening PEFR. 7) COPD symptoms (wheeze, dyspnoea, cough, chest tightness). 8) additional medication use.
Notes	Testing for reversible airflow obstruction with a bronchodilator was not required. Unpublished standard errors obtained from Boehringer Ingelheim and converted to standard deviations. Study quality details provided by Boehringer Ingelheim.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated
Allocation concealment (selection bias)	Low risk	Third party, off site.