Tashkin 2011

Methods	Country: USA (17 centres), Spain (3 centres), France (4 centres), Italy (3 centres) Setting: 27 research centres. Aim: To test efficacy and safety of varenicline in smokers with COPD Dates conducted: May 2006 ‐ April 2009 Study Design: Double‐blind placebo‐controlled RCT Analysis: Power calculation (81% to detect a diff in CAR 9 ‐ 52 wks based on an OR of 2.21 and a placebo rate of 9%); ITT denominators. Logistic regression with treatment group and study site as independent variables
Participants	504 adult smokers with mild‐to‐moderate COPD, aged 35+, smoking 10+ CPD, motivated to quit; allocated to varenicline (250), or placebo (254). 62% men, mean age 57, CPD 24 ‐ 25, FTND score 5.9 ‐ 6.2 Treatment groups were comparable at baseline Exclusion criteria: Standard pharmacotherapy trial criteria, + treatment with systemic corticosteroids or hospitalised for COPD in previous 4 wks
Interventions	1. Varenicline 1.0 mg x 2/day for 12 wks, preceded by 1 wk titrated dose 2. Placebo tablets as above Both groups received SC educational booklet, + brief (≤ 10mins) counselling at weekly clinic visits throughout treatment phase, and phone call 3 days post‐TQD. At each visit smoking status reported and CO verified; throughout treatment and at wk 52 lung function, respiratory symptoms, weight, BP, pulse, temperature, ECGs, haematology and serum chemistry assessed, + adverse events Follow‐up phase: smoking status + CO measured at wks 13, 16, 24, 32, 40, 48 and 52; counselling and self‐reported status by phone at wks 14, 20, 28, 36 and 44
Outcomes	Primary outcome: CO‐validated CAR at wks 9 ‐ 12 Secondary outcomes: CO‐validated CAR at wks 9 ‐ 52 and 9 ‐ 24; 7‐day PPA at wks 12, 24 and 52 Other outcomes: Adverse events; serious adverse events; weight change Validation was by expired CO ≤ 10 ppm Cessation analyses were ITT (all participants randomised), while tolerability and safety analyses were based only on those known to have used the intervention drug (N = 499). Attrition was 17% in the varenicline group and 24% in the placebo group during treatment phase, and 29% varenicline and 38% placebo who did not complete the study. This includes 2 deaths in the varenicline group and 1 in the placebo group
Treatment type	Medication: VARENICLINE
Notes	The study was funded by Pfizer Inc New for 2010 update
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"participants were randomized"
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"double blind" but details not stated
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not stated
Selective reporting (reporting bias)	Unclear risk	All expected and predicted outcomes covered
Other bias	Unclear risk	None noted