Rennard 2012

Methods	Countries: Argentina, Brazil, Canada, China, Czech Republic, France, Germany, Hungary, Italy, Korea, Mexico, Taiwan, UK, USA Setting: 33 research centres Aim: To evaluate efficacy and safety of varenicline allowing a self‐selected quit date Dates conducted: September 2008 ‐ December 2009 Study Design: Double‐blind placebo‐controlled RCT Analysis: Power calculation (90%, alpha = 0.05) assuming a true abstinence rate at 9 ‐ 12 wks of 0.24 (placebo) and 0.46 (varenicline); Logistic regression with treatment and centre as independent variables
Participants	659 healthy volunteer smokers, aged 18 ‐ 75, motivated to quit, smoking at least 10 CPD. 60% men, mean age 43, 68% white, mean CPD 21, mean FTND 5.5, 66% had tried to quit at least once before. Allocated to varenicline (493) or placebo (166) Exclusion criteria: Standard pharmacotherapy trial criteria, + use of NRT, bupropion, clonidine or nortriptyline within last 3m, ever use of varenicline; use of marijuana or tobacco other than cigarettes with last month
Interventions	1. Varenicline 1 mg x 2/day, titrated in 1st wk 2. Placebo inactive tablets, same regimen Participants could choose their own quit date between days 8 and 35 Treatment period was 12 wks. All participants received Clearing the Air: Quit smoking today booklet at baseline, + brief counselling (≤ 10 mins) at each clinic visit. Weekly visits throughout treatment phase, and in follow‐up phase clinic visits at wks 13, 16, 20 and 24. Phone calls at wks 14, 18 and 22
Outcomes	Primary outcome: CO‐validated CAR at 9 ‐ 12 wks Secondary outcomes: CO‐validated CAR at 9 ‐ 24 wks; 7‐day PPA at wks 12 and 24 Other outcomes: Adverse events, SAEs; timing and number of quit attempts Validation was by expired CO ≤ 10 ppm Dropouts and losses to follow‐up were included in the analyses as continuing smokers (ITT analysis) Attrition to end of study (24 wks) was 12.4% from varenicline, 20.5% from placebo
Treatment type	Medication: VARENICLINE
Notes	New for 2012 update. Additional information supplied by the authors The study was funded and managed by Pfizer Inc
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"a predefined, central, computer‐generated randomization sequence...assigned subjects in a 3:1 ratio". Block size: 4, stratified by centre
Allocation concealment (selection bias)	Low risk	See above
Blinding (performance bias and detection bias) All outcomes	Low risk	Triple‐blind (participant, care‐giver, investigator)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dropouts and attrition rates fully reported
Selective reporting (reporting bias)	Low risk	All predicted and expected outcomes reported
Other bias	Unclear risk	None noted