Bolliger 2011

Methods	Countries: Brazil, Colombia, Costa Rica, Egypt, Jordan, Lebanon, Mexico, Saudi Arabia, South Africa, United Arab Emirates, Venezuela Setting: 42 research centres (51.2% Latin America, 30.6% Africa, 18.2% Middle East) Aim: To test the efficacy and tolerability of varenicline in regions not previously exposed to smoking cessation RCTs of varenicline Dates conducted: April 2008 ‐ August 2009 Study Design: Double‐blind placebo‐controlled RCT Analysis: Power calculation (90%, alpha = 0.05); ITT denominators and logistic regression analysis (step‐down procedure)
Participants	593 adults, recruited from smoking cessation clinics, aged 18 ‐ 75, weight > 45.5 kg, BMI 15 ‐ 38, smoking ≥ 10 CPD, motivated to quit. Randomised to varenicline 394 (390 got medication), or placebo 199 (198 got medication). Mean age 43.5, 63.6% men, mean CPD 23.8, mean FTND 6.0. 55% had no prior quit attempt Exclusion criteria: Standard pharmacotherapy trial criteria, + participants must not have used NRT, bupropion, clonidine or nortriptyline in previous 6m
Interventions	1. Varenicline 1mg x 2/day, titrated during wk 1 2. Placebo inactive tablets, same regimen Treatment period was 12 wks. All participants received You can quit smoking self‐help booklet (available in English, Spanish, Portugese and Arabic) at baseline, and brief counselling (≤ 10 mins) at each clinic or telephone contact. TQD set for wk 1. Clinic visits at wks 2, 3, 4, 6, 8, 10 and 12 throughout treatment phase, plus a phone call 3 days post‐TQD In follow‐up phase, clinic visits at wks 13, 16, 20 and 24, plus brief 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, clinically significant changes in vital signs, SAEs. Abstinence was assessed using the Nicotine‐Use Inventory (NUI); validation was by expired CO ≤ 10 ppm Dropouts and losses to follow‐up were included in the analyses as continuing smokers (ITT analysis). [4 (V) 1 (P) who did not receive allocated intervention reincluded in denominators in this analysis.] Attrition in treatment phase was 11.2% (V) and 20.6% (P); in follow‐up phase 2.5% (V) and 0.5% (P)
Treatment type	Medication: VARENICLINE
Notes	New for 2012 update 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	"Using a block randomization within each site, eligible participants were randomly assigned in a 2:1 ratio to receive varenicline or placebo"
Allocation concealment (selection bias)	Low risk	"a web‐based or telephone call‐in drug management system directed by the sponsor"
Blinding (performance bias and detection bias) All outcomes	Low risk	"All of the study personnel and participants were blinded to treatment assignment until the end of the nontreatment follow‐up phase"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dropouts and attrition fully reported
Selective reporting (reporting bias)	Low risk	All predicted and expected outcomes reported