Jorenby 2006

Methods	Country: USA Setting: 14 research centres Aim: To test the efficacy and safety of varenicline for smoking cessation Dates conducted: June 2003 ‐ March 2005 Study Design: Double‐blind placebo‐controlled RCT. Analysis: Power calculation (90%, alpha = 0.05); ITT denominators and logistic regression analysis (step‐down procedure)
Participants	1027 healthy adult volunteers. Allocated to varenicline (344), bupropion (342) or placebo (341). 58% men, 84% white, mean age 43.3, mean CPD 22, mean FTND score 5.3. No significant differences between groups at baseline Exclusion criteria: Standard pharmacotherapy trial criteria, + use of tobacco products other than cigarettes; use of NRT, clonidine, nortriptyline within last month; BMI < 15 or > 38 or weight < 45.5 kg; any prior use of bupropion or varenicline
Interventions	1. Varenicline 1 mg x2/day 2. Bupropion 150 mg x2/day 3. Placebo inactive tablets, same regimen Treatment period was 12 wks. All participants received brief counselling (≤ 10 mins) at each clinic visit Weekly visits throughout treatment phase, plus a phone call 3 days post‐TQD In follow‐up phase, clinic visits at wks 13, 24, 36, 44 and 52, plus brief phone calls at wks 16, 20, 28, 32, 40 and 48
Outcomes	Primary outcome: CO‐validated CAR at 9 ‐ 12 wks Secondary outcomes: CO‐validated CAR at 9 ‐ 24 wks and 9 ‐ 52 wks; 7‐day PPA at wks 12, 24 and 52 Other outcomes: Weight change, withdrawal symptoms (using MNWS, QSU‐brief and mCEQ), adverse events Validation was by expired CO ≤ 10 ppm Dropouts and losses to follow‐up were included in the analyses as continuing smokers (ITT analysis) Attrition in treatment phase was 29.3%, losses to follow‐up 8% of treatment completers
Treatment type	Medication: VARENICLINE / BUPROPION
Notes	This trial had the same aims and study design as Gonzales 2006. The trial was funded by Pfizer Inc
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"computer‐generated list"
Allocation concealment (selection bias)	Low risk	"completed centrally ... and sites used an electronic system to assign participants to treatment"
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"in a double‐blind manner"
Incomplete outcome data (attrition bias) All outcomes	Low risk	CA for missed visits: if self‐reported abstinent at next visit, assumed abstinent, except at wk 52 visit when all criteria had to be met
Selective reporting (reporting bias)	Low risk	All expected and predicted outcomes covered
Other bias	Unclear risk	None noted