Aubin 2008.

Study characteristics
Methods	Country: Belgium, France, Netherlands, UK, USA Setting: 24 research centres Aim: to compare the efficacy of varenicline with nicotine patch, both open‐label Dates conducted: January 2005‐June 2006 Study design: open‐label randomised trial
Participants	757 healthy adults, recruited from SC clinics or by local advertising, aged 18‐75, weight > 45.5 kg, BMI 15‐38, smoking ≥ 15 CPD. Varenicline arm 378, NRT arm 379. Mean age 42.9, 49.2% men, 93% white. Mean CPD 22.7. Previous use of nicotine patch 47.4%, previous use of bupropion 20%. Mean FTND 5.5. Exclusion criteria: standard pharmacotherapy trial criteria, + participants must not have been in a varenicline trial in previous year, or used NRT in previous 6 months
Interventions	Varenicline 1 mg x 2/day for 12 weeks, titrated 1st week Nicotine patch (21 mg weeks 2‐6, 14 mg weeks 7‐9, 7 mg weeks 10‐11) All participants received Clearing the Air booklet at baseline, and brief counselling (≤ 10 min) at each clinic visit or by phone. TQD was at week 1 visit. Weekly visits throughout treatment phase, plus a phone call 3 days post‐TQD In follow‐up phase, clinic visits at weeks 13, 16, 24, 32, 40, 48 and 52, plus brief phone calls at weeks 14, 20, 28, 36 and 44
Outcomes	CO‐confirmed CAR for last 4 weeks' treatment (varenicline weeks 9‐12, NRT weeks 8‐11) CO‐confirmed CAR at weeks 9‐24 and 9‐52 (varenicline) and 8‐24 and 8‐52 (NRT) 7‐day PPA at EoT and at weeks 24 and 52 Other outcomes: weight change, withdrawal symptoms (using MNWS and mCEQ), AEs 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 17.3% varenicline, 20.3% NRT. Losses to follow‐up 17% in each group 65.7% of varenicline and 62.2% of NRT groups completed study
Notes	New for 2008 update Study funding: study funded by Pfizer Author declaration of interests: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Using a central computer‐generated sequence"
Allocation concealment (selection bias)	Low risk	Central allocation
Blinding (performance bias and detection bias) All outcomes	Low risk	"Using an open‐label design". However, comparators were two active treatments, minimising risk of performance bias, and abstinence was biochemically validated
Incomplete outcome data (attrition bias) All outcomes	Low risk	"Missing CO data were assumed to be < 10 ppm provided other conditions were met", i.e. no NRT other than prescribed patches. Missing = negative assumption reduced successes by 1 in each group
Selective reporting (reporting bias)	Low risk	All predicted outcomes fully reported