Gonzales 2014

Methods	Country: 37 centres in 8 countries: USA (8), Australia (4), Belgium (4), Canada (4), Czech Republic (4), France (3), Germany (5), UK (5) Setting: Clinics, hospitals, academic research centres Aim: To evaluate the efficacy and safety of retreatment with varenicline in smokers who had taken varenicline for ≥ 2 weeks in a previous smoking cessation attempt Study Design: Double‐blind placebo‐controlled multinational RCT Dates conducted: December 2010 ‐ November 2012 Analysis: "A sample size of 490 participants randomized to varenicline or placebo in a 1:1 ratio was estimated to provide ≥90% power for a comparison of varenicline vs. placebo using a two‐group continuity corrected two‐sided χ² test at the 0.05 significance level for the primary end point (CAR for weeks 9–12), assuming an OR of 3.36 with a placebo CAR of 12% and a varenicline CAR of 31%. It was also estimated to provide 80% power for the treatment comparison in the key secondary end point (CAR for weeks 9–52) for an OR of at least 2.55 with a 6% CAR in the placebo group and 14% in the varenicline group."
Participants	498 adult smokers (varenicline 251, placebo 247) with previous use of 2+ wks of varenicline at least 3m prior to screening, aged 18+, CPD 10+, motivated to quit. Mean age 47.5, 50.4% women, 93% white, mean CPD 20.5, mean FTND 5.5
Interventions	1. Varenicline 12 wks, titrated in 1st wk, 1 mg x 2/day 2. Placebo, identical regimen Brief (< 10 mins) counselling at each contact. TQD set for wk 1 visit. Clinic visits at wks 1, 2, 3, 4, 6, 8, 9, 10, 11, 12; 13, 16, 24, 32, 40, 48, 52. Brief phone calls at wks 5, 7, 14, 20, 36, 44. Dosage could be halved if intolerable
Outcomes	Primary: CAR at wks 9 ‐ 12, 9 ‐ 52 Secondary: CAR at wks 9 ‐ 24; 7‐day PPA at wks 12, 24, 52 Validation: CO < 10 ppm
Treatment type	Medication: VARENICLINE
Notes	New for 2016 update Funding: Pfizer
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Eligible participants were randomly assigned to receive either varenicline or placebo at a 1:1 ratio for 12 weeks of drug treatment using computer‐generated block randomization within each site"
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not stated
Incomplete outcome data (attrition bias) All outcomes	Low risk	Losses to follow‐up fully reported. ITT analyses conducted
Selective reporting (reporting bias)	Low risk	None noted
Other bias	Low risk	None noted