Baker 2016

Methods	Country: USA Setting: 2 University sites in Wisconsin (Madison, Milwaukee) Aim: To compare the efficacy of varenicline with nicotine patch, and with combination NRT (C‐NRT) Dates conducted: May 2012 ‐ November 2015 Study design: Open‐label randomised trial (no placebo) Analysis: Logistic regression, comparing varenicline and C‐NRT arms against nicotine patch (reference) arm. Power calculations based on detecting a 10% difference, with > 80% power; numbers required: patch 227, varenicline and C‐NRT 387
Participants	Healthy adults, recruited from participants in the ongoing Wisconsin Smokers Health Study or by media and community outreach, aged 17+, smoking ≥ 5 CPD, motivated to quit. Varenicline arm 424, nicotine patch arm 241, combination NRT arm 421 Mean age 48.1, 47.9% men, 67% white. Mean CPD 17. Mean FTND 4.8 Exclusion criteria: Standard pharmacotherapy trial criteria, CO < 4 ppm, no suicide attempts in previous 5 years, or current suicidal ideation,diagnosis or treatment of psychoses in previous 10 years
Interventions	1. Varenicline 1mg x 2/day for 12 wks, titrated 1st wk 2. Nicotine patch: 11+ CPD on 21 mg wks 1 ‐ 8, 14 mg wks 9 ‐ 10, 7 mg wks 11 ‐ 12; 5 ‐ 10 CPD on 14 mg wks 1 ‐ 10, 7 mg wks 11 ‐ 12 3. Nicotine patch as for (2), plus nicotine lozenge (2 mg or 4 mg), at least 5 times a day for 12 wks No placebo control group. All participants received counselling (20 mins at visits 1, 2 and 3, and 10 mins by phone and at visits 4, 5) at 1 week pre‐TQD and at TQD, wks 1, 4, 12 post‐TQD, plus phone call at wk 8 In follow‐up phase, participants were contacted at wks 26 and 52 by phone
Outcomes	All comparisons were based on varenicline and C‐NRT versus patch (reference arm), and on varenicline versus C‐NRT CO‐confirmed PPA at wk 26 CO‐confirmed PA from day 7 post‐TQD to day 181 CO‐confirmed PPA at wks 4, 12, 52 Other outcomes: Adherence, withdrawals, adverse events Validation was by expired CO ≤ 9 ppm and ≤ 5 ppm Dropouts and losses to follow‐up were included in the analyses as continuing smokers (ITT analysis) Withdrawal rates were 8.3% varenicline, 6.2% nicotine patch, 3.1% C‐NRT
Treatment type	Medication: VARENICLINE / NRT OPEN‐LABEL
Notes	The trial was funded by grant 5R01HL109031 from National Heart, Lung, and Blood Institute, and by grant K05CA139871 from the National Cancer Insitute New for 2016 update Not included in the main MA, as no placebo group
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"computer‐based randomisation"
Allocation concealment (selection bias)	High risk	"Treatment assignment was unblinded" [open‐label]
Blinding (performance bias and detection bias) All outcomes	High risk	"Treatment assignment was unblinded" [open‐label]. "The follow‐up telephone assessments were intended to be blinded, but a database search by interviewers could have revealed treatment assignment"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low rates of attrition, ITT analysis used
Selective reporting (reporting bias)	Low risk	All predicted outcomes reported, protocol available
Other bias	Low risk	None noted