Oncken 2006.

Methods	Double‐blind parallel‐group placebo and active treatment‐controlled randomised clinical trial Study period: study dates not reported
Participants	N = 647 Participants were healthy cigarette smokers. Recruitment methods not reported Inclusion criteria: 18 to 65 years of age, smoke ≥ 10 cigarettes/d Exclusion criteria: treatment with an investigational drug within the previous month; major depression within the prior year; panic disorder, psychosis, or bipolar disorder; use of nicotine replacement or bupropion within the previous 3 months; cardiovascular disease; clinically significant medical disease; drug or alcohol abuse or dependence within the past year; use of tobacco products other than cigarettes or marijuana within the previous month
Interventions	0.5 mg twice‐daily non‐titrated varenicline (n = 129) 0.5 mg twice‐daily titrated varenicline (n = 130) 1.0 mg twice‐daily non‐titrated varenicline (n = 129) 1.0 mg twice‐daily titrated varenicline (n = 130) Placebo (n = 129) Participants received study medication for 12 weeks. Specifically, participants in each of these groups received the following medication: 0.5 mg twice daily non‐titrated (i.e. 0.5 mg twice daily for 12 weeks); 0.5 mg twice daily titrated (i.e. 0.5 mg once daily for 7 days, then 0.5 mg twice daily for 11 weeks); 1.0 mg twice daily non‐titrated (i.e. 1.0 mg twice daily for 12 weeks); 1.0 mg twice daily titrated (i.e. 0.5 mg once daily for 3 days, then 0.5 mg twice daily for 4 days, then 1.0 mg twice daily for 11 weeks); or placebo (i.e. 2 placebo tablets twice daily for 12 weeks). All participants received a smoking cessation booklet at the baseline visit and brief smoking cessation counseling (up to 10 minutes) at each visit.
Outcomes	Primary outcomes: carbon monoxide–confirmed 4‐week continuous quit rate for weeks 4 through 7 and weeks 9 through 12 during treatment and continuous abstinence rates for weeks 9 through 52 for each dose relative to placebo. Continuous abstinence was defined as self‐report of no cigarette use during the specified time period confirmed by an exhaled carbon monoxide measurement ≤ 10 ppm Other outcomes: carbon monoxide–confirmed 7‐day point prevalence abstinence, changes in the Minnesota Nicotine Withdrawal Scale and the modified Cigarette Evaluation Questionnaire, carbon monoxide–confirmed 7‐day point prevalence abstinence at weeks 24 and 52
Funding source	Pfizer Inc. provided funding for this study. Pfizer Inc. was involved in all elements of this study, including, but not limited to, study design and monitoring.
Declaration of interest	Dr Oncken has received research grants, consulting fees, and honoraria from Pfizer; nicotine replacement and placebo products from GlaxoSmithKline at no cost for smoking cessation studies; and honoraria from Pri‐Med. Dr Gonzales has received research contracts, consulting fees, and honoraria from Pfizer, Sanofi‐Aventis, and GlaxoSmithKline, and owns 5 shares of Pfizer stock that he received as a gift from his parents. Dr Rennard has had or currently has a number of relationships with companies that provide products and/or services relevant to outpatient management of chronic obstructive pulmonary disease. These relationships include serving as a consultant (for Adams, Almirall, Altana, Array Biopharma, AstraZeneca, Aventis, Biolipox, Centocor, Dey, Critical Therapeutics, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Ono Pharma, Otsuka, RJ Reynolds, Roche, Sankyo, Schering‐Plough, Scios, and Wyeth), advising regarding clinical trials (Altana, AstraZeneca, Aventis, Centocor, GlaxoSmithKline, Novartis, Pfizer, and Philip Morris), speaking at continuing medical education programs and performing funded research at both basic and clinical levels (Altana, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis). He does not own any stock in any pharmaceutical companies. Dr Nides has received research grants, consulting fees, and honoraria from Pfizer, Sanofi‐Avenits, and GlaxoSmithKline. Drs Watsky and Reeves and Messrs Billing and Anziano are employees of Pfizer and own Pfizer stock or hold Pfizer stock options.
Notes	Analysis of pharmacogenetics was reported in King 2012.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details reported
Allocation concealment (selection bias)	Unclear risk	No details reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and investigators were blinded to study drug treatment assignment. Participants were not encouraged to guess their treatment assignment.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding was appropriate, and the outcome of the study was objective.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	More dropout in the placebo group and specific dropout for lack of efficacy occurred more often in the 1.0 mg twice‐daily titrated varenicline group. Dropouts were assumed to be smoking.
Selective reporting (reporting bias)	Unclear risk	No protocol was found.
Other bias	Low risk	Additional analyses of pharmacogenetics were conducted in King 2012 in a subset of the original randomised trial population, but baseline characteristics were comparable between treatment groups, so selection bias seems unlikely.