Nides 2006.

Study characteristics
Methods	Country: USA Setting: 7 research centres Aim: to test efficacy, tolerability and safety of 3 doses of varenicline over 6 weeks Dates conducted: February 2000‐January 2003 Study design: phase 2 double‐blind placebo‐controlled RCT
Participants	638 healthy volunteer smokers, aged 18‐65, smoking at least 10 CPD on average. 48% men, 87% white, average age 42, average CPD 20, mean FTND 5.5. Allocated to varenicline group 1 (128), group 2 (128), group 3 (127), bupropion (128), placebo (127) Exclusion criteria: standard pharmacotherapy trial criteria, + use of bupropion within previous 12 months, use of NRT within past 3 months
Interventions	Varenicline tartrate 0.3 mg x 1/day for 6 weeks, + 1 week placebo Varenicline tartrate 1.0 mg x 1/day for 6 weeks, + 1 week placebo Varenicline tartrate 1.0 mg x 2/day for 6 weeks, + 1 week placebo Bupropion 150 mg x 2/day (titrated in week 1) for 7 weeks Placebo tablets x 2/day for 7 weeks All groups received self‐help booklet Clearing the Air at baseline, + brief (≤ 10 min) counselling at weekly clinic visits throughout treatment phase. At each visit smoking status reported and verified; lab samples taken at screening, baseline and weeks 1, 2, 4, 6 and 7 Follow‐up phase (optional): clinic visits at weeks 12, 24, 52 for brief counselling, smoking status and vital signs. Phone calls every 4 weeks from week 16
Outcomes	Primary outcome: continuous verified 4‐week abstinence for any part of treatment period Secondary outcomes: CQR weeks 4‐7; CQR from week 4 to weeks 12, 24, and 52 Other outcomes: weight change; reduction of craving and withdrawal using MNWS, QSU‐brief and mCEQ; AEs Validation was by expired CO ≤ 10 ppm Trial report ITT analysis based on numbers treated (N = 626); for consistency our MA used numbers randomised (N = 638). Attrition was 30% during treatment period, 25% of follow‐up consenters lost during follow‐up phase
Notes	Previous users of bupropion > 12 months before were not excluded, unlike Gonzalez and Jorenby trials; prior use ranged from 13% to 20.6% across groups Denominator in trial report is all treated; we have used all randomised in our MA The trial was funded by Pfizer Inc Author declaration of interests: "Dr Nides has received research grants, consulting fees, and honoraria from Pfizer, Sanofi‐Aventis, and GlaxoSmithKline. Dr Oncken has received research grants, consulting fees, and honoraria from Pfizer; received, at no cost, nicotine replacement and placebo products from GlaxoSmithKline for smoking cessation studies; and received honoraria from Pri‐Med. Dr Gonzales reports having received research contracts from Pfizer, Sanofi‐Aventis, GlaxoSmithKline and Nabi Biopharmaceuticals; consulting fees and honoraria from Pfizer, Sanofi‐Aventis, and GlaxoSmithKline; and owning 5 shares of Pfizer stock. Dr Rennard has had or currently has a number of relationships with companies that provide product and/or services relevant to outpatient management of chronic obstructive pulmonary disease. These relationships include serving as a consultant (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 owns no stock in any pharmaceutical companies. Drs Watsky and Reeves and Mr Anziano are employees of Pfizer and own Pfizer stock or have stock options."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"computer‐generated using a method of randomly permuted blocks and a pseudo‐random number generator"
Allocation concealment (selection bias)	Low risk	"assigned ... medication to subjects in numerical order of acceptance into the study"
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"double‐blind", "to preserve treatment blinding"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No information
Selective reporting (reporting bias)	Low risk	All expected and predicted outcomes covered