Piper 2009.

Methods	Double‐blind placebo‐controlled single and combination pharmacotherapy intervention randomised clinical trial Study period: September 2004 to August 2010
Participants	N = 1504 Participants were smokers seeking treatment who were recruited through mass media. Inclusion criteria: 18 years of age or older who reported smoking ≥ 10 cigarettes/dfor the past 6 months, expired CO > 9 ppm, motivated to quit (3 or 4 on a 4‐point self‐report scale), able to read and write English, and willing to complete assessments Exclusion criteria: using any form of tobacco other than cigarettes, currently taking bupropion, or having a current psychosis or schizophrenia diagnosis. In addition, participants were excluded if they had medical contraindications for any of the study medications, including high alcohol consumption (6 drinks/d on 6 or 7 days of the week), a history of seizure, high blood pressure (> 160/100 mm Hg), bipolar disorder, an eating disorder, a recent cardiac event, or allergies to any of the medications. Only 1 person per household could participate. Finally, pregnant and breastfeeding women were not eligible for participation; eligible female participants had to agree to take steps to prevent pregnancy during the medication treatment phase of the study.
Interventions	Active (bupropion SR) pharmacotherapy for 9 weeks ‐ 1 week prequit, 8 weeks post quit (n = 264) Nicotine lozenge (2 or 4 mg for 12 weeks post quit) (n = 260) Nicotine patch (24‐hour patch 21, 14, and 7 mg over 8 weeks post quit) (n = 262) Nicotine patch (8 weeks post quit) plus nicotine lozenge (12 weeks post quit) (n = 267) Active bupropion pharmacotherapy plus nicotine lozenge (n = 262) Placebo pharmacotherapy (placebo bupropion, placebo lozenge, placebo patch, placebo patch plus lozenge, and placebo bupropion plus lozenge) (n = 189) Participants attended 5 baseline (prequit) screenings (physical exam, questionnaires to assess medical/psychological exclusions, and nicotine dependence inventories, and cardiovascular assessments). Participants were randomised to 1 of 6 intervention arms for 9 to 12 weeks of treatment at the fifth baseline visit. Participants attended study visits on their quit day and 1, 2, 4, and 8 weeks post quit, and received six 10‐ to 20‐minute counseling sessions at the third and fifth baseline visits, on their quit day, and at weeks 1, 2, and 4.
Outcomes	Primary outcome: 7‐day point prevalence abstinence at 1 week post quit, at end of treatment, and at 6 months post quit, confirmed via CO (breath) analysis Secondary outcomes: initial cessation, days to lapse, days to relapse, latency to relapse after lapse
Funding source	This research was conducted at the University of Wisconsin–Madison and was supported by grant P50 DA019706 from the National Institute on Drug Abuse and by grant M01 RR03186 from the General Clinical Research Centers Program of the National Center for Research Resources. Dr Piper was supported by an Institutional Clinical and Translational Science Award, University of Wisconsin–Madison (KL2 grant 1KL2RR025012‐01). Medication was provided to participants at no cost under a research agreement with GlaxoSmithKline.
Declaration of interest	Study authors report the following potential conflicts of interest for the past 5 years: Dr Smith has received research support from Elan Corporation. Dr Baker has served as an investigator on research projects sponsored by pharmaceutical companies, including Sanofi‐Synthelabo, Pfizer Inc., and Nabi Biopharmaceuticals. Dr Jorenby has received research support from the National Institute on Drug Abuse, the National Cancer Institute, Pfizer Inc., Sanofi‐Synthelabo, and Nabi Biopharmaceuticals. He has received support for educational activities from the National Institute on Drug Abuse and the Veterans Administration, and consulting fees from Nabi Biopharmaceuticals. Dr Fiore has received honoraria from Pfizer. He has served as an investigator on research studies at the University of Wisconsin that were funded by Pfizer, Sanofi‐ Synthelabo, GlaxoSmithKline, and Nabi Biopharmaceuticals. In 1998, the University of Wisconsin appointed Dr Fiore to a named chair funded by an unrestricted gift to University of Wisconsin from Glaxo Wellcome.
Notes	This work did not report analyses of pharmacogenetics, but these were reported in Bergen 2013.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Blocked on sex and self‐reported race but no other description
Allocation concealment (selection bias)	Low risk	Allocation was concealed until the moment of randomisation (3 different types of pharmacotherapy).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Research staff and participants were blind to active vs placebo pharmacotherapy randomisation.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessment was done by self‐report, with biochemical (CO) verification at 6 and 12 months.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition was very modest and did not differ by treatment arm during treatment or follow‐up.
Selective reporting (reporting bias)	Low risk	Primary and secondary outcomes were reported.
Other bias	Low risk	DNA samples were provided for 83% of self‐identified white trial participants for analysis of pharmacogenetics. Most (˜ 99%) DNA samples were successfully genotyped. Pharmacogenetic analyses are distributed equally amongst treatment groups in Bergen 2013, so selection bias is unlikely in these arms and subsamples.