Hall 2009.

Methods	Randomised parallel‐group open‐label efficacy clinical trial consisting of 2 phases: phase 1, lasting 12 weeks during which all participants receive a standard treatment of NRT, bupropion, and 5 group counseling sessions; followed by phase 2, randomization to 1 of 4 treatments for another 40 weeks. Outcomes are measured at multiple time points to 104 weeks. Study period: 2002 to 2004
Participants	N = 402 N = 403 were enrolled, but 1 individual died before randomisation. Recruited through multi‐media advertising, public service announcements, flyers, and direct mailing. Inclusion criteria: treatment‐seeking smokers 50 years of age or older who currently smoke 10 cigarettes/d Exclusion criteria: history of seizure or head injury resulting in unconsciousness; any condition that might predispose to seizures (brain tumour or stroke); current or history of anorexia nervosa or bulimia; any disease acutely life‐threatening or so severe that the patient is judged unable to comply with the protocol; use of a protease inhibitor or MAO inhibitor within the past 2 weeks; current use of psychiatric drugs that would interfere with interpretation of study results, including antidepressants; treatment for alcohol dependence during the past year, or evidence of alcohol abuse so severe that the patient is judged potentially unable to comply with the protocol; patients who know they are leaving the Bay Area within the study period and non‐English speakers; suicidal or homicidal ideation; current major depression; history of bipolar disorder; recent (within 12 months) myocardial infarction; any other medical condition that would contraindicate use of NRT or bupropion; physical limitation so severe that participation in a programme of moderate exercise is not possible; and pregnancy or lactation
Interventions	All participants receive 10 weeks of NRT (gum, 2 mg for those smoking < 25 cigarettes/d, up to 12 pieces a day, or 4 mg for heavier smokers or heavy users of 2‐mg gum still reporting withdrawal) and 12 weeks of bupropion treatment (150 mg for a week, then 300 mg the second week and thereafter, with no adverse effects) and 5 mandatory group counseling sessions (90 minutes each). At week 8 (to permit NRT tapering for those assigned to no further treatment), participants are randomly assigned to 1 of 4 treatment groups: (a) no further treatment, with assessments at weeks 12, 24, 36, 52, 64, and 104 (standard assessments for all treatments); (b) extended NRT (to week 52) with no further counseling; (c) extended NRT with extended cognitive‐behavioural therapy to prevent relapse and encourage abstinence in case of relapse before week 12, and in case of lapses after week 12, where extended individual (20 to 40 minutes) counseling occurred at week 10, every 2 weeks thereafter, then every 4 weeks, then at weeks 44 and 52, with telephone contact in between clinical visits; and (d) extended NRT and extended counseling. Extended counseling sessions included additional information focusing on motivation, social support, mood management, weight gain, and dependence/withdrawal.
Outcomes	Primary outcome: biochemically verified 7‐day point prevalence abstinence at weeks 12, 24, 52, 64, and 104
Funding source	Clinical trial and publications (portion related to this trial) were supported by grants from the National Institute on Drug Abuse (R01 DA02538, K05 DA016752, K23 DA018691 and P50 DA 09253, and R01 DA15732).
Declaration of interest	Declarations of interest were not reported.
Notes	Neither this paper nor the clinicaltrials.gov record provided analyses of pharmacogenetics. These were provided in Bergen 2013.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised allocation performed by study statistician who did not have contact with participants.
Allocation concealment (selection bias)	Low risk	Assignment for individual participants was transmitted electronically to staff.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Trial was open‐label, but other aspects of trial suggest rigorous management and lower probability of high performance bias to unclear.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessment was done by self‐report and by 2 biochemical methods using exhaled breath and urine (i.e. very thorough outcome assessment).
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition rates were low (ranging from 3.2% at week 12 to 13.4% at week 104). Per‐arm assessment rates averaged 93%, and abstinence assessments were available for 92% of participants.
Selective reporting (reporting bias)	Low risk	Outcome assessment was very thorough, with 3 pieces of information required to note an individual as abstinent. Only 17/905 urine determinations had data discordant with outcomes of self‐report and CO measurement (< 2%).
Other bias	Low risk	Analyses of pharmacogenetics performed on ˜ 42% of total study; ˜ 55% of self‐identified “Caucasian”; minimum arm N was 35; no significant differences by arm with respect to proportion of arm analysed. Not generalisable to other ancestries