Cinciripini 2013

Methods	Country: Houston, TX, USA Setting: University of Texas MD Anderson Cancer Center Aim: To assess the relative efficacy of varenicline and bupropion SR plus intensive counselling on smoking cessation and emotional functioning Study Design: Double‐blind placebo‐controlled RCT Dates conducted: August 2006 ‐ October 2007 Analysis: "our sample size provided adequate power for assessing our primary outcome of prolonged abstinence at EOT (ie, ß= 0.99 for differences relative to placebo for varenicline and ß = 0.84 for differences relative to placebo for bupropion SR) but modest power for detecting drug group differences ( ß = 0.74)."
Participants	294 volunteer smokers, aged 18 ‐ 65, 5+ CPD, fluent in English, no uncontrolled chronic illness, baseline CO > 6 ppm. Mean age 44, 39% women, 66% white, mean CPD 20, mean FTND 4.5, mean baseline CO 24.5 ppm. Allocated to varenicline (86), bupropion (102) or placebo (106) Exclusions: Usual pharma exclusions, current or history of psychotic disorder, moderate or high risk of suicidality, contra‐indications to varenicline or bupropion
Interventions	1. Varenicline: 12‐week course (1 mg x 2/day) + non‐active bupropion course (placebo) 2. Bupropion: 12‐week course (150 mg x 2/day) + non‐active varenicline course (placebo) 3. Placebo: 12‐week course (placebo pill x 2/day) Blinded study physician could adjust dosages to reduce side effects if required throughout study All participants got intensive counselling, i.e. 6 x in‐person 30‐minute individual counselling sessions and 4 x 15‐minute phone calls during treatment phase, based on MI techniques. During follow‐up, each participant got a 15‐minute in‐person visit at 3m and 6m, and a 15‐minute phone call at 4m
Outcomes	Primary: PA at EoT Secondary: PA at 3m post‐quit, 6m post‐quit; CA at 3m post‐quit, 6m post‐quit; 7‐day PPA at EoT, 3m post‐quit, 6m post‐quit Validation: CO < 10 ppm. Self‐reported abstainers were asked to send a salivary cotinine sample (< 15 ng/mL) by post
Treatment type	Medication: VARENICLINE and BUPROPION
Notes	New for 2016 update Funding: NIDA grant DA017073, NCI grant P50CA70907; varenicline supplied by Pfizer
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Adaptive randomization (minimization) was used to stratify the groups for sex, race/ethnicity, history of depression, and baseline smoking rate."
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study physician was blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Losses to treatment and follow‐up reported, and key variables with significant differences (FTND, years of education) identified between those who stayed in and those who left. ITT analysis conducted. By 6m, 21/86 for varenicline (24.4%), 29/102 for bupropion (28.4%) and 30/106 for placebo (28.3%) had been lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	None noted
Other bias	Unclear risk	Study began as nortriptyline vs bupropion; 3 months later, 19 people had been recruited to bupropion and 18 to placebo; nortriptyline was replaced as the target treatment by varenicline. The nortriptyline phase group (cohort 1) had 19 days of medication and 3 counselling sessions before TQD, whereas varenicline phase group (cohort 2) had 12 days of medication and 2 counselling sessions before TQD. No differences were found between the 2 cohorts, nor between overall findings and cohort 2 findings. Authors therefore combined both groups into a single study cohort for analysis.