Nahvi 2014a

Methods	Country: USA Setting: 3 urban outpatient clinics for substance use disorder (SUD) in the Bronx, NY Aim: to test the efficacy and safety of varenicline for smoking cessation among opioid‐dependent people on a maintenance regimen Study Design: Randomised quadruple‐blind controlled trial Dates conducted: August 2009 ‐ September 2011 Analysis: 50 participants in each arm would give 80% power to detect a 22% abstinence rate in the varenicline users (½ the expected rate in non‐MM participants)
Participants	112 smokers in methadone treatment for substance abuse, aged 18+, CPD 5+, motivated to quit within next 6m. Allocated 57 varenicline, 55 placebo. 52% women, 54% Hispanic, mean CPD 15, mean FTND 4
Interventions	All participants set a TQD 1 wk after treatment began. All were offered structured, brief (≤ 10 mins) individual in‐person counselling by a physician or tobacco specialist at baseline and at 2‐, 4‐, 8‐ and 12‐wk visits. All participants were also offered free quitline support 1. Varenicline: 12‐wk standard regimen, titrated for 1st wk 2. Control: Identical placebo tablets and regimen
Outcomes	7‐day PPA at 12 and 24 wks Validation: Expired CO < 8 ppm
Treatment type	Medication: VARENICLINE
Notes	Funding: National Center for Research Resources grant UL1 RR025750 to SN, and the National Institute on Drug Abuse grants K23 DA025736 to SN and R25 DA023021 to SN and JHA New for 2016 update
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Treatment group allocation was computer‐generated, and stratified by the three clinic sites in blocks of six within each stratum"
Allocation concealment (selection bias)	Low risk	"a central data manager concealed the allocation sequence using a password‐protected file, assigned subjects to treatment groups and faxed pre‐printed medication orders to the study pharmacist. The pharmacist prepared the research medication by compounding varenicline tablets or placebo lactose powder to create identical‐appearing capsules. The pharmacist marked medication bottles with subjects’ study identification numbers, and delivered medications for individual study subjects to clinical sites, where they were distributed to each subject by the research assistant"
Blinding (performance bias and detection bias) All outcomes	Low risk	"The pharmacist prepared the research medication by compounding varenicline tablets or placebo lactose powder to create identical‐appearing capsules. The pharmacist marked medication bottles with subjects’ study identification numbers, and delivered medications for individual study subjects to clinical sites, where they were distributed to each subject by the research assistant" "All subjects, research assistants, counsellors and physicians were blinded to treatment assignment"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Losses during treatment (varenicline 6, placebo 9) and during follow‐up (varenicline 2, placebo 3) fully reported; ITT analyses conducted
Selective reporting (reporting bias)	Low risk	None noted
Other bias	Low risk	None noted