Littlewood 2017.

Study characteristics
Methods	Country: USA Setting: at home with in‐person study visits (unclear setting) Aim: to evaluate the effectiveness of varenicline for SC, and examine the influence of psychological factors on treatment outcome Study design: double‐blind, placebo‐controlled, RCT
Participants	205 current cigarette smokers interested in quitting, 34% female, mean age 34, baseline average CPD 16
Interventions	Placebo Varenicline ‐ 2 x 1 mg/day (titrated for first week) Participants were randomised in a 1:1 ratio. Interventions lasted 12 weeks. All participants received in‐person interactive behavioural support, comprising a 30‐min baseline counselling session and a 10‐20‐min follow‐up at weeks 2, 6, and 12.
Outcomes	CA for the past month, biochemically confirmed with exhaled CO < 6 ppm Average number CPD 7‐day PPA
Notes	New for 2022 update Funding by National Institute on Drug Abuse (NIDA) 1R01DA025074‐01A2.  Author declaration of interests: "The authors declare that they have no conflict of interest."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Urn‐randomisation used
Allocation concealment (selection bias)	Low risk	"In order to maintain the blind, the pharmacist controlled the pre‐generated urn randomization schedule and packed varenicline tablets in opaque capsules with microcrystalline cellulose, an inert powder commonly used in packaging medications."
Blinding (performance bias and detection bias) All outcomes	Low risk	Participants and staff measuring the outcome were blinded to allocation. Abstinence biochemically validated.
Incomplete outcome data (attrition bias) All outcomes	High risk	52% of participants lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	No trial registration but reports expected outcomes