Gray 2019.

Study characteristics
Methods	Country: USA Setting: university outpatient clinic  Aim: to evaluate whether varenicline, when added to brief cessation counselling, is efficacious and safe for SC in adolescents Study design: parallel double‐blind placebo‐controlled RCT
Participants	157 treatment‐seeking adolescent current smokers, aged 14‐21, and motivated to quit. 40% female, mean age 19.4, baseline average CPD 11.3. Participants must have smoked daily for at least 6 months and had at least one failed attempt at quitting.  Exclusion criteria: history of mood or psychotic disorder, suicidality, homicidality, or significant hostility or aggression; substance dependence other than nicotine, unstable medical disorder, pregnancy, breastfeeding, or use of medications with SC efficacy; known hypersensitivity to varenicline
Interventions	Varenicline 2 x 1 mg/day  Placebo  Participants were randomised in a 1:1 ratio. All participants received in‐person interactive behavioural support weekly for 12 weeks.
Outcomes	Primary: 7‐day abstinence at the end of the 12 weeks of treatment. Confirmed with urine‐cotinine level Secondary: weekly abstinence throughout active treatment; abstinence at post‐treatment follow‐up visits; time to first 7‐day abstinence
Notes	New for 2022 update. Study authors provided additional results data upon request Funding by grants from then NIH, and varenicline and placebo were supplied at no cost by Pfizer.  Author declaration of interests: "Dr Gray reported consulting for Pfizer, Inc, and receiving grant support from the National Institutes of Health (NIH). Mr Baker reported receiving grant support from the NIH. Dr McClure reported receiving grant support from the NIH. Dr Tomko reported receiving grant support from the NIH during the conduct of the study and outside the submitted work. Dr Squeglia reported receiving grant support from the NIH. Dr Saladin reported receiving grant support from the NIH. Dr Carpenter reported consulting for Pfizer, Inc, during the conduct of the study. No other disclosures were reported."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Stated randomised, but randomisation method not specified
Allocation concealment (selection bias)	Unclear risk	Concealment not reported
Blinding (performance bias and detection bias) All outcomes	Low risk	Trial described as double blinded and equivalent face to face contact identical between study arms. Abstinence biochemically validated
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition rates were similar between study arms
Selective reporting (reporting bias)	Low risk	Pre‐specified outcomes reported