O'Malley 2018.

Study characteristics
Methods	Country: USA Setting: home, 2 x outpatient substance abuse treatment and research facilities Aim: to test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment, and to evaluate the secondary effects on smoking abstinence Study design: phase 2, randomised, double‐blind, parallel‐group, placebo‐controlled trial
Participants	131 adult smokers with alcohol use disorder. Eligible participants met alcohol‐dependence criteria and reported heavy drinking (≥ 5 drinks for men and ≥ 4 drinks for women) ≥ 2 times per week and smoking ≥ 2 times per week. 29.8% female, mean age 42.7, baseline average CPD 11.4 Exclusion criteria: current, clinically significant disease or abnormality; diagnosis of a serious psychiatric illness; current suicidal ideation or lifetime history of suicidal behavior; risk of aggression; current diagnosis of drug dependence; risk of clinically significant alcohol withdrawal; medications in the past 3 months to treat alcohol or tobacco dependence; psychotropic medications in the past month. Women of childbearing age could not be pregnant or nursing and had to be practicing effective contraception.
Interventions	Placebo Varenicline 2 x 1 mg/day Intervention duration was 16 weeks. Participants did not receive any behavioural support for SC ‐ solely for alcohol use reduction.
Outcomes	Percentage of heavy drinking days weeks 9‐16 No heavy drinking days weeks 9‐16 Prolonged smoking abstinence weeks 13‐16
Notes	New for 2022 update Funding by grants from the National Institutes of Health and by the State of Connecticut Department of Mental Health and Addiction Services. Pfizer provided varenicline and placebo pills at no cost.  Author declaration of interests: "Dr O’Malley reported having been a consultant or an advisory board member for Alkermes, Amygdala, Arkeo, Cerecor, Mitsubishi Tanabe, Opiant, Pfizer; a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative supported by Abbott, Amygdala, Ethypharm, Lilly, Lundbeck, Otsuka, Pfizer, Arbor Pharmaceuticals, and Indivior; a coinvestigator on studies receiving donated medications from Astra Zeneca, Novartis; a site principal investigator for a multisite trial by Lilly; and a scientific panel member for Hazelden Foundation. Dr Petrakis reported being a consultant to Alkermes. Dr Fucito reported registering with the US Patent and Trademark Office the name and content of a web‐based program to help with sleeping and drinking (ie, Call it a Night). No other disclosures were reported"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomization list was generated by our study statistician (R.G.) and was implemented through a web‐based system (Endpoint Systems)."
Allocation concealment (selection bias)	Low risk	"The randomization list was generated by our study statistician (R.G.) and was implemented through a web‐based system (Endpoint Systems)."
Blinding (performance bias and detection bias) All outcomes	Low risk	"Participants, treatment providers, and research staff were blind to the assignment throughout the study" and abstinence biochemically validated
Incomplete outcome data (attrition bias) All outcomes	Low risk	"N=94 (71.8%) provided data at the 12 month follow‐up" Similar between arms
Selective reporting (reporting bias)	Low risk	Prespecified outcomes reported