Steinberg 2018.

Study characteristics
Methods	Country: USA Setting: community  Aim: to conduct a proof‐of‐concept RCT of varenicline for smokers willing to reduce, but not quit smoking Study design: parallel, placebo‐controlled RCT
Participants	53 current adult smokers, smoking at least 10 CPD for the past 6‐months, and interested in cutting down, but not in quitting in the next 30  days. 49.2% female, mean age 44.3, baseline average CPD 15 Exclusion criteria: any past use of varenicline, current use of bupropion/nortriptyline/nicotine preparations, use of tobacco products other than cigarettes more than once per month, currently receiving tobacco use disorder counselling, alcohol use disorder, drug abuse, psychosis, depression or suicidal ideation
Interventions	Placebo  Varenicline 2 x 1 mg/day (titrated for the first week) Participants were randomised on a 1:1 ratio. All participants received in‐person interactive behavioural support, which comprised 3 x 20‐min and 1 x 35‐min counselling visits
Outcomes	Relevant outcomes Cigarette reduction goal (> 50% reduction) at 6 months  Mean CPD over time at 1, 3 and 6 months Exhaled CO at 3 months and EoT Number of quit attempts
Notes	New for 2022 update.  Abstinence data were provided upon request by study authors Funding by Global Research Award for Nicotine Dependence (GRAND) grant #WS777117 – An independent competitive grants program supported by Pfizer. Pfizer had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. Author declaration of interests: "MLS and JMW have consulted for and received unrestricted educational grants and research grant support from Pfizer. SE‐L has no conflicts to declare."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Participants were randomized to active or placebo varenicline using an urn randomization procedure"
Allocation concealment (selection bias)	Unclear risk	Concealment not reported
Blinding (performance bias and detection bias) All outcomes	Low risk	Abstinence biochemically validated
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition rates 12% in placebo arm and 29% in varenicline arm
Selective reporting (reporting bias)	Low risk	Abstience a prespecified outcome, but results not published. However, abstinence data were provided upon request by study authors