Bohadana 2020.

Study characteristics
Methods	Country: Israel Setting: Pulmonary Institute of Shaare Zedek Medical Center (SZMC), Jerusalem, Israel, in participants' home Aim: to assess whether varenicline preloading for 6 weeks prior to the TQD reduced pre‐quit smoke intake and enhanced 6‐month abstinence outcomes compared with the standard 1‐week preloading. Study design: parallel placebo‐controlled RCT
Participants	242 daily smokers, smoking ≥ 10 CPD, and had smoked for ≥ 5 pack years, and were motivated to quit. 27% female, mean age 48, average CPD at baseline 25
Interventions	1 week of varenicline preload: 5 mg of varenicline once daily for 3 days and 0.5 mg twice daily for 4 days (week 1), followed by varenicline 1 mg twice daily for 5 additional weeks 6 weeks of varenicline preload: matched placebo tablets for 5 weeks, followed by a 1‐week titration of varenicline as in group 1 TQD was 6 weeks post‐initiation of treatment.
Outcomes	Primary: 24‐week biochemically verified CAR from weeks 6–30 Secondary: 23‐week CAR from 1‐week post‐TQD (week 7) to week 30; 7‐day PPA at week 30 Biochemically validated: expired CO ≤ 5 ppm and urine cotinine equivalent concentration ≤ 1 mg/mL
Notes	New for 2022 update  Study funding: "2013 Global Research Award for Nicotine Dependence (GRAND) supported by Pfizer, Inc. (#WI182915)" Author declaration of interests: "None"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Randomisation was accomplished by extracting a systematic sample via a pre‐prepared list of alternate allocations"
Allocation concealment (selection bias)	Unclear risk	"These procedures were performed by the randomisation monitor (VP) in a secure room where the study medication, provided free of charge by Pfizer Inc., NY, was stored in identically packaged, blinded bottles containing varenicline or placebo. Participants were referred to the secure room where they were randomly allocated (in a 1:1 ratio) to the experimental group."
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind during preloading phase (open‐label afterwards as both groups were receiving identical treatments).
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition similar in both groups, overall < 50%
Selective reporting (reporting bias)	Low risk	Outcomes reported as in clinical trials record