Power and sample size

This study is powered to estimate the efficacy of PrOMOTE compared to TAU on abstinence from smoking at EOT. Investigations on the efficacy of varenicline note increases in 7-day PPA in active varenicline treatment arms as compared to placebo (Week 12: 50.3% vs. 21.2%; Δ = 29.1% and 50.3% vs. 20.8%; Δ = 29.5%).[64, 65] Similarly, Ashare and colleagues completed a trial of varenicline compared to placebo in PWH and noted that varenicline was superior to placebo at the close of treatment (PPA: 28.1% vs. 12.1%; Δ = 16.0%).[26] Further, dual NRT (long term patch + ad lib NRT) was similarly efficacious for abstinence at 6 months post quit as varenicline [dual NRT: abstinent = 36.5% (95% Confidence Interval [CI] = 28–45) and varenicline abstinent = 33.2% [29–38]].[13] Sample size will be based on a conservative estimate of the effect sizes provided above (Δ = 17%). Thus, a TAU abstinence rate of 15% is anticipated with a PrOMOTE abstinence rate of 32% at EOT. To detect this clinically-relevant effect size with 80% power and a type 1 error rate of 5%, n = 95 participants will be randomized to each of the two treatment assignments. Continuous abstinence from study Week 9 through 12 (4 weeks) will also be assessed as a primary efficacy outcome. Estimates on the efficacy of varenicline as compared to placebo note significant increases in 4-week end of study abstinence in the active varenicline treatment arms as compared to placebo at the close of study treatment (Week 12: 44.0% vs. 17.7%[64]; Δ = 26.3% and 43.9% vs. 17.6%; Δ = 26.3%[65]). Based on preliminary data, TAU continuous abstinence rate of 10% is anticipated with a PrOMOTE abstinence rate of 25% at the Week 12 (Δ = 15%). To detect this effect size with 80% power and a type 1 error rate of 5%, n = 97 participants will be randomized to each of the two treatment assignments. The study design will employ remote intervention delivery and follow-up assessments reducing participant burden and enhancing data collection. This, combined with the flexibility of medication management using PrOMOTE, a moderate to low attrition rate at EOT (15%) is anticipated. Thus, n = 115 participants randomized to each study treatment assignment (n = 230 total) will provide adequate power at a 5% type 1 error rate to detect the anticipated effect sizes.