VergeRx for Smokers Not Ready to Quit

Background and rationale. People who smoke but are not ready to quit in the next 30 days (SNRTQ) are underserved by conventional cessation treatments, which typically require a near-term commitment to quit. Substantial questions remain about how best to treat this population, including whether combination NRT outperforms monotherapy for these smokers and how long NRT patch treatment should be provided. This study applies the optimization phase of the Multiphase Optimization Strategy (MOST) to efficiently evaluate multiple candidate components within a single experiment, guided by a Phase-Based Framework for smoking cessation.

Design. The study is a fully-crossed 2×2×2×2 factorial experiment with 16 treatment conditions and a planned enrollment of 592 participants (\~37 per condition). Four components are independently randomized:

VergeRx (yes vs. no): Participants receive up to three pre-quit modules with a local pharmacist or pharmacy technician to promote NRT adherence. Readiness to quit is assessed at weekly REDCap check-ins conducted by the research team; participants may also report readiness to their pharmacist during or between sessions. Upon reporting readiness, participants advance to six treatment sessions delivered over four weeks. If readiness is not reported after four weekly check-ins, the VergeRx component ends.

SmokefreeTXT (yes vs. no): Participants receive up to three 7-day pre-quit modules ("Daily Challenges") to prepare for a quit attempt. Upon reporting readiness at a weekly check-in, participants transition to the SmokefreeTXT program, which delivers 3-5 messages per day for seven weeks. If readiness is not reported after four weekly check-ins, the component ends.

Combination NRT Lozenge + NRT Patch (vs. patch alone): Participants assigned to this component receive nicotine lozenge in addition to the NRT patch, testing whether combining delivery mechanisms improves outcomes relative to patch monotherapy in this population.

16 weeks of NRT patch (vs. standard 8 weeks): This factor tests whether an extended patch duration improves cessation relative to the standard 8-week course.

All participants receive at least 8 weeks of NRT patch beginning in Week 1. Recruitment. Participants are referred by physicians and pharmacists at their local FQHC through an ask-advise-connect model, supplemented by advertisements placed around the FQHC. Eligible participants do not intend to quit in the next 30 days, a motivational cutoff based on prior literature.

Analysis. Consistent with the factorial/MOST approach, the 16 conditions are not compared individually. The main effect of each component is estimated by pooling data across all conditions-for example, the main effect of VergeRx compares abstinence among the \~296 participants who received it against the \~296 who did not. This design uses data from all participants to estimate each component's main effect, providing adequate statistical power with approximately 37 participants per condition. A conceptual model based on the Phase-Based Framework specifies the mediating constructs (proximal outcomes) through which the components are hypothesized to influence cessation, and these mediators are assessed alongside the cessation outcomes.

Outcomes. The primary outcome is biochemically confirmed point-prevalence cigarette abstinence at the 26-week follow-up. A secondary outcome is biochemically confirmed point-prevalence abstinence at the 52-week follow-up.

• Biochemically confirmed 7-day point prevalence cigarette abstinence at 52 weeks [Срок оценки: 52 weeks after enrollment]