Rationale, design, and protocol for a sequential, multiple assignment, randomized trial of adaptive treatment for smoking cessation: The ADAPT trial

Abstract

Background

Most attempts to quit smoking cigarettes end in failure, even when FDA-approved pharmacotherapies are used. Despite the frequency of treatment non-response, few trials have investigated the best path forward after treatment failure. This trial will assess two primary aims: 1) determine whether switching pharmacotherapies following initial failure promotes abstinence more effectively than repeated attempts with the same pharmacotherapy, and 2) determine whether switching to e-cigarettes following successive failures with pharmacotherapy promotes abstinence from combustible cigarettes better than continuing with pharmacotherapy.

Methods

Adults in South Carolina and Alabama who smoke daily and are willing to set a quit date will be assigned in a counterbalanced fashion to receive a 4-week supply of FDA approved smoking-cessation medication (either combination nicotine replacement therapy or varenicline) and asked to set a quit date. After four weeks of treatment, treatment non-responders will be assigned in a 2:1 fashion to either switch medications or continue with the same medication (Aim 1). After a second four weeks of treatment, non-responders will be assigned in a 2:1 fashion to either switch to e-cigarettes or continue with the same pharmacotherapy (Aim 2), with outcomes assessed through 6 months (Aim 3). The primary outcome is biochemically confirmed 7-day abstinence from smoking, assessed repeatedly across separate study aims. Secondary outcomes include smoking reduction, nicotine dependence, and duration of abstinence.

Conclusion

This trial is positioned to provide strong, data-driven guidance on treatment decision-making following treatment failure. The trial results will provide a significant opportunity to optimize cessation outcomes for people who smoke and continue to struggle with quitting.