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

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.