The rationale behind EXIT begins with a candid assessment of why conventional cessation programs fail this population. The researchers identify structural inequities as central barriers: the lack of stable housing, limited access to treatment services, and the fragmentation of care that forces people to navigate multiple disconnected systems. Layered on top of these structural obstacles are high rates of serious mental illness and substance use disorders among homeless smokers, which compound the physiological grip of nicotine dependence. Existing cessation treatments, the authors note, are often brief in duration, rarely integrated into community service settings, and short on the kind of ongoing behavioral support that sustained quitting demands. A single counseling session and a starter pack of patches, in other words, is poorly matched to the realities of life without a home.

EXIT was engineered around two design principles that distinguish it from prior efforts. The first is duration: rather than offering weeks of support, the intervention extends pharmacotherapy and coaching across a full six months, reflecting evidence that longer treatment courses improve cessation odds. The second is accessibility: the intervention routes treatment through community pharmacies and delivers behavioral support by telephone, so participants do not need to travel to clinics, keep rigid appointments, or negotiate unfamiliar healthcare bureaucracies. Community pharmacies have long been recognized as a promising venue for expanding access to evidence-based tobacco treatment, because pharmacists are numerous, trusted, geographically distributed, and empowered in many states to prescribe or recommend nicotine replacement products. Until now, however, pharmacy-based approaches have mostly been tested in short-duration interventions, leaving open the question of whether they can sustain quitting over the long term.

The trial itself is a two-arm, parallel-group randomized controlled trial conducted in transitional shelters in Los Angeles and San Francisco, two cities where homelessness has reached crisis scale. The investigators plan to enroll 150 adults experiencing homelessness who smoke at least five cigarettes per day, whose tobacco exposure is confirmed objectively by an expired carbon monoxide reading of at least 8 parts per million, and who report an intention to quit within six months. That carbon monoxide threshold is an important methodological safeguard, ensuring that self-reported smoking status is corroborated by a biochemical marker before randomization. Participants will then be allocated, in equal numbers, either to the full EXIT intervention or to a pharmacist-only comparator condition, allowing the trial to isolate the added value of extended pharmacotherapy and wellness coaching.

The comparator arm is deliberately pragmatic. Dubbed the pharm-only condition, it consists of a single pharmacist-delivered telephone session structured around the 5As framework, the established clinical sequence of asking about tobacco use, advising cessation, assessing readiness, assisting with a quit plan, and arranging follow-up, plus three months of nicotine replacement therapy. This condition represents a reasonable standard of care that a person might receive through a well-functioning pharmacy-based service, making it a meaningful benchmark against which to measure EXIT’s incremental benefits. Any advantage observed for the full intervention can therefore be attributed with some confidence to the additional months of medication and the intensive coaching component, rather than to mere contact with the healthcare system.

EXIT builds on that foundation in two decisive ways. Participants in the intervention arm receive the same initial 5As session, but their nicotine replacement therapy extends to a full six months, doubling the comparator’s treatment duration. More distinctive still is the behavioral component: 14 wellness-focused telephone coaching sessions delivered over six months by trained health coaches. The framing of these sessions as wellness-focused rather than narrowly cessation-focused is a deliberate design choice. Coaching conversations encompass broader health behaviors, including diet and physical activity, alongside smoking cessation goals. The investigators anticipate that this holistic approach may improve engagement and retention among participants for whom smoking is only one of many competing health and survival concerns, and for whom a single-issue intervention may feel disconnected from their priorities.

The trial’s primary outcome is adherence itself, an unusually honest choice for a feasibility-stage study. Adherence will be measured by the number of coaching sessions attended and by participants’ adherence to the nicotine replacement regimen, since an intervention only works if people actually use it. Secondary outcomes include biochemically verified seven-day point prevalence abstinence at three and six months, again confirmed by carbon monoxide readings of 5 parts per million or below. Assessment visits occur at baseline and at one, three, and six months, capturing a rich panel of measures: tobacco use and nicotine dependence, health behaviors such as diet and physical activity, mental health, substance use, and adherence to nicotine replacement therapy. This longitudinal design allows the team to track not only whether people quit, but how the intervention reshapes the broader health landscape that sustains addiction.

Methodologically, the protocol reflects the iterative logic of modern behavioral intervention science. Rather than leaping directly to a large, fully powered effectiveness trial, the EXIT team is first testing feasibility, acceptability, and preliminary efficacy in the very settings where a scalable program would ultimately operate. This staged approach guards against the familiar failure mode of cessation interventions that perform well in controlled academic clinics but collapse when transplanted into community environments with high participant mobility, competing survival needs, and limited staffing. By embedding the trial within transitional shelters and partnering with pharmacy infrastructure from the outset, the investigators are stress-testing the delivery model under real-world conditions. The findings are explicitly intended to inform a future fully powered trial that could establish a scalable model for delivering tobacco cessation treatment to people experiencing homelessness nationwide.

The scientific significance of the trial extends beyond its immediate population. Smoking among homeless adults is a major driver of the stark mortality gap between housed and unhoused populations, contributing to cardiovascular disease, respiratory illness, and cancer at rates that dwarf the risks posed by many problems that receive far more public attention. Yet tobacco is frequently deprioritized in homeless services, treated as a concern to be addressed only after housing, addiction, and mental health needs are met. EXIT challenges that triage logic by demonstrating that evidence-based tobacco treatment can be woven directly into homeless services and pharmacy systems rather than deferred. The trial is funded by the California Tobacco-Related Disease Research Program, with additional support to the first author from the National Institute on Drug Abuse, and it is registered at ClinicalTrials.gov under identifier NCT07148232.

If EXIT proves feasible, acceptable, and even preliminarily effective, the implications could ripple across public health practice. A model that pairs six months of nicotine replacement with sustained telephone coaching, initiated through a pharmacist visit and anchored in transitional shelters, could be replicated in cities across the country at comparatively low cost, since it relies on existing pharmacy networks and remote coaching rather than new clinics. The trial also contributes a methodological template for studying cessation in transient populations, combining biochemical verification, extended follow-up, and outcome measures that respect participants’ full health context. For the roughly seven in ten homeless adults who smoke, most of whom express a desire to quit but lack access to sustained treatment, EXIT represents a rigorous test of whether the healthcare system can finally meet them where they are, for as long as quitting truly takes.

Subject of Research: A randomized controlled trial testing an extended pharmacy-linked tobacco cessation intervention with telephone coaching for adults experiencing homelessness.

Article Title: Extended Intervention for Tobacco Use (EXIT) for people experiencing homelessness: study protocol for a randomized controlled trial

Article References: Extended Intervention for Tobacco Use (EXIT) for people experiencing homelessness: study protocol for a randomized controlled trial. (n.d.). https://doi.org/10.1186/s13722-026-00720-z

Image Credits: AI Generated

DOI: 10.1186/s13722-026-00720-z

Keywords: tobacco cessation, homelessness, nicotine replacement therapy, randomized controlled trial, community pharmacies, telephone coaching, health inequity, smoking prevalence, transitional shelters, public health, clinical trial protocol, addiction science