We will conduct a nonrandomized, single-arm feasibility study.

We will recruit 40 participants. In order to ensure diversity with respect to age, gender, race, and socioeconomic status, we will purposefully recruit participants through a variety of methods, including the research boards of Centre for Addiction and Mental Health (CAMH), where recruitment flyers are posted for patients to explore research opportunities; health care providers at CAMH programs (eg, Smoking Treatment for Ontario Patients [STOP] program, Aboriginal services, and Rainbow services) and partnering organizations (Rainbow Health Ontario); the STOP program’s list of people who are seeking treatment for smoking and who have consented to be contacted for future research studies; and social media and community boards. Research staff members will conduct a prescreening for those who are interested, and if eligible, participants will be enrolled in the study.

The inclusion criteria include individuals who are seeking treatment for their tobacco use who smoke 10 or more cigarettes a day, are willing to set a quit date in the next 30 days, are willing to take varenicline for 12 weeks, are aged 18 years, speak and read English, have a smartphone with a data plan, report being committed to answering questions during follow-up, and live in Ontario.

The exclusion criteria include having contraindications to varenicline use, being pregnant, planning to become pregnant, breastfeeding, or participating in the co-design phase.

The CAMH Research Ethics Board (REB #050/2022) has provided approval to conduct the study, and all participants will provide written informed consent before participation. It has been registered at ClinicalTrials.gov (NCT05997901). Any amendments to the protocol are noted, and substantial changes will be reported to the ethics committee. All interested participants will receive an information sheet and a consent form describing the study and providing sufficient information for the participant to make a decision regarding study participation. A research staff member will arrange a personal meeting with the prospective participants and inform them again about all study procedures, benefits, risks, and their rights regarding study participation. Afterward, the consent form is signed by both the participant and the research staff before the participant undertakes any study procedure. The informed consent process is documented in Research Electronic Data Capture (REDCap; Vanderbilt University).

All study-related documents and data will be held in strict confidence and stored on CAMH servers that will follow CAMH policies and procedures to ensure participant privacy and confidentiality. Any data collected as part of the participants’ completion of the electronic consent form will be securely stored in REDCap, a CAMH-approved data collection tool.

In addition to free medication (for 12 weeks), participants will receive an honorarium in the form of a CAD $30 (US $22) gift card after completion of the 4-week follow-up survey and a CAD $40 (US $30) gift card after completion of the 12-week interview.

The research team will inform potential participants about the study and evaluate if they meet the inclusion criteria. If they qualify, participants will receive a consent form and arrange a phone-based discussion to obtain consent. After obtaining consent, participants (n=40) will complete an internet-based questionnaire covering sociodemographic characteristics, nicotine dependence [35], and an adapted scale to measure varenicline adherence self-efficacy [36-38]. After completing the questionnaire, participants will have an internet-based or in-person visit with a health care provider for eligibility confirmation and to obtain a prescription for varenicline for the first 4 weeks (1 tablet [0.5 mg] daily for the first 3 days, 1 tablet [0.5 mg] twice daily for the next 4 days, and 1 tablet [1 mg] twice daily for 3 weeks). In addition, research staff will show participants how to use the health bot on their phones. Medication will be provided in person or, in the case of internet-based contacts, mailed to the participants. A follow-up visit will be scheduled at 2 weeks, where health care providers will assess the participant’s tolerance of varenicline and provide a prescription for the remaining 8 weeks (1 tablet [1 mg] twice daily or a different dose depending on the tolerance of each participant). Any unanticipated problems (ie, adverse events that are unexpected in terms of severity, nature, or frequency; are related or possibly related to participation in the research; and suggest that the research places other research participants at greater risk of harm) will be documented and reported to the research ethics board, and adverse drug reactions will be reported to the market authorization holder (Apotex) as applicable.

Participants will be required to complete surveys at 1, 4, 8, and 12 weeks. When participants join the study, they will be able to opt to respond to these questions using either the health bot or an internet-based platform. Those who do not complete the internet-based or health bot follow-up within the designated time frame will receive a phone call from our research staff. Additionally, after 12 weeks of joining the study, participants will be invited to participate in a 1-hour semistructured phone interview.

We will calculate descriptive statistics, including means, medians, ranges, and SDs, for the demographic data as well as for the AIM, IAM, and analytics data captured by the health bot internal logs. All scores will be analyzed using the appropriate guidelines provided by Weiner et al [40] (acceptability and appropriateness) and Brooke [42] (usability). Consistent with previous studies, adherence will be defined as taking ≥80% of the prescribed varenicline [45-48]. We will not treat adherence as a continuous variable because it is likely to be strongly bimodal and is not necessarily linearly associated with the cessation outcome. We will calculate the percentage of participants who were adherent at week 12 and who reported not having smoked in the last 7 days. These results will serve as progression criteria to determine whether a full-scale RCT is warranted. Although the sample size will be insufficient for meaningful regression analysis, especially given the potentially nonlinear effects of age, we will also test for differences across age and gender groups using 2-tailed t tests and chi-square tests. The power for these comparisons will be low; therefore, this analysis will be an exploratory evaluation of large adherence or outcome differences that may be important to future study design, and interpretation will focus on observed differences and CIs.

We will use framework analysis [49] to analyze the data. Specifically, we will use the implementation outcomes of Proctor et al [39] with an intersectional lens as the a priori framework. Framework analysis is a method used to draw descriptive and explanatory conclusions from qualitative data and includes the following six steps: (1) verbatim transcription of interviews, (2) familiarization of interviews, (3) coding and labeling the data, (4) developing a framework by grouping and categorizing codes, (5) indexing transcripts using the developed framework, and (6) reducing and charting data into a matrix. Interview findings will help us contextualize the findings from the surveys and the information collected from the use of the health bot. For example, we will understand why the health bot was or was not used (adoption); if it was used as intended (fidelity), what about the health bot the participants found agreeable and what they did not (acceptability); what features, if any, aligned with participants’ attitudes, needs, and background (appropriate); and how other features would need to change in order to align with their needs. In addition, we will be able to understand how social identity (eg, age and gender) and power structures (eg, ageism and sexism) played a role in these results. This will provide us with important information to improve the health bot through an equity lens.

Once the survey data and interviews are analyzed, we will triangulate the results by listing all the findings on the same page to identify instances where findings from each method align (convergence), provide additional insights on the same topic (complementarity), or seem to conflict with one another (discrepancy or dissonance) [50,51]. Triangulating the data will allow us to contextualize the quantitative findings and explore “intermethod discrepancy” that might lead to a better understanding of how the health bot works and the modifications needed.

This study, using “stop, amend, and go” progression criteria for pilot studies [51], will help determine if proceeding with an RCT is a logical next step and whether additional adjustments are necessary. We will only conduct a full-scale RCT if none of the criteria outlined in Table 2 meet the “stop” criterion (unless we see that there are contextual issues that can be modified to overcome the identified problems). If 1 or more of the concepts in Table 2 meet the “amend” criterion, the trial will proceed to an RCT only if the issues can be addressed. If all concepts in Table 2 satisfy the “go” criterion, we will proceed with planning an RCT.