Efficacy of Smartphone Applications to Help Cancer Patients Quit Smoking: Protocol of the Quit2Heal Randomized Controlled Trial

Abstract

Cigarette smoking is highly prevalent among cancer patients in the United States (US), with up to half of cancer patients smoking at the time of their initial cancer diagnosis. However, evidence-based cessation programs are rarely implemented in oncology care, and smoking is not consistently treated in cancer treatment settings. Consequently, there is an urgent need for accessible and efficacious cessation treatments that are uniquely tailored to the needs of cancer patients. Here we describe the design and implementation of a randomized controlled trial (RCT) testing the efficacy of a smartphone app (Quit2Heal) versus a US Clinical Practice Guidelines-based app (QuitGuide) for smoking cessation among a planned sample of 422 cancer patients. Quit2Heal is designed to address cancer-related shame, stigma, depression, anxiety, and knowledge about the consequences of smoking/quitting. Quit2Heal is based on the principles of Acceptance and Commitment Therapy, a behavioral therapy that teaches skills for accepting cravings to smoke without smoking, values-driven motivation to quit, and preventing relapse. The primary aim of the RCT is to determine whether Quit2Heal has significantly higher self-reported 30-day point prevalence abstinence at 12 months relative to QuitGuide. The trial will also determine whether Quit2Heal’s effect on cessation is (1) mediated by improvements in cancer-related shame, stigma, depression, anxiety, and knowledge about the consequences of smoking/quitting; and (2) moderated by baseline factors (e.g., cancer type, stage, time since diagnosis). If successful, Quit2Heal will offer a more efficacious, broadly scalable smoking cessation treatment that could be implemented alongside existing oncology care, thereby improving cancer outcomes.

1. Introduction

Cigarette smoking is highly prevalent among cancer patients in the United States (US), with 15% to 54% of cancer patients reporting smoking at the time of their initial cancer diagnosis.^1–3 Up to 80% of cancer patients who smoke continue to smoke after their diagnosis.^4–6 This persistence in post-diagnosis smoking occurs in spite of the serious medical outcomes, including poorer treatment efficacy (e.g., lower response to radiation and chemotherapy for cancer treatment),^7–10 increased risk of second primary cancers,¹¹ and all-cause and cancer-related mortality.^12,13 By contrast, quitting smoking after a cancer diagnosis dramatically reduces these harms and improves prognosis and odds of survival.^6,12,13 With up to half of cancer patients smoking at the time of diagnosis, accessible, low-cost, efficacious treatments specifically designed to help this special population stop smoking are urgently needed.

While efficacious evidence-based smoking cessation treatments exist for the general population, existing treatments are rarely implemented in oncology care or offered to cancer patients.^14–16 And while cancer research centers in the US do offer smoking cessation services to cancer patients, including the National Cancer Institute (NCI) Moonshot-funded Cancer Center Cessation Initiative (C3I) at NCI-designated cancer centers, these cessation programs are limited by hospital financial resources and availability of training to clinical staff.^17–20 Furthermore, only a small proportion of cancer patients receive cancer care in designated cancer centers,²¹ thereby limiting their potential impact on smoking among cancer patients nationwide. In fact, there are tremendous accessibility inequities among cancer patients who live in rural areas and those who do not have access to cancer centers, as they are primarily located in urban areas.²²

Remotely delivered behavioral programs for smoking cessation such as smartphone applications (“apps”) may provide a low-cost alternative to in-clinic programs since apps do not require health insurance or travel, and can be specifically tailored to cancer patients’ needs.^23,24 Apps require no provider training or integration into complex hospital systems, and they are available anytime at the convenience of the patient. Apps also have potential to reach cancer patients at the population level, especially since 85% of adults in the US own smartphones.²⁵ Specific to cancer populations, a recent observational study among cancer patients in the US (N=631) reported that 74% of cancer patients used mobile technologies regularly, including smartphones.²⁶ Importantly, that study also found that up to 60% of cancer patients expressed interest in smartphone apps to learn about supportive care services.²⁶

To directly address the need for smoking cessation treatments that are accessible and uniquely tailored to cancer patients, our research team followed an agile, user-centered design framework²⁷ to develop the first known smartphone app (called “Quit2Heal”) specifically designed to help cancer patients quit smoking.²⁸ We posit that an app-based behavioral treatment for smoking cessation that addresses the unique challenges of cancer-related (1) shame,^29–32 (2) stigma,³³ (3) depression,^34,35 (4) anxiety,^35,36 and (5) lack of knowledge about the consequences of continued smoking vs. quitting^37,38 may be more efficacious for helping cancer patients quit smoking than a standard treatment that does not address these core determinants of cessation. These five core processes have predicted smoking frequency,^33,34,36 cessation,^33,35,36 and relapse in cancer patients.³⁵ Quit2Heal is also based on the principles of Acceptance and Commitment Therapy (ACT), a behavioral approach that promote smoking cessation by teaching skills to observe and accept cravings to smoke without smoking.³⁹ Previous studies have demonstrated that ACT-based digital interventions, including smartphone apps for the general population, promote smoking cessation.^40–42 In contrast, standard approaches for cessation, such as the US Clinical Practice Guidelines (USCPG), teach avoidance of cravings that trigger smoking.⁴³

In a two-arm pilot randomized controlled trial (RCT), the Quit2Heal app was tested against a USCPG-based app (QuitGuide) among 59 adults who smoke and were diagnosed with cancer within the past 12 months (40.7 years old; 58% female; 34% from a racial/ethnic minority group).²⁸ Quit2Heal participants were more satisfied with their app (90% Quit2Heal vs. 65% QuitGuide; p=.047). Self-reported 30-day point prevalence abstinence (PPA) rates were 20% for Quit2Heal vs. 7% for QuitGuide (OR=5.16; 95% CI: 0.71-37.29; p=.10) at the 2-month follow-up. Compared to QuitGuide participants, Quit2Heal participants showed greater improvements in shame, stigma, depression, and anxiety, albeit not statistically significant (all p>.05).

This paper describes the design and implementation of the Quit2Heal two-arm parallel group RCT among a planned sample size of 422 adult cancer patients who smoke and are being recruited nationwide. The primary aim of the Quit2Heal trial is to determine whether Quit2Heal has significantly higher self-reported 30-day PPA at 12 months relative to QuitGuide. The trial will also determine whether Quit2Heal’s effect on the 12-month cessation outcome is (1) mediated by improvements in shame, stigma, depression, anxiety, and knowledge about the consequences of smoking/quitting; and (2) moderated by the following baseline factors: cancer type, cancer stage, time since diagnosis, age, sex, having a partner who smokes, receiving advice to quit by their provider, and recruitment source.

2. Methods

2.1. Overview

Quit2Heal is a 12-month, two-arm, parallel group RCT. The study was pre-registered on ClinicalTrials.gov (Identifier: NCT04409236; trial dates, July 2021 to May 2026). All study activities were approved by the Institutional Review Board at the Fred Hutchinson Cancer Center (Protocol number: IR-10432/RG1007577).

2.2. Specific aims

2.2.1. Primary cessation aim

Determine whether Quit2Heal has significantly higher self-reported 30-day PPA at 12 months post-randomization relative to QuitGuide.

2.2.2. Secondary cessation aim

Determine whether Quit2Heal has significantly higher self-reported 30-day PPA at 12-months post-randomization relative to QuitGuide, adjusted for biochemically verified smoking status in a randomly selected 10% subsample of participants.

2.2.3. Mediation aim

Determine whether the effect of Quit2Heal on 12-month smoking cessation is mediated by improvements in cancer-related shame, stigma, depression, anxiety, and knowledge about the consequences of smoking vs. the benefits of quitting.

2.2.4. Moderation aim

Determine whether the following baseline factors moderate the cessation outcome: cancer type, cancer stage, time since diagnosis, sex, age, having a partner/spouse who smokes, whether participant was advised to quit by their cancer care provider, and recruitment source.

2.3. Participants, recruitment, and randomization

2.3.1. Eligibility

2.3.1.1. Inclusion criteria.

(1) age 18 and older; (2) diagnosed with cancer (all types and stages of cancer) within the past 24 months or currently receiving or planning to receive cancer treatment in the next three months; (3) smoked a cigarette (even a puff) in the past 30 days; (4) interested in learning skills to quit smoking; (5) willing to be randomly assigned to either app; (6) live in the US and will remain in the US for the next 12 months; (7) have at least daily access to their own smartphone; (8) know how to download an app; (9) able to read English; (10) not currently (i.e., within past 30 days) using other smoking cessation interventions; (11) have never participated in our prior research trials; (12) have never used the NCI’s QuitGuide app; (13) being willing to complete a follow-up survey at 3-month, 6-month, and 12-month follow-ups; and (14) provide email, phone number(s), and mailing address.

2.3.1.2. Exclusion criteria.

(1) currently (i.e., within past 30 days) using other non-pharmacological smoking cessation interventions; (2) has participated in our prior research trials; (3) has used the NCI’s QuitGuide app; (4) not willing to complete follow-up surveys; and (5) not providing email, phone number(s), and mailing address. To be consistent with previous randomized trials of cessation among cancer patients,^44,45 use of FDA-approved medication for cessation is not included as an exclusion criterion.

2.3.2. Recruitment and enrollment

Participants are being recruited nationally through social media, radio, and in-clinic methods from two US cancer centers (Fred Hutchinson Cancer Center and Memorial Sloan Kettering (MSK) Cancer Center) via fliers posted in these centers and mailed to eligible patients and phone calls to eligible patients at MSK. We have also shared a description of the study on the C3I listserv (NCI Moonshot-funded Cancer Center Cessation Initiative listserv) and contacted clinics and hospitals around the country to determine interest in mailing or posting study fliers. Also to help meet our planned enrollment, the American Cancer Society (ACS) is assisting with national recruitment by: (1) providing a press release about the study; (2) posting a notice about the study on their website’s smoking cessation page; (3) promoting the study in social media posts; (4) providing study fliers at reception desks at ACS Hope Lodges nationwide; and (5) posting a weekly notice about the study along with a link to the study website on ACS’s Facebook page. All recruitment sources refer individuals to the registration website that contains information about the study, FAQs, a brief video describing the study, and information about the study team and academic institutions. All interested individuals are then directed to complete a web-based eligibility screening survey. Those who screen eligible are sent an email inviting them to complete the online informed consent and baseline survey (Figure 1). Recruitment and eligibility screening methods are designed to achieve a broad representation of patients that is at least 30% male and 30% from racial/ethnic minority groups.

Figure 1.

Experimental Design Schema

To deter fraud we check for, (1) CAPTCHA authentication; (2) IP addresses that are previously used, suspicious, or outside the US; (3) participants’ information if survey response times, email, or preferred communication method appear suspicious; (4) duplicates and participants in previous studies; (5) whether phone numbers are virtual; (5) consistency of questions that are both in the screening and baseline surveys (e.g., sex, cancer type and stage); and (6) whether hidden questions that only bots would see are answered. Everyone not eligible for any reason is sent a link to the smokefree.gov website and 800-QUIT-NOW to reach their state’s quitline. Those completing the enrollment process and randomized are emailed a secured link with instructions to download their randomly assigned app.

2.3.3. Randomization and double blinding

A randomly permuted block stratified randomization is being used. Stratification factors include (1) heaviness of smoking index (score >four),⁴⁶ (2) confidence in quitting smoking (>70 on a 0-100 scale), and (3) whether participants were recruited via social media or in-clinic methods. Random assignments are concealed from participants throughout the trial and both interventions are branded as “Quit2Heal”. Research staff are blinded to random assignment, and treatment allocation remains concealed until data collection is completed.

2.4. Smartphone Interventions Applications

2.4.1. Quit2Heal

Details of the design and development of the Quit2Heal app have been previously published.²⁸ In brief, users first set up a personalized quit plan that encourages selection of the National Comprehensive Cancer Network (NCCN) recommendations for use of FDA-approved cessation medications,⁴⁷ and how to obtain them. Users then go to the home screen where they begin progress through all levels of the behavioral intervention content, receive on-demand help in coping with smoking urges, and track their daily smoking behaviors (Figure 2). The program is self-paced, and content is unlocked in a sequential manner. For the first five levels, the content and exercises are designed to prepare users for their chosen quit day. A tobacco treatment guide navigates the user through the app and teaches skills for coping with shame, stigma, depression, anxiety, and common triggers to smoke (e.g., being around other smokers). The last four levels contain content and exercises designed to help the user stay smoke-free. Within each level, exercises are unlocked after the prior exercise is viewed; however, the next level will not unlock until users record seven consecutive smoke-free days. These levels contain 25 exercises that focus on coping with depression and anxiety, withdrawal symptoms, slips, potential weight gain, and building a smoke-free life with activities aligning with the user’s values. If participants record a lapse, the program encourages (but does not require) them to set a new quit date and return to first levels for preparation.

Figure 2.

Quit2Heal screenshots, including examples of tailored content to cancer patients

2.4.2. QuitGuide

The NCI’s QuitGuide app (version 2.30) is posted on the Google Play and Apple Store in a password-protected private format branded “Quit2Heal” (for blinding). QuitGuide is a non-tailored smoking cessation app designed for the general population of adults who smoke that follows the USCPG.⁴³ QuitGuide is non-proprietary and free to the public. Its content is based on the NCI’s smokefree.gov website, a digital therapeutic for smoking cessation recommended as a resource by NCCN.⁴⁷ Users track their cigarette cravings and moods, monitor their progress toward quitting, determine their reasons for quitting, identify smoking triggers and develop strategies to cope with them, and includes tips on how to quit smoking and address nicotine withdrawal. QuitGuide’s education content on learning how to quit smoking has four main sections: (1) “Steps to Prepare” for developing a customized quit plan, identify smoking behavior, triggers, and reasons for being smoke-free, identify social support for quitting, and education on FDA-approved cessation medications; (2) “Cravings” for identifying triggers to smoke and learning skills for coping with cravings to smoke, such as finding replacement behaviors (e.g., chewing on carrot sticks) and staying busy; (3) “Withdrawal” for learning about withdrawal symptoms; (4) “Slips” for identifying the triggers for slips and methods for recovering from slips; and (5) “Staying Smokefree” with tips for remaining smoke-free and skills for fighting cravings and staying positive.

2.4.3. Shared and distinct components of Quit2Heal and QuitGuide smartphone apps

Shared components of Quit2Heal and QuitGuide apps for smoking cessation include (Table 1): (1) education on risks of continued smoking and benefits of quitting; 2) quit planning, including setting a quit date; (3) identifying personal motivations to quit smoking; (4) education on FDA-approved cessation medications; (5) seeking general social support for quitting; (6) identifying triggers for smoking; (7) teaching skills to cope with cravings; and (8) relapse prevention. Content covered only in Quit2Heal (specifically designed for cancer patients) includes: (1) education on risks of continued smoking and benefits of quitting for cancer patients; and (2) skills to cope with cancer-related shame, stigma, depression, and anxiety. All participants are emailed identical once weekly reminders to use their assigned intervention. In addition, both smartphone apps, include push notification options that could be turned on or turned off depending on participants’ preferences.

Table 1.

Comparisons between Quit2Heal and QuitGuide smartphone apps for smoking cessation

Content covered in both Quit2Heal & QuitGuide

Content covered only in Quit2Heal

1. Education on risks of continued smoking and benefits of quitting. 2. Quit planning, including setting quit date. 3. Identifying personal motivations to quit smoking. 4. Education on FDA-approved cessation medications. 5. Seeking general social support for quitting. 6. Identifying triggers for smoking. 7. Teaching skills to cope with cravings and other common triggers. 8. Relapse prevention, including skills to cope with withdrawal and slips.

1. Education on risks of continued smoking and benefits of quitting for cancer patients. 2. Skills to cope with cancer-related shame. 3. Skills to cope with cancer-related stigma. 4. Skills to cope with cancer-related depression. 5. Skills to cope with cancer-related anxiety

2.5. Measures

2.5.1. Baseline assessment

The baseline survey collects data on (1) demographics; (2) cancer information (i.e., type, stage, time since diagnosis); (3) partner who smokes; (4) whether the patient was advised to quit by their care provider, (5) nicotine/tobacco use, (6) nicotine dependence; (7) years of smoking, (8) confidence in being smoke-free/readiness to quit, (9) quit attempts, (10) shame, (11) stigma, (12) depression, (13) anxiety, and (14) knowledge of smoking/quitting consequences (Table 2).

Table 2.

Measurements by timepoint

Measure	Screen	Baseline	3-month	6-month	12-month
Eligibility criteria	X
Demographics		X
Cancer type, stage, and time since diagnosis		X
Partner who smokes		X
Advised to quit by cancer care provider		X
Nicotine & tobacco use		X	X	X	X
Nicotine dependence		X	X	X	X
Cessation pharmacotherapy		X	X	X	X
Readiness to quit		X	X	X	X
Quit attempts		X	X	X	X
Cancer-related shame		X	X	X
Cancer-related stigma		X	X	X
Depression		X	X	X
Anxiety		X	X	X
Knowledge of smoking/quitting consequences		X	X	X

2.5.2. Smoking abstinence

Self-reported data on smoking abstinence will be collected at baseline, 3-month, 6-month, and 12-month follow-ups. The primary cessation outcome is self-reported 30-day PPA for cigarette smoking at 12 months post-randomization. The secondary cessation outcome is self-reported 30-day PPA for cigarette smoking at 12 months post-randomization, adjusted for biochemical confirmation being conducted among a 10% of all participants who are randomly selected at randomization. The choice of self-reported cessation as primary and biochemical as secondary is based on the pros and cons of each approach for remotely-conducted interventions with minimal contact^48–50 while also being both logistically and financially feasible for the trial.⁴⁹ Additional cessation outcomes include: (1) self-reported 24-hour and 7-day PPA for cigarette smoking; (2) abstinence from other nicotine/tobacco products (e-cigarettes, pods, snus, smokeless tobacco, hookahs, cigars, cigarillos, tobacco pipes, and kreteks); and (3) harm reduction: reporting only use of e-cigarettes, pods, or snus (but not other tobacco products) within the past 30 days at all timepoints.

After completing each survey, 10% of participants randomly selected to complete the biochemical verification procedure are mailed an Alere saliva-based cotinine test which indicates the presence or absence of cotinine and is a preferred rapid measure of cotinine.^51,52 This random selection is expected to help reduce false reporting as the verification will be provided regardless of self-reported smoking status. During the informed consent, all trial participants are informed of the verification testing procedure, but not of their selection to: (1) help them understand the importance of the verification testing, (2) anticipate this testing, and (3) prevent differential reporting of smoking status between those selected and not selected for testing. Participants who self-report abstinence and NRT or e-cigarette use, and who have elevated salivary cotinine, will not be re-classified as smoking. Cotinine data will help determine whether false reporting differs by arm and will allow for adjustment of secondary cessation outcomes using multiple imputation for participants who are not randomly selected to provide a sample. Based on the procedures of Heffner et al.,⁴⁸ participants will take the test, and upload photos of themselves taking it and their test results in a secure online survey. Anyone having difficulty with the online survey can contact study staff, who help participants conduct the test and display their results using a HIPAA compliant live video-conferencing website.

2.5.3. Potential mediators

Potential mediators will be measured at baseline, 3-month, and 6-month follow-ups. We posit that the Quit2Heal treatment addressing cancer-related shame, stigma, depression, anxiety, and knowledge about the consequences of smoking/quitting may be more efficacious for helping cancer patients quit smoking than the standard treatment that does not target these core determinants of cessation for cancer patients. Following our conceptual model (Figure 3), hypothesized mediators are: (1) shame, defined as the perception that one’s illness sets one apart from others who are well and feeling a need for secrecy about the illness, which is measured using the 5-item internalized shame subscale of the Social Impact Scale;⁵³ (2) stigma, defined as the emotional experience of rejection, blame, and devaluation based on the belief that one has caused one’s illness, which is measured via the 9-item internalized cancer stigma subscale of the Lung Cancer Stigma Inventory³³ with a modification to focus on cancer broadly; (3) depression, measured using the 10-item Center for Epidemiologic Studies Depression Scale;⁵⁴ (5) anxiety, measured using the 7-item Generalized Anxiety scale (GAD-7);⁵⁵ and (6) smoking/quitting consequences, measured via the 10-item smoking/quitting knowledge scale.⁵⁶

Figure 3.

Conceptual model for smoking cessation for cancer patients

Given that the focus of this study is cancer patients, we will first examine potential mediators mentioned above that are specific to cancer patients (i.e., cancer-related shame and stigma, etc.) since Quit2Heal was developed to addresses these core processes. As a secondary mediation aim, we do intent to use the data collected on changes in ACT-based acceptance of cues to smoke and values and explore whether increases in acceptance and enactment of values mediate the effect of Quit2Heal (but not QuitGuide) on cessation outcomes.

2.5.4. Exploration of Potential moderators

We will explore whether the following baseline variables moderate cessation outcomes of an app tailored to cancer patients: (1) cancer type, (2) cancer stage, (3) time since diagnosis, (4) whether participant was advised to quit by their cancer care provider, (5) having a partner who smokes, and (6) recruitment source. For example, patients with cancers well-known to be attributable to smoking (e.g., lung) may respond better to a tailored app because they can see the relevance of content focused on shame and stigma (“I caused my lung cancer”); while people recruited from a clinic (vs. social media) may have higher quit rates with a tailored app because they may perceive the app as a natural extension of their cancer care. We will also assess sex, age, race/ethnicity, and education as potential demographic moderators.

2.5.5. Treatment adherence and satisfaction

Objective usage data is collected on engagement with each app over the 12-month intervention period. As the standard digital intervention engagement metric,^57–59 the primary engagement measure will be the number of times users interact with their assigned intervention (i.e., number of logins). Secondary measures of engagement will be: (1) number of days from first to last use, (2) unique number of days of use, (3) time spent using the app, (4) content areas participants spent the most time reviewing and % completion of the levels/exercises, and (5) the frequency of revisiting content areas. Satisfaction with the app is assessed via study surveys at each follow-up.

2.5.6. Methods for outcome data retention

An established protocol that has yielded high outcome data retention rates (85-90%) in our previous trials,⁶⁰ and proven feasible in the Quit2Heal pilot trial²⁸ is currently being implemented. The online-telephone-mailed sequence protocol is as follows: participants are first mailed a $2 pre-incentive letter 7 days before the first email link invitation to the online survey at all timepoints. If there is no response, on days 5 and 9, a second and third email link invitation is sent. When necessary, the process is followed by eight attempts to complete a telephone version of the survey (one call per day on days 14 through 21). If all of this fails, on day 22, a paper version of the survey is sent via mail; followed by a second copy of the mailed survey on day 29. The data completion window ends on Day 90. Participants receive $25 for completing each follow-up survey and a $10 bonus incentive for completing the online survey within 24 hours of the initial email invitation. In addition, after completing each survey, 10% of all participants randomly selected to complete the biochemical verification procedure are reminded about completing the procedure first via email reminders the day they are eligible to take their follow-up survey (day 0) and on days 2 and 5. If there is no response, five attempts are made via telephone between days 7-21. The data completion window ends on Day 55. Participants receive $35 for completing each test.

2.6. Statistical Analysis Plan

2.6.1. Sample size

With a sample of 422 (211 in each arm), wherein missing outcome data is imputed as smoking, if we observe a 13.6% 30-day PPA at the 12-month follow-up in the Quit2Heal arm and a 4.7% 30-day PPA at the 12-month follow-up in the QuitGuide arm, we will have at least 80% power to detect a clinically meaningful difference in smoking cessation between treatment arms. These estimates are based on the self-reported quit rates at the 2-month follow-up observed in the Quit2Heal pilot trial, relapse by 12 months, and participant outcome data attrition.^28,61–63

2.6.2. Approach

Baseline socio-demographic factors, cancer information, nicotine and tobacco use, and mental health characteristics will be summarized by treatment arm. For the comparison of treatment arms for the primary and secondary aims, we will use logistic regression models. Models will adjust for the three stratification factors as well as baseline factors that are significantly related to the outcome.^64,65 All those with missing outcome data will be coded as smokers, as is standard in digital intervention smoking cessation trials.^66,67 Sensitivity analyses of the main outcome will include multiple imputation of missing outcomes^68–70 and complete case analysis of those providing follow-up data. The imputation model will incorporate important baseline factors (e.g., heaviness of smoking) associated with the cessation outcome.

Mediation analyses will test whether the effect of Quit2Heal on the 12-month cessation outcome is mediated by improvements from baseline to 3-months in shame, stigma, depression, anxiety, and knowledge about consequences of smoking/quitting. For each mediator, the model is expressed as three regression equations that relate (1) the total effect of the intervention on the 12-month cessation outcome, (2) the effect of the intervention on the mediator, and (3) the simultaneous effects of the intervention and mediator on the outcome. Since the outcome is binary, the empirical distribution of the mediation effect will be estimated via bootstrapped samples using the PROCESS macro^71,72 for SAS (SAS Institute Inc, Cary, NC).

Finally, for moderation analyses, we will estimate separate logistic regressions for each moderator that include the moderator, intervention arm assignment, and an interaction between moderator and group assignment. Statistically significant interactions will be assessed with subgroup analyses corresponding to the estimated effect of the intervention on 12-month cessation at each value of the moderator.

3. Discussion

Evidence-based digital therapeutics for smoking cessation that are uniquely tailored to the needs of cancer patients could help cancer patients quit smoking nationwide. The Quit2Heal RCT aims to demonstrate whether two scalable behavioral approaches for smoking cessation differ in their efficacy. The first is the traditional USCPG-based approach that focuses on using reason and logic to control urges to smoke. The second, more innovative approach focuses on helping cancer patients increase their willingness to experience cravings that cue smoking and also addresses cancer-related shame, stigma, depression, anxiety, and knowledge about the consequences of smoking/quitting. Given our recent success with Quit2Heal in a pilot study, digital therapeutics that are uniquely designed to address the needs of cancer patients have the potential for greater success than standard digital smoking cessation programs and may ultimately be used to complement more intensive tobacco treatment embedded in cancer care settings.

3.1. Strengths

The strengths of this trial include: (1) randomized controlled study design; (2) active control comparison; (3) double blinding random assignments; (4) long-term follow-up; (5) objectively measured smoking status among a randomly selected 10% subsample; (6) fully powered sample size to detect smoking cessation outcomes; (7) examination of potential treatment mediators and moderation of baseline factors; (8) nationwide recruitment; (9) empirically validated assessments; and (10) follow-up data collection methods that yielded high retention rates in our previous trials.

3.2. Challenges & Potential Limitations

There are four main challenges of this trial, all of which are primarily due to the challenges of study participants being in active cancer treatment (i.e., multiple treatments and appointments, shame about being a smoker with cancer, fatigue from cancer and treatment, fatalism about the benefits of quitting):^29–32,73 (1) trial recruitment; (2) app intervention engagement, (3) outcome data retention, and (4) remote biochemical verification of cessation. To help minimize the potential challenges associated with trial recruitment, we are employing social media recruitment strategies that yielded nationwide recruitment in previous digital smoking cessation trials in addition to in-clinic recruitment at two designated cancer centers.^40,60 To help reduce risk of smoking relapse after initial quit, both apps include content for relapse prevention, including skills to cope with withdrawal and slips. Regarding retention, we will use our well-honed multimodal survey methods, collect information on collateral informants, and incentivize completion of all assessments, with pre-incentives and bonus incentives for completing surveys within 24 hours. These survey data collection methods have yielded 85-90% follow-up rates in our other studies of digital therapeutics for smoking cessation.^28,60 To help minimize issues associated with remote biochemical verification, our staff has conducted a number of procedures aimed at improving return rates and reporting accuracy.

4. Conclusions

If successful, Quit2Heal for smoking cessation specifically designed for cancer patients will offer a more effective, broadly scalable cessation treatment that could be implemented alongside existing oncology care, thereby improving cancer outcomes.

Abbreviations:

ACT

Acceptance and Commitment Therapy

RCT

Randomized Controlled Trial

US

United States

Data availability

Data will be made available on request.