Using User-Centered Design to Facilitate Adherence to Annual Lung Cancer Screening: Protocol for a Mixed Methods Study for Intervention Development

Background Lung cancer is the leading cause of cancer-related death in the United States, with the majority of lung cancer occurrence diagnosed after the disease has already metastasized. Lung cancer screening (LCS) with low-dose computed tomography can diagnose early-stage disease, especially when eligible individuals participate in screening on a yearly basis. Unfortunately, annual adherence has emerged as a challenge for academic and community screening programs, endangering the individual and population health benefits of LCS. Reminder messages have effectively increased adherence rates in breast, colorectal, and cervical cancer screenings but have not been tested with LCS participants who experience unique barriers to screening associated with the stigma of smoking and social determinants of health. Objective This research aims to use a theory-informed, multiphase, and mixed methods approach with LCS experts and participants to develop a set of clear and engaging reminder messages to support LCS annual adherence. Methods In aim 1, survey data informed by the Cognitive-Social Health Information Processing model will be collected to assess how LCS participants process health information aimed at health protective behavior to develop content for reminder messages and pinpoint options for message targeting and tailoring. Aim 2 focuses on identifying themes for message imagery through a modified photovoice activity that asks participants to identify 3 images that represent LCS and then participate in an interview about the selection, likes, and dislikes of each photo. A pool of candidate messages for multiple delivery platforms will be developed in aim 3, using results from aim 1 for message content and aim 2 for imagery selection. The refinement of message content and imagery combinations will be completed through iterative feedback from LCS experts and participants. Results Data collection began in July 2022 and will be completed by May 2023. The final reminder message candidates are expected to be completed by June 2023. Conclusions This project proposes a novel approach to facilitate adherence to annual LCS through the development of reminder messages that embrace content and imagery representative of the target population directly in the design process. Developing effective strategies to increase LCS adherence is instrumental in achieving optimal LCS outcomes at individual and population health levels. International Registered Report Identifier (IRRID) DERR1-10.2196/46657


DESCRIPTION (provided by applicant):
Lung cancer is the leading cause of cancer death in the US, with most lung cancer diagnosed at advanced stages. Low-dose CT screening of high-risk individuals is the only evidence-based tool available to diagnose lung cancer at an early stage when curable treatment options exist. The promising mortality reduction benefit of lung cancer screening (LCS) is presently overwhelmingly unfulfilled due to suboptimal population-based adherence to annual screening guidelines. Outside of research settings, adherence to annual LCS is less than half of the rates observed in the practice-changing, landmark clinical trials. There is an urgent need for effective and feasible interventions to improve LCS adherence and achieve optimal individual and population health benefits. Research during the F99 phase will leverage an innovative, multi-phase, mixed methods design to describe how LCS patients process health information regarding health protective behavior and utilize this information to develop and evaluate reminder messages with individuals eligible for LCS. Using a four-step process, data collected in a survey of LCS program participants (step 1) will inform the development of a pool of candidate reminder messages (step 2). In the final two steps, the reminder messages will be evaluated by LCS experts (step 3) and further evaluated and refined with LCS program participants (step 4) using mixed methods, including surveys and interviews. Differences between health information processing constructs by demographic or clinical characteristics found to be significant from step 1 will be the focus for message targeting (group level) and/or tailoring (individual level). At the conclusion of the F99 phase, I will have a formalized set of clear, engaging, and efficient messages to support LCS annual adherence, ready to be evaluated in a clinical setting. Research proposed in the K00 phase will focus on gaining real-world experience with hybrid effectiveness implementation study designs and pragmatic outcome measures to simultaneously assess effectiveness and implementation outcomes. Specifically, I propose a mentored pre-post type 1 hybrid effectiveness-implementation trial, within a parent trial, that will allow concurrent assessment of effectiveness and implementation outcomes of the F99 reminder strategy in real-world LCS programs. Effectiveness will be tested using a pre-post design, comparing percent screening participants adherent to annual screening guidelines before and after implementation of the reminder strategy. Secondary implementation outcomes (i.e., acceptability and feasibility) will be assessed with surveys and key informant interviews of personnel involved in the reminder system implementation (e.g., LCS program directors, navigators, coordinators). This body of research will prepare me for a career as an independent cancer-focused intervention scientist with expertise in the development and implementation of effective, low-burden interventions aimed at improving LCS adherence, maximizing screening benefit, and reducing lung cancer mortality.

PUBLIC HEALTH RELEVANCE:
Lung cancer screening efficacy is highly dependent on adherence to recommended guidelines, with annual screening indicated for approximately 90% of all individuals who receive baseline scans. Initial reports of real-world screening implementation show adherence to annual screening guidelines are less than 50%, demonstrating a critical need for improvement to optimize the individual and population health benefits of lung cancer screening. I aim to address the urgent need for low-cost, feasible, and effective interventions focused on facilitating lung cancer screening adherence by developing and implementing a set of clear and engaging reminder messages that target and tailor information specific to lung cancer screening participants.

CRITIQUE:
The written critiques of individual reviewers are provided in essentially unedited form in this section. Please note that critiques and criteria scores, prepared prior to the review meeting, may not have been revised following discussions at the meeting. The "Resume and Summary of Discussion" section summarizes the final opinions of the review committee. Overall Impact/Merit: This is an outstanding candidate with a strong background who provided an excellent description of her career development/training and research plans to address an important problem. She has identified an outstanding sponsor/sponsorship team who are ideally suited to help her in this work. A minor limitation is the lack of prior collaboration with her team due to the recent departure of her primary mentor, but the suitability of her sponsor and the clear engagement in the candidate's proposal and current and ongoing work temper this limitation. Minor limitations in the proposed research are also addressable.

Fellowship Applicant Strengths
• Candidate has strong commitment to career focused on implementation research to identify effective and low burden interventions to improve lung cancer screening • Substantial prior research experience as a clinical research coordinator, including work focused on expanding use of lung cancer screening • Three papers published (two as first author that are directly related to proposed research); another submitted • Strong candidate for career as an independent researcher • Outstanding letters suggest a strong commitment to and high potential for a career as an independent researcher Weaknesses • None noted.

Sponsors, Collaborators, and Consultants Strengths
• Although candidate's prior mentor left academic practice, she quickly identified an outstanding mentor and mentorship team and together they have developed a well-planned dissertation research program and plans for transition to postdoctoral training • Candidate began collaborating with her mentor even before his arrival at the University of Colorado • Expertise of sponsor and co-sponsor is complementary and matches the candidate's interests • Dr. J Studts (sponsor) has expertise in behavioral aspects of lung cancer early detection and survivorship • Dr. C Studts (co-sponsor) has expertise in dissemination and implementation science • Dr. Scherer has expertise in medical decision making and will assist with reminder messaging • Dr. Glasgow has expertise in implementation science • Dr. Thomas directs the lung cancer screening program and will provide clinical expertise • Sponsor has very strong track record in mentoring, mentorship awards • Team structure is well justified • Applicant has described a strong plan for identifying a mentor and institution for the K00 phase of the award. • Sponsor team members were very engaged in F99/K00 process • There are adequate research funds to support the applicant's proposed research and training Weaknesses • New relationship with sponsors and co-sponsors because prior mentor left, but candidate has done an extraordinary job at engaging a new primary mentor and mentorship team that are extremely well suited for the work, turning this into a strength.

Research Training Plan Strengths
• Research addresses important questions, well grounded in theory, and is well integrated with training plan • Both phases of research well designed/described • F99 phase leads directly to plans for K00 phase • Research is synergistic with sponsor's but sufficiently distinct from sponsor's and consistent with applicant's stage of development and research career objectives • Time frame is feasible to accomplish proposed dissertation research training • Candidate provides a clear outline of feasible research milestones Weaknesses • Lack of discussion about representativeness of likely survey participants versus non-participants and how nonresponse and focus on individuals at one lung cancer screening program may affect external validity of findings • For K00 phase, pre-post design is reasonable given the goal of a pragmatic trial in a real-world setting in which all eligible participants receive the intervention. However, the lack of a 1 F99 CA264409-01 5 ZCA1 SRB-H (M1) HIRSCH, E comparison group is a limitation, as rates of follow up screening could be changing over time. The study would be enhanced tremendously if they identified a comparison group that is not exposed to the reminder intervention (e.g., if in Colorado, perhaps making use of the Colorado all payer claims data would allow this)

Training Potential/Career Development Plan Strengths
• F99 phase has high potential to provide a strong foundation for K00 phase • Additional course work proposed in F99 and K00 is appropriate for research goals.
• Training plan designed to fill gaps and provide key skills for transition to career development phase • Milestones for F99 phase are outlined clearly • Sponsor and cosponsor have clearly described plans for supervision during the training period Weaknesses • None noted.

Institutional Environment & Commitment to Training Strengths
• Outstanding environment • Clear description of research facilities, resources, and many training opportunities that will increase candidate's likelihood of success • Strong institutional commitment to fostering the applicant's mentored training in the F99 phase (including additional funds from the University of Colorado Cancer Center (UCCC) Deputy Directory Dr. Cathy Bradly to demonstrate very strong support for the candidate. • Excellent description of needs for transition to K00 phase and good ideas about possible opportunities that will support candidate and match the research program anticipated in that phase.

Weaknesses
• None noted. • Excellent description Comments on Subject Matter (Required):

Protections for Human
• Excellent description Comments on Faculty Participation (Required): • Excellent description Comments on Duration (Required): • Excellent description Comments on Frequency (Required): • Excellent description Overall Impact/Merit: This is a well-written application from an excellent candidate. The training plan is well developed and, in conjunction with the research project, will help Ms. Hirsch develop new skills and expertise and enhance her existing skills. The research project addresses an important question and is of high scientific quality. The sponsors and collaborators, as well as the environment and available resources for the proposed research project and training are excellent. Overall, the fellowship is expected to provide Ms. Hirsch with the skills and knowledge to develop, design and implement effective intervention strategies for early detection of cancer and to significantly enhance her potential to become a successful independent cancer researcher.

Fellowship Applicant Strengths
• The applicant, Ms. Hirsch, has an outstanding academic record and research background. She has shown a clear commitment to a career as an independent researcher specifically focused on the development, design and implementation of effective intervention strategies for early detection of cancer. • Strong letters of reference that confirm Ms. Hirsch's strong commitment to and high potential for becoming an independent researcher. Weaknesses • None noted. • The two proposed sponsors, Drs. J. Studts and C. Studts, have complementary expertise and skills, and are well-positioned to successfully mentor and train Ms. Hirsch. Both have previously successfully mentored multiple graduate students, fellows and junior faculty. Ms. Hirsch will further be supported by the three collaborators, Drs. Glasgow, Thomas and Scherer, and together the team offers expertise in every area targeted in her training plan. • Adequate funds are available to support Mr. Hirsch's proposed project and training during the F99 phase. The University of Colorado Cancer Center will provide an additional $10,000 in support. • An appropriate set of characteristics for the K00 institution as well as the K00 mentor and environment are described.

Research Training Plan Strengths
• The proposed research project is outstanding. The project addresses a critical issue, suboptimal adherence to annual lung cancer screening guidelines, and is well integrated with the proposed training plan. The project will leverage a multi-phase, mixed methods design to describe how lung cancer screening patients process information regarding health protective behavior and utilize this information to develop and evaluate reminder messages with individuals eligible for lung cancer screening. The project is highly relevant to Ms. Hirsch's research career objectives. • The proposed research project is sufficiently distinct from her sponsors' funded research.
• The proposed timeline is feasible.
• The application includes a clear description of research and training planned during the K00 phase. Research proposed for the K00 phase will focus on gaining real-world experience with hybrid effectiveness implementation study designs and pragmatic outcome measures to simultaneously assess effectiveness and implementation outcomes. The applicant proposes to conduct a mentored pre-post type 1 hybrid effectiveness implementation trial, within a parent trial, that will allow concurrent assessment of effectiveness and implementation outcomes of reminder strategy developed in the F99 phase in real-world lang cancer screening programs. Weaknesses • None noted.

Training Potential/Career Development Plan Strengths
• The proposed research project and training plan are well-developed and well-reasoned. They will allow Ms. Hirsch to gain experience in qualitative and mixed-methods research, learn health behavior theory for application to user-centered design, and to further enhance her expertise in dissemination and implementation science. Training activities planned include individualized tutorials by the sponsors as well as formal course work. • Career, scientific and professional milestones are clearly described. The application includes detailed plans for mentoring as well as for monitoring and evaluating Ms. Hirsch's research and career development progress. Weaknesses • None noted.

Institutional Environment & Commitment to Training Strengths
• The facilities and resources required for the proposed research project are all available. is dedicated to engaging and building knowledge in rigorous qualitative and mixed methods research across the University of Colorado Anschutz Medical Campus, and the Dissemination and Implementation (D&I) Science Program which is led by collaborator Dr. Glasgow and includes co-sponsor Dr. C. Studts as a core team member. • The environment at the University of Colorado Anschutz Medical Campus is excellent for the proposed research project and training. In addition, there is a strong collaborative network of specialists in lung cancer screening in the Greater Denver -Aurora area that Ms. Hirsch will also be able to utilize for advice and collaborations. • The applicant plans to focus her postdoctoral research on developing advanced skills in D&I science, hybrid study design, and pragmatic research outcomes. • The application includes detailed information on training goals/objectives and planned training activities for both the F99 and K00 phases. The facilities, resources and training opportunities for the K00 phase adequately match the research program anticipated during that phase.

Weaknesses
• None noted. • Comprehensive. In addition to standard topics, the applicant plans to also specifically address challenges related to doing research on lung cancer screening in under-served communities. Comments on Faculty Participation (Required):

Protections for Human
• Sessions and lectures are led by faculty members. In addition, subjects like authorship, protection of human subjects, conflict of interest will also be discussed with the sponsors. Comments on Duration (Required): • More than eight contact hours in total Comments on Frequency (Required): • Adequate Overall Impact/Merit: The application describes a detailed plan to develop informed annual lung cancer screening decisions in lapsed individuals. Candidate has developed a close, supportive mentored relationship with leaders in her field. The methods for the research plan and the contributions of mentors are well articulated. The proposed plan has a high chance of facilitating successful career development.

Fellowship Applicant Strengths
• 3.9+ GPA in MS program in Clinical Science, U. Colorado.
• Establishing credentials in lung cancer screening adherence and interventions through publications and presentations. 10 or more years work experience in clinical studies of lung cancer. • Strong support letters indicating high probability of success. Weaknesses • None noted.

Sponsors, Collaborators, and Consultants Strengths
• Strong complimentary mentoring team of faculty in decision making, implementation science, behavioral interventions, and lung cancer screening expertise. Leaders in the field. Closely aligned with applicant's plans. • Specific training skills that applicant seeks in collaboration with mentors well described.
• Clinical trial study design mentoring closely aligned with applicant goals. Weaknesses • None noted.

Research Training Plan Strengths
• The need for the proposed project is justified. interventions, and appears to be independently developed. Timeframe is feasible. • Transition from developmental work in f99 to clinical intervention in K phase is appropriate.
• Proposed studies are feasible within timeframe.
• Time course of developing new skills fits well with background.

Weaknesses
• No apparent evaluation of reminder message content from previous studies and how that guides the proposal.

Training Potential/Career Development Plan Strengths
• Plan details the transitions and skills needed at each step.
• Training goals and professional development described.

Institutional Environment & Commitment to Training Strengths
• Excellent interdisciplinary mentoring team that are leaders in respective fields and expertise in the specific goals of applicant. • Applicant describes overall need and training-specific need for risk communication science in lung cancer screening, but training will allow for using skill set beyond lung screening. • Home institution has resources to support proposed project.

Protections for Human Subjects: Acceptable Risks and Adequate Protections. Minimal risk
Data and Safety Monitoring Plan (Applicable for Clinical Trials Only): Acceptable. Not a clinical trial, but DSMB will oversee.

Inclusion Plans
• Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution justified scientifically • For NIH-Defined Phase III trials, Plans for valid design and analysis: • Inclusion/Exclusion Based on Age: Distribution justified scientifically • Sample population includes all lung cancer screened individuals. Children are not eligible, as those outside the age range of 55-80 will be excluded.

Renewal: Not Allowed
Training in the Responsible Conduct of Research: Acceptable.