An Automated Text Messaging Intervention to Reduce Substance Use Self-Stigma (Project RESTART): Protocol for a Feasibility and Acceptability Pilot Study

Background Stigma is a barrier to treatment and harm reduction seeking in people who use drugs. Most stigma reduction interventions offer psychotherapy or psychoeducation in group-based clinical settings, failing to reach people who are not in treatment. SMS text messaging is an effective and acceptable modality for delivering health information to people who use drugs and may be a suitable conduit for providing information and advice to understand and cope with stigma. Objective This paper presents the protocol for a study that aims to determine the feasibility, acceptability, and preliminary effectiveness of a 4-week automated SMS text message intervention to increase stigma resistance and reduce self-stigma in people who use drugs. Methods We designed a novel automated SMS text message intervention to address the four personal-level constructs of stigma resistance: (1) not believing stigma and catching and challenging stigmatizing thoughts, (2) empowering oneself through learning about substance use and one’s recovery, (3) maintaining one’s recovery and proving stigma wrong, and (4) developing a meaningful identity and purpose apart from one’s substance use. Theory-based messages were developed and pilot-tested in qualitative elicitation interviews with 22 people who use drugs, resulting in a library of 56 messages. In a single-group, within-subjects, community-based pilot trial, we will enroll 30 participants in the Resisting Stigma and Revaluating Your Thoughts (RESTART) intervention. Participants will receive 2 daily SMS text messages for 4 weeks. Implementation feasibility will be assessed through recruitment, enrollment, retention, and message delivery statistics. User feasibility and acceptability will be assessed at follow-up using 23 survey items informed by the Theoretical Framework of Acceptability. Primary effectiveness outcomes are changes in self-stigma (Substance Abuse Self-Stigma Scale) and stigma resistance (Stigma Resistance Scale) from baseline to follow-up measured via a self-administered survey. Secondary outcomes are changes in hope (Adult Dispositional Hope Scale) and self-esteem (Rosenberg Self-Esteem Scale). Feasibility and acceptability will be assessed with descriptive statistics; effectiveness outcomes will be assessed with paired 2-tailed t tests, and group differences will be explored using ANOVA. Overall, 12 participants will also be selected to complete acceptability interviews. Results This pilot study was funded by the National Institute on Drug Abuse in April 2023 and received regulatory approval in January 2024 by the University of North Carolina-Chapel Hill Institutional Review Board. Recruitment and enrollment began in March 2024. Follow-up visits are expected to conclude by May 2024. Results will be disseminated in relevant peer-reviewed journals. Conclusions To the best of our knowledge, this is the first study to address substance use stigma via a self-help SMS text messaging program. Results will add to the nascent literature on stigma reduction in people who use drugs. This protocol may interest researchers who are considering text messaging to address psychosocial needs in hard-to-reach populations. Trial Registration ClinicalTrials.gov NCT06281548; https://clinicaltrials.gov/ct2/show/NCT06281548 International Registered Report Identifier (IRRID) DERR1-10.2196/59224

ZRG1 F16-L (20) SIBLEY, A research and training plan will contribute to the applicant's career trajectory as an independent mixedmethods substance use and stigma researcher.
PUBLIC HEALTH RELEVANCE: Self-stigma is a key barrier to help-seeking during the opioid epidemic, especially in rural areas, yet there are remarkably few evidence-based interventions to address this phenomenon.The present research uses a behavioral theory-informed, mixed-methods approach to develop and evaluate a novel text message intervention to promote resilience to stigma and reduce feelings of self-stigma among rural people who use drugs.Findings will add to scientific knowledge about feasible and acceptable stigma reduction interventions and provide further evidence of whether text messaging is a productive, cost-effective approach for engaging this hard-to-reach population.Overall Impact:/Merit: The applicant is a 3rd year PhD student in Health Behaviors at UNC-Chapel Hill.The applicant had 6 years of experience working in an academic community-engaged research center that collaborated with regional government on prisoner reentry and youth violence prevention, and now in graduate school has several years of high-level involvement in a large community-engaged research project that focuses on opioid overdose prevention in Appalachia.Letters of support highlight extraordinary motivation and advanced analytic and leadership skills.The applicant has a good track record of publications.The strong mentorship team has expertise in stigma research, health communication, mHealth interventions, and the primary sponsor has good mentorship experience (4 K awards, 2 T32 trainees).The research project focuses on developing and pilot testing an mHealth text message intervention that is tailored to the needs of rural persons who use drugs (PWUD).Significance is high because few studies have established how to address self-stigma and research on stigma resistance will advance the field.The sponsorship team has the expertise to guide the applicant and the project is aligned with the training plan.Training will include formal coursework (e.g., usability testing for mHealth interventions), self-directed learning (e.g., programming with Python language), and meetings with sponsors and co-sponsors.This is a resubmission, which was responsive to the prior mostly minor critiques by paring down the number of planned courses and teaching duties.Overall, this is an outstanding application from an accomplished student who is already immersed in the field of opioid overdose prevention and is able to articulate a clear and compelling plan for achieving research independence.The potential for impact in the field is very high.

Strengths
• Letters of support and sponsor statement categorize the applicant as one of the most talented students they have ever worked with.
• Strong foundation in qualitative research and recognizes the need to bolster quantitative and mixed methods skills.ZRG1 F16-L (20) SIBLEY, A • Demonstrates excellent understanding of community needs in regards to modifiable barriers to SUD treatment or harm reduction interventions.Likely stems from years working in this field and experience with community-engaged research.
• Already has grant writing experience -wrote a COVID supplement for the sponsors' UG3/UH3 grant.
• Six publications during graduate training

Strengths
• The Sponsor, Dr. Vivian Go, has expertise in SUD-related stigma and has mentored 13 doctoral students, 8 post-doctoral fellows, and 6 junior faculty members.She has supervised 4 students on F31 awards.
• Dr. William Miller is an infectious diseases physician and epidemiologist with extensive experience in implementation research and research mentorship.
• Dr. Nisha Gottfredson will provide expertise in quantitative methods.
• Dr. Kate Muessig will provide expertise in mHealth intervention design and evaluation.
• Dr. Seth Noar will provide expertise in health communications and the text messaging intervention.The applicant has published with Dr. Noar previously.

Strengths
• Strong rationale for focusing on self-stigma, good theoretical underpinning for the tailored intervention.
• Conceptualizing substance use stigma and developing interventions to build stigma resistance and mitigate self-stigma (or internalized stigma) will provide a meaningful project and opportunities for future funding.
• An mHealth/text message intervention will be low burden for participants, and may not reach 100% of PWUD, but could be a good addition to the tools used to engage PWUD who have experienced discrimination in healthcare settings.
• Sponsor's Ohio Opioid Project, the parent grant, is focused on community-level interventions to reduce opioid overdose deaths, and will provide an outstanding platform for the planned intervention development component of the study that the applicant has proposed.
• Using Latent Class Analysis to identify unobserved groups based on stigma measures in the parent study will aid in tailoring stigma messages.There will also be in-depth qualitative interviews with PWUD to adapt specific messages.
• Pilot testing of the mHealth/text message intervention will include concrete measures of feasibility, acceptability and usability.ZRG1 F16-L (20) SIBLEY, A • Applicant will gain experience with stigma resistance and self-stigma measures.

Weaknesses
• There is a lot of work proposed for a 2-year fellowship, considering the amount of ongoing coursework that is also proposed.There will only be 4 months for intervention pilot test recruitment and enrollment.

Strengths
• Strong theoretical rationale for the tailored intervention, applicant conveys mastery of health behavior concepts that will be incorporated into this work.
• There will be coursework in mHealth interventions for Behavior Change and usability testing of digital products.A prior reviewer questioned the need for coursework post-qualifying exam, but I think this will be another outstanding opportunity for the applicant to deepen knowledge and complement applied learning experiences.The mentorship team also has technical expertise to guide the applicant through development of the mHealth intervention.
• Statistical modeling coursework will be applied in the research project, where the applicant will use Latent Class Analysis to categorize stigma sub-groups.
• Developing the text messaging intervention should lead to future opportunities for scholarship.

Strengths
• UNC offers desired coursework in mHealth intervention and Multimedia design.
• Communicating for Health Impact Lab directed by Dr. Noar is a unique resource and ideal for the planned activities.
• Collaboration within the Rural Opioid Initiative will provide future opportunities.

Protections for Human Subjects:
Acceptable Risks and Adequate Protections • Potential for breach of confidentiality.
Data and Safety Monitoring Plan (Applicable for Clinical Trials Only):

Acceptable
o Will be included within parent study's DSMP

Inclusion Plans:
• Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution justified scientifically • For NIH-Defined Phase III trials, Plans for valid design and analysis: Not applicable • Inclusion/Exclusion Based on Age: Distribution justified scientifically • Will attempt outreach to recruit Latinx participants.

Vertebrate Animals:
Not Applicable (No Vertebrate Animals)

Biohazards:
Not Applicable (No Biohazards) Resubmission: • Critiques were mostly minor relating clarifying gaps in skills, detailing content of meetings with sponsors, and reducing teaching and coursework.The revised application was responsive.

Not applicable
Training in the Responsible Conduct of Research:

Acceptable
Comments on Format (Required): • Grad school courses and web-based CITI training.
Comments on Subject Matter (Required): • Additional coursework on research ethics.

Comments on Faculty Participation (Required):
• There will be discussions with advisors.
Comments on Duration (Required): • Weekly meetings with advisors, 14-hour research ethics course.
Comments on Frequency (Required): • Will need CITI refresher courses in 2023 and 2024.The applicant is also strong, with significant research and leadership experience, albeit with a modest publication record.I was enthusiastic about the research proposal and the training potential of this applicant.

Strengths
• Has a stated overarching research goal of improving the health and well-being of people who use drugs and has worked towards that goal through choice of employment as an academic community-engaged research coordinator.
• Excellent academic background, indicating a commitment to education and achieving career goals.
• Modest publication record; four publications (2 first authors); one in Lancet Regional Health.
• Strong letters of recommendation; one referee lauded the applicant's detailed approach to the data analysis process.

Sponsors, Collaborators, and Consultants:
• Dr. Go is a social epidemiologist and implementation scientist with expertise in substance use treatment; Dr. Go has considerable experience mentoring students in HIV, implementation science, and SUD research; 25 doctoral students and 8 postdocs.
• Dr. Go is funded and will provide the resources needed for the applicant to complete the study; expertise on stigma reduction will be useful for mentoring/training of the applicant.
• Dr Miller has advised 37 doctoral students and serve on 48 dissertation committees, thus adding to the strength of the mentoring team; has established working relationship with the applicant's primary sponsor; has focused on substance use in Appalachia.
• Dr. Gottfredson will provide expertise in EMA and higher-level statistical analysis training, Dr.
Noar, an expert in health communication, will provide training in communication theory and message development, Dr Muessig will provide expertise in the design of mHealth.

Strengths
• Stigma, while recognized as an important barrier to ending the opioid epidemic, is understudied.
Understanding what self-stigma looks like among people who use drugs, including attitudes and beliefs, and which ones can be changed can potentially be one avenue to addressing the opioid crisis.Thus, the proposed study is of significant public health interest and, if successfully conducted, can be of high impact.
• Use of SMS as part of an mHealth treatment is practical and can be of broad reach, thus also increasing the potential impact of the study.
• The proposed study is based on sound theoretical frameworks and conceptual models.
• The proposed study is nested in an ongoing study, the Ohio Opioid Study (which is one site in a larger multisite study) • The study team has established relationships and trust with SHRPS, a syringe service program where participants will be recruited from.
• Data analysis plan are thorough and well justified.

Weaknesses
• It appears that the applicant will be doing a lot of the research activities.This gives me slight concern about feasibility.
• The proposed sample is disproportionately white thus limiting the impact of the study.

Strengths
• Sponsors and other members of the mentoring team are engaged in the applicant's training and the proposed study.
• Applicant has provided clear training goals and delineated how these goals will be met.
• Candidate proposes to submit three dissertation manuscripts for publication.
• Knowledge gaps are clearly delineated, and training needed to gain more knowledge described.

Strengths
• Gillings School of Global Public Health is highly rated, with strong emphasis on community engagement, which is integral to research in the applicant's area of interest.
• The Odum Institute for Research in Social Science provides courses and workshops, which can be utilized by the applicant.
• UNC Injury Prevention Research Center supports and conducts research in opioid addiction and overdose and provide mentorship, expertise, and resources.

Protections for Human Subjects:
Acceptable Risks and Adequate Protections Data and Safety Monitoring Plan (Applicable for Clinical Trials Only): Unacceptable o No information was provided about DSMB.Given that an intervention will be offered, a DSMB should be given.

Inclusion Plans:
• Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution not justified scientifically

Renewal:
Not applicable outlined in the application will position the applicant for research independence and productivity after graduate training is completed.

Strengths
• The applicant worked six years as academic community-engaged research coordinator, developing skills that will contribute to the proposed research.
• The applicant has been productive, contributing to six peer-reviewed publications (four from the parent project); four more are in progress (applicant is first-author on two focused on stigma).
• The applicant's academic record is strong.including multiple PhD courses that provide a foundation for the proposed training activities.
• Letters emphasize the applicant's research skills and commitment to the proposed training and research.

Strengths
• The Sponsor and Co-Sponsor have worked together on funded research for more than a decade; their collaborative work supports trainees at both institutions.
• Both sponsors have very strong track records of garnering grant support and placing papers in high impact journals.
• The Co-Sponsor, though not at the applicant's institution, interacts with the applicant often as part of their collaborative work on the parent grant.
• The mentorship team is well chosen, offering the applicant access to high-level expertise in health messaging, intervention design, and advanced statistical modeling.
• The sponsors have ample funds to support the research and training activities.

Strengths
• The applicant is well positioned to reach a high-risk population, rural opioid and injection drug users, ensuring that information that shapes the intervention will be relevant and tailored to the intervention target group.
• The proposed research takes advantage of the sponsors' and the applicant's key roles in the parent study, which has produced evidence of pervasive self-stigma.
• Technical aspects of the mHealth intervention development are well described and will benefit from expertise provided by members of the mentor team.
• The goal of reducing stigma as a step toward reducing the negative consequences of use or harm reduction strategies is innovative and important.ZRG1 F16-L (20) SIBLEY, A

Weaknesses
• The preliminary intervention will enroll a small number of participants, precluding meaningful comparisons of subgroups such as those identified by the latent class analyses.

Strengths
• The long-term goal of becoming an independent mixed methods substance use researcher with an emphasis on stigma against users is clearly articulated by the applicant and sponsors, and the beginning of its pursuit is clearly outlined in the research and training plans.
• The sponsors and members of the mentor team are well equipped to oversee and participate in achieving the training goals.

Strengths
• The environments at UNC and Ohio State are very strong and will provide all of the resources needed for achieving the training and research goals.

Protections for Human Subjects:
Acceptable Risks and Adequate Protections • For focus groups, recordings deleted after transcription; identifying info removed from transcripts.
• Minor risk of distress, but participants can choose not to answer any question; will be provided list of local counseling services.
• All staff trained in confidentiality protection; any confidentiality issues discussed at weekly staff meetings.
• Research staff will ensure participants' phones are password protected so no one can get to their text messages.
Data and Safety Monitoring Plan (Applicable for Clinical Trials Only): Not Applicable (No Clinical Trials) Inclusion Plans: • Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution justified scientifically • Children were not included in the parent study and are therefore excluded; no exclusion for adults.
• No restriction for gender; approximately equal proportions women and men.
• No exclusion on race/ethnicity; additional efforts to recruit Hispanic/Latinx participants to increase sample representativeness.

Vertebrate Animals:
Not Applicable (No Vertebrate Animals)

Biohazards:
Not Applicable (No Biohazards) Resubmission: • Added missing descriptions of how training plan addresses current gaps and is connected to aims.
• Information is provided about interactions with sponsors and consultants with reference to training goals.
• Power analysis has been added and its limited relevance for analyses of the pilot data described.
• A plan to accommodate potential participants with no mobile phone is now described.
• The number of formal courses and TA responsibilities have been reduced.
• Clarity is provided about the clinical trial aspects of the work, making clear that documentation required of clinical trials is managed by the sponsors, who lead the parent study.

Not applicable
Training in the Responsible Conduct of Research:

Acceptable
Comments on Format (Required): • Web based certification courses, coursework, discussion with sponsors.
Comments on Subject Matter (Required): • Ethics, research misconduct, human subjects research, informed consent, IRBs, intellectual property.
Comments on Faculty Participation (Required): • Graduate course will be led by a faculty member; faculty sponsors will discuss ethics with applicant at regular meetings.
Comments on Duration (Required): ZRG1 F16-L (20) SIBLEY, A • Four-hour online course, portion of regular meetings with sponsors, semester-long graduate course.
Comments on Frequency (Required): • Certification course every three years, graduate course on one occasion, biweekly meetings with sponsors.

Applications from Foreign Organizations:
Not Applicable Footnotes for 1 F31 DA058452-01A1; PI Name: Sibley, Adams Longstreet + Derived from the range of percentile values calculated for the study section that reviewed this application.

Select
NIH has modified its policy regarding the receipt of resubmissions (amended applications).See Guide Notice NOT-OD-18-197 at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-SIBLEY,A 197.html.The impact/priority score is calculated after discussion of an application by averaging the overall scores (1-9) given by all voting reviewers on the committee and multiplying by 10.The criterion scores are submitted prior to the meeting by the individual reviewers assigned to an application, and are not discussed specifically at the review meeting or calculated into the overall impact score.Some applications also receive a percentile ranking.For details on the review process, see http://grants.nih.gov/grants/peer_review_process.htm#scoring.

Foreign Organizations:
Overall Impact:/Merit: The applicant seeks to develop and evaluate a stigma resistance text message intervention for people who use drugs (opioids).The candidate's training goals include developing a strong understanding of the theoretical underpinnings of stigma in context of substance use, develop expertise in advanced-level statistics, such as LCA, mHealth development and health communication interventions, and build publication record.The applicant has assembled a well-qualified mentoring team, with significant experience mentoring and training doctoral students and postdoctoral fellows.
In this revised application, the applicant has strengthened a research training plan that was generally viewed favorably by reviewers.The relatively small number of concerns have been addressed effectively through clearer articulation of training goals and activities and clearer linkage between the training activities and the proposed research.The result is a strong application with substantial promise as described in the uniformly positive comments from sponsors and in the letters of recommendation.The Sponsor and Co-Sponsor have strong publication, funding, and mentorship records and have collaborated for more than a decade on research and training in areas close to the focus of the application.The research plan is sound and will lay the groundwork for high-impact work by the applicant after completing graduate studies.The two-year training plan is thorough and cohesive, and will be implemented in an outstanding training environment.Overall, it is likely that the activities ZRG1F16-L (20)