Leveraging Social Determinants Via Artificial Intelligence and Peer Coaching to Address Racial Disparities in Primary Care Among People Who Use Opioids
Phase: NA
Conditions: Opioid Use Disorder
Sponsor: Friends Research Institute, Inc.

 
Leveraging social determinants via artificial intelligence and peer 
coaching to address racial disparities in primary care among people who use opioids  
 
 
 
 
Principal Investigators: 
 
 
Babak Tofighi, MD, MSc  
 
 
 
 
 
 
Crystal Lewis, PhD 
 
 
 
 
 
 
Helen-Maria Lekas, PhD 
 
Co-Investigators: 
 
 
 
Ali Jalali, PhD 
Sean Murphy, PhD 
Sharifa Williams, PhD 
 
 
 
 
 
Ryan McCormack MD, MSc 
 
 
 
 
 
Joshua D. Lee MD, MSc 
 
 
 
 
 
Eric Oermann MD, PhD 
 
 
 
 
 
Kerstin Pahl, PhD 
 
 
 
 
 
 
Protocol Date: August 13, 2024 
 
Version 2.0 

 
Table of Contents 
Study Team .................................................................................................................................. 5 
Study Synopsis ........................................................................................................................... 7 
Study Timeline ............................................................................................................................ 8 
Study Workflow ........................................................................................................................... 9 
Introduction ............................................................................................................................... 10 
Study Strategy ........................................................................................................................... 12 
Study Design ............................................................................................................................. 15 
Aim 1: Does AI texting + peer supported texting improve linkage to OUD services? ... 15 
Cohort ................................................................................................................................. 16 
Enrollment, Consent, Workflow, Data Gathered ................................................................. 17 
Subject Payment ................................................................................................................. 19 
Proposed Analyses ............................................................................................................. 20 
Aim 2: Can the multimodal intervention be equitably implemented in clinical care?.....22 
Approach ............................................................................................................................. 23 
Data Analysis ...................................................................................................................... 23 
Aim 3: How Cost-Effective is the multimodal intervention? ............................................. 25 
Health Economic Measures ................................................................................................ 25 
Data Analysis ....................................................................................................................... 26 
Aim 3b ................................................................................................................................. 26 
Study Population ...................................................................................................................... 27 
Recruitment ........................................................................................................................... 27 
Patient Participants. ............................................................................................................ 27 
Patient eligibility screening and enrollment. ....................................................................... 29 
Inclusion/Exclusion criteria ................................................................................................. 30 
Patient Participants. ............................................................ 30Error! Bookmark not defined. 
Retention plan and projected attrition rates .......................... 30Error! Bookmark not defined. 
Frontline provider and administrator 
participants……………………………………………31Error! Bookmark not defined. 
Informed consent .................................................................................................................. 31 
Patient Participants ............................................................................................................. 31 
Clinician Participants. .......................................................................................................... 31 
Inclusion of Women and Minorities .................................................................................... 32 
Study Procedures: Patients ..................................................................................................... 33 
All Patients ............................................................................................................................ 33 
Day 0 ................................................................................................................................... 33 
Intervention Arm-1: AI texting + peer texting  ..................................................................... 35  
Intervention Arm-2: AI texting only………………………………………………………………………………….36 
Intervention Arm-3 (Control) .............................................................................................. 36 
Participant discontinuation and follow-up  ......................................................................... 37 

 
 
sIRB Plan ................................................................................................................................... 38 
Study Research Infrastructure ................................................................................................ 39 
Data Safety and Quality Assurance ........................................................................................ 39 
Potential risks to participants .................................................................................................. 41 
Adequacy of Protection Against Risks ................................................................................... 42 
Informed Consent ................................................................... Error! Bookmark not defined. 
Protection Against Risk ........................................................... Error! Bookmark not defined. 
Vulnerable Subjects ................................................................ Error! Bookmark not defined. 
Potential benefits of the proposed research to research participants and others .......... Error! 
Bookmark not defined.4 
Importance of Knowledge to be Gained  ............................... Error! Bookmark not defined.4 
Data-safety and Monitoring Plan ............................................................................................. 45 
Data Monitoring Plan .............................................................................................................. 45 
Data Entry & Analysis .............................................................. Error! Bookmark not defined. 
Quality Assurance Plan ........................................................................................................ 47 
Collection and Reporting of SAEs and AEs ........................... Error! Bookmark not defined. 
Reporting mechanisms of IRB actions to NIDA ...................................................................... 50 
Plan for Incidental Findings Management ............................................................................. 50 
Interim Data Analysis Plans .................................................................................................... 51 
References ................................................................................................................................. 52 
 

 
Study Team 
This project involves Investigators at four institutions, with three multiple Principal Investigators 
(mPIs), including Drs. Babak Tofighi (Friends Research Institute/Nathan Kline Institute), Crystal 
Lewis (NYU/NKI), Helen Maria-Lekas (NYU/NKI).  Each Principal Investigator will be primarily 
responsible for oversight of their assigned study components as described in the mPI Plan.  
 
Drs. Joshua D. Lee (Co-I), Ryan McCormack (Co-I), and Eric Oermann will support the MPI 
team in the successful implementation of Aims 1-3 and serve on the DSMB. 
 
A collaborative research support team will consist of: 
§ 
Research Coordinator (FRI/NKI) 
§ 
Graduate Research Assistant/Interviewer (FRI) 
§ 
Data analyst (NKI) 
§ 
x2 Peer Recovery Coaches (NKI) 
§ 
Research Assistant (WCM) 
 
Friends Research Institute (FRI) 
 
The FRI Research Coordinator and Graduate Research Assistant/Interviewer will support the 
mPI team with patient and clinical staff enrollment, data collection, and oversee the day-to-day 
management of data collection and management, and quality control data analytic checks. 
 
Dr. Tofighi and the study team will lead development of the text messaging intervention and 
PRC web dashboard to communicate with patient participants. Dr. Tofighi will be responsible for 
creating project plans, meeting project timelines, troubleshooting, and resolving technical 
problems that arise in collaboration with Dr. Oermann. 
 
NYU Grossman School of Medicine (NYUGSOM) 
Dr. Eric Oermann will provide general guidance and feedback to the study team in the 
operationalizing of the AI-driven texting software, including natural language processing 
algorithms.  
 
Drs. Joshua D. Lee (Co-I), Ryan McCormack (Co-I), and Eric Oermann will provide general 
feedback to the the MPI team in the successful implementation of Aims 1-3 and serve on the 
DSMB. 
 
Nathan Kline Institute (NKI) 
The two NKI-funded Peer Recovery Coaches will oversee daily intervention activities, including 
organizing schedules, coordinating and monitoring patient load, scheduling recruitment and 
enrolling patients, and overseeing, undergoing quality control activities (collecting field notes, 
brief in-depth interview check-ins, quarterly), supporting and coordinating community 
engagement activities (meeting with supervisors and frontline clinical and social services staff), 
and contributing to the intervention integrity and fidelity assessment. They will also lead the 
training of field staff (e.g. ethics and data collection) and lead coordination of study protocol 
development for the investigative team.  
 
The Data Analyst will support Dr. Williams (Co-I) in performing statistical analysis in Aim 1.  
 
Cornell University  

 
In Aim 3, identifying intervention-related resources and the comprehensive economic evaluation 
will be led by Dr. Jalali (Sub-contract PI) with guidance from Dr. Murphy (Co-I). Specifically, the 
Cornell team will ensure that site-specific information is collected to inform the tailored micro-
costing questionnaire for the trial; control for potentially confounding factors in multivariable 
regressions and identify relevant factors for sensitivity analyses; tailor statistical methods to 
accommodate site heterogeneity; appropriate price weights for resources required to implement 
and continually manage each strategy; and conduct a comprehensive economic evaluation of 
the intervention. 
 
Each site and collaborating investigators/study teams will be responsible for all study 
procedures, including but not limited to: recruitment, consent, data collection, and data storage 
and shipment. WCG will be the IRB of Record for the study and therefore will submit all protocol 
documentation for review and approval and will be responsible for reporting any updates and/or 
events that occur throughout the study procedures. Data will be collected and stored at both 
sites (NKI and FRI) with FRI periodically sending the data to NKI. Any process measures 
pertaining to the text messaging tool will be collected and stored at FRI in partnership with the 
HIPAA compliant texting vendor, QliqSOFT.  

 
Study Synopsis 
Black and Latinx people who use opioids (PWUO) bear a disproportionate burden of opioid 
overdose deaths. The economic burden faced by Black and Latinx PWUO has also risen due to 
costs associated with excess mortality and utilization of high-cost healthcare services. 
Compared to White PWUO, Black and Latinx PWUO are less likely to be initiated on 
buprenorphine in emergency department (ED) settings and establish care in primary care for the 
treatment of opioid use disorder (OUD). Racial disparities among PWUO in primary care are 
driven by social determinants of health (SDH; e.g., lack of peer support or health insurance) and 
may be partially addressed by adopting innovative mobile health and peer coaching strategies.  
 
With NIH support, we have validated a theory-driven, artificial intelligence (AI)-driven texting tool 
using natural language processing to facilitate real-time text responses to patient queries 
combined with automated texts facilitating receipt of buprenorphine in office-based opioid 
treatment (OBOT) and social services that address social determinants of health (SDH). This 
open-source texting tool offers passive reminders, informational content, and interactive two-
way response algorithms without personal staff contact. In addition, we have adapted an 
efficacious cultural and structural humility training for PRCs that goes beyond SDH to also 
address stigma reduction, discrimination, health habitus, and patient navigation to enhance 
uptake of primary care and social services for PWUO.  
 
Using a three-arm, comparative effectiveness trial design, our specific aims are to: (1) Assess 
the efficacy of PRC supported text-based care/services coordination with PWUO + AI-driven 
SDH-enhanced text messaging (intervention arm-1) vs. AI-driven SDH-enhanced text 
messaging only (intervention arm-2) vs. TAU or printed social/medical services referrals 
(control) to enhance the receipt of buprenorphine in OBOT among community and ED-enrolled 
Black / Latinx PWUO (N=252); (2) Evaluate the implementation of the multimodal intervention 
(arm-1) guided by the RE-AIM and CFIR frameworks using in-depth interviews among 3 
stakeholder groups: (a) frontline providers (n=10); (b) administrators (n=10); and (c) a subset of 
the Black and Latinx PWUO from the multimodal intervention arm-1 (n=30); and (3) Identify the 
resources and estimate the associated cost of implementing and sustaining the multimodal 
intervention and incorporate this information into a customizable budget-impact tool and conduct 
a comprehensive economic evaluation to calculate the relative economic value (e.g., cost-per 
quality-adjusted life years, cost-per OUD treatment days) of each study arm from the healthcare 
sector, state policymaker, and societal perspectives which will also inform implementation 
framed by RE-AIM.  
  
 
 
 

 
Study Timeline 
 
Study Activity 
Year 1 
Year 2 
Year 3 
Year 4 
Q
1 
Q
2 
Q
3 
Q
4 
Q
1 
Q
2 
Q
3 
Q
4 
Q
1 
Q
2 
Q
3 
Q
4 
Q
1 
Q
2 
Q
3 
Q
4 
Survey development 
• 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
IRB approval 
• 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hiring and staff 
development 
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Aim 1: Surveys (n=252) 
- 
Assess efficacy 
of PRC-patient 
text contact + 
AI-driven text 
messaging  
- 
vs. AI-driven 
text messaging 
text messaging 
only  
- 
vs. TAU (i.e., 
printed 
social/medical 
services 
referrals) 
  
  
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
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Aim 2: In-depth 
interviews (n=40) 
- 
Evaluate 
implementation 
of the 
multimodal 
intervention 
  
  
  
  
  
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
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Aim 3: Cost-
effectiveness analysis 
  
  
  
  
  
  
  
  
• 
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• 
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• 
• 
• 
Quality Control 
  
  
• 
• 
• 
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• 
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• 
• 
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• 
• 
• 
• 
• 
Data Analysis 
  
  
• 
• 
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Data dissemination: 
scientific meetings, 
manuscript development 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
• 
• 
 

 
Study workflow 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Candidate enters ER and identified in 
EMR by study team (+opiates in urine) 
Eligibility determined via 10 minute 
mobile screener + consent 
Randomization (via random block design) 
+ Baseline Data Collection Session  
AI Texting Only 
(intervention arm-2) 
Phone number logged into 
software dashboard 
Participant receives passive 
reminders and supportive 
content 
Participant can query software 
for educational and clinical 
/social services content  
Access to health system 
smartphone app EMR portal 
Data collection via REDCap 
AI texting + peer texting 
(intervention arm-1) 
Phone number logged into 
software dashboard 
PRC text check-ins x3/week + 
active reminders and supportive 
content 
Participant can query software for 
educational and clinical/social 
services content  
Access to health system 
smartphone app EMR portal 
Data collection via REDCap 
Intervention activities conducted for 6 
months post-randomization 
Baseline, 3-, 6-, 12-month 
assessments conducted over 1-year 
data collection period 
Study Withdrawal 
Treatment Dropout 
Loss to Follow-up 
Treatment as Usual 
(Control Arm) 
Informational pamphlets on 
clinical and social services 
Access to health system 
smartphone app EMR 
portal 
Data collection via REDCap 
Study participants debriefed @ 12-
month visit; given treatment 
access/retention info and counseling; 
and linkage to social services 
Candidate approached in community 
by study team (+opiates in urine) 

 
 
Introduction 
 
Aim 1 will proceed in the last 6 months of Year 1. Study start-up, including IRB approval, training 
of research staff, ClinicalTrails.gov registration, and deployment of our AI texting system will 
proceed for the first 3 months of Year 1. Enrollment of the first patient-participant will occur at the 
end of the second quarter and will continue until the first quarter of Year 3. Longitudinal data 
collection will end in the first quarter of Year 4. Initial analyses for Aim 1 will begin at the end of 
Year 4. A manuscript reporting the results of Aim 1 is expected in Year 4. Study close-out, 
including submission of results through ClinicalTrials.gov, is also expected in Year 4. 
 
Aim 2 will begin in the second quarter of Year 2. Participants will be recruited to undergo in-
depth interviews (n=50) which will occur until the beginning of Year 4. Aim 2 analysis will 
culminate in publications in Year 4. 
 
Aim 3 will begin in the second half of Year 1, with the economics team working alongside the lead 
team to complete local and sIRB applications. Site visits to identify resources (labor, materials, 
etc.) required for implementation will also begin in Year 1 and will continue into Year 2. Additional 
Year 2 activities will consist of the development of a site-level budget impact tool; identification of 
appropriate price weights for the aforementioned resources; and estimation of implementation 
costs. In Year 3, the econ team will follow-up with the sites to identify the resources required to 
sustain the intervention; estimate the associated sustainment costs; conduct an environmental 
scan; and tailor statistical methods to accommodate site heterogeneity. In Year 4, the economics 
team will complete the tasks begun in prior years, and ensure that analyses are complete, 
manuscripts are prepared, and findings are disseminated in a timely manner. A manuscript 
regarding the required implementation and sustainment costs is expected in Year 4 quarter 1, 
and the comprehensive cost-effectiveness analysis manuscript is expected at the end of Year 4. 
 
Background 
 
Office-based opioid treatment (OBOT) is effective in reducing opioid overdose1–4. However, few 
primary care physicians prescribe buprenorphine relative to rising overdose deaths, particularly 
in Latinx and Black American (henceforth Black) communities5,6. Treatment drop-out in OBOT 
remains high among Black (85.1%) and Latinx (84.5%) patients compared to White patients 
(31.8%) at 1 year7–9 and is attributed to cultural and social determinants of health (CSDH; e.g., 
racism, social isolation, food insecurity)10–12.        
Since the COVID-19 pandemic, racial disparities among PWUO has markedly worsened13. 
Opioid overdose deaths among Black / Latinx PWUO are disproportionately higher despite lower 
rates of opioid use disorder (OUD) compared to White adults14–19 and are exacerbated by 
systemic racism20–26. During 2020 in NYC, Black / Latinx communities endured high rates of 
overdose deaths (e.g., Harlem: 56/100,000 persons, Bronx: 49/100,000 persons) compared to 
their White counterparts (28.7/100,000 persons)27. Nationally, racial disparities persist in the 
provision of OUD treatment services among PWUO in emergency department (ED) settings28,29.   
Integrating telemedicine and mHealth in OBOT offers an evidence-based approach to 
easing access to buprenorphine30–34. Our prior findings during COVID-19 among Black / Latinx 
PWUO revealed: 1) major reductions in OUD and social services in NYC; 2) preferences among 
NYC H+H administrators, clinicians, and community pharmacists to expand access to 
telemedicine-delivered buprenorphine treatment in primary care among ED and community 
referrals35–38; and 3) feasibility of integrating AI-driven texting to facilitate receipt of buprenorphine 
and naloxone during telemedicine and in-person primary care visits35,39,40. 

 
AI-driven texting offers an innovative approach for remote monitoring of buprenorphine 
treatment recruitment and engagement with social services. SAMHSA Physician Clinical Support 
System challenges identified by our team included managing medication dosing and coordinating 
social services referrals41. Further, providers rely on patient-initiated calls to staff to resolve clinical 
and administrative issues that are rarely used by patients35,38,42,43. Texting is cost-effective in 
scaling patient-provider communication and reducing substance use44–47. Studies conducted by 
our team revealed: 1) low rates of acceptability for smartphone applications (30%) versus texting 
(82%) to reduce illicit opioid use38,48; 2) absence of evidence-based smartphone apps supporting 
PWUO seeking OUD service49–51; 3) texting as the most popular mobile phone feature nationally 
and among underserved Black / Latinx PWUO38,52–55; 4) prolific input by Black / Latinx PWUO 
participants informing the scripting of over 650 texts and delivery preferences (e.g., timing, 
frequency) to enhance OUD outcomes56–61; 5) no prior participant mobile phone privacy issues 
due to our adoption of federal privacy safeguards; and 6) feasibility of integrating the proposed 
texting tool to enhance receipt of social services addressing SDH and OBOT entry among 
community and ED-referrals62. The AI-driven texting tool aligns with key objectives outlined in 
SAMHSA and CDC guidelines to scale sustainable, patient-centered, and risk mitigation 
strategies that enhance uptake of evidence-based interventions in primary care among Black / 
Latinx PWUO33,41,63–68. The text message content (650+ texts) and delivery frequency is based on 
extensive mixed-methods studies demonstrating minimal burden among participants56,58,60,61. 
SDH-focused cultural and structural humility (CSH) training for peer recovery coaches 
(PRCs) is uniquely positioned to address racial disparities among PWUO69,70,71. Per SAMHSA 
and consensus guidelines, PRCs with lived experience of OUD72 are effective in coordinating 
OUD and social services referrals for peers with these conditions73–75. Our CSH training 
addresses stigmatization of PWUO and can enhance access to primary care by focusing on: 1) 
the cultural and social determinants of health and health outcomes, including OUD; 2) the health 
burden of intersectional stigma (e.g., explicit and implicit bias facing racially minoritized PWUO); 
and 3) strategies for PRCs to establish boundaries while providing support to PWUO that is 
informed by their own recovery experiences.  
Economic evaluations of treatments and services for PWUO provide necessary data to 
inform decision-making by stakeholders and policymakers. Drs. Jalali and Murphy are leading 
comprehensive economic evaluations in ongoing NIDA trials assessing the impact of medications 
(R01DA045042) and services (including mHealth, R01DA048892) on OUD outcomes on PWUO 
with the clinical team. Similar analyses are proposed here to identify the resources required to 
implement and sustain the proposed intervention and calculate their economic value for 
stakeholders. This proposal will leverage the collaborative research experience gained from the 
completed and in-progress economic evaluations described above, as well as the established 
mentorship between senior (Dr. Murphy) and early-career (Dr. Jalali) health economists, 
supported by the CHERISH research infrastructure at Weill Cornell, to ensure the successful 
completion and scientific integrity of the proposed economic analyses. The economic team has 
extensive experience evaluating health economic outcomes of treatment interventions for PWUO, 
including mobile health interventions with the clinical investigators of this proposal83,108,109,166. 
 
The primary aim of this proposal is thus to determine whether a multimodal intervention that 
combines artificial intelligence (AI)-driven texting that delivers cultural and social determinants of 
health (CSDH)-focused content prioritizing access to social services to enhance receipt of OUD 
services (3-5 texts/daily) in primary care among PWUO combined with peer recovery coach 
(PRC)-supported text-based care/services coordination that ensures real-time responses for 
unanticipated social, administrative, and clinical issues to enhance receipt of social services and 
OUD services (3-4 texts/weekly) can improve receipt of buprenorphine in primary care. j 
 

 
Study Strategy 
 
The proposed three-arm comparative effectiveness trial will evaluate the efficacy of a 
multimodal intervention among community and ED-enrolled Black / Latinx PWUO that combines: 
1) Artificial intelligence (AI)-driven texting that delivers cultural and social determinants of health 
(CSDH)-focused content prioritizing access to social services to enhance receipt of 
buprenorphine (3-5 texts/daily) in primary care among PWUO (intervention arm-2); 2) Peer 
recovery coach (PRC)-supported text-based care/services coordination that ensures real-time 
responses for unanticipated social, administrative, and clinical issues to enhance receipt of social 
services and buprenorphine in primary care (3-4 texts/weekly); and 3) employing a novel and 
evidence-supported Cultural & Structural Humility (CSH) training for PRCs that attends to the 
cultural and social determinants (CSDH) including contending with intersectional stigma and 
discrimination through empowerment/advocacy, health habitus insights, and patient navigation 
(intervention arm-1).  
 
Aim 1 will entail 252 Black / Latinx PWUO screened in the hospital ED and randomized to AI-
driven CSDH-enhanced texting + PRC-supported text-based care/services coordination 
(intervention arm-1) vs. AI-driven CSDH-enhanced texting only (intervention arm-2) vs. TAU 
(control) defined as receipt of printed social/primary care services referrals. Intervention activities 
will span 26 weeks and data collection will include in-person or virtual REDCap surveys at 
baseline-, 3-, 6-, and 12-months, and in-depth interviews following survey period to assess fidelity, 
implementation, and characterization of intervention efficacy.  
 
Primary outcomes: Participants, regardless of study arm, will complete remote and/or in-person 
follow-up assessments at 3-, 6-, and 12-months. The primary outcome for this efficacy study is 
self-reported linkage to OUD services (i.e., time to initial buprenorphine prescription that is 
prescribed in OBOT programs or other OUD treatment providers per the Non-study Medical and 
Other Services form.  
 
Secondary outcomes include durability of treatment effect at 52 weeks (e.g., continuous 
retention in OBOT with buprenorphine), receipt of social services, and longitudinal engagement 
with the proposed intervention (up to 26 weeks) 
 
Aim 2 will evaluate the implementation of the multimodal intervention (arm-2) at 3-, 6-, and 12-
months using RE-AIM and CFIR linked to a public hospital setting offering OBOT with 
buprenorphine. In-depth interviews with frontline providers (n=10), administrators (n=10), and a 
subset of PWUO participants from intervention arm-2 (n=30) will be interviewed to contextualize 
patient-, provider-, and systems-level factors influencing intervention delivery.  
 
Aim 3 will identify resources and cost estimates required to implement and sustain the multimodal 
intervention, incorporate these costs into a customizable budget-impact tool (Aim 3a), and 
conduct a rigorous economic evaluation to calculate the relative economic value of each arm 
(incremental cost / QALY) from the healthcare, state-policymaker, and societal perspectives (Aim 
3b). 
 
  
 
  

 
Successfully harnessing mHealth tools to address primary care clinical outcomes (Aim 1)  
Over the last decade, our team has refined mHealth strategies to address disparities in primary 
care. Our initial findings demonstrated that the adoption of telephone encounters among Bellevue 
primary care providers during Hurricane Sandy in 2012 were not associated with any increases 
in missed appointments (p=0.52) or illicit opioid reuse (p=0.66) at 6 months (N=132)125,126. In 2020, 
our team co-founded the city-wide NYC H+H telemedicine program that provides same-day 
prescribing of buprenorphine and naloxone (N=199)35,42,106. These findings demonstrated that the 
adoption of a multimodal mobile health strategy offers an innovative risk mitigation strategy to 
minimize the impact of disasters on primary care engagement among PWUO.  
Can the multimodal intervention be equitably implemented in clinical care? (Aim 2) 
The RE-AIM and CFIR will be used as process and determinants frameworks that will allow us to 
adapt the intervention in arm 1 as it is unfolding, and guide the evaluation of its effectiveness from 
the perspective of key stakeholder groups197–199. Specifically, we will assess intervention Reach 
(among both PWUO and frontline providers); Effectiveness (defined as PWUO linking with 
primary care-based buprenorphine treatment and social services, and as successful integration 
of PRCs in care teams); Adoption (by providers and administrators); Implementation (assessing 
fidelity of key implementation features and potential intervention adaptations during 
implementation, and resources and costs on a systems-level per administrator interviews and 
economic data analyzed in Aim 3); and Maintenance (assessing whether the intervention 
becomes integrated into routine practice, i.e., assessing the institutionalization of primary care-
based buprenorphine treatment and social services. We will complement RE-AIM with the CFIR 
to evaluate multi-level barriers/facilitators associated with intervention reach, effectiveness, 
adoption, implementation fidelity / adoption, and maintenance. The CFIR76 specifies five main 
implementation determinants, including characteristics of the Innovation being implemented, the 
Outer and Inner Settings in which an intervention is being implemented, characteristics of 
Individuals involved with implementing, delivering, and/or receiving the innovation, and the 
implementation Process.  
How Cost-Effective is the multimodal intervention? (Aim 3) 
For Aim 3, the economic team will work closely with the implementation team to identify and 
collect data on the resources and estimate the associated cost needed to implement and sustain 
the intervention using study data and semi-structured interviews with study staff. The resulting 
information will be incorporated into a customizable budget-impact tool, which will allow the 
economic team to calculate a per participant intervention cost which will be incorporated into a 
comprehensive economic evaluation to calculate the relative economic value (e.g., cost-per 
QALY) of each study arm from the healthcare sector, state-policymaker, and societal perspectives 
at 6- and 12-month time points. The budget impact tool will serve as a publicly available resource 
allowing stakeholders to assess the feasibility and sustainability of the interventions (or similar 
interventions) based on their specific needs and expected costs to their specific setting.  
The economic evaluation will be conducted from multiple stakeholder perspectives. The 
healthcare-sector perspective includes all formal medical costs incurred by the health system 
on behalf of study participants, including the cost of the intervention and patient out-of-pocket 
costs. Since Black / Latinx PWUO are at an increased risk of incurring high healthcare costs85,86, 
evaluating the extent to which increases in treatment-related services may lead to downstream 
cost-offsets via decreases in acute care services is critical for decision-making. The state-
policymaker perspective will be included to inform resource allocation decisions on behalf of 
the public that is often responsible for funding healthcare among vulnerable populations (e.g., 

 
Medicaid)93,94, the direct costs associated with criminal-legal resources, and social safety-net 
programs (e.g., disability/SSI/unemployment).95,96 Further, the societal perspective accounts for 
many of the indirect costs, such as reduced school and labor market outcomes97,98, and costs 
incurred by victims of crime will also be considered99,100.  

 
Study Design 
Aim 1: Does AI texting + peer supported texting improve linkage to OUD services? 
 
To achieve Aim 1, potential study participants with opioid use disorder (OUD) will be identified 
and recruited in the hospital emergency department (ED) and community settings. The study 
team has over two decades of experience enrolling and tracking patient participants in these 
high-risk communities. Each of these cohorts includes people who use opioids who are not 
prescribed any medication for opioid use disorder (MOUD), including methadone or 
buprenorphine, in the 30 days preceding their study enrollment.  
Study settings 
Planned study sites for participant enrollment will include NYC Health+Hospitals affiliated 
hospitals (e.g., Lincoln Hospital), the START Treatment and Recovery centers, and community 
settings associated with high rates of opioid overdose deaths among Black and Latinx adults in 
New York City.   
 
 
The study sample of 252 Black and Latinx PWUO with a positive urine toxicology result per the 
Hospital EMR will be identified by the study team and approached in the ED or in community 
settings among PWUO self-reporting OUD and confirmed with random saliva toxicology testing 
and recruited over a 2-year period and followed for a duration of 12-months with purposeful 
recruitment of male: female adults along a 2:1 target ratio (169 males: 83 females) and a target 
minimum 25% aged 18-29 (see Figure 1). We will use venue-based and street outreach in 
spaces where opioid-related overdose rates are highest, and in neighborhoods where harm 
reduction services are located. 
Potential study participants will be informed of study details by the study team, undergo 
informed consent, complete baseline REDCap assessment, and will then be randomized (1:1:1) 
using a random block design (block sizes 3, 6, 9) to 1 of 3 study arms, stratified by gender. 
Finally, participants will be compensated for their time at visit end and given an appointment 
schedule for in-person or remote survey visits. Randomly selected participants from intervention 
arm 1 (n=30) will be invited for the qualitative implementation interviews (see Aim 2). All 
randomized participants who need a phone will be provided one by the study and tracked over 

 
time by leveraging Drs. Lewis’, Lee’s, and Tofighi’s study tracking and retention expertise in the 
event of changes to mobile phone numbers. 
Participants will be given instructions to complete remote or in-person follow-up assessments that 
will be conducted in one of three data collection sites in Manhattan (i.e., NYS OMH Harlem field 
office site, Lincoln Hospital, and START Treatment and Recovery centers). All potential 
participants will complete informed consent, computer-assisted baseline survey, will be 
administered the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) for OUD by 
the study team to differentiate between participants with OUD versus individuals misusing opioids 
to quell untreated pain symptoms only. Next, participants will be randomized (1:1:1) following a 
random block design (block sizes 3, 6, 9) to interactive texting + Peer Recovery Coach-supported 
text contact, interactive texting only, or TAU, and include stratification by gender. 
 
Study posters and flyers will be developed for distribution in the emergency department and 
community settings.  
Participants randomized to intervention Arm-1 (n=84) will be assigned to receive AI-driven 
CSDH-enhanced texting + PRC-supported text-based care/services coordination. The AI-driven 
texting goals, operational sequences, and content have been iteratively refined in numerous 
studies among Black/Latinx PWUO to ensure optimal adoption (see Table 1)129,131. Text contents 
are based on federal and consensus guidelines on optimizing medical management for PWUO 
with buprenorphine167,168, and addressing CSDH169–171.  Participants randomized to intervention 
Arm-2 will receive the AI-driven CSDH-enhanced text messaging only (as described above; see 
Table 1). Participants in this arm (n=84) will not receive text support from the PRC. Participants 
randomized to control Arm-3 will receive treatment as usual (i.e., verbal instructions, NYC Dept 
of Health pamphlets detailing access to OUD and social services, health system smartphone 
application EMR patient portal). No services will be provided except for social/clinical service 
referrals given at the end of each REDCap visit. 
 
Cohort 
The sample size, N=252, was chosen to provide sufficient power for analyses associated with the 
defined primary outcomes and accounting for 20% attrition. In the absence of normative data, 
based on results of prior studies among emergency department enrolled PWUO that indicate 
modest uptake of MOUD (~5%191), and completing referrals to MOUD services (~25%192-194), we 
compute the power to detect significant effects. Using these estimates as the baseline, we 
anticipate that interactive texting will increase completing referrals to primary care from 25% to 
35%195-197. The combination of interactive texting and PRC support will enhance time to 
completing referrals to primary care from 25% to 45%. These anticipated changes indicate odds 
ratios for intervention versus TAU (effect size) of between 1.5 to 2.0 for OUD-related outcomes. 
We use these estimated odds ratios (ORs) as the proxy for the rate in treatment versus the control. 
Evidence from methodological studies assert a useful equivalence involving the hazard ratio (HR), 
such that when the PH assumption is reasonable, the HR is equivalent to the odds that a randomly 
chosen person with hazard represented in the numerator will experience the event of interest 
before a randomly chosen person with hazard represented in the denominator198-200. The power 
to detect these effects with α=0.05 (two-tailed) using log-rank comparisons for survival outcomes 
via the power procedure in SAS v9.4 is ~80%.  
 

 
 
Enrollment, Consent and Workflow 
Over a 2-year period, Black / Latinx PWUO (N=252) identified in the ED or community by the 
study team using the electronic medical records (EMR) or self-report will be screened and 
enrolled by the study team. Specifically, ED-recruited Black and Latinx PWUOs with a positive 
urine toxicology per the Hospital EMR or self-reporting illicit opioid use among PWUO 
approached in community settings and confirmed with random saliva toxicology testing will be 
enrolled over a 2-year period. Community-recruited PWUO participants will complete enrollment 
in the in private conference rooms located in Lincoln Hospital or START Treatment and 
Recovery centers or in the NYS OMH Harlem field office site. Given the ethical importance to 
expand enrollment of vulnerable and hard-to-reach persons living with substance use, including 
women, unstably housed, and uninsured adults, we will provide reimbursement for peer-driven 
recruitment ($25, max 3 referrals per participant). 
Potential study participants will be informed of study details by the study team, undergo informed 
consent upon discharge, complete baseline REDCap survey, and will then be randomized (1:1:1) 
using a random block design (block sizes 3, 6, 9) to 1 of 3 study arms, stratified by gender. Finally, 
participants will be compensated for their time at visit end and given an appointment schedule for 
in-person or remote survey visits. Randomly selected participants from intervention arm 1 (n=30) 
will be invited for the qualitative implementation interviews (see Aim 2). Of note: All randomized 
participants who do not have a phone will be provided one by the study and tracked over time by 
leveraging Drs. Lewis, Lee, and Tofighi’s expertise in the event of changes to mobile phone 
numbers (i.e., participant tracking).  
 
Recruited Black and Latinx PWUO will be followed for a duration of 12-months with purposeful 
recruitment of male: female adults along a 2:1 target ratio (167 males: 83 females) and a target 
minimum 25% aged 18-29. Follow-up assessments will be conducted in one of three data 
collection sites in Manhattan. Alternatively, we will conduct follow-up interview-administered 
computer-assisted REDCap surveys virtually (video or phone) to mitigate COVID-19 exposure 
and ensure optimal convenience for study participants. Participants lacking mobile phone 
ownership will be provided with a phone and subsidized mobile phone payment plan to ensure 
equal access to participating in the study. The study team will track and record the unique ISBN 
number for phones purchased in the study. In the event that the study team purchases a surplus 
of phones that are not offered to patient participants by the end of the study, these phones will be 
returned to the vendor and a refund receipt will be provided to AHRQ upon request. 
 
PWUO participants will then be encouraged to establish care with OBOT to initiate buprenorphine. 
These OBOT programs are based on the medical management model by initiating eligible 
patients on buprenorphine, naloxone, with referrals to specialty care services (e.g., HIV services, 
psychiatry, hepatology), baseline laboratory testing, and encouragement to engage with self-help 
groups (AA/NA/DA) and psychosocial counseling.  
 
PWUO participants randomized to intervention arm-1 in Aim 1 will receive AI-driven text 
messaging combined with PRC supported text message contact. The PRC will complete SDH-
focused training through the NKI-CCASE Cultural & Structural Humility Training (CSH)71. The 
integration of PRC into health care systems and service settings is effective in improving 
engagement with health care and clinical outcomes among persons with OUD72 and is aligned 
with the recovery movement, and SAMSHA priorities. Key PRC tasks will consist of: 1) reducing 
stigma (internalized, anticipated, and experienced) among PWUO; 2) generating cultural and 
structural humility and self-reflection; 3) enhancing PRC recognition of the cultural and SDH-
formed health habitus and behavior; 4) integrating the health habitus of participants into their text 

 
message-mediated coaching; 5) strengthening PRC-participant rapport and communication; 6) 
bolstering participant navigation skills to ensure optimal engagement with OUD services; and 7) 
establishing meaningful boundaries between PRC and participants to mitigate role conflict. 
Trainings will also enhance PRC awareness of social/clinical services, understanding of overdose 
risk reduction, prevention, and treatment, and addiction training drawn from our earlier work and 
modified to include the use of primary care-based buprenorphine treatment.   
 
Data Gathered 
 
During the screening visit, participants will complete the Screener. At the baseline visit, data 
collection will include Demographics, Locator Form, Urine Drug Screen, Mobile Phone Use 
Characteristics and DSM V OUD Checklist 228.  
 
Semi-structured surveys will be administered at baseline, 3-, 6-, and 12-weeks among PWUO 
participants. These surveys include the Patient-Reported Outcomes Measurement Information 
System (PROMIS)229 and General Anxiety Disorder 7- item scale (GAD-7)227. The Risk Assessment 
Battery (RAB)226 will be collected at 6 and 12 months only. Administrative data will be collected 
from the Hospital EHR or self-report to capture PWUO participant utilization of clinical services 
for exploratory purposes only. Process measures logged in the text messaging software will 
capture PWUO participant engagement with the fully automated AI-driven text messaging tool 
and PRC-PWUO participant text message contact.  
Baseline and follow-up surveys will be identical (with few exceptions i.e., age, sex, race / ethnicity) 
including: Demographic and CSDH characteristics172; and PhenX consensus measures, 
including the Addiction Severity Index174,fatal and non-fatal overdose episodes177,178, 
intersectional opioid-related stigma180, Everyday Discrimination Scale,181 social network 
characteristics182 and Medical Outcomes Study Social Support Survey183, harm reduction and 
social services use184, MOUD and Buprenorphine Treatment and Adherence, and Non-Study 
Medical and Other Services (NMOS) ( See Table 2).  
 
During follow-up, the REDCap Survey will capture Timeline Follow Back interview173 and the 
domains of the Technology Acceptance Model187 (see Figure 2): perceived usefulness, 
perceived ease of use, attitudes, behavioral intentions, and intervention usage. In addition, 
data for each of these components will be derived from:  the texting software (e.g., rate of 
participant responses to software-initiated text queries, number of participant-initiated requests 
for physician telephone assistance53,129,188,189), and through PRC communication logs and 
qualitative interviews to inform fidelity, implementation, and contextualize intervention efficacy, 
enhancing RE-AIM and CFIR frameworks.  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Payment 
 
Participants will receive monetary incentives for their time spent on data collection procedures 
and other study related tasks. Additionally, they will be provided with snacks (granola bars, 
protein bars, jerky, etc.) and coffee during their participation. We will reimburse participants for 
their time and participation in study activities using the Greenphire ClinCard system or a gift card 
of the participant’s choice (e.g., Target, Amazon). Participants in the study will complete surveys 
at baseline/point of study enrollment, and will complete follow-up surveys at 3 months, 6 months, 
and 12 months. We hope to increase participant retention in the study by increasing the subject 
reimbursement rate by $5 increments. Participants will receive $50 at baseline, $30 at the 3-
month follow-up visit, $35 at the 6-month visit, and $40 at the 12-month follow-up visit. 
Additionally, participants will receive a roundtrip MetroCard valued at $6.50 each time they 
complete a survey. The MetroCard cards purchased from the NYC Transit Museum in Grand 
Central will cover roundtrip travel to complete surveys. We anticipate that some participants will 
be lost to follow-up. Thus, we intend to survey 252 individuals at baseline, 202 at the 3-month 

 
follow-up visit, 172 at 6 months, and 155 at the 12-month visit. In Year 2, we will begin to hold in-
depth interviews among 3 stakeholder groups (n=10 frontline providers, 10 administrators and 10 
PWUO selected from among the survey participants randomized in intervention arm 1). The 
frontline providers and administrators will receive $75 for their time and is commensurate with the 
average of the combined standard salaries for social workers, physicians, and nurse practitioners.   
We employ previously approved compensation structures to promote retention in study 
participation during the full longitudinal period. Payments will not be tied to primary outcomes.   
 
 
Year 1 
Year 2 
Year 3 
Year 4 
Baseline Survey 
($25) 
$25 x 44 
= $1,100 
$25 x 84 
= $2,100 
$25 x 84 
= $2,100 
$25 x 40 
= $1,000 
3-month Survey 
($30) 
$30 x 17 
= $510 
$30 x 68 
= $2,040 
$30 x 68 
= $2,040 
$30 x 47 
= $1,410 
6-month Survey 
($35) 
$0 
$35 x 58 
= $2,030 
$35 x 56 
= $1,960 
$35 x 58 
= $2,030 
12-month Survey 
($40) 
$0 
$40 x 28 
= $1,120 
$40 x 52 
= $2,080 
$40 x 52 
= $2,080 
Totals 
$1,670 
$7,290 
$8,180 
$7,453 
 
 
Participants randomized to TAU will receive similar payments at the same time points as 
participants in the intervention arm-1 and arm-2 groups. At the completion of each of the follow-
up sessions all participants are compensated for their time. 
  
Proposed Analyses 
Aim 1 is a 3-year RCT involving community and ED-enrolled Black / Latinx PWUO who will be 
screened and enrolled (N=252) Primary outcomes will be based on remote and/or in-person 
follow-up assessments at 3-, 6-, and 12-months and consists of self-reported linkage to primary 
care-based OUD services (i.e., time to initial receipt of buprenorphine in primary care). 
Secondary outcomes include durability of treatment effect at 52 weeks (e.g., continuous 
retention in OBOT with buprenorphine), receipt of social services, and longitudinal engagement 
with the proposed intervention (up to 26 weeks). 
Our primary hypothesis is that the rate of linkage to OBOT, i.e., time to first 
buprenorphine prescription, will be highest among PWUO participants randomized to texting + 
PRC, followed by those randomized to texting only, then to TAU. To assess this hypothesis, we 
will utilize Cox proportional hazards (PH) regression to investigate differences in time to service 
linkage (in days) by intervention group. Cox PH regression is a method for investigating the effect 
of several variables on the time to a specified event170. Cumulative hazards functions for the 
intervention groups will be examined using Nelson-Aalen plots and use the supremum test which 
uses martingale residuals to check the proportional hazards assumption. If the assumption is 
violated such that there is no difference in the direction of the association but there is variation in 
the magnitude of the association, i.e., the hazards ratio (HR) changes over time, then the 
coefficient that we estimate for that covariate is akin to an ‘average effect’ over timepoints that 
are observed in a dataset and the Cox PH model will perform moderately. If the hazards cross, 
i.e., a change in the direction of the association, the Cox PH model will perform poorly, and we 
will extend the Cox model to allow for nonproportional hazards using time dependent covariates. 
Intervention group as assigned will be the sole explanatory variable in the models (see 
Methodological Considerations and Alternatives). 

 
Secondary and exploratory analysis will rely on data collected at 3-, 6-, and 12-month 
follow-up surveys that will permit analysis of secondary outcomes of: (1) durability of treatment 
effect at 52 weeks (e.g., continuous retention in OBOT with buprenorphine); (2) engagement with 
social services; and (3) longitudinal engagement with the proposed intervention (up to 26 weeks). 
For these analyses, we will use generalized linear mixed effects regression to model binary 
outcomes indicating longitudinal engagement in 26-week treatment (yes/no) and continuous 
retention in buprenorphine treatment at 3-, 6-, and 12-months (yes/no) with no more than a 28-
day gap in receiving an active buprenorphine prescription over each period. These models will 
include a participant-specific random intercept to account for the repeated-measures structure of 
the data.  
Methodological Considerations and Alternatives: To assess whether randomization 
was successful, we will compare the distribution of demographic characteristics, PhenX 
consensus measures, medical/psychiatric history, technology use patterns, and risk behavior 
variables (see Data Collection) by intervention arm. Variables contributing to baseline imbalance 
will need to be included as adjustment variables in regression models.  
Missing Data and Sensitivity Analysis will rely on ensuring that the model assumption 
of non-informative study dropout or missing at random is reasonable and avoid potential bias, we 
will compare dropout rates between intervention groups as well as other measured variables, e.g., 
medical/psychiatric history, technology use patterns, and risk behavior variables. If there is 
empirical evidence of nonrandom dropout, we will model the dropout event using available factors 
to identify and estimate their influence. To meet missing at random model assumption, variables 
that predict dropout will be included as auxiliary variables via multiple imputation.  
Intervention fidelity is an important consideration with “real world” research 
interventions. Lack of fidelity can increase the possibility of a type I or II error and make study 
findings difficult to interpret. Certain study design considerations are incorporated to support 
intervention fidelity, e.g., use of a standardized, established training for PRCs, collection of 
important study measures like PRC-participant communication logs. In the data analysis, we will 
confirm that the intervention is received in the same way within each intervention arm across 
participants and through time by comparing type and frequency of topics discussed as well as 
process measures (see Data Collection); we will also compare fidelity metrics by participant 
characteristics. In the unlikely event that we do not observe an intervention effect, participant data 
on social determinants, risk behaviors, patient-centered care, clinical and social services use, and 
technology use will be instrumental in the interpretation of study findings and recommendations 
for practice. 
The sample size, N=252, was chosen to provide sufficient power for analyses associated 
with the defined primary outcomes and accounting for 20% attrition. In the absence of normative 
data, based on results of prior studies among emergency department enrolled PWUO that 
indicate modest uptake of MOUD (~5%191), and completing referrals to MOUD services (~25%192-
194), we compute the power to detect significant effects.   
 
 
 
 
 
 
 
 
 

 
Aim 2: Can the multimodal intervention be equitably implemented in clinical care? 
 
Aim 2 is designed as a study of multi-perspective stakeholder feedback (N=50) of our proposed 
multimodal intervention to inform how best to integrate this approach into care teams using the 
RE-AIM framework to guide the evaluation of the intervention177–179. Our sample size is driven by 
qualitative methods. We propose to recruit frontline providers (n=10), administrators (n=10), and 
a subset of PWUO participants randomized to intervention arm-1 (n=30) for a total N=50.  
 
The RE-AIM and CFIR will be used as process and determinants frameworks that will allow us to 
adapt the intervention in arm 1 as it is unfolding, Additionally, they will be provided with snacks 
and coffee during their participation. and guide the evaluation of its effectiveness from the 
perspective of key stakeholder groups197–199. Specifically, we will assess intervention Reach 
(among both PWUO and frontline providers); Effectiveness (defined as PWUO linking with 
primary care-based buprenorphine treatment and social services,  and as successful integration 
of PRCs in care teams); Adoption (by providers and administrators); Implementation (assessing 
fidelity of key implementation features and potential intervention adaptations during 
implementation, and resources and costs on a systems-level per administrator interviews and 
economic data analyzed in Aim 3); and Maintenance (assessing whether the intervention 
becomes integrated into routine practice, i.e., assessing the institutionalization of primary care-
based buprenorphine treatment and social services (see Table 3). 
We will complement RE-AIM with the CFIR to evaluate multi-level barriers/facilitators associated 
with intervention reach, effectiveness, adoption, implementation fidelity / adoption, and 
maintenance. The CFIR76 specifies five main implementation determinants, including 
characteristics of the Innovation being implemented, the Outer and Inner Settings in which an 
intervention is being implemented, characteristics of Individuals involved with implementing, 
delivering, and/or receiving the innovation, and the implementation Process.  
 
The RE-AIM and CFIR assessments will be based on the REDCap survey, EHR data (see Table 
2), PRC communication logs and qualitative longitudinal interviews with PWUO, frontline 
providers (including PRCs), and administrators. These findings will capture data on the processes 
of intervention implementation as they occur, and the reasons why they unfolded in particular 
ways at the individual, interpersonal (e.g., PRC-PWUO), and system-levels (see below for details 
on Interview Guide).  

 
 
Approach  
In-depth qualitative interviews will be conducted remotely using the HIPAA-compliant WebEx 
platform or in-person for PWUO participants with limited internet access. A key feature of the 
stakeholder groups is the between- and within-group heterogeneity (i.e., varying roles in 
intervention/responsibility/authority) that will enrich the interview data feedback on the relevance 
and utility of the intervention. These findings will enable us to evaluate the multimodal intervention 
from multiple perspectives and thus, better tailor it to the needs of all key stakeholders. There is 
also heterogeneity within each stakeholder group that can enrich the interviews. For instance, we 
will interview providers across the hierarchy from PRC to clinicians, and administrators, whereas 
in the PWUO sample, we anticipate some variety in treatment histories, structural barriers to care, 
technology savvy, and importantly, involvement, perceived benefit, and longitudinal engagement 
with the intervention.  
Key CFIR topics incorporated in the PWUO interview guide to contextualize experiences with 
the intervention will include: 1) the intervention components, including ease or complexity to 
use, advantages and disadvantages relative to previously utilized OUD services, compatibility 
with participants’ daily lives, barriers to sustained engagement, and participants’ interpersonal 
interactions with the PRCs; 2) experiences with the inner settings of the social and clinical 
service organizations that participants were referred to and/or engaged with during the 
intervention, including stigma/discrimination, perceptions of the culture- and person-centeredness 
of the settings, and perceptions of the structural barriers and resources available to meet their 
needs (e.g., inclusive eligibility for services, timely appointments, care coordination/linkages, 
trauma-informed clinic/office design); 3) the outer settings in which participants live, including 
neighborhood safety and social barriers that influence OUD and that influence engagement with 
OUD services  (e.g., OUD stigma in the community, telephone/internet access, peer support); 4) 
individual characteristics, including histories of opioid use and overdose, accessing OUD and 
social services; and 5) the implementation process, including interactions with the study team 
for recruitment and intervention delivery, as well as recommendations for improving intervention 
reach, effect, fidelity/adaptation, adoption and maintenance to overcome barriers that are 
identified throughout the interview. Frontline provider and administrator guides will cover: 1) the 
intervention components, including their ease or complexity to be integrated into routine care, 
their advantages and disadvantages relative to implementing other programs, intervention 
adaptability to local contexts, costs, and modifications made during the project. PRCs will also 
provide feedback on interactions with PWUO participants; 2) the inner settings of the 
participating institution, including PRC integration challenges into care teams (from both the PRC 
and other providers’ perspectives), leadership support for the interventions, the degree of fit 
between the intervention and institutional missions/values, and institutional challenges providing 
primary care-based buprenorphine treatment (e.g., administrative, resource-related obstacles); 3) 
the outer settings of participating institutions, including potential barriers/facilitators to promote 
intervention reach in primary care,  regulatory barriers/facilitators towards delivering OUD 
services; and perceptions on how CSDH impacts PWUO and their engagement with OUD and 
social services; 4) individual characteristics, including perceptions of, and experiences with, 
providing care for underserved Black / Latinx PWUO; and 5) the implementation process, 
including interactions with MPIs for intervention training, and feedback for improving intervention 
reach, effect, fidelity, adoption and maintenance. 
 
Data Analysis 
The analysis of the qualitative interviews will begin alongside the data collection. This will enable 
the timely identification of intervention implementation limitations and enable course correction as 
the study is unfolding. The interview transcripts will be content analyzed using a 7-step process 

 
developed over the years by our team120,122,148,204. This process allows for a systematic 
identification of subcode, codes and themes while keeping the data contextualized. Specifically, 
we will complete the following tasks: Step 1, identify the principal issues discussed by participants; 
Step 2, construct preliminary definitions of the analytic themes; Step 3, develop and apply core 
codes and subcodes to the initial set of interviews at each interview round. Blocks of text within 
text tagged with core codes will be assigned subcodes; Step 4, develop a provisional coding 
scheme; Step 5, test the provisional coding scheme by coding new transcripts; Step 6, reconcile 
coding differences and construct a final coding scheme; and Step 7, apply the coding scheme to 
the full dataset. Close reading of the coded interview transcripts will reveal data patterns withing 
each sample, but importantly, also highlight differences/similarities across the stakeholder groups 
that will inform intervention adaptation. For instance, an emerging qualitative data pattern midway 
through the data collection process (i.e., 6-month assessment) could be that PWUO are 
encountering regulation barriers and strongly recommend changes in guidelines that will afford 
them flexibility in enrollment and referrals to better engage PWUO in care. This lack of flexibility 
might also emerge in the administrators’ interviews. This prismatic assessment of the intervention 
will enable us to draw inferences that will inform the refinement of the intervention as it unfolds. 
Qualitative findings from PWUO participants (N=30) will be analyzed in tandem with: a) the PRC 
notes on CSDH for these participants (i.e., the health habitus note); b) their electronic 
administrative data, EHR data (e.g., primary care missed visits); and c) their REDCap survey data 
(baseline, 3-,6, and 12-month follow up). For instance, we will analyze whether PWUO with 
numerous patient-initiated requests for telephone assistance from physicians (based on 
Participant Feedback Survey; a domain in the REDCap survey) who also report patient-
centeredness will also be consistently engaged with the different features of the multimodal 
intervention. Such a triangulation of data conducted over time will inform intervention 
effectiveness and maintenance. Findings from the PRCs’ interview data will be analyzed in 
tandem with: a) the downloaded PRC-PWUO participant text exchanges in intervention arm-1; b) 
the training and supervising notes of the MPIs as part of their PRC CSDH training and supervision; 
and c) notes from weekly research meetings pertaining to PRC experiences and their integration 
in care teams to add to the rigor of the intervention’s assessment. 
Intervention feasibility, fidelity and adaptation. Intervention feasibility will be assessed by 
examining fidelity to core components of the intervention (e.g., linkage to primary care-based 
buprenorphine treatment) and implementation strategies (e.g., training for PRCs in cultural and 
structural humility). Importantly, we will also examine any necessary intervention adaptations and 
the reasons for these changes, via the qualitative interview analysis. Again, we will employ 
different forms of data, including the PRC-PWUO participant text exchanges. Specifically, 10% of 
PRC-PWUO participant text exchanges will be reviewed among participants (n=25) providing 
written consent to this process to assess for consistency with CSDH-focused CSH training 
principles during the first two months following enrollment. Intervention fidelity will also rely on 
periodic reviews of the PRCs’ notes to determine if they have elicited the cultural and social 
barriers and facilitating factors influencing PWUO engagement with services and how they are 
integrating these insights into their text exchanges with participants. Lastly, three cycles of in-
depth interviews with administrators, frontline providers including PRCs and PWUO participants 
in intervention arm 1 will assess intervention implementation as it unfolds in real time and inform 
modifications to the AI-driven texting algorithm and/or PRC training. The risk of contamination 
across intervention conditions is minimal given its technology mediated nature. However, to 
minimize this risk, study participants will be asked not to share any study content or experiences 
with peers. Potential contamination will also be assessed by asking participants if they heard 
about the study or knew any participants prior to entry. 
 
 

 
 
Aim 3: How Cost-Effective is the multimodal intervention?  
Aim 3 is an economic evaluation of the proposed multimodal intervention using well-established 
guidelines of prospective economic evaluations alongside clinical trials.102,194,195 Outcome 
measures will be analyzed using multivariable generalized-linear mixed models (GLMMs) to 
adjust for potential confounding factors and the skewed distributions commonly associated with 
healthcare cost data and censored outcomes (e.g., QALY).195 The GLMM, an extension of the 
GLM, allows the most appropriate mean and variance functions to be chosen based on the 
observed data,195 as well as for the inclusion of random effects.202  The primary outcomes for Aim 
3a will be the budget impact tool consolidating the resources and associated costs required 
to implement and sustain the PRC-participant text contact + interactive text messaging, and 
interactive text messaging only interventions compared to TAU. The primary outcome of Aim 3b 
will be the incremental cost-effectiveness ratio (ICER),194,195 defined here as the incremental 
mean cost between the two intervention arms and TAU divided by the incremental mean 
effectiveness (QALY and OUD treatment days) of the two arms calculated separately. HRQoL is 
increasingly recognized as a key indicator of patient well-being that is not captured in clinical 
measures. The QALY is a measure that combines the HRQoL associated with an individual’s 
health state and their time spent in that state.102,194,195 The QALY is recommended as the 
primary effectiveness measure in economic evaluations due to its ability to be compared 
across interventions and disorders, and its association with commonly-accepted value thresholds 
(i.e., cost-per-QALY).194,195 OUD treatment days is an important continuous measure of 
effectiveness for clinical stakeholders and calculating cost-per-OUD treatment days enables 
comparisons with prior published economic evaluations of OUD interventions reporting similar 
clinical effectiveness measures.112 As part of the process of estimating ICERS, we will be able to 
test the 6- and 12-month post-intervention differences between arms of a) the average total costs 
to the healthcare sector, state policymaker, and society by resource categories; and b) the 
average QALYs and OUD treatment days; thus, two ICERs will be calculated for each of the three 
stakeholder perspectives for each of the aforementioned evaluation periods. 
 
Health Economic Measures 
 
Health-Related Quality of Life (HRQoL) will be measured using the validated Patient-Reported 
Outcomes Measurement Information System (PROMIS)–Preference (PROPr) instrument.232–234 
PROMIS (including PROPr) was developed using item response theory (IRT), with support from 
the NIH. Because of its IRT foundation, PROPr is more flexible, and improves upon common 
deficiencies of alternative HRQoL instruments.235 The PROPr scoring system uses the 
respondent’s scores for each of the following domains to calculate a HRQoL index value that 
represents the general US population’s preference for a respondent’s health state: Cognitive 
Function–Abilities, Depression, Anxiety Fatigue, Pain Interference, Pain Intensity, Physical 
Function, Sleep Disturbance, and Ability to Participate in Social Roles and Activities.236,237 HRQoL 
values produced by PROPr range from -0.022 to 1, where 0 represents death, 1 represents 
perfect health, and values below 0 represent states perceived to be worse than death. The HRQoL 
value is then used to calculate regression-adjusted QALYs per study arm as our team and others 
have done in similar studies.103,122–125,238 
 
Healthcare, Non-Medical and Other Services. The utilization of healthcare services by 
participants will be measured using study data and the Timeline Follow-Back (TLFB)191 
methodology via the Non-study Medical and Other Services (NSMOS) form. Healthcare services 
will include inpatient, outpatient, telehealth, and ED services; opioid use disorder treatment 

 
medications, and residential and outpatient substance use disorder treatment days; hospital 
detoxification days; and mental health treatment visits. The reliability and validity of self-reported 
data is well established over recall periods similar to those in this proposal196,204,239–241. Non-
medical and other resources required to determine the costs from the state policymaker and 
societal perspectives (e.g., recidivism, workplace productivity, etc.) will be collected via the 
NSMOS form, Addiction Severity Index – Lite (ASI), and other study instruments. The NSMOS, 
ASI, and other study instruments have been successfully used by the economic team in prior 
economic evaluation studies122,124,125, and is currently in-use in numerous clinical trials of 
substance use disorder treatments, including those associated with the NIDA Clinical Trials 
Network (CTN) and Justice Community Opioid Innovation Network (JCOIN)120,123,242. 
 
Aim 3 Data Analysis 
 
Aim 3a will involve the development of a customized budget impact tool using implementation-
related data collected by the trial to capture all relevant healthcare resources (see “Intervention 
Costs”) following recommended methods.200 The resource-costing method will be used to value 
all relevant, non-research resources. Resource costing involves determining a per-unit price-
weight for each relevant resource and multiplying the price-weights by the number of resource 
units utilized. The budget impact tool will include 5 Microsoft Excel worksheets, with drop-down 
menus incorporated throughout to increase ease of use, and limit data-entry errors. The first 
worksheet is a dashboard that is automated by linking data from the other worksheets and 
displays the total costs differentiated by resource category identified in the microcosting analysis 
(see Intervention Costs). The remaining worksheets include the various resources that could be 
associated with different OUD treatment models, and their associated unit costs.  Thus, users will 
select the quantity of each relevant resource, change the unit costs if desired and be able to view 
detailed cost estimates by fixed, variable, and time-dependent components.  
 
Aim 3b. Separate multivariable GLMM regressions will be used to estimate predicted mean costs 
for all resource categories (see healthcare resource utilization, non-medical and other resources), 
according to each stakeholder perspective, and then summed with the intervention costs (see 
Intervention costs) to calculate total costs. Thus, the GLMM will be used to estimate predicted 
mean effectiveness measures by study arm for months 6 and 12 after randomization. Final 
predicted costs and effects will be generated using the statistical method of recycled 
predictions;195 and these values will then be used to construct estimated ICERs and cost-
effectiveness acceptability curves will be constructed (see Cost-effectiveness Acceptability 
Curves) to illustrate the probability that a given intervention is cost-effective across a range of 
value thresholds (i.e., cost-per-QALY gained, and cost-per-additional day of OUD treatment).195 
Results will also be disaggregated by sex; for example, research by our CHERISH colleagues 
suggests that outcomes derived by measures of HRQoL (i.e., QALYs) differs by sex among 
individuals receiving medication treatment for OUD.203  P-values and 95% confidence intervals 
will be estimated using nonparametric bootstrapping techniques within the multivariable GLMM 
framework,195 to account for sampling uncertainty.  
 
Determining Cost-effectiveness. A health intervention is considered cost-effective if the value 
of the ICER falls below the stakeholder’s willingness-to-pay value for each unit increase in 
effectiveness measures (QALYs, OUD treatment days). We will determine if PRC-participant text 
contact + interactive text messaging, and/or interactive text messaging only is cost-effective 
compared to TAU using the generally-accepted willingness-to-pay threshold range of $100,000 - 
$200,000 per QALY gained204, and evaluate the confidence of that assessment by calculating the 
cost-effectiveness acceptability curves (CEAC).205 The CEAC displays the probability that the 
ICER would fall below a given willingness-to-pay threshold, i.e., the likelihood that the intervention 

 
is considered cost-effective, across a range of values per QALY and treatment outcomes. We will 
calculate CEACs using the distribution of cost and effectiveness parameters obtained from the 
recommended non-parametric bootstrap procedure.102,195, 201 
Missing Data and Sensitivity Analysis in Aim 3b will be addressed using recommended 
approaches for prospective economic evaluations conducted alongside clinical trials,195 and 
combining such methods within the nonparametric bootstrap based on our recent work.201  We 
will also conduct extensive sensitivity analyses to account for uncertain precision in assumptions 
and parameter estimates applied in the analyses.102 For example, we will test the robustness of 
the results as they pertain to variations in  unit costs, and values estimated using the more robust 
and efficient GLMM regression will be compared to those estimated using the more transparent 
ordinary least squares regression, as well as to the unadjusted mean values.  
 

 
Study Population 
Recruitment 
Emergency department and community recruitment of Black / Latinx PWUO in Aim 1 will 
involve identifying potential study participants with opioid use disorder (OUD). A sample of 252 
community and ED-recruited Black and Latinx PWUO will be recruited over a 2-year period and 
followed for a duration of 12-months with purposeful recruitment of male: female adults along a 
2:1 target ratio (169 males: 83 females) and a target minimum 25% aged 18-29 (see Figure 1).  
 
 
Potential study participants approached by the study team will be informed of study details, 
undergo informed consent, complete baseline REDCap assessment, and will then be 
randomized (1:1:1) using a random block design (block sizes 3, 6, 9) to 1 of 3 study arms, 
stratified by gender. Finally, participants will be compensated for their time at visit end and given 
an appointment schedule for in-person or remote survey visits. Randomly selected participants 
from intervention arm 1 (n=30) will be invited for the qualitative implementation interviews (see 
Aim 2). All randomized participants who need a phone will be provided one by the study and 
tracked over time by leveraging Drs. Lewis’, Lee’s, and Tofighi’s expertise in the event of 
changes to mobile phone numbers. 
Participants will be given instructions to complete remote or in-person follow-up assessments 
that will be conducted in one of three data collection sites. All potential participants will complete 
informed consent, computer-assisted baseline survey, will be administered the Diagnostic and 
Statistical Manual of Mental Disorders-5 (DSM-5) for OUD by Dr. Tofighi to differentiate 
between participants with OUD versus individuals misusing opioids to quell untreated pain 
symptoms only. Next, participants will be randomized (1:1:1) following a random block design 
(block sizes 3, 6, 9) to interactive texting + Peer Recovery Coach-supported text contact, 
interactive texting only, or TAU, and include stratification by gender.   
Our proposed recruitment schedule is highly feasible since prior NIDA-funded trials involving 
recruitment of vulnerable persons who use opioids and other illicit substances in the identified 

 
hospitals resulted in successful enrollment of study samples ranging from 180 - 200 ED-
recruited participants annually, as well as timely completion of all study timelines. As in our 
previous work, participants will be recruited in-person by study staff.   
Study posters and flyers will be developed for distribution in the emergency department using 
input from our entire study team and the NY Statewide Multicultural Advisory Committee in 
which NKI-CCASE has active membership, and comprised of 30-40 behavioral health 
community stakeholders, each representing socially and culturally diverse backgrounds. This 
committee advises the NYS Office of Mental Health on cultural relevance and appropriateness 
of evaluation and training tools, training curriculum, research and practice protocols, and new 
and existing patient/client programs as it relates to representation of diverse populations based 
on race, ethnicity, gender identity, sexual minority identity, and spoken language.  
Eligibility Screening and Enrollment: We anticipate most interested participants will undergo 
a brief in-person 10-minute screener using a mobile application that affords sufficient privacy. 
Once eligibility is determined, study details will be explained to the participant and will be given 
instructions for study enrollment upon discharge from the emergency department, including 
completion of informed consent, baseline assessment (REDCap), DSM-5 for OUD checklist, 
followed by randomization. Participants will receive $25 at baseline, $30 at the 3-month follow-
up visit, $35 at the 6-month visit, and $40 at the 12-month follow-up visit. Participant 
compensation will be delivered via timely deposit to a reloadable debit card using the 
Greenphire ClinCard system, which we have used in both past and ongoing projects. This 
system allows for timely reimbursement of participants completing remote study visits.  
Alternatively, we will provide interviewer-administered computer-assisted REDCap follow-up 
surveys virtually (video or phone) to ensure optimal convenience for study participants by 
mitigating unanticipated barriers to study visit completion. Study participants will also be 
provided with addresses to follow up at any one of the three study offices that is most desirable 
for participants.  
Finally, all PWUO study participants who screen eligible will be characterized on a screening 
contact log sheet which will indicate gender, race/ethnicity, and opioid type which will provide 
data to help gauge those who follow through with study enrollment vs. those who are lost 
between screening and enrollment, baseline, and randomization follow-up visits. This 
information will inform final results of the study with respect to the representativeness of our 
study sample and provide insights to the intervention’s reach (key implementation feature).   
Of note, a select number of PWUO will be drawn from the Aim 1 study participants who were 
randomized to the PRC-supported text contact + interactive text messaging intervention arm-2 
(n=30) to participate in in-depth interviews in Aim 2 lasing approximately 60 minutes. For Aim 2, 
the inclusion and exclusion criteria for PWUO participating in the in-depth interviews (Aim 2) are 
identical to those for Aim 1, since we will recruit a subset of participants randomized in 
intervention arm-1 (n=30). 
 
 
 
 
 
 
 

 
Inclusion/Exclusion criteria  
PWUO Study Participants 
Inclusion criteria: 1) ≥18 years of age; 2) fluent in English; 3) self-reported non-prescription opioid 
use <30 days prior to consent; 4) provision of informed consent; 5) planned stay in NYC ≥12 
month; 6) Black and/or Latinx race/ethnicity; 7) positive urine toxicology for opioids per EMR 
records or study staff administered random saliva drug testing; 8) diagnosis of OUD per the 
Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5); 9) self-reported interest in 
initiating buprenorphine in primary care, or elsewhere; and 10) must have a mobile phone data 
plan. 
Exclusion criteria: 1) inability to comprehend text content written at a 3rd grade reading level; and 
2) physical or visual disability preventing mobile phone use  
 
Retention Plan for PWUO in Aim 1 centers around methods previously utilized by the MPIs in 
their prior NIH-funded studies that have yielded rates of study retention above 80%. 
Components of our planned participant retention strategy include: 1) Completion of a locator 
form at baseline and at all follow-up visits to assist in locating participants in the event of a 
missed study visit (e.g., participant’s current address, email, phone numbers, contact 
information for at least 3 trusted friends/family); 2) soliciting consent to contact the participants’ 
3 trusted contacts as well as health care staff at the study site hospital; 3) providing timely study 
visit telephone call and text reminders; and 4) coordination with trained study staff to conduct 
outreach to assist with in-person searchers at their homes, shelters, or other community sites. 
On the day of a missed study visit, the participant will receive two phone calls and two text 
messages at different times of the day. If there is no response within 24 hours, mailed follow-up 
reminder letters and/or emails will be sent encouraging contact with research staff. If there is no 
contact within 72 hours, the participant’s locators will be contacted at varying hours. Study staff 
will also check for incarceration status using http://www.vinelink.com/, and google.com, 
intellius.com, and spokeo.com for updated contact information. All contact with participants 
and/or their locators will be documented in the Participant Communication Log. No information 
from this form will be used in data analyses. Participants will be offered incentives to respond in-
person or via telephone to ensure improved retention during scheduled study follow-up visits.  
Projected attrition rates  
Projected patient attrition rates for the 12-month study duration are presented in the table below. 
Note that these conservative attrition rates are higher than those we have observed in past 
cohorts engaged with our intervention. We estimated the greatest ‘attrition’ between Intake and 
Month 1, as participants may consent and decline to participate in follow-up assessments or 
decline to continue engagement with the intervention(s).   
Intake 
Month 0 
Month 3 
Month 6 
Month 12 
Attrition % 
-- 
20% 
15% 
10% 
Sample retained (N) 
252 
200 
170 
153 
 
 

 
 
 
 
Frontline provider and administrator participants in Aim 2. 
 
Recruitment of Providers, Administrators, and PWUO in Aim 2 will comprise 50 total 
stakeholders who will represent 3 groups including providers (n=10), administrators (n=10), and 
PWUO (n=30) to undergo in-depth interviews to assess implementation and scale-up upon 
completion of the trial.  
Provider and administrator stakeholders will be enrolled from partnering hospitals and health 
systems. Frontline providers (PRCs, DEA-waivered buprenorphine prescribers, behavioral health, 
and social service providers) and administrators (i.e., departmental supervisors and health 
systems leadership) will be recruited for Aim 2 during the second quarter of Year 2 through the 
end of the third quarter in Year 4.  
The study team will also approach staff employed in outpatient OUD services programs (e.g., 
opioid treatment programs, office-based opioid treatment) who provide methadone and/or 
buprenorphine treatment. Providers will be recruited by full-time research staff working onsite 
conducting study activities.   
Inclusion Criteria 
Frontline provider and administrator: current affiliation with the collaborating hospital or hospital 
system as a DEA-waivered buprenorphine prescriber, and social service provider working with 
PWUO, or departmental supervisors and hospital leadership responsible for programs and 
policies on OUD services.  
 
Inclusion Criteria 
1. Licensed prescriber or administrator employed by the respective site, or at a clinical 
partner of the respective site, where they will act as participants and be part of the 
treatment team 
2. Currently practicing in the treatment of OUD with either Buprenorphine or Methadone; 
3. Able to speak, read, and write English fluently and to provide informed consent in 
English 
 
Exclusion Criteria 
None 
Informed consent 
Patient Participants 
All OUD patients will be consented by the research coordinators, with research training approved 
by the IRB (see sIRB Plan). If participants indicate willingness to be contacted by research staff, 
they will be given the opportunity to read the informed consent document and/or review the 
document with staff.  
Clinician and Administrator Participants. 
All providers will be provided with written consent by research staff to participate in the study. 
They will be given the opportunity to read the informed consent document and discuss any 
potential concerns with staff. 

 
Inclusion of Women and Minorities 
Our study will enroll women and Black and Latinx adult persons who use opioids (PWUO). Opioid 
overdose deaths among Black / Latinx PWUO are disproportionately higher despite historically 
lower rates of opioid use disorder (OUD) compared to White PWUO. There are fewer available 
providers prescribing medications for OUD in underserved Black and Latinx communities. Finally, 
Black and Latinx patients initiating buprenorphine for OUD in emergency department settings 
experience higher rates of loss to follow-up relative to their White peers. Hence, the proposed 
study will focus on community and ED-enrolled Black and Latinx PWUO who carry the highest 
burden of OUD and opioid overdose events. We will use venue-based and street outreach in 
spaces where opioid-related overdose rates are highest, and in neighborhoods where harm 
reduction services are located. 
 
This study will set a target enrollment of 33% women who use opioids. Women experience lower 
rates of opioid use disorder (OUD) treatment utilization versus men since services fail to tailor 
care for women, particularly underserved Black and Latinx women, so their inclusion is critical. 
However, the proposed 2 : 1 ratio (male:female) reflects the distribution of illicit opioid use by 
gender. The proposed multimodal intervention (i.e., AI-driven texting tool, peer recovery coach-
supported text contact) is also suited to address social determinants of health experienced by 
women with referrals to housing, peer support groups, reentry support among criminal justice 
involved women, domestic violence support groups, legal aid, medical services, employment 
training, and other services tailored to underserved women with substance use disorders. No 
PWUO will be excluded or included based on gender identity regardless of biological sex at birth.  
 

 
Study Procedures: Patients 
 
All Patients 
Day 0 
1. Subjects will be enrolled and consented in person. 
 
2. All subjects will complete the following surveys before randomization (3 hours to 
complete): Demographic and CSDH characteristics172; and PhenX consensus 
measures, including the Addiction Severity Index174, Risk Assessment Battery (RAB)279, 
fatal and non-fatal overdose episodes177,178, Disparate Health Care Quality179, 
intersectional opioid-related stigma180, Everyday Discrimination Scale,181 mobile use 
characteristics and Medical Outcomes Study Social Support Survey183,  
 
Table 2 includes REDCap survey data definitions and variables, including: 
● Demographic instrument (age, race, ethnicity, veteran status, legal history, type of 
residence, employment, education); 
● Sociocultural & demographic determinants of health; 
● Clinical interview to ascertain medical and psychiatric/addiction history (family 
substance use history, primary, secondary and tertiary substances, pattern and 
severity of substance use, treatment history, individual and family medical history, 
current health status, prior and current medications, and psychiatric symptoms); 
● Substance use and sexual risk behavior; 
● Clinical and social services use; and  
 
3. Participants randomized to Intervention arms-1 and 2 will have their phone numbers 
entered in the AI texting software dashboard. The AI-driven texting goals, operational 
sequences, and content have been iteratively refined in numerous studies among 
Black/Latinx PWUO to ensure optimal adoption (see Table 1)129,131.  
 
Text content are based on federal and consensus guidelines on optimizing medical 
management for PWUO with buprenorphine167,168, and addressing CSDH169–171 and 
include:  
a. CSDH content, delivered once/day, include: (a) stigma-reduction (e.g., internalized and 
anticipated stigma); (b) social resources identified in our community resources & 
services scan (e.g., peer support groups for PWUO and other minoritized groups); (c) 
educational resources (e.g., GED, vocational training); (d) economic stability (e.g., 
public assistance, employment / vocational services, transportation vouchers); (e) food 
security (e.g., food stamps, food pantries, subsidized farmers markets); (f) free legal 
aid; and (g) emergency housing. 
b. Harm reduction content, sent 2x/week, includes opioid overdose prevention training, 
instructions linking with primary care to receive opioid overdose education, naloxone, 
and instructions to access city-wide harm reduction sites offering sterile syringes, 
naloxone, and supervised injection services if desired;  
c. Motivational enhancement content, sent 3x/week, encourage uptake of OBOT services 
by evoking self-motivational replies and commitments to text prompts, building 
motivation for planned uptake, establishing a plan for uptake, adopting treatment 
adherence and maintenance strategies after confirming uptake per text queries, and 
applying coping strategies for high-risk situations that may precipitate the risk of illicit 
use; 

 
d. Medical Management content tailored to OBOT after confirming entry in treatment using 
2x/week text “check-ins”. Text categories will consist of: (1) Support during induction 
and stabilization to buprenorphine that targets buprenorphine adherence and self-
management with a once daily text at 9:00 am assessing for withdrawal symptoms. For 
a “Yes” response to withdrawal symptoms, participants will receive: (a) instructions on 
buprenorphine and/or comfort medication administration; (b) query for continued opioid 
use; and c) repeat queries at 12:00pm and 6:00pm for cravings and withdrawal 
symptoms. If participants report “Yes” to opioid use, they will be informed of the risk of 
overdose and may request a physician phone call during regular clinic hours (i.e., 
patient-provider communication); (2) Appointment adherence “tips” (e.g., setting 
written/mobile phone calendar reminders) that enhance self-management sent 
1x/week; (3) Supportive content comprise alternating messages between medication 
adherence (e.g., buprenorphine), reinforcement of reducing harmful substance use, or 
12-step meeting and counseling participation (i.e., hotlines, meeting sites / schedules, 
free online resources); (4) Educational content that enhance self-management with 
medication dosing, side-effects, overdose prevention, and online public-facing 
resources;  
e. Instant help allows participants to query the texting software and receive personalized 
motivational enhancement, educational, or clinic/social services contact details via 
menu items and open-ended queries captured by natural language processing to 
enhance patient-physician communication.  

 
 
Intervention Arm-1. Individuals (n=84) will be assigned to receive AI-driven CSDH-enhanced 
texting and PRC-supported text-based care/services coordination. PRC-supported text check-
ins to participants (3x/week) will be provided by 2 PRC study staff in addition to automated AI-
driven texts in intervention arm-1. The PRC will personalize text “check-ins” to participants based 
on: (a) baseline CSDH needs (e.g., food insecurity, legal aid); (b) initial intake visit in primary care 
or challenges with service entry; and (c) content outlined in the CSH training addressing emerging 
participant challenges. The CSH training comprises a self-guided (45 minutes) and remote, live 
segment (2.5 hours) provided by Drs. Lewis, Lekas, and Pahl70, focusing on how to build rapport, 
establish meaningful boundaries, and infuse their interactions with participants with insights 
regarding participant health habitus (i.e., tendency to care for health and wellbeing in certain 
ways) and its sociocultural determinants that hinder engagement in care (e.g., addressing 
internalized, anticipated, and experienced stigma, generating cultural and structural humility and 
self-reflection, and bolstering navigation skills). Any clinical challenges will be deferred to Drs. 

 
Tofighi and Lee (e.g., linkage to OUD services). PRC text exchanges with participants will take 
place during regular hours (M-F, 9-5pm). If participants query PRCs with any clinical / CSDH 
challenges, PRCs will contact participants once daily to help support participants in resolving 
barriers. The PRC will log text interactions focusing on participant sociocultural barriers or 
resources (i.e., health habitus notes) that will inform Aim 2 as such interactions have been found 
to be an effective approach to services engagement among persons with OUD72.  
The intervention fidelity of PRC text contact is critical with real-world studies to reduce the risk 
of a type I or II error. Study design considerations are incorporated to support intervention fidelity 
(e.g., use of a standardized, established training for PRCs, collection of key study measures like 
PRC-participant communication logs). In the data analysis, we will confirm that the intervention is 
received in the same way across participants and through time by comparing type and frequency 
of topics discussed as well as process measures. We will also compare fidelity metrics by 
participant characteristics. In the unlikely event that we do not observe an intervention effect, 
participant data on sociocultural determinants, risk behaviors, patient-centered care, clinical and 
social services use, and technology use will be instrumental in the interpretation of study findings 
and recommendations for practice. 
Intervention Arm-2 participants will receive the AI-driven CSDH-enhanced text messaging only 
(as described above; see Table 1). Participants in this arm (n=84) will not receive text support 
from the PRC.  
Intervention Arm-3 (Control). Individuals randomized to the control arm (n=84) will receive 
treatment as usual (i.e., verbal instructions and NYC Dept of Health pamphlets detailing access 
to OUD and social services). No services will be provided except for social/clinical service referrals 
given at the end of each REDCap visit. 
During follow-up at months 3-, 6-, and 12, the REDCap Survey will capture the domains listed 
above at enrollment (see Table 2) as well as the Technology Acceptance Model187 (see Figure 
2): perceived usefulness, perceived ease of use, attitudes, behavioral intentions, and 
intervention usage. In addition, data for each of these components will be derived from:  the 
texting software (e.g., rate of participant responses to software-initiated text queries, number of 
participant-initiated requests for physician telephone assistance53,129,188,189), and through PRC 
communication logs and qualitative interviews to inform fidelity, implementation, and 
contextualize intervention efficacy, enhancing RE-AIM and CFIR frameworks.  
 
 
 
 
 
 
 
 
 
 
 
 
  
  

 
Participant Discontinuation, Follow-up 
 
Follow-up will establish one of the following conditions as the cause of discontinuation: 
 
(1) Participant failed to return to clinic and unable to contact 
(2) Participant terminated due to practical problems (no childcare, transportation, other) 
(3) Participant moved from area 
(4) Participant incarcerated 
(5) Participant terminated due to AE/SAE 
(6) Participant terminated for other clinical reasons 
(7) Participant had a significant psychiatric risk (suicidal, homicidal, psychotic) 
(8) Participant withdrew consent 
(9) Participant deceased 
(19) Participant terminated due to protocol deviation 
(99) Participant terminated for other reason 

 
sIRB Plan 
The single IRB of record for this human subject research study will be the WCG IRB, which serves 
as Friends Research Institute’s IRB. FRI has established a partnership with the WCG IRB to serve 
as the IRB through a master services agreement. Acting as single IRB – the Friends Research 
Institute and the WCG IRB is authorized through a dual use agreement with all sites referenced 
below.  
The collaboration with Nathan Kline Institute, NYU, and Cornell will all be able to approve, seek 
modifications, and monitor research activities related to community enrollment and referrals to 
clinical or social services. The FRI and WCG IRB also has the authority to suspend, place 
restrictions on, or terminate approvals of research activities that fall within its jurisdiction that are 
not being conducted in accordance with IRB requirements, or that have been associated with 
unexpected serious harm to subjects.  
WCG IRB is registered with the Office for Human Research Protections (OHRP and FDA) as 
IRB00000533. The Friends Research Institute holds a federal-wide assurance (FWA), 0002948. 
The FWA is an assurance of compliance with the federal regulations for the protection of human 
subjects in federally-funded research.  All institutions/sites/organizations that will rely on the 
Friends Research Institute and the WCG IRB in this study will also be required to maintain a FWA 
throughout the course of the study.  
Research Sites: FRI, NYU, Nathan Kline Institute, and Cornell. 
All participating sites, prior to initiating human subject research activity, will sign an 
authorization/reliance agreement that will clarify the roles and responsibilities of the sIRB and 
participating sites. Sites will be required to sign an agreement before the sIRB review will 
commence for that site. Any sites added after award must also rely on the sIRB. 
General Communication with sIRB and sites 
The Friends Research Institute and WCG IRB will maintain records of the reliance agreements 
with all sites and will identify and document key communication roles. All communication with 
sites regarding sIRB policies, decisions and requirements will be communicated directly to the 
participating site’s principal investigator and any other entities as referenced in the reliance 
agreement.  
Information related to specific communications will be outlined in a detailed communication plan 
and will address the responsible parties for the following areas of communication:  
Ø Local context information  
Ø Local context review 
Ø Conflict of Interest review 
Ø Ancillary reviews 
Ø Study team training  
Ø Study team qualifications 
Ø Study Wide IRB submissions (initial, continuing, reportable events and modifications) 
Ø Site IRB submissions (initial, continuing, reportable events and modifications) 
Ø IRB Determinations 
Ø IRB Approved Documents  

 
Ø IRB Policy Review  
Ø Reporting Unanticipated Problems, Suspensions and Terminations 
 
 
Study Research Infrastructure.  
 
There will be six collaborating research sites in this study, Friends Research Institute, Nathan S. 
Kline Institute (NKI), NYU, Weill Cornell Medicine, NYC Health+Hospitals Lincoln Hospital Center, 
and START Treatment and Recovery. Each site and collaborating investigator will be responsible 
for all study procedures, including but not limited to recruitment, consent, data collection, analysis, 
and data storage. Community and ED-enrollment of potential PWUO participants will rely on CITI-
trained study staff responsible for conducting on-site research activities including administering 
written consent, baseline assessments, and providing instructions for follow-up study visits.  
 
WCG will serve as the IRB of Record for the study and therefore, it will review and approve all 
protocol documentation, and be responsible alongside the MPI for review and approval of any 
updates, revisions and for reporting and addressing any adverse events should they occur. 
Moreover, a master dataset with personal identifiable information will be maintained by the study 
coordinator at FRI.  
 
Data Safety and Quality Assurance  
 
The investigators will meet quarterly with the Data and Safety Monitoring Board (DSMB) to ensure 
the periodic review of study procedures, study data, and progress to ensure optimal participant 
safety. These meetings will allow DSMB members to make recommendations to the study 
investigators concerning the continuation, modification, or termination of the trial. The proposed 
DSMB plan will ensure optimal oversight and privacy safeguards for all participants by including 
individuals with extensive expertise in health information technology research and trials enrolling 
vulnerable populations.   
 
Materials: All devices and platforms utilized by the study team will be password- and virus-
protected with regular software updates and periodic mandatory changes of passwords. Study 
devices (i.e., tablets) will be encrypted, and data transfers will occur through secure file transfer 
between FRI server-maintained computers to NKI server-maintained computers (both accessible 
by each MPI).  
 
Sources of participant data in Aim 1 will rely on 3 sources of administrative data which will derive 
from study records (i.e., PRC-PWUO participant contact logs), the text message software 
communication logs, and for exploratory purposes only, the Hospital EHR. Data will be 
documented as follows: (1) process measures captured in PRC-PWUO participant contact logs 
(i.e., proportion of PWUO participants replying to PRC queries, PWUO participant queries to the 
PRC, topics discussed, actions required to address PWUO participant queries); (2) process 
measures captured in the text messaging software communication logs (i.e., messages sent to 
patients, percent of text queries that generated a participant response); (3) technology use 
patterns from the system level point of view (i.e., rates of mobile phone ownership, mobile phone 
turnover, mobile phone number turnover); and (4) receipt of OBOT or other OUD services 
elsewhere will be identified in the EHR and follow-up assessments (OBOT clinic appointments 
and visits completed, buprenorphine and/or naloxone fill/refill data). PRC-PWUO participant 
contact logs will be completed on computer-based forms using REDCap. The hospital EHR will 

 
also be utilized on an exploratory basis to provide records data on: (1) OUD treatment / prevention 
retention data (i.e., weeks-in-treatment); (2) abstinence (i.e., proportion of opioid positive urine 
samples, overtime); (3) adherence to buprenorphine (i.e., buprenorphine positive urine samples); 
and (4) health outcomes (e.g., specialty care clinic visits data, including diagnoses, 
symptomology, treatment). 
 
Privacy provisions pertaining to the AI-driven text messaging platform and software specifications 
are aligned with FRI, NIH, and federal guidelines and will be strictly adhered to, including 
mandatory Security Awareness and HIPAA training of all employees involved in the proposed 
study, including mandatory GCP training for all clinical trials staff, which includes Protection of 
Human Subjects training. All staff must sign a confidentiality agreement upon employment. FRI 
meets or exceeds all HIPAA requirements. For instance, faculty and staff are prohibited from 
keeping any clinical data, including clinical research data or study participant communication and 
metadata on their desktop computers; instead, it is stored on servers residing in the secured off-
site data center. Transaction logs and database backup procedures allow the recreation of a 
clinical study at any point in time. All data for this project is stored in a secured database, only 
available to the study team. Amazon Web Services (AWS) Lex uses HTTPS protocol to securely 
communicate with clients (encryption in transit) as well as between services. Access to services 
are API-driven and tied to NYU user credentials via IAM privileges (see Figure 1). FRI has strict 
security policies to ensure the privacy and confidentiality of data and to guard against physical, 
accidental, or malicious loss of data or the hardware on which it resides. All resources, including 
web, database, and file servers, are protected from outside intrusion by a firewall that blocks 
unauthorized access to the LAN by any unauthorized user originating from the Internet, using a 
sophisticated combination of secure application proxies and packet filtering. Internal network 
security is maintained through Active Directory authentication. Intrusion detection software is 
employed to scan for attempted break-ins. User IDs and passwords are assigned and controlled 
as per SOP, and users are required by the system to change their passwords regularly. Access 
to clinical trials or other sensitive data is strictly limited and is granted only by the Director, 
Technical Support Unit. Such access is controlled by easily identifiable group policies. 
 
Minimizing participant re-enrollment and quality assurance: As there is potential for a participant 
to enroll in the study more than once, we will take steps to minimize this occurrence. First, all 
participants will be asked to provide their name, phone number, birth date, and later, will be asked 
for identification such as the NYS Benefits ID card, driver’s license, or any work identification 
cards. Prior to enrollment, prospective participants’ names will be checked against this master 
database which will be merged at least weekly. While these efforts may not fully protect against 
duplicate enrollment, they will greatly minimize this occurrence.  
 
Strict security procedures will help ensure confidentiality/security of data. Any data transference 
between FRI and NKI will be conducted by the study team using a password protected device as 
mandated by the IRB. Any hard copy study documentation will be kept in locked files in the offices 
of the MPIs at FRI. Personal identifiers will be collected and saved on a HIPAA-compliant server 
and kept separate from the data. All devices, software platforms, and mobile phones utilized by 
the study staff will be password- and virus-protected with regular software updates and periodic 
mandatory changes of passwords. Any tablet devices utilized the study team will be encrypted by 
FRI information technology staff. In the event of data transfers, secure file transfers will only be 
performed between FRI server-maintained computers to NKI server-maintained computers (both 
accessible by each MPI). All study-related data will be edited, cleaned, de-identified and analyzed 
as needed for the preparing of conference abstracts and manuscripts. 

 
 
Potential risks to participants 
 
Participants across all components of this research project will experience minimal attendant risk. 
The intervention being proposed, including the use of text messaging and feedback of risk of 
negative treatment outcomes to the patient themselves imposes minimal risk above the patient’s 
existing efforts to enroll in telemedicine-based opioid treatment. However, since the study involves 
the enrollment of PWUO, we will further minimize potential risks in the study by: 1) having all study 
staff conducting study procedures to undergo the Collaborative Institutional Training Initiative 
(CITI) program prior to performing any study activities; 2) receive a federal Certificate of 
Confidentiality to minimize any social and/or legal risks associated with inadvertent disclosure to 
others of one’s same sex behavior, drug use and any other potentially stigmatizing statuses; and 
3) providing NYC Department of Health pamphlets offering information on accessible harm 
reduction, OUD treatment, primary care, and social services to avert threats to voluntariness in 
which potential participants may feel obligated to join the study since they lack access to available 
services.  
 
Risk of loss of confidentiality: As private identifiable information will be collected as part of study 
procedures, the risk of loss of confidentiality is recognized for all participants. OUD patients 
additionally may face the inconvenience of repeated study visits and engagement with the peer 
recovery coach. Protections against this risk are described in 2b. 
 
Risks of distress associated with text messaging: This project centers on a text messaging system 
that supports PWUO participants to engage with opioid use disorder and social services. Although 
our prior feasibility studies have not yielded any adverse events related to the use of text 
messaging, the clinical application of any mobile health intervention comes with the attendant 
risks of imperfect understanding and use of this information. However, to mitigate this risk, the 
proposed multimodal texting intervention has undergone extensive refinement and to date, has 
not elicited any episodes of emotional distress. In the event PWUO participants find that the 
intervention is intrusive, eliciting emotional distress, or any other adverse events, they can simply 
reply Stop to the texting software and/or notify study staff to discontinue their continued receipt of 
passive reminders and informational texts. Protections against this risk are described further in 
2b. In addition, during enrollment, PWUO participants in Aim 1 will be given verbal and printed 
instructions by the study staff to exclude the use of any identifiers during text communication, to 
regularly delete text messages exchanged with study staff and the HIPAA-compliant server, 
password protect their mobile phones and periodically change phone passwords, avoid sharing 
their mobile phone with friends or family, immediately report any breach of privacy committed by 
peers, avoid granting mobile app permissions, remain vigilant when downloading files or clicking 
hyperlinks from suspicious texts or emails on their phone, considering mobile phone device 
protection with security software that ensure personal firewalls, spam filters, anti-virus and anti-
spyware tools, encrypt all data stored on their phone (e.g., for Android phones version 4.0 or 
greater, iOS running version 4.0 or higher) using federally verified encryption applications that 
offer a passcode to automatically encrypt all data, and avoid using open Wi-Fi. 
 
Risks of distress associated with text message contact with PRCs: The efficacious CSH training 
developed by Drs. Lewis and Lekas has reliably trained PRCs to mitigate any conflicts of interest, 
bias, stigma, or role conflict by emphasizing the following training topics: 1) reducing stigma 
(internalized, anticipated, and experienced) among PWUO; 2) generating cultural and structural 
humility and self-reflection; 3) strengthening PRC-participant rapport and communication; and 4) 
establishing meaningful boundaries between PRC and participants to mitigate role conflict.  Their 
prior studies have not elicited any adverse events related to PRC support for study participants.  

 
Adequacy of Protection Against Risks 
Informed Consent and Assent will be accomplished by ensuring that all PWUOs will be 
consented by trained research staff, with research training approved by the IRB (see Single IRB 
Plan). If PWUOs indicate willingness to be contacted by research staff, they will complete verbal 
consent by trained study staff. If requested, PWUOs will be given paper copies to read the 
informed consent document and/or review the document with staff, and a HIPAA review will be 
provided during their baseline enrollment. The risks of study participation will be clearly defined 
for all participants.  Consent will be obtained via REDCap, and we will request from the IRB and 
obtain a waiver of signed consent. HIPAA will be signed using secure IRB-approved signing 
software. Throughout the consent process, the study staff member will be assessing consent 
capacity and if the individual is deemed to have the capacity to consent, they will be enrolled once 
consent and HIPAA procedures are completed. For Aim 2, informed consent (for all 3 stakeholder 
groups) and HIPAA (for the PWUO participants) procedures will be completed via video (Zoom 
or WebEx).  
 
Protections Against Risk and Risk of loss of confidentiality. Our team has decades of 
research experience working with underserved community-enrolled people who use opioids. We 
recognize that some participants may feel uncomfortable when answering certain questions, 
especially PWUO participants. Specifically, discussions about drug use and other risk behavior, 
and about their experiences with the healthcare system, including OUD services may be 
distressing. Description of prior overdose and incarceration experiences may also cause some 
psychological discomfort or distress. Participants may choose to skip these questions. Additional 
social services referrals will be provided and transportation fare for immediate specialty care 
consults.  All study staff will be trained in the provision of immediate referrals to primary care and 
social services. 
 
As a guard against the loss of confidentiality, all information will be stored in locked password-
protected files which will be accessible only to members of the research staff for this project and 
stored on secure filesystems. No names or other identifying information will be used in 
publications, which will stem from this research. All data collected (including results of tasks, tests 
and questionnaires) will be identified with a unique subject-specific code and will be kept in 
password-protected electronic files that will be stored in a secure drive designated for this study. 
Survey data, and audio files will be assigned an identification code and collected on password-
protected, encrypted tablets. Survey data will then be downloaded to a password-protected 
desktop at the respective collaboration sites and stored on their HIPAA drive. Participant personal 
identifying information will be kept separately from survey and the audio files/transcript data and 
identification codes will not be linked to participant's personal information. Participant information 
will be destroyed once data collection is complete and all participants have received their 
compensation. All records will be kept for at least 3 years after the end of the study. After this 
retention period expires and the study is closed, all records will be electronically scanned and any 
paper records will be thereafter shredded or otherwise destroyed. Great care will be taken to 
comply with The Confidentiality of Alcohol and Drug Abuse Patient Records Regulation under the 
Code of Federal Regulations 45 CFR Part 2 and the HIPAA Privacy Rule: Programs may not use 
or disclose any information about any patient unless the patient has consented in writing (on a 
form that meets the requirements established by the regulations) or unless another very limited 
exception specified in the regulations applies. Any disclosure must be limited to the information 
necessary to carry out the purpose of the disclosure. The Privacy Rule permits uses and 
disclosures for “treatment, payment and health care operations” as well as certain other 
disclosures without the individual’s prior written authorization. Disclosures not otherwise 
specifically permitted or required by the Privacy Rule must have an authorization that meets 

 
certain requirements. With certain exceptions, the Privacy Rule generally requires that uses and 
disclosures of PHI be the minimum necessary for the intended purpose of the use or disclosure 
(Health & Services, 2004). 
For the PWUO survey participants, consent and data collection taking place will be either 
over the phone or in a quiet and private location in the listed study offices where, if necessary, 
noise machines will also be used. For the in-depth interviews with key stakeholders in Aim 2, 
the HIPAA compliant version of Zoom and Webex platforms will be utilized.  
During Aim 2, we will also obtain a signed HIPAA authorization from participants to audit the 
EPIC EHR “Care Everywhere” feature to capture health systems utilization in the study site 
hospital and elsewhere. Drs. Lekas and Lewis will lead the data collection and analysis of the 
implementation data including triangulation of the qualitative interview data with the EHR data 
and other process data to evaluate the adoption, implementation, and maintenance of the 
intervention.  
Due to the remote nature of this study, additional precautions have been taken to ensure 
protection against loss of confidentiality in the transmission or storage of mHealth data. The 
proposed texting intervention we propose to employ for data capture is built on a standard 
HIPAA-compliant platform by QliqSOFT, which employs encryption protocols defined for use in 
the United States National Institute of Standards and Technology (NIST) publication FIPS 140-
2, or any superseding documents according to the date of implementation. The use of the 
Advanced Encryption Standard (AES) allows for symmetric encryption and is certified as HIPAA 
compliant.  
QliqSOFT's platform includes a chatbot feature that enables secure communication. This 
chatbot will use patient identifiers, such as names, to personalize the user experience. It's 
important to note that the chatbot requires participants to have a data plan, as it operates 
through a hyperlink rather than standard SMS. This ensures a secure and seamless interaction 
experience, further enhancing the confidentiality and security of the communication. 
Incidental Findings: Participants will not complete medical imaging or pregnancy testing as a 
component of study procedures, so we do not anticipate these incidental findings. During Aim 1, 
patient participants will have access to study staff during regular work hours where they may 
incidentally report imminent threats to themselves or others. Incidental findings of imminent threat 
will be handled in the same way as in in-person research, as reviewed by our sIRB. Specifically, 
incidental findings will be escalated to Dr. Babak Tofighi (MPI) who will determine appropriate 
follow-up based on the perceived level of threat. All SAEs will be logged and reviewed as 
explained elsewhere in this application. 
 
Vulnerable Subjects. Participants with a history of criminal justice involvement will be eligible for 
recruitment into this study. Their capacity to consent is not considered to be different from the rest 
of the participants in this study; therefore, capacity to consent will be assessed with the same 
consent comprehension tool as other participants. Individuals from age 18-21 may be consented 
into this study as they may be interested in engaging engaged in treatment for OUD, but children 
under the age of 18 will not be eligible for participation.  
 
Participants with a history of OUD will be approached by study staff to assess for eligibility in 
the study. Since nearly all potential participants will be experiencing socio-economic and health-
related challenges (e.g., lack of housing, unemployment, healthcare access), we will minimize 
potential ethical challenges and risks in the study by: 1) training study staff in the ethical conduct 
of research with populations experiencing substance use disorders, led by Dr. Tofighi, who 
presents the same topic to medical students, trainees, and research staff; 2) training study staff 
in coordinating receipt of federal Certificates of Confidentiality for participants to minimize any 
social and/or legal risks associated with inadvertent disclosure to others of one’s same sex 
behavior, drug use and any other potentially stigmatizing statuses; 3) providing NYC Department 

 
of Health pamphlets offering information on accessible harm reduction and treatment services for 
all individuals approached by study staff to avert threats to voluntariness in which potential 
participants may feel obligated to join the study since they lack information or access to treatment 
options; 4) to overcome additional challenges with voluntariness, potential PWUO participants will 
also be given city government pamphlets clarifying how to access social services that address 
social determinants of health, since PWUO may be in dire social, financial and health 
circumstances that would make them feel obligated to join a research study to receive financial 
reimbursements and potential support linking with treatment and social services; and 5) given the 
severity of OUD and its impact on reducing access to healthcare, individuals may be experiencing 
undiagnosed, unmanaged, and/or undermanaged medical and/or psychiatric conditions, and will 
be provided with informational pamphlets published by the NYC Department of Health on free 
healthcare services tailored to low-income and vulnerable PWUO. In addition, potential PWUO 
participants will be informed by the study team using written pamphlets that publicly listed primary 
care clinics in proximity to the patient’s location may facilitate referrals to psychiatric and specialty 
care services to ensure optimal and personalized care. 
 
Potential Benefits of the Proposed Research to Research Participants and Others. There 
are no direct clinical benefits for participating in this study, for PWUOs, providers, or caregivers. 
However, participants may find engagement with our texting intervention and/or text contact with 
the peer recovery coach satisfying, as has been observed in our prior pilot studies. Thus, the 
relation of minimal benefits to minimal risk of loss of confidentiality (which is greatly attenuated by 
our extensive privacy and security systems) is commensurate with other basic behavioral 
research. 
 
Importance of Knowledge to be Gained. The unifying goal of all Aims of this proposal is to 
develop a multimodal intervention that leverages text messaging to support patient engagement 
with OUD- and social services, based on the mechanisms underlying treatment outcomes. If 
successful, this suite of studies would contribute not only to the basic understanding of factors 
influencing engagement with treatment among underserved Black and Latinx PWUOs, but also 
would set the stage for a potential future effectiveness-implementation hybrid type 1 trial, at low 
cost and with key stakeholder support. In the context of rising rates of OUD and opioid overdose 
among underserved Black and Latinx PWUOs, the development of such a tool provides a 
substantial contribution not only to science, but also to human health that aligns with federal 
guidelines to reduce health inequities among PWUO. Thus, the substantial benefits of the 
knowledge to be gained outweigh the minimal risk of loss of confidentiality (attenuated as above). 

 
Data-safety and Monitoring Plan 
The IRB’s Principal Investigator (Tofighi; MPI) will be responsible for monitoring the safety and 
efficacy of this trial, executing the Data and Safety Monitoring (DSM) plan, and complying with 
the reporting requirements. The IRB’s PI will provide a summary of the DSM report to NIDA on 
an annual basis as part of the progress report. The DSM report will include the participants’ 
sociodemographic characteristics, expected versus actual recruitment rates, treatment retention 
rates, any quality assurance or regulatory issues that occurred during the past year, summary of 
AEs and SAEs, and any actions or changes with respect to the protocol.   
 
Data Monitoring Plan  
As a guard against the loss of confidentiality, all patient participant survey instrument responses 
will be stored in REDCap, which is an encrypted password-protected platform that will be 
accessible only to members of the research staff for this project and stored on secure filesystems. 
No names or other identifying information will be used in publications, which will stem from this 
research. All records will be kept for at least 3 years after the end of the study. After this retention 
period expires and the study is closed, all paper records will be electronically scanned, and any 
paper records will be thereafter shredded or otherwise destroyed. Information about study 
subjects will be kept confidential and managed according to the requirements of the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA). Further information about data 
transmission is presented in our Protection of Human Subjects document, under “Protections 
Against Risk”, and is depicted in Supplemental Figure 1. The platform we propose to employ for 
the texting intervention is built on a standard HIPAA-compliant cloud, and the entire end-to-end 
solution has been certified as HIPAA compliant. Complete details can be found in the Protection 
of Human Subjects section. This HIPAA-compliant system maintains fully auditable data access 
logs that are required for any HIPAA system.     
 
Data Entry & Analysis 
Data analysis will be automated as much as possible. As there is negligible transcription of data, 
errors in data entry introduced by experimental staff should be minimal. When data must be 
entered by hand (for example during focus group sessions), data will be double-entered and 
checked for accuracy using standard data shells.  
 
In Aim 1, all participants will be assigned a survey ID accompanied by their phone number and 
name. This master-list survey database will be stored in a password protected FRI server. 
Participant data will be stored in REDCap and will be accessible only to members of the research 
staff. Data analysis will be automated as much as possible. As there is negligible transcription of 
data, errors in data entry introduced by experimental staff should be minimal. When data must be 
entered by hand (for example during focus group sessions), data will be double-entered and 
checked for accuracy using standard data shells. Our proposed analysis will use all available 
data, under an intent-to-treat principle. As a first step, we will generate descriptive statistics to 
characterize the sample at baseline on sociodemographic, health and psychiatric symptoms, 
substance use, and technology use characteristics, both overall and by intervention group (texting 
+ PRC vs. texting only vs. TAU). Descriptive statistics include means, standard deviations, 
percentiles, and frequencies with percentages, as appropriate. Then, in support of Aim 1, we will 
investigate the impact of the three-arm intervention on primary outcomes. To assess these 
hypotheses (see Data Analysis, Aim 1), we will utilize the Cox regression model to investigate 
whether there are differences in time to service linkage (in weeks) by intervention group. Cox 
regression is a method for investigating the effect of several variables upon the time to a specified 
event. Data collected at 3-, 6-, and 12-month follow-up surveys as well as from the participant 

 
EHR will permit analysis of secondary outcomes of engagement in intervention and durability of 
treatment effect. For these analyses, we will use logistic regression to model binary outcomes 
indicating longitudinal engagement in 26-week treatment (yes/no) and continuous retention in 
primary care-based buprenorphine treatment at 3-, 6-, and 12-months (yes/no) with no more than 
a 28-day gap in receiving an active buprenorphine prescription over each period. To assess 
whether randomization was successful, we will compare the distribution of demographic 
characteristics, PhenX consensus measures, medical/psychiatric history, and technology use 
patterns (see Data Collection) by intervention arm. Variables contributing to baseline imbalance 
will be included as model adjustment variables. To ensure that model assumption of non-
informative censoring/study drop out is reasonable and avoid potential bias, we will compare 
dropout rates between intervention groups as well as other measured variables, e.g., 
demographic, social determinants, and risk behavior variables. If there is empirical evidence of 
nonrandom dropout, we will model the dropout event using available factors to identify and 
estimate their influence.  
 
In Aim 2, interview transcripts will be content analyzed by the study team by utilizing a 7-step 
process refined by our team following numerous NIDA-funded studies. This process allows for a 
systematic identification of subcode, codes and themes while keeping the data contextualized. 
The process is comprised of the following stages: In step 1, we will identify the principal issues 
discussed by participants. During step 2, we will construct preliminary definitions of the analytic 
themes. In step 3, we will Develop and apply core codes and subcodes to the initial set of 
interviews. Blocks of text within text tagged with core codes will be assigned subcodes. In step 4, 
we will develop a provisional coding scheme. In step 5, we will test the provisional coding scheme 
by coding new transcripts. During step 6, we will reconcile coding differences and construct a final 
coding scheme. Lastly, during step 7, we will apply the coding scheme to the full dataset. Close 
reading of the coded interview transcripts will reveal data patterns withing each sample, but 
importantly, highlight differences/similarities across the stakeholder groups, key to intervention 
adoption implementation and maintenance. For instance, an emerging data pattern in the frontline 
provider interviews could be that they strongly recommend changes in policies and guidelines 
that will afford them with flexibility in enrollment and referrals to better engage PWUO in care, 
whereas the PWUO might emphasize the role of OUD intersecting stigma in undermining their 
engagement in care and highlight how interactive texting from PRCs reduces internalized stigma 
and increases intervention adoption. This prismatic assessment of the intervention will enable us 
to draw inferences that will inform the refinement of the intervention for a future scale up project. 
 
In Aim 3, the economic evaluation will be conducted using well-established guidelines of 
prospective economic evaluations alongside clinical trials. Outcome measures will be analyzed 
using multivariable generalized-linear mixed models (GLMMs) to adjust for potential confounding 
factors and the skewed distributions commonly associated with healthcare cost data and 
censored outcomes (e.g., QALY). The GLMM, an extension of the GLM, allows the most 
appropriate mean and variance functions to be chosen based on the observed data, as well as 
for the inclusion of random effects. The primary outcomes for Aim 3a will be the budget impact 
tool consolidating the resources and associated costs required to implement and sustain the PRC-
supported text contact + interactive text messaging, and interactive text messaging only 
interventions compared to TAU. The primary outcome of Aim 3b will be the incremental cost-
effectiveness ratio (ICER), defined here as the incremental mean cost between the two 
intervention arms and TAU divided by the incremental mean effectiveness of the two arms 
calculated separately. HRQoL is increasingly recognized as a key indicator of patient well-being 
that is not captured in clinical measures. The QALY is a measure that combines the HRQoL 
associated with an individual’s health state and their time spent in that state. The QALY is 

 
recommended as the primary effectiveness measure in economic evaluations due to its ability to 
be compared across interventions and disorders, and its association with commonly accepted 
value thresholds (i.e., cost-per-QALY). OUD treatment days is an important continuous measure 
of effectiveness for clinical stakeholders and calculating cost-per-OUD treatment days enables 
comparisons with existing economic evaluations of other inpatient interventions reporting similar 
clinical effectiveness measures. As part of the process of estimating ICERS we will be able to test 
the 6- and 12-month post-intervention differences between arms of a) the average total costs to 
the healthcare sector, state policymaker, and society by resource categories; and b) the average 
QALYs and OUD treatment days; thus, two ICERs will be calculated for each of the three 
stakeholder perspective for each of the aforementioned evaluation periods. 
 
Safety Monitoring Plan  
During screening in Aims 1 and 2, potential study participants will be approached by study staff 
to determine their eligibility for their participation in this study. Information about their substance 
use history, current pharmacological treatment, history of prior treatment or illicit opioid reuse, 
along with other relevant clinical information, will, with the participant’s consent, be asked of them 
during baseline enrollment.  
 
Data pertaining to patient participant entry into primary care-based buprenorphine treatment will 
include EHR appointment records, dispensing records, completion of specialty care referrals, and 
appointment adherence data that will be audited from their clinical chart by the research staff.   
 
A social harm monitoring plan will be utilized during scheduled study visits to query for any 
potential social harms due to study enrollment. Inherent in research among PWUO is the potential 
for physical, emotional, and psychosocial harm to study participants that are non-medical adverse 
experiences. Case Report Forms will systematically capture social harm in a two-tiered manner 
by asking participants whether they “experienced any problems since the last study visit as a 
result of being enrolled in the study or receiving text messages from the study?” If respondents 
confirm social harm, they will be asked in more detail regarding categories of experienced harms, 
including emotional, physical, economic, and/or “other” harms. Each social harm incident will be 
characterized as being related to peers, friends/family, partner(s), employers, and/or healthcare 
and social service providers. Participants will then be asked to specify the adverse social 
incidences, including stigma, discrimination, and/or difficulties in personal relationships following 
study enrollment and receipt of text message content. Lastly, study staff will query respondents 
regarding the frequency of past week distress symptoms and resolution status (Yes/No). Any 
social harm events will be communicated to Drs. Tofighi and Lekas (MPIs) within 24 hours and 
will coordinate with trained PRC staff to provide multichannel support to promptly address events 
using information-based approaches (e.g., informational pamphlets) and skills-building 
approaches (e.g., in-person or audio/visit sessions with PRCs). This multi-intervention approach 
is based on prior study findings describing the need to maximize responses that can ensure 
optimal support and potentially synergistic benefits among PWUO and persons living with HIV 
enrolling in clinical trials.   
 
Quality Assurance Plan  
We realize that there is potential for a participant to enroll in the study more than once if 
protections are not put in place to prevent, or at least minimize, this occurrence. To begin with, 
all participants will be asked for identification and in the event that a participant does not have 
ID, other items that include name and birth date such as the Benefits ID card, medical 
documents, birth certificate, voter registration, court papers, etc. will be accepted if 
accompanied by a picture ID that shows the participant’s name and photo (student ID, 
employment ID, etc.). In addition, personal identifying information such as birth date and 

 
mother’s maiden name will be collected at enrollment and research staff will log this information 
into a password protected database that will be updated into a master list of participants 
enrolled every day. Prior to enrollment, participants’ names will be checked in this master 
database. While these efforts may not fully protect against duplicate enrollment, we feel it will 
greatly minimize this occurrence and potential bias.  
 
Approximately 5% of sessions from each intervention arm will be randomly selected to be audio-
recorded. Participants will sign a separate consent form to agree to this recording. If a 
participant declines, the next randomly selected individual will be recorded. To ensure the 
quality and integrity of the randomization, it is important to minimize contamination across 
conditions. Therefore, we will (1) schedule in-person study visits in a private room or space to 
ensure conversations are not overheard; (2) reduce the potential for overlap of participants 
assigned to different arms by scheduling only one study arm on a particular day; and (3) assess 
potential contamination by asking participants if they heard about the study prior to entry, if they 
know anyone who has participated in the study and compare these instances by study arm. Our 
past work indicates that contamination is unlikely. However, if a participant reports knowing 
others in the study, they will be asked to share the individual’s name so that a variable can be 
created that indicates potential contamination which will be considered in the analysis.  
 
Collection and Reporting of SAEs and AEs 
 
Patient Cohort. In this study we will use the FDA definition of serious adverse events (SAEs). Both 
adverse events (AEs) and SAEs will be systematically assessed at each clinic visit for the patient-
participants. We do not anticipate SAEs are AEs related to the use of text messaging which is our 
intervention. Any SAE, whether or not related to study intervention, will be reported to the IRB 
and NIDA. The initial SAE report will be followed by submission of a completed SAE report to both 
institutions. In the event that a patient either withdraws from the study or the investigator decides 
to discontinue a patient due to SAE, the patient will be monitored by the investigator via ongoing 
status assessment until 1) a resolution is reached, for example the problem requiring 
hospitalization has resolved or stabilized with no further changes expected, 2) the SAE is 
determined to be clearly unrelated to the study intervention, or 3) the SAE results in death. SAEs 
would include hospitalization (for example as the result of an opioid overdose, which is not 
uncommon among high-risk OUD patients) or opiate overdose resulting in death. The study team 
will conduct, at a minimum, an annual Data Safety Board meeting to review all SAEs. All PI’s will 
attend this meeting. If more than 2 SAEs occur in any year, meetings of the board will be increased 
in frequency. All observed SAEs (again, regardless of relation to the study intervention) will be 
periodically reported to NIDA. A summary of the SAEs that occurred during the previous year will 
be included in the annual progress report to NIDA. The MPIs will be responsible for monitoring 
and recording both AEs and SAEs. 
 
Provider and administrator study participants providing in-depth interview data. We do not 
anticipate any AEs or SAEs for the clinician and administrator participants undergoing virtual in-
depth interviews (Aim 2). For this sample we will also adopt the FDA definition of an SAE. AEs 
and SAEs for the provider and administrator sample will be handled exactly as specified for the 
PWUO participant cohort. 
 
Standard AE definitions will include the following: 
 
Adverse event:  Any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (for example, abnormal physical exam or laboratory finding), 

 
symptom, or disease temporally associated with the subject’s participation in the research, 
whether or not considered related to the subject’s participation in the research.  
 
Adverse events encompass both physical and psychological harms.  They occur most 
commonly in the context of biomedical research, although on occasion, they can occur in the 
context of social and behavioral research. For the purposes of this study, we will not monitor 
known reactions to methadone or buprenorphine treatment as adverse reactions. These 
known reactions are specified on the FDA-approved package inserts for the medications used 
in this study. These include dizziness, drowsiness, withdrawal symptoms, tongue pain, 
nausea, vomiting, constipation, headache, insomnia, and trouble concentrating. 
 
Serious Adverse Event:  Any AE that results in any of the following outcomes: 
• 
Death 
• 
Life-threatening  
• 
Event requiring inpatient hospitalization or prolongation of existing hospitalization 
• 
Persistent or significant disability/incapacity 
• 
Congenital anomaly/ birth defect 
• 
Based on the appropriate medical judgement, may jeopardize the subject’s health 
and may require medical or surgical intervention to prevent one of the other 
outcomes listed in this definition.   
AEs are graded according to the following scale: 
Mild:  An experience that is transient and requires no special treatment or intervention.  
The experience does not generally interfere with usual daily activities.  This includes 
transient laboratory test alterations. 
Moderate:  An experience that is alleviated with simple therapeutic treatments.  The 
experience impacts usual daily activities.  Includes laboratory test alterations indicating 
injury, but without long-term risk. 
Severe:  An experience that requires therapeutic intervention.  The experience interrupts 
usual daily activities. If hospitalization (or prolongation of hospitalization) is required for 
treatment it becomes an SAE. 
 
The study uses the following AE attribution scale: 
Not related:  The AE is clearly not related to the study procedures (i.e., another cause of 
the event is most plausible and/or a clinically plausible temporal sequence is inconsistent 
with the onset of the event).   
Possibly related:  An event that follows a reasonable temporal sequence from the 
initiation of study procedures, but that could readily have been produced by a number of 
other factors. 
 
Related:  The AE is clearly related to the study procedures.   
 
Appropriately qualified and trained study personnel will elicit participant reporting of AEs and 
SAEs at each study visit designated to collect AEs. Adverse events assessment and collection 
will begin when the participant signs the informed consent form and follow-up will continue through 
30 days after the last study visit. Study personnel will obtain as much information as possible 
about the reported AE/SAE to complete the AE/SAE forms and will consult as warranted.  
 
All AEs and SAEs are reported to the WCG IRB according to their reporting guidelines.  
Standard reporting, within 7 calendar days of the site becoming aware of the event, is required 
for reportable AEs. Expedited reporting (within 24 hours of their occurrence and/or site staff's 

 
knowledge of the event) is required for reportable SAEs (including death and life-threatening 
events).  
 
Reporting mechanisms of IRB actions to NIDA 
Any IRB action that impacts study protocol or that has no impact on study protocol will be 
reported to NIDA program official within 24 hours of notification from IRB. This will be done via 
email and followed up with official documentation. Any changes to study protocol that is not an 
IRB action, but a sole decision of the PI will also be communicated to NIDA program prior to the 
implementation of the change.  
 
Plan for Incidental Findings Management 
If an incidental finding is discovered during screening procedures, the participant will be notified 
and given a proper referral to a service provider. Moreover, Dr. Tofighi will draft and approve the 
training of study staff protocols for the referrals to OUD treatment and primary care services. In 
case of an adverse event as a result of study participation, the contact PI will be responsible for 
reporting to the IRB of record. 
 
Conflict of interest 
Any conflicts of interest will be reported to the IRB. 
 
Responsibility for data and safety monitoring  
The MPIs (Lekas, Lewis and Tofighi) will be responsible for monitoring the study. 
 
Frequency of DSM reviews 
As indicated above, on a monthly basis, the MPI will meet with the study team to review notes 
and assess issues of community concern about potential disclosure issues or reports of adverse 
consequences.  
 
Content of DSM report 
The following will be included in the DSM report: 1) brief description of protocol, 2) baseline 
socio-demographic characteristics, 3) retention and disposition of study participants, 4) quality 
assurance issues, 5) AEs, 6) SAEs, 7) efficacy, 8) suggested and actual protocol changes 
 

 
Interim Data Analysis Plans 
Interim analyses will be performed to evaluate safety. At each DSMB meeting, all SAEs will be 
evaluated and compared between study groups. If SAEs differ between groups in a manner 
determined to be related to study procedures, the study will be paused. Decisions to pause the 
study will be made by the independent DSMB.  
 
In addition to consistent monitoring by members of the research team for adverse events, 
quarterly interim analyses of the survey data, quality control checks, and study activities will also 
be performed to ensure that all participant data are protected and there are no adverse events 
or harm to participants. During this review, validity and integrity of the data will also be 
monitored. 
 
 

 
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