Facebook Intervention for Preventing Opioid Relapse Among American Indian Women: Wiidookaage'Win Pilot Preparatory Study (Aim 1)
Phase: NA
Conditions: Opioid Use
Sponsor: Mayo Clinic

 
 
Facebook Intervention for Preventing Opioid 
Relapse Among American Indian Women: 
Wiidookaage'Win Pilot Preparatory Study (Aim 1) 
 
NCT05340855 
 
1/12/2023 

NIDA CTN Protocol 0123 
Facebook Intervention for Preventing 
Opioid Relapse among American 
Indian Women: Wiidookaage’win Pilot 
Preparatory Study (Aim 1)
LI: Dr. Christi Patten 
Sponsor: National Institute on Drug Abuse (NIDA) 
IRB approved 1/12/2023 
Version 1.4
CONFIDENTIAL 

NIDA CTN-0123 
Version 1.4 
Facebook Intervention for Preventing Opioid Relapse among American Indian Women 
[Date of submission] 
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Lead Investigator (LI): 
Christi Patten, PhD 
 
NIDA CTN NorthStar Node 
 
Mayo Clinic 
 
 
Co-LI(s): 
, DrPH 
 
NIDA CTN NorthStar Node 
 
Mayo Clinic 
 
 
 
, PhD 
 
NIDA CTN NorthStar Node 
 
Mayo Clinic 
 
, PhD 
NIDA CTN NorthStar Node 
Mayo Clinic 
 
MD, PhD, FACP, FASAM 
NIDA CTN NorthStar Node (LI) 
University of Minnesota 
 
, PhD 
NIDA CTN Northeast Node 
Dartmouth College 
 
, PhD 
NIDA CTN Greater New York Node 
Columbia University Irving Medical Center 
 
, PhD 
NIDA CTN Southwest Node 
Center on Alcohol, Substance Use and Addictions 
 
, MD 
MIDA CTN NorthStar Node 
Community-University Health Care Center 
 
 
CCTN Scientific Officer: 
, MS 
 
National Institute on Drug Abuse 
 
 
 
 

NIDA CTN-0123 
Version 1.4 
Facebook Intervention for Preventing Opioid Relapse among American Indian Women 
[Date of submission] 
 
CONFIDENTIAL 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes 
agreement by the recipient that no unpublished information contained herein will be published or 
disclosed without prior approval of the LI or other participating study leadership and as consistent 
with the NIDA terms of award. 

 
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TABLE OF CONTENTS 
1.0 LIST OF ABBREVIATIONS ................................................................................................................... 1 
2.0 PROTOCOL SUMMARY ........................................................................................................................ 3 
Synopsis .................................................................................................................................................... 3 
3.0 STUDY SCHEMA ................................................................................................................................... 5 
3.1. Key Research Site Roles ................................................................................................................... 6 
4.0 INTRODUCTION ..................................................................................................................................... 7 
4.1 Study Rationale ................................................................................................................................... 7 
4.2 Background and Significance to the Field ........................................................................................... 8 
4.3 Risk/Benefit Assessment .................................................................................................................. 10 
4.3.1 Risks .......................................................................................................................................... 10 
4.3.2. Benefits ..................................................................................................................................... 12 
5.0 OBJECTIVES ....................................................................................................................................... 13 
5.1 Primary Objective .............................................................................................................................. 13 
5.2 Secondary Objective(s) ..................................................................................................................... 13 
5.3 Exploratory Objective(s) .................................................................................................................... 13 
6.0 STUDY DESIGN ................................................................................................................................... 14 
6.1 Overview of Study Design ................................................................................................................. 14 
6.2. Community-Based Participatory Research (CBPR) Approach ........................................................ 14 
6.3. Duration of Study and Visit Schedule .............................................................................................. 15 
7.0. OUTCOME MEASURES ..................................................................................................................... 16 
7.1 Primary Outcome Measure ............................................................................................................... 16 
A Culturally Relevant Facebook Intervention ...................................................................................... 16 
7.2 Secondary Outcome Measures ......................................................................................................... 16 
Feasibility and Acceptability ................................................................................................................ 16 
7.3. Exploratory Outcome Measures....................................................................................................... 16 
7.4 Study Timeline................................................................................................................................... 17 
8.0 STUDY POPULATION ......................................................................................................................... 18 
8.1 Phase 1 ............................................................................................................................................. 18 
8.1.1. AIAN Women ............................................................................................................................ 18 
8.1.2. Health Care Providers and AIAN Interested Parties ................................................................. 18 
8.2 Phase 3 ............................................................................................................................................. 18 
8.3 Participant Inclusion Criteria ............................................................................................................. 18 
8.3.1. Phase 1 ..................................................................................................................................... 18 
8.3.2 Phase 3 ...................................................................................................................................... 19 
8.4 Participant Exclusion Criteria ............................................................................................................ 20 

 
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8.5 Strategies for Recruitment and Retention ......................................................................................... 20 
8.5.1 Phase 1 ...................................................................................................................................... 20 
8.5.2 Phase 3 ...................................................................................................................................... 21 
8.5.3 Recruitment Documentation ...................................................................................................... 21 
9.0 SITE SELECTION ................................................................................................................................. 22 
9.1 Number of Sites ................................................................................................................................ 22 
9.2 Site Characteristics ........................................................................................................................... 22 
9.3 Rationale for Site Selection ............................................................................................................... 22 
9.3.1 Mayo Clinic ................................................................................................................................. 22 
9.3.2 The Research Team .................................................................................................................. 23 
10. STUDY PROCEDURES........................................................................................................................ 24 
10.1  
Phase 1: Qualitative Work to Develop Facebook Content .......................................................... 24 
10.1.1 Projected Facebook Content ................................................................................................... 24 
10.1.2. Moderator Guides for Qualitative Interviews ........................................................................... 25 
10.1.3. Interviewer Training ................................................................................................................ 25 
10.1.4. Screening Visit ........................................................................................................................ 26 
10.1.5. Enrollment ............................................................................................................................... 26 
10.1.6. Interview Methods ................................................................................................................... 26 
10.1.7 Phase 1 Table of Assessments ............................................................................................... 28 
10.2 
Phase 2: Prototype Development, Content Library, and Moderator Exchange .......................... 28 
10.2.1. Prototype Development .......................................................................................................... 28 
10.2.2. Content Library and Intervention Moderator Guidelines ......................................................... 29 
10.2.3. Facebook Intervention Moderators ......................................................................................... 29 
10.2.4. Moderator Exchange ............................................................................................................... 30 
10.3.  Phase 3: Beta-Testing of the Facebook Intervention ................................................................ 33 
10.3.1. Screening Visits and Consent Procedures ............................................................................. 33 
10.3.2. Informed Consent ................................................................................................................... 35 
10.3.3. Baseline Visit........................................................................................................................... 35 
10.3.4. Enrollment ............................................................................................................................... 37 
10.3.5. Study Intervention Administration ........................................................................................... 37 
10.3.6. Study Intervention Adherence................................................................................................. 37 
10.3.7. Discontinuation of Study Intervention ..................................................................................... 37 
10.3.8 Follow-Up ................................................................................................................................. 38 
10.3.9. Phase 3 Table of Assessments .............................................................................................. 39 
10.3.10. Data Collected by Study Staff ............................................................................................... 40 
10.3.11. End of Intervention Form ...................................................................................................... 40 
10.3.12. Study Completion Form ........................................................................................................ 41 
11.  CLINICAL AND SAFETY ASSESSMENTS ........................................................................................ 42 
11.1. Adverse Events (AEs) and Serious Adverse Events (SAEs) ..................................................... 42 
11.2. K6 Scale ..................................................................................................................................... 42 
11.3.  Assessment of Suicidality at Screening .................................................................................... 43 
12. PREMATURE WITHDRAWAL OF PARTICIPANTS ........................................................................... 44 
13. STUDY HALTING RULES .................................................................................................................... 45 

 
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14. PARTICIPANT REIMBURSEMENT/REMUNERATION ...................................................................... 46 
15. DISSEMINATION .................................................................................................................................. 47 
16. TRAINING REQUIREMENTS ............................................................................................................... 48 
16.1 Overall ............................................................................................................................................. 48 
16.2 Protection of Human Subjects......................................................................................................... 48 
17.0 STATISTICAL DESIGN AND ANALYSES ........................................................................................ 49 
17.1 General Design ............................................................................................................................... 49 
17.1.1 Study Hypothesis ..................................................................................................................... 49 
17.1.2 Primary and Secondary Outcomes (Endpoints) ...................................................................... 49 
17.2 Rationale for Sample Size and Statistical Power ............................................................................ 49 
17.2.1 Projected Number of Sites ....................................................................................................... 49 
17.2.2 Projected Number of Participants ............................................................................................ 49 
17.3 Statistical Methods .......................................................................................................................... 49 
17.3.1 Qualitative Analyses ................................................................................................................ 50 
17.3.2 Quantitative Analyses .............................................................................................................. 51 
17.3.3 Missing Data and Dropouts ...................................................................................................... 52 
17.3.4 Safety Analysis ........................................................................................................................ 53 
17.3.5 Interim Analyses ...................................................................................................................... 53 
18.0 REGULATORY COMPLIANCE, REPORTING AND MONITORING ................................................. 54 
18.1 Statement of Compliance ................................................................................................................ 54 
18.2 Institutional Review Board Approval ............................................................................................... 54 
18.3 Informed Consent ............................................................................................................................ 54 
18.4 Quality Assurance Monitoring ......................................................................................................... 55 
18.5 Participant and Data Confidentiality ................................................................................................ 56 
18.5.1 Certificate of Confidentiality ..................................................................................................... 56 
18.6 Health Insurance Portability and Accountability Act (HIPAA) ......................................................... 57 
18.7 Investigator Assurances .............................................................................................................. 57 
18.8 Financial Disclosure/Conflict of Interest ...................................................................................... 57 
18.9 Clinical Monitoring ........................................................................................................................... 57 
18.10 Inclusion of Women and Minorities ............................................................................................... 58 
18.11 Inclusion of Individuals across the Lifespan .................................................................................. 58 
18.12 Prisoner Certification ..................................................................................................................... 58 
18.13 Regulatory Files ............................................................................................................................ 59 
18.14 Records Retention and Requirements .......................................................................................... 59 
18.15 Reporting to Sponsor .................................................................................................................... 59 
18.16 Audits ............................................................................................................................................ 59 
18.17 Study Documentation .................................................................................................................... 59 
18.18 Protocol Deviations ....................................................................................................................... 60 

 
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18.19 Safety Monitoring .......................................................................................................................... 60 
18.19.1 Adverse Events (AEs) ............................................................................................................ 61 
18.19.2 Serious Adverse Events ......................................................................................................... 62 
19.0 DATA MANAGEMENT ....................................................................................................................... 63 
19.1 Design and Development ................................................................................................................ 63 
19.2 Site Responsibilities ........................................................................................................................ 64 
19.3 Data Center Responsibilities ........................................................................................................... 64 
19.4 Data Collection ................................................................................................................................ 64 
19.5 Data Acquisition and Entry .............................................................................................................. 65 
19.6 Data Editing ..................................................................................................................................... 65 
19.7 Data Transfer/Lock .......................................................................................................................... 65 
19.8 Data Training ................................................................................................................................... 65 
19.9 Data Quality Assurance .................................................................................................................. 65 
20.0 DATA SHARING, PUBLIC ACCESS AND PUBLICATIONS ............................................................ 67 
20.1 Data Sharing Plan ........................................................................................................................... 67 
21.0 PROTOCOL AMENDMENT HISTORY .............................................................................................. 68 
22.0 REFERENCES .................................................................................................................................... 70 
23.0 APPENDIX A: ADVERSE EVENT REPORTING AND PROCEDURES ........................................... 81 
Adverse Event Reporting (Chart) ............................................................................................................ 85 
1.0 ....................................................................................................................................................... 85 
24.0 APPENDIX B: DATA AND SAFETY MONITORING PLAN (DSMP)................................................. 86 
 

 
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1.0 LIST OF ABBREVIATIONS  
 
Abbreviation 
Definition 
AE 
Adverse Event 
AIAN 
American Indian and Alaska Native 
CAC 
Community Advisory Committee 
CBPR 
Community-Based Participatory Research 
CCTN 
Center for the Clinical Trials Network 
CFR 
Code of Federal Regulations 
CHRT-SR 
Concise Health Risk Tracking – Self-Report 
CoC 
Certificate of Confidentiality 
CTN 
Clinical Trials Network 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HHS 
Department of Health and Human Services 
HIPAA 
Health Insurance Portability and Accountability Act 
HSP 
Human Subjects Protection 
IRB 
Institutional Review Board 
LI 
Lead Investigator 
MOUD 
Medication for Opioid Use Disorder 
NIDA 
National Institute on Drug Abuse 
NIH 
National Institutes of Health 
OHRP 
OUD 
Office for Human Research Protections 
Opioid Use Disorder 
PTrax 
Participant Tracking System 
RCT 
Randomized Controlled Trial 

 
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Abbreviation 
Definition 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
TLFB 
Timeline Follow-Back 
UDS 
Urine Drug Screen 
UP 
Unanticipated Problem 
 
 

 
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2.0 PROTOCOL SUMMARY 
Synopsis 
Title 
Facebook Intervention for Preventing Opioid Relapse among 
American Indian Women: Wiidookaage’win Pilot Preparatory 
Study (Aim 1) 
Study Number 
CTN-0123 
IND Number 
N/A 
Study Description 
This Phase I, pilot preparatory study aims to develop a culturally 
relevant Facebook intervention for American Indian and Alaska 
Native (AIAN) women in Minnesota recovering from illicit opioid 
use. The study will consist of three phases: (1) qualitative 
interviews, (2) intervention content refinement and a moderator 
exchange (i.e., bi-directional sharing of knowledge between 
intervention moderators and trainers), and (3) a beta-testing 
period. A study-specific Community Advisory Committee (CAC) 
was formed whose members contributed to the study protocol 
and will continue to provide guidance and input on the study 
implementation and dissemination. At the advice of the CAC, a 
Native Elder woman named the study. Wiidookaage’win is an 
Ojibwe word that means “the place for help and time for helping,” 
and reflects healing and community. We expect the participatory 
approach to treatment development will result in a social media 
intervention with cultural relevance for Native women to maintain 
recovery from opioid use. 
Objectives 
Primary Objective: To develop a culturally relevant Facebook 
intervention for AIAN women in Minnesota that will support 
continued recovery from illicit opioid use. 
Secondary Objective: To conduct a beta-test to assess the 
preliminary feasibility and acceptability of the Facebook 
intervention. 
Outcome Measures 
Primary Outcome Measure: A culturally relevant Facebook 
intervention prototype to support recovery from opioid use. 
Secondary Outcome Measures: Recruitment feasibility, study 
retention, level of intervention engagement and intervention 
satisfaction.  
Exploratory Outcome Measures: Abstinence from illicit opioid 
use and MOUD continuation at the end of the intervention.  
Study Population 
We will enroll up to 18 AIAN participants and 12 interested parties 
for the qualitative interview phase, and 10 different AIAN 
participants for the beta-testing phase. The AIAN participants will 
be women at least 18 years of age who reside in Minnesota, have 
opioid use disorder (OUD) with at least one month of opioid 
abstinence and are currently receiving MOUD. The interested 
parties will be health care providers or AIAN community partners 
with knowledge of AIAN culture and/or OUD treatment and 
recovery among AIAN people. 
Phase or Stage 
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Description of 
Sites/Facilities Enrolling 
Participants 
The study site is Mayo Clinic. AIAN women with OUD will be 
referred to this study by clinicians and staff from addiction 
treatment programs,community organizations and programs in 
and surrounding Minneapolis, Minnesota, United States, and 
community flyers. Interested parties will be referred primarily by 
our CAC.  
Description of Study 
Intervention/Experimental 
Manipulation  
During the qualitative phase, feedback from individual interviews 
with AIAN women and stakeholders will be used to develop the 
intervention. The web-based study intervention to be developed 
will be a private, hidden, moderated, Facebook group that will be 
active for 3 months. Moderators will post content every 1-2 days 
from a content library of about 30 postings each repeated twice 
during the 3 months. Content (moderator postings) will consist of 
pictures/images combined with text and videos designed to 
provide information and stimulate participant discussion. The 
intervention will be beta-tested for a 30-day period using a single 
arm design with assessments conducted at baseline and at the 
end of the intervention. 
Safety Reporting 
Adverse Events (AEs) and Serious Adverse Events (SAEs) that 
occurred within the 30-day intervention period will be self-reported 
by the participants in the follow-up visit. 
Analyses 
In the qualitative interview phase, content analysis supplemented 
with QSR NVivo software will be used to generate interview 
response themes. In the beta-testing phase, descriptive statistics 
will be used to summarize the sample for baseline demographic 
characteristics, study retention, treatment satisfaction ratings, 
intervention engagement level, MOUD retention, and opioid 
relapse, operationalized as opioid positive urine or any self-
reported illicit opioid use at follow-up.  
Study Duration 
The duration of the study, from enrollment for the qualitative 
interview phase to the follow-up visit of the beta-testing phase, 
will be approximately 7 months. 
Participant Duration 
Participants in the qualitative phase will engage in one interview 
lasting approximately 60-90 minutes. Participants in the beta-
testing phase will complete all study-related tasks, including urine 
collection, participation in the intervention, and surveys, within a 
2-month period. 
 

 
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3.0 STUDY SCHEMA  
Phase 1 
Screening/ 
Time 1 
 
 
 
 
Phase 2 
 
 
 
 
Phase 3 
Time 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total N = 24-30 
(N = 12-18 AIAN women participants + N = 12 stakeholders) 
Screen potential participants, conduct informed consent process. Perform 
qualitative phone interview lasting approximately 60-90 minutes 
Moderator exchange, refine the intervention content library 
Total N = 10 
(New AIAN women participant pool) 
Conduct screening including UDS and TLFB Interview, informed consent 
process. Perform baseline survey. 
Beta-test Facebook intervention group for 30 days 
Perform end-of-intervention assessments 
Survey, Timeline Follow-back Interview, UDS, AE/SAE reporting, assess 
intervention engagement level (Facebook analytics)  
Dissemination newsletter 

 
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3.1. Key Research Site Roles 
 
Site LI (MD; DO; PhD) 
Site Clinician (RN; NP; PA; MD; DO) 
Site Psychiatrist (MD; PhD) 
Program Coordinator 
Study Coordinator 
Intervention Moderator 
Statistician 

 
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4.0 INTRODUCTION  
4.1 Study Rationale  
Illicit use of opioids is a major public health problem associated with significant morbidity and 
mortality related to HIV, hepatitis C and overdose (Nelson et al., 2011; Salomon et al., 2000; 
Scholl et al., 2019). As defined by the DSM-5, opioid use disorder (OUD) is “a problematic pattern 
of opioid use leading to clinically significant impairment or distress,” including a constant desire 
and/or unsuccessful attempts to control opioid use (American Psychiatric Association, 2013). 
American Indian and Alaska Native (AIAN) adults are particularly at high risk for OUD due to 
elevated risk of chronic health conditions influenced by depression and anxiety, early trauma and 
childhood abuse, cultural displacement, unemployment, and poverty (Rieckmann et al., 2012). In 
2019, AIAN adults in Minnesota were seven times more likely to die of an overdose involving 
opioids than white adults, representing the greatest disparity between AIANs and whites in the 
United States (Minnesota Department of Health, 2021).  
OUD is a chronic, relapsing condition (Bell & Strang, 2020). Medication for OUD (MOUD) is an 
evidence-based, first-line treatment approach (Bart, 2012; Lillie et al., 2021; Mattick et al., 2009; 
Schuckit, 2016; Sofuoglu et al., 2019), and behavioral strategies to promote continuation of 
pharmacotherapy and support OUD recovery are important to prevent relapse (Bell & Strang, 
2020; Nunes et al., 2018; Sofuoglu et al., 2019; U.S. Department of Health and Human Services, 
2018).  
Gender-specific factors affecting opioid use relapse that are more prevalent in women compared 
with men include perceived stress, trauma, enhanced biological stress reactivity; as well as less 
social support for abstinence (Becker, McClellan, & Reed, 2017; NIDA, 2020). AIAN gender-
specific interventions for OUD do not exist. Research has documented the positive impact of 
strong ties in social networks and high levels of social support on abstinence from substance use. 
Strong social bonds contribute to the maintenance of behavior that is perceived as positive within 
a social context (Shanmugam, 2017). However, understanding how best to leverage social 
support remains a key challenge for the addiction treatment field (Venniro et al., 2018).  
We propose to address these gaps by developing a social digital intervention to promote stress 
management and social network support for opioid abstinence among AIAN women. We will 
utilize Facebook for this platform. Now more than ever with the COVID-19 pandemic, virtual digital 
platforms have potential for greater reach and scale (Brewer et al., 2020; Robinson et al., 2020). 
Consistent with the AIAN cultural value of interdependence, social media-formed groups to 
prevent opioid relapse could lead to greater adoption and sustainability by encouraging 
collaborative efforts across generations of AIAN women and leveraging community resilience for 
coping with stress (Coyhis & White, 2002; Mohatt, McDiarmid, & Montoya, 2000; Teufel-Shone et 
al., 2016; Walters & Simoni, 2002). 
The Specific Aim of this study is to develop and beta-test a Facebook group intervention prototype 
for AIAN women who are abstinent from illicit opioid use and receiving MOUD. We expect that 
the participatory approach to treatment development will result in a Facebook intervention with 
cultural relevance for Native women to maintain recovery from opioid use. Interventions to 
enhance opioid recovery among AIAN women are significant for reducing the substantial public 

 
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health burden of illicit use of opioids.  A virtual Facebook platform has potential for greater 
intervention reach to AIAN women and scalability, enhancing the significance and overall impact.  
Our approach follows the stage model of addiction therapies development (Rounsaville et al., 
2001). If successful, preliminary findings from this proof-of-concept study will be used to support 
pilot randomized controlled trial (RCT) of the intervention within the NIDA Clinical Trials Network 
(CTN). This study is the first step to an intervention that could ultimately be widely disseminated 
through community and addiction health care settings as a treatment adjunct, as well as social 
media; and serve as a model for developing social digital addictions treatment in other 
populations, enhancing overall reach and impact.   
  
4.2 Background and Significance to the Field  
Among 91,799 drug overdose deaths in the United States in 2020, 68,630 (74.8%) involved opioid 
use (Hedegaard et al., 2021). OUDs have increased among US women; from 2002 to 2013, heroin 
use among women increased by 100% in comparison to 50% among men (Centers for Disease 
Control and Prevention, 2015). In 2019, women admitted for addictions treatment in Minnesota 
were more likely than men to report opioids as their primary substance of use (22% vs. 13%), but 
among AIAN women, this rate was greater (45%) (Minnesota Department of Health, 2021). AIAN 
women were 8.7 times more likely to be diagnosed with maternal OUD during pregnancy 
compared to whites, and their infants were 8.0 times more likely to be born with neonatal 
abstinence syndrome (March of Dimes, 2017; Minnesota Department of Health, 2021).  
MOUD is the first-line treatment for OUD. Food and Drug Administration (FDA) approved 
medications for treating OUD are methadone, buprenorphine, and naltrexone (National 
Academies of Sciences, Engineering, and Medicine, 2018). MOUD has efficacy for reducing 
opioid use, retaining patients in care, and decreased risks of all cause and overdose-related 
mortality (Bart, 2012; Lillie et al., 2021; Schuckit, 2016). Relapse rates following discontinuation 
of medication are about 40-60% (Nunes et al., 2017; U.S. Department of Health and Human 
Services, 2016), thus behavioral strategies to promote continuation of MOUD and support opioid 
abstinence are important (Sofuoglu et al., 2019).  
Women are more vulnerable to relapse to substance use than men (Becker et al., 2017; NIDA, 
2020; Kennedy et al., 2013; Walitzer & Dearing, 2006); factors affecting relapse among women 
include stress and less social support for abstinence (Becker et al., 2017; NIDA, 2020). AIAN 
gender-specific interventions for OUD are lacking (Barbosa-Leiker et al., 2020; Meyer et al., 2019; 
Saraiya et al., 2020).  
Substantial evidence documents the positive influence of social reinforcement, social networks, 
and social support on drug abstinence (Al Ghafri et al., 2022; Christakis & Fowler, 2008; Patten 
et al., 2016; Shanmugam, 2017; Venniro et al., 2018). Prior studies examined face-to-face 
interventions to support treatment engagement, MOUD retention and recovery involving 
concerned others (Brigham et al., 2014; Osilla et al., 2020) or peer outreach workers (Scott et al., 
2017; Scott et al., 2020). The COVID-19 pandemic has accelerated the need for virtual digital 
models of care delivery (Brewer et al., 2020; Robinson et al., 2020). Social-media-formed social 
networks hold promise as novel and scalable platforms for providing social support for opioid 

 
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abstinence. Recent studies indicate that individuals recovering from opioid use utilize social media 
technologies (e.g., Reddit) for peer support and advice (Bergman et al., 2018; D’Agostino et al., 
2017). Social media technologies have been adopted to be culturally relevant for AIAN people 
(Intahchompoo, 2018; Mathieson et al., 2017; Rushing & Stephens, 2011; Schlichting, 2016; 
Hensel et al., 2019). However, the use of online social networks among AIAN people for opioid 
recovery support has ben understudied.  
The online social media platform Facebook may effectively engage AIAN people and align with 
AIAN value of interdependence. Facebook users can post, comment, and react to posts from 
other members of a group they are in. Facebook is the dominant social networking platform used 
by US adults across most age groups (18-29: 70%, 30-49: 77%, 50-64: 73%), with lower use 
among individuals >=65 years old (50%) (Auxier & Anderson, 2021). In the LI’s current pilot RCT 
of a Facebook intervention for nicotine use enrolling AIAN people in Alaska statewide, the study 
is well-represented by participants of different ages (range 22 to 76 years); over half (54%) are 
younger than 40 years of age. Another pilot RCT of a Facebook intervention for nicotine use 
enrolled only young adults (18-25 years) and the researchers found high levels of intervention 
engagement for that population (Thrul et al., 2015). The proposed content for a Facebook 
intervention will be transportable to other social media platforms as indicated. For example, 
Instagram is predominantly used by adults aged 18-29 years (Auxier & Anderson, 2021) and 
groups are possible by creating a study-specific Instagram profile and setting it as private.  
The LI’s NIDA-funded work (DA046008) demonstrates the feasibility of a Facebook social support 
group for nicotine use among AIAN people (Merculieff et al., 2020; Sinicrope et al., 2019). Only 1 
of 290 total screened for formative work, beta-testing, and a pilot RCT was excluded due to not 
having a smartphone or access to broadband internet. In the beta-testing phase (n=10; 90% 
women, 70% from rural villages) all completed the 1-month follow-up survey (Sinicrope et al., 
2022). All 10 engaged in the intervention, e.g., the number of comments made ranged from 1-24 
(median 5). Mean treatment satisfaction score based on the Social Media Usability measure was 
4.1 ± 0.6 of 5.0, indicating high perceived usefulness, ease of use, and willingness to recommend 
the intervention to others. In the current pilot RCT, although participants were recruited during the 
COVID-19 pandemic, the research team exceeded the target sample of 60 (N=61) enrolled. 
Retention at six months follow-up is 69%. The LI’s team also provided guidelines for the addictions 
treatment field on Facebook intervention moderator training and lessons learned (Sinicrope et al., 
2022). 
The Lead Investigator (LI) has experience using community-based participatory research (CBPR) 
to develop content (moderator postings) for Facebook group interventions for community 
engagement (Patten et al., 2021), and for nicotine cessation among AIAN people living in Alaska 
described above (Merculieff et al., 2020, Sinicrope et al., 2019). Facebook intervention content 
will be developed to include culturally relevant stress management strategies leveraging 
community strengths. Stress, trauma, and dysregulation in biologic stress response systems 
contribute to substance use (McCabe et al., 2016; Sinha, 2008), and women are particularly 
susceptible to stress-induced relapse (Kennedy et al., 2013; Walitzer & Dearing, 2005; Greenfield 
et al., 2010). The LI’s work with AIAN women highlighted the role of stress in persistence of and 
relapse to nicotine use (Patten et al., 2018; Patten et al., 2020). After adjusting for covariates, 
Perceived Stress Scale scores were positively associated with current smoking among AIAN 

 
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women (OR=1.13, 95% CI 1.02-1.24, p=0.016), but not among men. Among pregnant AIAN 
women, relapse to tobacco use was 78% at 1-2 years postpartum. The primary reason reported 
for relapse was stress (84%) and addiction (52%) (Patten et al., 2019). Integrated interventions 
focused on managing stress-related symptoms (e.g., mindfulness) are effective for improving 
abstinence and reducing relapse to opioids and other substance use (Bowen et al., 2014; Garland 
et al., 2014; Vowles et al., 2019; Price et al., 2019; Witkiewitz, Bowen et al.; 2013; Witkiewitz et 
al., 2014); but these were evaluated using in-person delivery formats. US women reported greater 
use of Facebook than US men (77% vs. 61%), so AIAN women may be more likely to utilize the 
proposed Facebook group intervention (Auxier & Anderson, 2021). The proposed study is 
innovative for developing a gender-specific, socially based, opioid relapse prevention intervention 
using social media technologies that are culturally relevant and already adopted.  
4.3 Risk/Benefit Assessment 
4.3.1 Risks 
Risks are minimal and include those associated with the inconvenience of completing assessment 
interviews and surveys by telephone/video or in-person, of providing urine samples, and some 
potential risks related to confidentiality. A trained member of the study staff will obtain the urine 
sample(s) from the participant. The urine sample test should not present risk to participants, but 
participants may experience discomfort if their result is positive. No medications will be 
administered as part of this study. The study poses no greater than minimal risk to pregnant 
women or fetuses if pregnant women are enrolled. No devices or drugs will be administered as 
part of the study. 
The Facebook intervention will consist of a moderated, closed and secret (completely private) 
group. This means that no one aside from study participants will be able to join the group, locate 
the group through a Facebook search, or see reactions or postings to the group through Facebook 
notification unless they are an official and invited member of the secret and closed group. 
In our moderated Facebook intervention, it is impossible to know in advance what might be 
posted by users, and it is possible that misinformation or postings that might cause emotional 
discomfort could occur. Participants will be encouraged to contact the study coordinator if any 
issue arises that causes them to feel uncomfortable. There are also some minimal risks with 
respect to confidentiality. As a member of a secret Facebook group, participants will be asked to 
discuss their own opioid recovery journeys and participate in discussions about moderated 
postings regarding AIAN opioid use, readiness to maintain their recovery from opioids, and 
opioid treatment resources, among others. Thus, it is possible that health information or other 
personal information about study participants or other AIAN members could be disclosed on 
Facebook postings. To ameliorate concerns, a list of do’s and don’ts for posting on the secret 
Facebook page will be posted at the front of the page so that whenever a participant joins the 
Facebook group, they will be reminded of these guidelines for sharing information, protecting 
confidentiality, and posting appropriately. Participants will be asked or encouraged to not 
mention specific names of people in their house or community. A trained moderator will monitor 
user postings and guide participants through culturally appropriate postings that do not violate 
confidentiality or harm intervention group members. If someone is offended by the postings, 

 
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they can message the moderator to resolve any concerns. Any adverse events related to the 
Facebook group will also be handled by the DSMP, if necessary. Despite these precautions, we 
do not anticipate any adverse consequences of participating in the intervention. In the beta-
testing of a Facebook intervention for nicotine use among AIAN people (Sinicrope et al., 2022), 
one participant shared content outside the group on a personal Facebook page. When this 
occurred, the moderator sent the participant a private message, redirecting the participant to the 
group rules. There were no other group confidentiality or boundary violation incidents. We will 
remind participants in the consent form and a script in the content library to not share personal 
information with potential guest speakers in order to prevent confidentiality breaches. 
   
Information from the participants will not be shared with anyone else except for the research team. 
No voices or images from the audio tapes from the individual qualitative interviews will be 
released. Permission to digitally record will be part of the consent form. Confidentiality of the 
recordings will be maintained by keeping these in a secure and protected computer. Only the 
research team will review the recordings. Once transcribed, the recordings will be destroyed after 
the analyses are completed. In the beta-testing phase, the posted group guidelines and 
intervention moderators will emphasize confidentiality of the group discussions.  
Data from this study will be published and presented in aggregate form only. Participants will be 
informed that their name, tribal affiliation, and other identifying information; or individual comments 
from the individual interviews or Facebook intervention discussions or postings will not be 
published. This will be done to protect the confidentiality and privacy of participants. 
Screening data will not include any unique identifiers and will be used for descriptive purposes 
only (i.e., to characterize the population of individuals screened who were found to be ineligible 
or not interested in participating). For enrolled participants, confidentiality will be maintained by 
assigning every participant a study number (no identifiers) and by numerically coding all data. All 
biospecimens will be labeled with the subject ID number only. The association of the ID number 
and the participant will be kept by the Mayo Clinic site LI and stored within Mayo’s firewalls and 
on a secured, regularly backed-up drive. All data obtained through interviews and other subject 
records will be kept in locked filing cabinets in offices that are kept locked when unoccupied, or 
electronically within Mayo’s firewalls on a secured, regularly backed-up drive. Subject files will be 
kept in a secure area, with access only by designated staff members (LIs and study staff). Any 
computer storage of data will be password protected and only available to the LIs and the project 
coordinator. 
All information connecting study ID numbers to participant names will be destroyed after 
completion of the project. Five years after publication of the results (per standard journal 
guidelines) all paper copies of interview forms, interview transcripts and the data base, will be 
destroyed. Only summaries of group data will be reported in any publications or presentations, 
with no identification of individuals or individual statements. All data elements and data transfer 
activities will be strictly compliant with HIPAA privacy regulatory requirements.  
Once the urine sample is processed at the point-of-contact and the study staff obtains the result, 
the sample will be discarded in a biohazard container and destroyed immediately. Interview forms 
will be labeled with subject ID numbers only; all personal identifiers will be removed before the 
data are coded and analyzed.  

 
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Standard security measures to store data are in place within the Mayo Clinic. Moreover, at Mayo 
Clinic the audio tapes from the individual interviews will be stored in a locked file drawer 
accessible only to the LI Dr. Patten, Co-Investigator Dr. 
, and the Program Coordinator 
Corinna Sabaque. 
For participants, withdrawal symptoms from cessation of illicit opioid use do not pose significant 
health risks as these participants will already be receiving medication for opioid use disorder (e.g., 
methadone or buprenorphine). What symptoms may occur are expected to be mild and may 
consist of: nausea and abdominal discomfort, muscle and joint pain, sweating, runny nose and 
eyes, yawning, irritability, and anxiety. 
4.3.2. Benefits 
The study is designed develop and obtain preliminary feasibility and acceptability data on a social 
media intervention to promote prevention of relapse to opioid use among AIAN women. In the first 
phase of the research, participants will be asked for feedback in designing the intervention. All 
subjects will potentially benefit from discussions about opioid use and maintaining abstinence. In 
the third phase of the research, all participants will have access to a culturally relevant social 
media-formed group that aims to provide support for maintaining abstinence and information on 
connecting to various local resources. The participants will have the opportunity to benefit by 
sustaining their abstinence from opioids, continuing MOUD, and gaining new skills in mindfulness, 
stress management, and resiliency. 

 
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5.0 OBJECTIVES  
5.1 Primary Objective  
To develop a culturally relevant Facebook intervention tailored for AIAN women in Minnesota 
that will support continued recovery from illicit opioid use. The participatory approach to 
treatment development will result in a Facebook intervention with cultural relevance for Native 
women to maintain opioid use recovery. 
 
5.2 Secondary Objective(s)  
To conduct a beta-test to assess the preliminary feasibility and acceptability of the Facebook 
intervention. 
 
5.3 Exploratory Objective(s)  
To assess abstinence from illicit opioid use and MOUD retention at the end of the 30-day beta-
testing of the Facebook intervention. 
 

 
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6.0 STUDY DESIGN  
6.1 Overview of Study Design  
This one-year, Phase I, single-site pilot preparatory study aims to develop a culturally relevant 
Facebook intervention for AIAN women in Minnesota recovering from illicit opioid use. Our 
approach follows the Stage model of iterative addiction therapies development (Rounsaville et 
al., 2001) and the study is consistent with Stage Ia. The study will consist of three phases. The 
first phase will consist of individual qualitative interviews conducted among AIAN women (N=18) 
and addiction care and interested parties (N=12) to develop the intervention content (moderator 
postings). The second phase will consist of development of the Facebook content library and a 
moderator exchange (i.e., bi-directional sharing of knowledge between intervention moderators 
and trainers). The third phase will consist of beta-testing and refinement of the intervention. The 
beta-testing phase will use a single group design enrolling 10 AIAN women participants who will 
have access to the Facebook intervention for a 30-day period. Assessments will be conducted for 
all participants at baseline and at the end of the intervention. Outcomes are recruitment feasibility, 
study retention, treatment satisfaction, level of intervention engagement, opioid abstinence and 
MOUD continuation. The feasibility of using Facebook as an intervention to maintain recovery 
from opioid use among AIAN women will be refined based on the beta-testing results. We have 
formed a Community Advisory Committee (CAC) who contributed to the study protocol and will 
continue to provide input and guidance on the study implementation and dissemination. We 
hypothesize that input from recovering AIAN women participants and the CAC, content refinement 
and a comprehensive moderator exchange, and a beta test of the intervention with recovering 
AIAN women participants will result in a culturally relevant Facebook intervention prototype to 
support recovery from illicit opioid use among AIAN women.  
If successful, preliminary findings from this preparatory study will be used to support a pilot RCT 
of the intervention through the NIDA Clinical Trials Network (CTN). This study is the first step to 
an intervention that could ultimately be widely disseminated through community and addiction 
health care settings as an adjunct to treatment as well as social media. 
 
6.2. Community-Based Participatory Research (CBPR) Approach  
This study utilizes a CBPR approach to ensure the intervention and study methods are culturally 
relevant and acceptable for use in AIAN communities. The need for and interest in a social media 
intervention for maintaining opioid abstinence came from our community partners in Minneapolis, 
Minnesota including the Native American Community Clinic and Minnesota Indian Women’s 
Resource Center. The study concept was co-developed with these community partners.  
When developing the study protocol, we formed a CAC who provided feedback on the intervention 
content (moderator postings), study procedures, and measures. The members consist of AIAN 
women with lived experience as former opioid users, AIAN health care providers, and AIAN 
community members and interested parties. Health care providers and community partner 
organizations include the Minnesota Indian Women’s Resource Center, Native American 
Community Clinic, Community-University Health Care Center, and Indian Health Board. We are 
continuing to enroll members on a rolling basis based on the CAC’s recommendations on 

 
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additional members who should join. The CAC met three times virtually by Zoom to develop and 
design the study protocol and materials and to discuss revisions to the protocol based on the 
feedback from NIDA CTN reviewers. Members have the option to receive an honorarium of $150 
per meeting, accept it on behalf of their organization, or donate it to a local organization or 
community. Members will continue to provide guidance on study implementation and 
dissemination.    
The LI presented the study to the Healthy Nations Advisory Board (HNAB), a group of Tribal 
leaders representing multiple AIAN communities throughout Minnesota. Tribal leaders provided 
feedback on the study population, recruitment, and intervention design. The PI will meet with the 
Healthy Nations Advisory Board on a quarterly basis for continued guidance and feedback 
throughout the project. 
6.3. Duration of Study and Visit Schedule 
The duration of the study, from enrollment for the qualitative interview phase to the follow-up visit 
for the beta-testing phase, will be approximately 7 months. All visits will be conducted by phone 
or in-person.  
Participants in the qualitative interview phase will engage in one phone interview lasting 
approximately  60-90 minutes, then their active participation in the study will be complete.    
Participants in the beta-testing phase will complete all study-related tasks, including urine 
collection, participation in the Facebook intervention, and baseline and end of intervention follow-
up phone surveys, within approximately two months. Their participation in the study will end after 
completing the follow-up visit survey and in-person UDS. 
 
 

 
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7.0. OUTCOME MEASURES  
7.1 Primary Outcome Measure  
A Culturally Relevant Facebook Intervention 
The qualitative work of Phase 1 will result in content that will be relevant to AIAN culture. The 
expected outcomes are development of the intervention which includes development and 
refinement of the content library (yes/no), development and refinement of the Facebook 
intervention prototype (yes/no), development and refinement of the intervention moderator 
guidelines (yes/no), and moderators trained (yes/no).  
The success of the Facebook intervention at supporting recovery from opioid use from the 
participants’ perspective will be assessed in the follow-up survey. Participants will be asked for 
any technical problems that occurred, advice for improving the moderator postings, advice for 
improving the Facebook group, and the potential for gaining lay moderating skills to encourage 
other AIAN women to start their recovery from opioids and begin treatment. 
7.2 Secondary Outcome Measures 
Feasibility and Acceptability  
Recruitment feasibility measures documented by study staff include the number of potential 
participants screened, number eligible, and number enrolled out of those eligible. Study retention 
will be defined as the proportion completing the end of intervention survey and a UDS. We will 
use the 13-item Social Media Usability scale (Lund, 2001) to assess participants’ satisfaction with 
the intervention including perceived usefulness, ease of use, and willingness to recommend the 
intervention to others. The total score is the mean of all 13 items, with a potential range of 1 (low) 
- 5 (high) satisfaction, with higher scores indicating greater acceptability. We will also ask open-
ended questions for feedback on any technical issues that occurred and suggested modifications 
to the prototype.  For intervention engagement assessment, study staff will extract data weekly 
from the Facebook application programming interface (Facebook, 2020) using an extraction 
program based on a Python module (https://pypi.org/project/facebook-scraper/) which we have 
utilized in prior work (Sinicrope et al., 2022). Standard engagement metrics for social media health 
promotion interventions (Pagato et al, 2016) include Facebook analytics of the number of posts 
‘seen by’ group members, reactions (i.e., “like”, “love”, “care”, “haha”, “wow”, “sad”, and “angry”), 
and comments. Engagement by participant includes the number of comments, reactions, 
responses to a Facebook poll or other activities, attendance at live events (e.g., guest speakers) 
and posts initiated (i.e., participant created a post with text, image, and/or video). A total 
engagement count will be calculated from these metrics. The text of participant-generated posts 
and comments will be exported into an excel spreadsheet for analysis of content.  Unlike many 
web-based platforms, Facebook analytics for private groups do not provide time spent on the 
Facebook page. 
7.3. Exploratory Outcome Measures 

 
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Abstinence from illicit opioid and other substance use will be assessed using the Timeline Follow-
Back (TLFB) interview (Sobell & Sobell, 1992; Wray et al., 2016) and a UDS at the end of the 
intervention. Relapse will be operationalized as either a positive opioid UDS or self-report of any 
illicit opioid use in the past 30 days or since study enrollment. Secondarily, we will summarize 
relapse as at least seven consecutive days of self-reported illicit opioid use in the past 30 days or 
since study enrollment (Nunes et al., 2018). Secondarily, we will also report outcomes considering 
missing UDS as missing and not positive/negative (King et al., 2020). MOUD retention will be 
assessed using the TLFB at the end of intervention visit and summarized as the proportion of 
days reporting MOUD use and current use.  
7.4 Study Timeline 
We included a detailed study timeline with the estimated duration and deadlines for each study 
task per quarter. CTN-0123 was funded as a 1-year study with a timeline that included the initial 
formation and implementation of a CAC to co-develop the study protocol with the research team. 
That milestone was successfully completed. 

 
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8.0 STUDY POPULATION  
8.1 Phase 1 
Using a stratified purposeful sample (Patton, 2015), we estimate up to 18 interviews with AIAN 
women participants and 12 interviews with stakeholders (see Section 17.2, Rationale for Sample 
Size). Consistent with best practices for community engagement (CDC, 2011), we chose to 
include a range of diverse interested parties in the initial qualitative work, including potential end-
users (AIAN women), AIAN addiction treatment and community professionals, and anybody who 
is otherwise knowledgeable of AIAN culture and opioid addiction and treatment within AIAN 
communities. AIAN addiction treatment and community professionals were included with the goal 
of developing a sustainable intervention for within healthcare and community settings. These 
individuals refer and provide addiction treatment and other services to support recovery for AIAN 
people and therefore have a stake in the health of AIAN women interested in maintaining their 
recovery. 
8.1.1. AIAN Women 
We will enroll up to 18 AIAN women participants for qualitative interviews participants to achieve 
data saturation (see Section 17.2, Rationale for Sample Size). If data saturation is reached at 12 
AIAN women participants, we will stop accruing AIAN women participants for interviews.  
8.1.2. Health Care Providers and AIAN Interested Parties  
We will enroll 12 health care providers for AIAN people and AIAN interested parties for qualitative 
interviews.  
8.2 Phase 3 
A new sample of 10 AIAN women participants will be enrolled (see Section 17.2, Rationale for 
Sample Size). Participants will be recruited from (1) clinician and staff referrals from addiction 
treatment programs at Hennepin County Medical Center and community clinics (e.g., Native 
American Community Clinic, Indian Health Board, Community University Health Care Center), (2) 
staff referrals from community organizations and programs (e.g., Minnesota Indian Women’s 
Resource Center, Avivo) located in Minneapolis and St. Paul, Minnesota, and (3) friends or 
colleagues affiliated with the CAC. A different community flyer intended for AIAN women in this 
phase will be posted publicly within Minneapolis containing the same information listed above, 
with an updated toll-free telephone number specific to Phase 3. 
8.3 Participant Inclusion Criteria  
Individuals must meet all the inclusion criteria to participate in the study.  
8.3.1. Phase 1 
8.3.1.1 AIAN Women 
(1) 
AIAN based on self-reported race 

 
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(2) 
Gender identity as a woman 
(3) 
Resides in Minnesota  
(4) 
At least 18 years of age with no upper age limit 
(5) 
Has OUD based on the DSM-5 Checklist (American Psychiatric Association, 2013) 
(6) 
Self-reports at least one month of abstinence from illicit opioid use based on Timeline 
Follow-Back (TLFB) interview 
(7) 
Currently receiving MOUD 
(8) 
Is comfortable speaking and reading English 
(9) 
Is familiar with Facebook    
(10) Has access to broadband internet on a mobile phone/computer/tablet at any location   
8.3.1.2 Health care providers/AIAN interested parties 
(1) 
Health care provider or AIAN interested party 
(2) 
Knowledge of Native culture and/or OUD treatment and recovery among AIAN people 
(3) 
Is comfortable speaking and reading English 
(4) 
Is familiar with Facebook 
(5) 
Has access to broadband internet on a mobile phone/computer/tablet at any location  
Having some familiarity with the Facebook platform is needed to provide feedback on content for 
a Facebook intervention. Access to the internet is needed to view online moderator postings for 
providing feedback during the interview. 
8.3.2 Phase 3 
(1) 
AIAN person based on self-reported race/ethnicity 
(2) 
Gender identity as a woman 
(3) 
At least 18 years of age with no upper age limit 
(4) 
Resides in Minnesota 
(5) 
Has OUD based on the DSM-5 Checklist (American Psychiatric Association, 2013) 
(6) 
Self-reports at least one month of abstinence from illicit opioid use based on TLFB interview 
and negative urine opioid screen 
(7) 
Currently receiving MOUD 
(8) 
Is comfortable speaking and reading English 
(9) 
Has an existing Facebook account or willing to set one up 
(10) Is willing and able to participate in the Facebook intervention for 1 month 
(11) Has access to broadband internet on a mobile phone/computer/tablet at any location 
(12) Is willing and able to travel to a community clinic in Minneapolis, Minnesota for the UDS. 
We carefully considered including AIAN women with OUD but not currently abstinent or receiving 
MOUD. However, as the first step, we are interested in developing an approach to support 
recovery from opioid use including MOUD retention among Native women for several reasons. 
First, MOUD is an evidence-based, first-line treatment and thus we want to ensure that all 
participants are receiving this care because MOUD will not be offered as part of the social media 
intervention. Research has highlighted the importance for the addictions treatment field to develop 
novel behavioral strategies for maintaining opioid abstinence and MOUD retention based on 
documented patterns of relapse. In NIDA’s initial review of this protocol, the significance of 

 
20 
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supporting recovery as an adjunct to treatment - a kind of continuing care via social support – was 
noted. Second, the intervention is group-based and delivered virtually without any in-person 
contact from the moderators. Thus, we want to ensure our participants are stable with respect to 
abstinence and currently receiving MOUD care to enhance the likelihood that they will engage 
with the Facebook group and to reduce potential adverse risks. Third, when co-designing the 
study concept for a social media intervention to support recovery with our AIAN community 
partners it was thought to be essential that women were connected to MOUD support, and that, 
as a treatment adjunct the proposed intervention could reinforce Native ways of knowing and 
cultural values to cope with stress and community resiliency for maintaining abstinence. Based 
on our community partner feedback it was also preferred that we did not restrict the duration of 
MOUD use at study enrollment so that the intervention could support MOUD initiation and 
continuation. Likewise, feedback from our CAC has reinforced this aspect of selecting our study 
population. The community-based participatory approach and working with our AIAN partner 
community clinics have been key to designing this study protocol and should enhance our 
recruitment efforts as well as all aspects of study implementation and dissemination. As the first 
step in this line of research, therefore, we chose to develop the intervention with a more 
homogenous sample of women who are abstinent from opioid use and receiving MOUD. 
Nonetheless, the intervention content could readily be expanded in future work for relevance to a 
broader population of Native women to encourage treatment-seeking and use of MOUD. In fact, 
our CAC discussed a pathway to later stages of the research to include Native women in recovery 
who can help to mentor other women to initiate abstinence within the same Facebook group.   
We do not specify a maximum age limit.  As discussed in the Background and Significance 
section, our prior work evaluating a Facebook intervention for nicotine use found a wide age range 
among participants. We will describe any patterns in intervention engagement by age to inform 
the refinement of the intervention and future research. 
8.4 Participant Exclusion Criteria  
AIAN potential participants in Phases 1 and 3 meeting any of the exclusion criteria listed below 
will be excluded from study participation. Interested party participants in Phase 1 will only fail the 
screening if they meet the second exclusion criterion. 
(1) 
Self-reports current suicidality 
(2) 
Inability or unwillingness of participant to provide verbal consent (Phase 1) or written 
informed consent (Phase 3) 
(3) 
(Phase 3 only) Was a participant in Phase 1 
Pregnant women, lactating women, or women who plan to become pregnant will not be excluded 
because the treatment being evaluated is a behavioral intervention and does not involve 
medication or risk to the fetus.  
 
8.5 Strategies for Recruitment and Retention  
8.5.1 Phase 1 

 
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AIAN women participants will be recruited from (1) clinician and staff referrals from addiction 
treatment programs (e.g., at Hennepin County Medical Center) and community clinics (e.g., 
Native American Community Clinic, Indian Health Board, Community University Health Care 
Center), (2) staff referrals from community organizations and programs (e.g., Minnesota Indian 
Women’s Resource Center, Avivo) located in Minneapolis and St. Paul, Minnesota, and (3) friends 
or colleagues affiliated with the CAC. We have included a one-page study information sheet 
developed with the CAC that will be provided to clinicians and staff at these locations. Clinic or 
program staff will approach potentially eligible AIAN women to assess their interest in the study. 
Clinic or program staff will provide interested women with a business card with the name of the 
study at Mayo Clinic and dedicated study toll-free phone number and email. Interested AIAN 
women will contact the study staff by phone, and study staff will complete a phone screening 
survey with them to determine if they are eligible for the study. A community flyer intended for 
AIAN women will be posted publicly within Minneapolis, which will contain the study aim, 
translation of the study name, study logo, abbreviated eligibility criteria, horizontal flow map and 
brief description of their study participation, and study content information (i.e., email and toll-free 
telephone number). It will have a Flesch-Kincaid Reading Level at or below 8.0. 
The CAC will help identify potential interested party participants who have knowledge of AIAN 
culture and/or OUD treatment and recovery among AIAN people. We will provide CAC members 
with the same 1-page study information sheet described above developed for clinic staff and 
business cards so that they can refer potentially interested stakeholders. Study staff will screen 
interested parties by phone to determine if they are eligible for the study.  
8.5.2 Phase 3 
We will use the same strategy for recruitment of potential AIAN women participants in recovery 
from illicit opioid use as described above. A toll-free telephone number will be included on the 
community flyer. 
8.5.3 Recruitment Documentation 
Potential participants will contact the study staff through the study phone number or email 
provided on the business card, information sheet, or community flyer. 
To document recruitment, study staff will use Mayo Clinic’s Participant Tracking System (PTrax). 
PTrax is how Mayo Clinic staff track potential participants throughout the screening and consent 
process. As the study staff conducts the screening process, they will enter the potential 
participant’s name into PTrax. They will then indicate in the system how the potential participant 
was identified and/or referred to the study.  
If the potential participant is not eligible, study staff will indicate the screen fail criteria. If the 
potential participant declines to participate, the study staff will indicate the reason the potential 
participant declines (e.g., “not interested,” “not able to travel to community clinic for UDS”). 
If we have many potential participants declining to participate, it will be helpful to track this in 
PTrax so we can consult the CAC for thoughts and suggestions on how to enhance our 
recruitment efforts.  

 
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9.0 SITE SELECTION 
9.1 Number of Sites  
This is a single site study. Mayo Clinic study staff will coordinate all research activities, including 
participant recruitment, enrollment, interviews, assessments, the UDS, moderating the Facebook 
intervention, the moderator exchange, and the beta-testing of the intervention.  
Though we will recruit from various community clinics and programs, they will only serve as 
locations for recruitment referrals and their staff will not conduct any study procedures. 
The Mayo Clinic study staff will conduct the UDS at the Indian Health Board community clinic in 
Minneapolis, Minnesota. Indian Health Board clinic staff will not conduct any study procedures. 
9.2 Site Characteristics  
Mayo Clinic is a charitable, nonprofit academic medical center that provides comprehensive 
patient care, education in clinical medicine and medical sciences, and extensive programs in 
research. Mayo Clinic includes Mayo Medical School, Mayo Graduate School, Mayo School of 
Graduate Medical Education, Mayo School of Continuous 
Professional Development and Mayo School of Health Sciences. The Mayo brothers pioneered 
the concept of medical group practice before the turn of the century in Rochester, Minnesota, 
and Mayo Clinic has grown to become the nation's largest medical group practice.  
 
Mayo traditions encompass world-renowned clinical and surgical expertise, as well as extensive 
research and educational activities. Clinical support is available from 4,729 faculty in medicine, 
surgery, and allied sciences. In addition to the consultants, there are over 2,400 residents, 
fellows, and medical students among the 64,000 total personnel. In Rochester, Mayo Clinic’s 
2,390 physicians and scientists staff two large campuses; Mayo Clinic Hospital — Rochester, 
Saint Mary’s Campus (1,265 beds) and Mayo Clinic Hospital — Rochester, Methodist Campus 
(794 beds). There is no functional distinction between hospital or clinic patients or physicians, 
as the entire spectrum of health care is integrated into a common practice. This organization 
attends over 1.3 million patients each year, who come from all over the United States and 
abroad. 
9.3 Rationale for Site Selection  
9.3.1 Mayo Clinic 
The facilities and resources available to the investigative team are outstanding and include 
everything needed to complete the proposed project successfully. The Mayo Clinic campus in 
Rochester, Minnesota is a large multi-building campus; the institution is home to the Mayo Clinic 
NCI-designated Comprehensive Cancer Center (MCCC) and the Mayo Clinic Center for Clinical 
and Translational Science (CCaTS), each providing exceptional resources to support this 
application.  
 

 
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At Mayo Clinic, Drs. Patten and 
hold faculty appointments in the Department of 
Psychiatry and Psychology. Dr. Patten directs the Behavioral Health Research Program and her 
research team has ample computer and office space at the Minnesota BioBusiness building. 
Other members of the team hold appointments in the Department of Health Sciences Research 
and Center for Digital Health/Connected Care. Together, MCCC, CCaTS, Center for Digital 
Health, and Department of Psychiatry and Psychology contribute a rich scientific environment 
and provide intellectual, technological, educational, and computing resources that will ensure 
the success of this project. Additionally, Mayo Clinic has several offices that will provide 
essential and unique support to carry out the proposed research, including the Office of 
Sponsored Projects Administration and the Office for Human Research Protection (OHRP) and 
IRB. 
9.3.2 The Research Team  
Collectively, this multidisciplinary research team brings complementary and unique expertise to 
the project. Dr. Patten, the LI, has experience with CBPR, AIAN women’s health, social media 
and behavioral nicotine treatments. Dr. 
 (Co-I) has expertise in qualitative and 
mixed methods and content development and moderator training for social media interventions 
(Patten et al., 2020). Dr. 
 (Co-I) has expertise in addictions treatment among 
women including mindfulness and cognitive behavioral therapies for reducing addiction relapse. 
Other team members bring complementary expertise in addictions treatment including MOUD 
(Drs. 
) and technology-assisted and gender-specific 
therapies for OUD (
) (Saraiya et al., 2020; Marsch et al., 2020). Dr. 
 
(
) has experience with AIAN culturally adapted behavioral interventions for 
substance use (Dickerson, Venner, & Duran, 2014). 
, MD (NorthStar Node), 
University of Minnesota, has joined the research team as a collaborator. Dr. 
 is a junior 
health disparities researcher who provides addiction care for AIAN patients at a local clinic in 
Minneapolis. 
 PhD, Mayo Clinic, has also joined the research team as a 
collaborator. Dr. 
is a post-doctoral clinical psychology fellow with expertise in acceptance 
and commitment therapy and other mindfulness-based therapies. Corinna Sabaque, MPH 
(Dine’) will serve as the Program Coordinator and will assist with the NIDA and IRB progress 
reports. Corinna Sabaque and Antonia Young, BA will conduct the qualitative interviews and 
moderate the Facebook intervention. Additional Mayo Clinic study staff include 
 
BA, who will assist with study design, screening, recruitment, enrollment, and assessments, and 
, MS, biostatistician who will assist with statistical analyses and summaries 
including AEs/SAEs.  
 

 
24 
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10. STUDY PROCEDURES  
10.1  Phase 1: Qualitative Work to Develop Facebook Content 
10.1.1 Projected Facebook Content  
Based on initial input from our community partners in designing the study, and subsequent advice 
from our CAC, potential Facebook content for the moderator postings will be derived from three 
sources:  
(1) Mindfulness-based relapse prevention (MBRP) treatment. MBRP focuses on managing 
stress-related symptoms and is an evidence-based intervention for improving abstinence 
and reducing relapse to opioids and other substance use (Bowen et al., 2014; Garland et 
al., 2014; Vowles et al., 2019; Price et al., 2019; Witkiewitz, Bowen et al.; 2013; Witkiewitz 
et al., 2014). Topics include recognizing the role of stress/trauma in substance use, 
mindfulness practices in daily life and high-risk situations, acceptance, and social support 
(Bowen et al., 2014; Vowles et al., 2019; Witkiewitz et al., 2013; Witkiewitz et al., 2014). 
 
(2) Stress Management and Resiliency Training (SMART) program. The SMART program 
has been shown to be effective in RCTs for reducing perceived stress among women and 
diverse populations (Bhagra et al., 2019). Topics include four key mindfulness concepts: 
gratitude, mindful presence, kindness, and resilient mindset translated for lay audiences 
(Resilient Option, 2020). 
 
(3) Existing opioid abstinence support resources and referral information. We have developed 
a web link on 
. It is a single webpage that includes links for 
participants to access existing cultural and community resources including shelters, 
childcare, mental/behavioral health clinics, substance use programs, and commercial 
tobacco cessation resources. Resources also connect or reconnect participants to MOUD 
and other treatments for OUD and other substance use. We have also added resources 
that address parenting, as well as preconception, prenatal and postpartum resources that 
could help to reinforce opioid abstinence. This focus aligns with the AIAN cultural value 
emphasizing families and interdependence in supporting addiction recovery. We worked 
with members of the CAC who are clinic staff from the Community-University Health Care 
Center, Native American Community Clinic, Indian Health Board, and Minnesota Indian 
Women’s Resource Center to gather these opioid abstinence and community support 
resources. The webpage on 
 will also include a link to email the study 
team if participants have recommendations for additional resources. 
We identified existing social media content such as digital story videos from Native people, 
images, and text that supplement the MBRP treatment and SMART program. Selection of 
potential content was made through feedback from the CAC. Some examples of CAC suggestions 
were to include pictures of nature from areas in Minnesota that were more relatable and to include 
artwork from local Native artists that feature Native women and spirituality. For mindfulness 
practices, it was important to recognize when individuals are already being mindful such as during 
smudging practices or watching a bird on a windowsill. In fact, it was recommended that all beta-

 
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testing participants receive a smudge kit at study enrollment to facilitate their participation in 
mindfulness exercises during the intervention. Gratitude exercises that focus on a specific person 
might be triggering so it was suggested to have the option of gratitude toward an animal or nature. 
Consistent with the value placed on families among AIAN people, content will reinforce healthy 
parenting and families that may be especially relevant to women who have children, and/or are 
pregnant or planning on becoming pregnant. Furthermore, the inclusion of Native songs was 
thought to be healing and could reinforce culture as a way to support opioid recovery. Based on 
this feedback, seven potential moderator postings (text/image and video postings) were created 
and will be used to obtain feedback from participants in the qualitative interviews. 
The CAC recommended that the study be named by a Native Elder woman to capture the essence 
of what the study is trying to accomplish and to have meaning in the community beyond the 
project. The CAC recommended Sharyl WhiteHawk (Ojibwe/Anishinaabe) who gave the study the 
name “Wiidookaage’win,” pronounced phonetically as “Wee doo kah gay win,” an Ojibwe word 
that means “the place for help and time for helping.” “Wiidookaage’win” reflects healing and 
community, which are values important to Native women recovering from addiction.The CAC also 
recommended Native artists in Minnesota for a relevant study logo, moderator postings, and 
Facebook cover photos. The logo was created by 
 featuring three Native 
women embracing each other and smiling, whichreflects the meaning of the study name. 
10.1.2. Moderator Guides for Qualitative Interviews  
We have included the semi-structured moderator guides for the individual interviews with AIAN 
women participants and interested parties respectively that were developed by the research team 
with input from our CAC. Interviews assess selected moderator postings for cultural relevance 
(Davis & Resnicow, 2012; Dickerson et al., 2020) and perceived effectiveness (Davis, 
Nonnemaker, Duke, & Farrelly, 2013) along with eliciting feedback on ways to engage AIAN 
women in the study and intervention. The seven moderator postings include three videos featuring 
digital stories from Native women and a Native song that range from 30 seconds to five minutes 
and 36 seconds in duration. The remaining postings are text/images encouraging mindfulness 
and gratitude practices and include Native artwork. For each posting, the interviewer will ask 
about cultural relevance. For example, “How did you relate to [the subject in the video]?” and 
“How, if at all, does this video relate to your values as a Native woman?” Interview questions also 
assess perceived effectiveness of each posting, i.e., “How do you think this posting might help in 
supporting Native women in their recovery from opioid use? Do you think it would work?  Why or 
why not?” Other topics covered in the interview are ways to optimize engagement with the 
Facebook intervention and how best to appeal to women to participate in the study.  
10.1.3. Interviewer Training  
Interviews will be conducted by female study staff trained in qualitative interviewing. Using the 
moderator guides developed, Dr. 
 will provide training with study staff including: 4 hours 
of didactic instruction, 4 hours of mock interview practice, and completion of a certification 
interview (Krueger & Casey, 2014).   
 

 
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10.1.4. Screening Visit   
Trained female study staff will use the Screening Form during a phone/video call with interested 
potential participants to determine the study eligibility criteria. For AIAN women participants only, 
the screening measures include the TLFB interview to assess illicit use of opioids in the past 30 
days, the Concise Health Risk Tracking—Self Report (CHRT-SR) Suicidal Behavior Evaluation 
(Trivedi et al., 2011) to assess current suicidality, and the OUD DSM-5 Checklist, an interviewer 
administered instrument that consists of each DSM-5 diagnostic criterion for OUD in the form of 
a closed question, and staff indicate “Yes” or “No” based on the potential participant’s responses. 
If the potential participant answers “Yes” to at least two questions, they will be eligible for the 
study and will be enrolled. If they do not, they will be provided referral resources. 
Those not meeting these criteria will be provided with referral resources. For those meeting the 
study eligibility criteria, we have included a Participant Contact Form that will be completed by 
study staff to obtain information to assist in contacting participants to schedule the interview. This 
form collects the participant’s email address and phone numbers. No information from this form 
is used in data analyses, nor is this information captured in the data capture system. 
Study staff will either move forward to complete the consent process and qualitative interview in 
the same call or it will be scheduled for the near future. The participant will be sent an email or 
text message with a web link and attachment for viewing online materials consisting of videos and 
text/image postings that will be reviewed during the interview.   
10.1.5. Enrollment 
Individuals who are eligible and complete the informed consent process (described below) will be 
enrolled.   
10.1.6. Interview Methods 
Trained female study staff will conduct an individual semi-structured interview by phone or video 
call (i.e., Zoom, Facetime) lasting approximately 60-90 minutes. We have included the moderator 
guides for the interviews with AIAN participants and interested parties, respectively and these are 
described above. The interviewer will begin by obtaining verbal consent from the participant to 
participate in the study and to be recorded for the qualitative portion before conducting the 
interview. If the participant is not comfortable being recorded, they can still participate, and the 
study staff will take detailed field notes. The potential research participant will be informed of the 
details of the study, the confidential nature of the study, and the fact that participation is entirely 
voluntary and will not affect their current or future medical care anywhere they get health care. 
If there is any sign of incoherence or report of current intoxication/substance use, the interviewer 
will offer referral resources and stop/reschedule the interview. If the interview is conducted by 
phone, the participant will be asked if they have the online link accessible to view during the 
interview. If not, the interviewer will resend the link by email or text. If the link cannot be accessed, 
the interview will be rescheduled. If the interview is done by Zoom/video call, the interviewer will 
share the materials on her screen so that the participant can view the postings during the 
interview. 

 
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First, the interviewer will begin with an icebreaker question to build rapport. For AIAN women in 
recovery, this will be “What was the last beautiful thing you saw?” For interested parties, this will 
be “Can you tell me a little bit about where you are from and how long you have worked at 
[organization/setting] in Minnesota?” Next, the interviewer will collect brief demographic 
information with items derived from the PhenX Toolkit Demographics form (Hamilton et al., 2011). 
For AIAN participants, this information will include race (in addition to AIAN), ethnicity, age, 
education, marital status, employment, and connectedness to their Native culture. The last item 
will be measured with the question, “For this next question, I’d like you to think of a number 
between zero and ten with zero meaning ‘Not at All Important’ and ten meaning ‘Very Important’.  
By choosing any number between zero and ten, how important is being Native to your overall 
identity?” (adapted from Resnicow et al 2009), and it will be scored using an 11-point Likert scale 
(0 = Not at all important, 10 = Very Important). For interested party participants, this will include 
race, ethnicity, gender identity, and their role working with AIAN women in recovery. No protected 
health information or identifying information will be collected from participants. For AIAN 
participants, the screening form will not be linked to the interview form and the interview form will 
contain a study ID number only with no identifiers. 
Next, the interviewer will begin the audio recording and tell the participant that they started 
recording. In the event the participant is not comfortable being recorded, or the audio equipment 
is malfunctioning, the interviewer will take detailed, written notes. First, the interviewer will 
describe the proposed Facebook group. Second, the interviewer will watch/share each video 
posting with the participant and read aloud or have the participant read each text/image posting, 
depending on the participant’s preference. For each posting, the participant will appraise the 
content for cultural relevance and perceived effectiveness as described above. Third, the 
interviewer will inquire about best ways to recruit and engage AIAN women in recovery in this 
type of program. We will ask about other content that might be helpful/relevant/interesting topics 
to include (e.g., beading, cooking).   
We pretested the moderator guides with research staff for duration, wording, and flow. We expect 
the interviews with AIAN women to last about 75-90 minutes and those with stakeholders about 
60-90 minutes. Participation in the study is completed after the interview is conducted. 
Participants will receive a $
 cash card as a thank you for their time. 
The study staff will ask the participant to provide a mailing address for the 
 
 cash card, which the study staff will document in REDCap. This information will not 
otherwise be included in the dataset. 
At the end of the interview, all participants (AIAN women and interested parties) will be asked 
their permission for study staff to contact them in the future to share results from the study. All 
participants willing to be recontacted will be mailed a dissemination newsletter to be created with 
our CAC that will share the study findings.  
We will also conduct a minimum of 2 member checks to increase the trustworthiness and 
credibility of results (Lincoln & Guba, 1985) and relevance to AIAN women. Once the interviews 
are transcribed and coded, for AIAN women participants who said they were willing to be re-
contacted, we will conduct a brief (15-20 minute) phone interview to review her individual 
transcript (responses) and how these were interpreted (coded). We will ask the participant if these 

 
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interpretations resonate and if she would change or add anything. We will conduct more member 
checks if major discrepancies in interpretations of interview responses are noted.  
 
10.1.7 Phase 1 Table of Assessments 
Concept 
Assessment 
Participant eligibility measures  
Screening survey  
 
AI/AN participants only: 
Meets Opioid Use Disorder criteria, based on the DSM-
5 checklist (American Psychiatric Association, 2013) 
 
Timeline Follow-Back interview (Sobell et al., 1988) to 
assess illicit opioid use in past 30 days 
 
Current suicidality based on last 3 items from the 
Concise Health Risk Tracking—Self Report (CHRT-SR) 
Suicidal Behavior Evaluation (Trivedi et al., 2011)  
Semi-structured interview 
Brief demographic questions (Hamilton et al., 2011) 
Questions assessing moderator postings for cultural 
relevance (Davis & Resnicow, 2012; Dickerson et al., 
2020) and perceived effectiveness (Davis et al., 2013) 
 
Questions to obtain feedback on ways to enhance 
study participation and Facebook group engagement  
 
10.2 Phase 2: Prototype Development, Content Library, and Moderator Exchange 
10.2.1. Prototype Development 
The intervention prototype will be developed with the Mayo Center for Digital Health and guided 
by recommendations for social media health communications (Centers for Disease Control and 
Prevention, 2016). To address potential privacy concerns, we are utilizing a private and closed 
group (i.e., invitation only, Facebook page and postings/news feeds not visible, searchable, or 
accessible to anyone on Facebook except the participants) and a group policy/guideline that 
emphasizes confidentiality of all content. We have included a screenshot of a draft Facebook 
cover with the logo/study name. We have included the initial participant guidelines for the 
Facebook group. Based on feedback from participants and the research team during Phase 1, 
we will ask the Facebook group members for their input on what guidelines we should include to 
ensure their comfort participating in the group. 

 
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10.2.2. Content Library and Intervention Moderator Guidelines 
The Facebook intervention will have a three-month duration consistent with other addiction social 
media intervention platforms (Meacham et al., 2021; Ramo et al., 2015; Sinicrope et al., 2019). 
Content (moderator postings) will be refined based on results from the qualitative interviews. We 
will develop a content library (digital and written) similar to a conventional treatment manual for 
use by the moderators (Pagoto et al., 2016). It will contain at least 30 moderator postings. 
Moderators will post once every 1-2 days for the three-month duration; postings will be repeated 
each of the three months. Content for moderator postings will consist of images, audio, and video 
combined with text designed to provide information and stimulate participant discussion. The 
postings have been refined based on the feedback from the Phase 1 qualitative interviews and 
CAC feedback. Some refinements included keeping posts focused on one topic, avoiding 
overuse. Meta-themes derived from interviews that will be addressed in the group include keeping 
the group a positive experience for the participants, encouraging the participants to build a toolkit 
of ways to deal with stress using MBRP and SMART principles, keeping the language and topics 
in the group authentic and relatable to the participants, and incorporating exercises or local 
resources for the participants to take action after viewing posts. The moderator posts will be 
organized by topic, and each posting will include sample text the moderators could add to initiate 
discussion or modify according to current group conversations. The content library will also 
include (1) welcome posts, group description, (2) options for Facebook covers, (3) moderator 
guidelines for handling challenging conversations and posting of inappropriate posts or 
misinformation (e.g., deleting unrelated or false posts), (4) closing posts including additional 
places to connect to resources after the group ends. Based on feedback from Phase 1 
participants, some specific types of postings will include personal stories from AIAN women in 
long-term recovery, coping mechanisms provided after introducing topics such as cravings and 
triggers, and Facebook live event to host a guest speaker who is knowledgeable of AIAN culture 
and/or opioid recovery. Participant information will not be disclosed to the guest speaker, but 
incidental occurrences may occur. To reduce the likelihood of these occurrences, we will tell 
participants in the consent form and a script in the content library to not share personal information 
so their identity and PHI can remain protected. We will incorporate artwork from Native artists as 
much as possible, also consistent with Phase 1 feedback. All data collection and study accrual 
for Phase 1 is complete. 
Although we will develop a three-month intervention, in this pilot preparatory study, we will beta-
test the intervention for a 30-day period only. A 30-day intervention should allow sufficient time to 
determine engagement levels with Facebook and may help to determine appropriate “dosing” for 
a subsequent clinical trial. In prior work developing a Facebook intervention for nicotine use 
(Sinicrope et al., 2022), a 30-day duration was sufficient for obtaining rich feedback on the content 
postings and end-user experience with the intervention; to note any technical issues that need to 
be remedied; and to obtain preliminary data on recruitment feasibility, study retention, and level 
of intervention engagement. Our goal is to refine the Facebook prototype for evaluation of the 
three-month intervention in a subsequent pilot RCT.  
10.2.3. Facebook Intervention Moderators 

 
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The intervention will be moderated by Corinna Sabaque, an AIAN woman (Navajo/Jemez 
Pueblo), with strong foundations in Native culture and knowledge of community resources and 
connections. Antonia Young will support Ms. Sabaque as a co-moderator. Dr. 
 will 
serve as a back-up moderator in the event that either Ms. Sabaque or Ms. Young is unavailable 
to moderate the group. In addition, as suggested by our CAC, we also plan to engage the same 
Native Elder woman, 
, who is an addictions counselor working with AIAN women 
and has experience using Facebook and other social media. She will act as a consultant who will 
assist Ms. Sabaque and Ms. Young as they moderate the group. Ms. Sabaque or Ms. Young will 
contact 
 to describe any incidents or issues that occur with no identifying 
information and get advice on how to address the situation. All moderators will participate in the 
moderator exchange described below. 
10.2.4. Moderator Exchange 
10.2.4.1. Overview 
The success of a social media group for health behavior change is dependent upon the skills of 
its moderators to promote engagement among their members (Sinicrope et al., 2022; Young, 
2013). Instead of a traditional training where information is sent in one direction, we have opted 
for a bi-directional exchange where our moderators and trainers can share knowledge with one 
another.  
 
The overall goal of the training will be to ensure that our moderators have the knowledge, skills, 
and confidence to moderate the Facebook intervention group. In the case of Wiidookaage’win, 
with input from our CAC and research team, we identified that understanding, appreciation, and 
inclusion of AIAN culture and values must be at the forefront of all exchanges. To accomplish 
this goal, we have developed 5 exchanges (about 20-22 hours in total) of knowledge and skills 
in the areas of: 1) Supporting Recovery from Opioid Use; 2) Culture and Gender Issues in 
Delivery of Substance Use Interventions for Native Women; 3) Teaching Mindfulness; 4) 
Communication Skills for Health Behavior Change; and 5) Online Community Management 
Skills.  
 
We have included a table below that details the content and length of each exchange session 
as well as who will lead and attend each exchange session. While each training exchange is 
separate, they will be provided in the sequence described here so that understanding of opioid 
recovery, gender, and culture issues for Native Women can be woven into all exchanges.  
 
Faculty trainers for the moderator exchange include members of the research team. We will 
engage other individuals with relevant expertise as consultant trainers including Ms. 
 
 at Mayo Clinic who leads the Mayo Clinic Facebook page and is an expert at online 
community management (Young, 2013), and Dr. 
 (University of Michigan An 
Arbor), an expert in lay motivational interviewing skills and application of these skills to a social 
media forum. Both individuals trained the AIAN moderators for the LI’s Alaska-based social 
media intervention for nicotine use (see Sinicrope et al., 2022). 
 

 
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10.2.4.2. Evaluation 
Successful moderators will report high levels of confidence to promote engagement with and 
across group members, to respond to a variety of posts, and to know when to seek support from 
other team members as needed. To evaluate the success of our training plan, a pre-post 
exchange assessment will be administered measuring their levels of confidence in each area of 
the exchange, satisfaction with the exchange process, and recommendations for     
improvement. If needed, additional exchanges will be provided. All moderators will receive a 
certificate of completion after completing all training modules. 
 
10.2.4.3.  Beta Test Exchange 
One of our faculty consultant trainers (
) will review moderator-participant 
discussions weekly meet with the moderators every two weeks over the beta testing period to 
share constructive feedback and support to one another as they hone their skills as moderators.  
 

 
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Wiidookaage’win Moderator Exchange Overview 
Title of 
Exchange 
Description 
Time/Days 
Faculty 
Trainers  
Supporting 
Recovery from 
Opioid Use 
A 1-hour online workshop that covers:  1) 
the role of peers in recovery; 2) opioids 
and the brain; 3) treatment options; and 4) 
supporting those using opioids 
. 
The training will include a 1-hour exchange 
via Zoom. 
2 hour training video and 
1 hour Zoom meeting to 
discuss and exchange 
information 
 
 
 
Culture and 
Gender 
Considerations 
for Delivery of 
Substance Use 
Interventions 
with Native 
Women 
A 2-hour exchange of information on how 
culture and gender affects opioid recovery 
and support, and the moderation of the 
Facebook group (support messaging, 
selection of content, and promoting 
engagement). 
2 hours: This topic will be 
built into all the training 
modules. We will include 
two 1-hour Zoom meeting 
to discuss this topic at the 
beginning and then end 
of the training. 
  
Teaching 
Mindfulness 
Includes a 3-hour training of MBRP 
provided by psychotherapy.net and a 1-
hour virtual training provided on SMART. 
4 hours: (3-hour training 
video and then Zoom 
meeting to discuss and 
exchange information.  
 
   
Online 
Community 
Management 
and Moderator 
Principles  
Virtual workshop focused on ways to 
increase engagement in a Facebook 
group. Will include didactic exchange and 
hands-on practice. 
6-8 hours  
 
 
Communication 
Skills for Health 
Behavior 
Change  
Virtual and face-to face workshop to build 
skills in lay motivational interviewing and 
communication. Will include didactic 
exchange and hands on practice 
6 hours (hands-on 
practice will be combined 
with online community 
management training. 
 
 
Human 
Subjects 
Training 
A training about protecting human subjects 
in research is required by Mayo Clinic for 
all people engaging in medical research 
involving human subjects.  
Study staff have already 
completed this training.  
-- 

 
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10.3.  Phase 3: Beta-Testing of the Facebook Intervention 
We will conduct a 30-day beta-test of the intervention prototype and study procedures with a new 
sample of 10 AIAN women participants in recovery from illicit opioid use. The purpose of this 
phase will be to expose participants to and obtain feedback on the 30 days of moderator postings, 
note any technical issues that need to be remedied, and facilitate any refinements of the program. 
This phase will use a single group design with study assessments at baseline and at the end of 
the intervention. Active study participation will be complete at the follow-up visit. The Facebook 
intervention prototype will be refined based on user feedback for use in a future pilot RCT. 
10.3.1. Screening Visits and Consent Procedures 
10.3.1.1. Phone Screen 
The study staff will either call the participant or vice versa to begin the screening process. They 
will first confirm their identity with their full name provided in their email or voicemail. Trained 
female study staff will screen interested participants by phone to determine the study eligibility 
criteria with an initial set of questions. The initial set of eligibility questions will include self-reported 
race/ethnicity, gender identity, age, current residence, OUD DSM-5 Checklist, current use of 
MOUD, comfort reading and speaking English, whether the individual has a Facebook account or 
is willing to set one up, access to broadband Internet at any location, and willingness to travel to 
a community clinic in Minneapolis for the UDS. If the individual is eligible for the study, study staff 
will give them the option to sign the informed consent form remotely using DocuSign via PTrax or 
meet the study staff at the Indian Health Board community clinic to sign a hard copy of the consent 
form before the UDS. In addition to the study eligibility criteria, participants will be asked if they 
have a current prescription for opioids on the Screening Form, but this information is neither an 
inclusion or exclusion criterion and will only be utilized in case their urine is positive for opioids in 
the UDS. 
At the UDS screening visit, the remaining screening procedures will include the same suicidality 
questions from Phase 1 and  the TLFB to assess past 30 day use of opioids such as oxycodone, 
opiates such as heroin, and fentanyl. Those not meeting these criteria will be provided with referral 
resources. For those meeting the study eligibility criteria study staff will complete a Participant 
Contact Form. This form collects the participant’s email address and phone numbers as well as 
secondary contact information. No information from this form is used in data analyses, nor is this 
information captured in the data capture system. 
The study staff member will then schedule the participant for a UDS to screen them for the 
presence of opiates, opioids, and fentanyl. They will be asked to bring their prescription bottle to 
the UDS to verify that they are taking MOUD, and, if the participant indicates that they have a 
prescription for opioids at screening, they will be asked to bring their opioid prescription bottle as 
well. 
10.3.1.2. In-Person Visit 
Participants meeting the initial study eligibility criteria will be asked to make an in-person visit to 
the Indian Health Board community clinic in Minneapolis, Minnesota. Mayo Clinic study staff will 

 
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confirm their identity by asking for their full name and date of birth. If remote electronic consent 
was not obtained, study staff will obtain written informed consent. The participant will be asked to 
answer the suicidality screening questions, provide a urine sample, and verify that they are taking 
MOUD by presenting their prescription bottle. A member of the CAC is a clinician at the Indian 
Health Board who has obtained permission for Mayo Clinic staff to perform the UDS at this 
location. In the event the potential participant does not come to their scheduled UDS, the study 
staff will attempt to contact the potential participant to reschedule the visit. Three attempts will be 
made over 4 weeks before the potential participant will be considered ineligible. 
All urine specimens will be collected using one-step temperature-controlled urine drug test cups 
 following the manufacturer's 
recommended procedures. This container is designed for safe, secure collection and 
transportation of biological specimens for laboratory evaluation. The container features accurate, 
easy-to-read, molded-in graduations on three sides. Top and bottom ribbed etchings ease the 
opening and closing process when wearing examination gloves. Containers are flexible, crack-
resistant and are manufactured from virgin, high clarity, chemically inert, medical grade 
polypropylene. Heavy duty polyethylene screw caps feature a unique dual fill circle thread design 
which provides a tight, leak-proof seal. 
The potential participant will have a private space away from the study staff to urinate into the test 
cup, which will have a thermometer strip attached to confirm that the sample is in the area of 
biological acceptance. The study staff will be required to wear protective clothing and gloves and 
treat it as an infectious agent. The study staff will use a script to instruct the potential participant 
on the minimum amount of urine necessary, that they should wash their hands after completing 
the sample, and how the study staff will read the result. The script will also reassure the potential 
participant that the urine sample will be destroyed after receiving the result, only the result will be 
kept if they are eligible, and they will receive a $
 cash card for their time. 
The study staff will use IDTC-II 12 Panel Instant Drug Test Cards 
 to test for recent (2-3 day window) substance 
use including opiates. The test will also detect amphetamine, barbiturates, buprenorphine, 
benzodiazepines, cocaine, methadone metabolite, methamphetamine, ecstasy, methadone, 
morphine, oxycodone, phencyclidine, tricyclic antidepressants, and marijuana. A separate drug 
test strip, the Instant Drug Test II Fentanyl, will be used to test for fentanyl 
(https://cliawaived.com/fentanyl-rapid-tests-20.html). The result for each substance measured 
with the IDTC-II cards can be “preliminary positive”, “negative”, or “invalid”. The result for the 
Instant Drug Test II Fentanyl can be “positive,” “negative,” or “invalid.” The study staff will be able 
to determine the presence of opiates and opioids within 5-60 minutes. If the result for opiates is 
“preliminary positive,” the woman will not be eligible for the study, and she will be provided referral 
resources. The UDS will only be used for research purposes, so the study staff will not share the 
specimen and pursue confirmation testing with a third party (i.e., CLIAwaived, Inc.). The specimen 
will only be used by the study staff and promptly destroyed after receiving the results. 
If the urine sample result is “preliminary positive” for opioids, the woman will confirm that she has 
been prescribed opioids for medical use, and will show her prescription to the study staff. The 
purpose of presenting the prescription bottle is to support the participant’s self-report of having a 
prescription for opioids. However, a limitation is that we will not know if the amount of medication 

 
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consumed exceeds the prescribed amount. If they do not have a prescription, they will not be 
eligible for this study and will be provided referral resources.  
The test will detect other commonly abused substances besides opiates, and the full results will 
be used to characterize the sample at baseline. Any other positive result besides opiates and 
opioids will be neither an inclusion nor exclusion criterion or outcome measure. Eligible 
participants may complete the baseline survey with the study staff immediately after the UDS 
during this visit, or it will be scheduled to be completed by phone in the near future. Participants 
will receive a $50 cash card for completing the UDS as a thank you for their time and for any 
travel costs incurred. 10.3.2. Informed Consent Participants will provide written informed consent 
via DocuSign or hard copy to participate. Study procedures and the potential risks and benefits 
of participating in the study will be explained by research staff. The potential research participant 
will be informed of the details of the study and the fact that participation is entirely voluntary and 
will not affect their current or future medical care anywhere they receive medical care. The study 
staff will ensure that all participants meet the inclusion/exclusion criteria as stated in the study 
protocol and that the potential participant clearly understands the study procedures and agrees 
to follow them. Standard language in our consent procedure assures potential participants of the 
confidential nature of the study. Those who participate will be clearly assured they may withdraw 
from the study at any time without adversely affecting current or future medical care anywhere 
they receive medical care. The consent form obtains HIPAA authorization from participants for 
use of protected health information. It also outlines the UDS procedure and sensitive questions 
(i.e., current suicidality) that will be asked in order to complete the screening procedure; it will 
note that potential participants will receive a $50 cash card in remuneration for the UDS and 
potential travel costs regardless of their ultimate eligibility. It will also note the potential risks of 
the UDS and sensitive questions, including potential discomfort in front of research staff if they 
receive a positive UDS result. If the woman agrees to participate, she will need to complete the 
UDS as part of the study screening process. Staff will answer questions about the consent form 
while participants are reviewing it. All screening and consent forms/processes are approved by 
the IRB and are at the eighth grade reading level. Potential participants will be provided with a 
copy of the consent form for their records. The consent form will include information on the nature 
of the study and alternatives to taking part, and contact information (email and toll-free number) 
for the LI and Program Coordinator. Participants will be encouraged to phone with concerns or 
problems that might occur during the study. During the informed consent process, we also ask 
permission to re-contact the participant in the future to share the study findings.  
10.3.3. Baseline Visit 
If the participant does not have time or wish to complete the baseline survey at the UDS visit, it 
will be scheduled for another time to be conducted by study staff by phone. We have included a 
copy of the Baseline Survey. Measures incorporated in this study were selected from the PhenX 
Toolkit version November 11, 2021, Ver 40.4 for screening and baseline demographic and 
substance use measures. The PhenX Demographics form (Hamilton et al., 2011) collects 
information about demographic characteristics of the participant, including age, ethnicity, race (in 
addition to AIAN), education, marital status, employment status, the number of children under the 
age of 18 residing in their household, and the same question from Phase 1 measuring the 
importance of being Native to the participant’s identity. We will utilize an item from the PhenX 

 
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Toolkit that lists seven major categories of different substances including stimulants (e.g., 
methamphetamine, Adderall), cocaine/crack, marijuana, sedatives/tranquilizers, club drugs, 
hallucinogens and inhalants/solvents; and inquire about the past 30-day use of each. For each 
substance endorsed, we will use the TLFB to assess the days of use. We will ask how the 
participant used opioids (i.e., injections, pills, patches, lozenges), as Dr. Resnicow noted that their 
recovery experiences may differ depending on how they consumed opioids. We will collect 
information on OUD treatments the participant completed within 30 days before baseline, such 
as inpatient or outpatient services, individual or group support services, or Narcotics Anonymous. 
Data on substance use will be collected to characterize the sample at baseline (and again at 
follow-up) and to explore patterns of intervention engagement by substance use.  
Based on feedback from the research team on the importance of spirituality in Native culture, the 
baseline survey will also include items from the World Health Organization’s Quality of Life 
Spirituality, Religion, and Personal Beliefs (WHOQOL SRPB) scale to measure the participant’s 
spiritual, religious, and personal beliefs and how they affect their quality of life (WHOQOL SRPB 
Group, 2006). Included in the PhenX toolkit (Hamilton et al., 2011), the WHOQOL SRPB was 
tested in a cross-cultural study and is highly correlated with psychological and social domains of 
Quality of Life. The items selected for the present study were based on a study that identified 
items with the strongest factor loadings in each facet of the WHOQOL SRPB (Skevington, 
Gunson, & O’Connell, 2013) as well as the study team’s input on which items would be most 
relevant to the Facebook group. Five items from the WHOQOL SRPB were included: “To what 
extent does any connection to a spiritual being help you to get through hard times?” covers the 
connection to the spiritual being facet; “To what extent are you able to experience awe from your 
surroundings? (e.g., nature, art, music)” covers the awe and wonder facet and most of our MBRP 
content; “How much does spiritual strength help you to live better?” covers the spiritual strength 
facet; “To what extent do you have inner peace?” covers the inner peace facet; and “To what 
extent does faith give you comfort in daily life?” covers the faith facet. The five items will be scored 
on a five-point Likert scale ranging from 0=not at all to 4=an extreme amount. The total score will 
range from 0 to 20.  
Finally, the baseline survey will include the K6 scale (Kessler et al., 2002) to characterize the 
sample at baseline and to monitor psychiatric symptoms at follow-up. Included in the PhenX toolkit 
(Hamilton et al., 2011), the K6 is a screening measure that assesses psychological distress 
including depressive and anxiety symptoms over the past month. The K6 measures distress with 
six questions (e.g., “How often did you feel nervous?” “How often did you feel hopeless?”) scored 
on a five-point Likert scale ranging from 0=none of the time to 4=all of the time. Total scores can 
range from 0 to 24, with a recommended cutoff score of 13 to indicate the presence of a 
psychiatric disorder. The K6 scale is a widely used indicator of nonspecific psychological distress 
and is highly correlated with mental illness. 
 
For individuals completing the baseline survey, the study staff will send the participant an 
invitation to the Facebook group by email or text message, depending on the participant’s 
preference. If the participant does not have a Facebook account, we have included instructions 
that will be provided to participants on how to set one up. We developed these instructions for 
use in prior studies (Sinicrope et al., 2022).  

 
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Participants will receive a $
 cash card for completing the baseline 
survey as a thank you for their time. Study staff will ask the participant to provide their mailing 
address for the 
 cash card, which the study staff will document in 
REDCap. This information will not otherwise be included in the dataset. 
10.3.4. Enrollment 
Eligible individuals providing written informed consent, completing the baseline survey, and 
accepting the invitation to join the Facebook group will be enrolled. Participants will be informed 
that the Facebook group will begin when all 10 participants have enrolled. The participant will be 
mailed or provided with a smudge kit and journal at the UDS visit to use for smudging and 
MBRP/SMART exercises posted to the Facebook group. The smudge kit is a bundle of cedar, 
sage, and sweetgrass inside an abalone shell approximately 2 to 3 inches in diameter, and it 
comes in a resealable travel bag.  
10.3.5. Study Intervention Administration 
The Facebook intervention was described above in Sections 10.1 and 10.2. Participants will 
receive a welcome message when they join the group and a closing message when the group 
ends. The intervention will be accessible for a 30-day period. Participation in the intervention is 
entirely virtual and asynchronous, and available 24 hours a day/7 days a week so they can 
comment, react, and click on posts/links on their own time. The moderators will post one 
selection from the intervention content library once every 1-2 days and prompt group discussions 
as needed.  Within the 30-day period, we may host up to 2  live guest speaker events. The guest 
speakers would be either a member of our research team that would present on a topic relevant 
to our content library posts or Native experts/Elders who are knowledgeable in opioid recovery 
and who are well-known and respected in the community.  
Moderators will check in with the group every 1-2 days to interact with the participants, monitor 
adherence to group guidelines, and take actions such as removing inappropriate postings and 
misinformation if necessary.  
10.3.6. Study Intervention Adherence 
Data will be extracted weekly from the Facebook application programming interface (Facebook, 
2020) as described in Section 10.3.9. Intervention adherence will be operationalized as the level 
of engagement with the intervention and assessed with objective data obtained from Facebook 
analytics. This includes, for each of the 10 participants in the sample, Facebook group 
participation through number of comments, postings, reactions; attendance at live Facebook 
events (e.g., guest speakers), and responding to polls or other activities. These metrics will be 
summed to create a total engagement count. Unlike many web-based platforms, Facebook 
analytics for private groups do not provide time spent on the Facebook page. 
10.3.7. Discontinuation of Study Intervention   
If the subject never engages in the Facebook group or discontinues from the intervention but not 
from the study, remaining study procedures will be completed as indicated by the study protocol.  

 
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If a clinically significant finding is identified (including, but not limited to changes on the K6 scale 
from baseline) after enrollment, the investigator or qualified designee will determine if any change 
in participant management is needed. Any new clinically relevant finding will be reported as an 
adverse event (AE) if it meets the definition specified in Appendix A of the protocol. A plan is in 
place for clinical management of depression and other psychiatric symptoms or medical 
problems. The study staff will refer participants to the appropriate on-call physician or behavioral 
health clinician at the appropriate medical facility. The study staff will have a list of contacts as 
participant issues or concerns arise that need medical or psychiatric attention, or when other types 
of referral or assistance are needed. Individuals who report suicidal intent or other severe 
psychiatric symptoms or medical problems will be referred for treatment and followed throughout 
the study period. Continued participation with the study will be voluntary and in cooperation with 
the health care professional treating the subject’s psychiatric or medical condition. 
The study staff will be trained by Dr. Patten, licensed clinical psychologist, and Dr. 
 
, Mayo Clinic Board Certified Psychiatrist, to observe and monitor depression and 
psychiatric symptoms. They will be available to consult with the study staff as needed. 
In the event a participant withdraws from the study or the LI decides to discontinue a participant 
due to an SAE, the participant will be monitored by the LI via ongoing status assessment until: 
(1) 
Resolution is reached (i.e., the problem requiring treatment has resolved or stabilized with 
no further changes expected) 
(2) 
The SAE is determined to be clearly unrelated to the study intervention 
(3) 
The SAE results in death. 
 
10.3.8 Follow-Up  
Assessments will be conducted at the end of the intervention with a six-week visit window for 
completion (King et al., 2020). The participants will complete a UDS and a Follow-up Survey (by 
phone or in-person at the UDS visit). Study staff will attempt to contact the participant up to three 
times to complete the assessments and additionally reach out to the participant’s secondary 
contact as needed. If the participant cannot be contacted within the six-week visit window, they 
will be considered lost to follow-up.  Participants will receive a $
 cash 
card for completing the Follow-Up Survey. They will receive an additional $
 
 cash card for completing the in-person UDS as a thank you for their time and for any travel 
costs incurred. 
Follow-up Survey measures will evaluate treatment satisfaction and user experience using the 
Social Media Usability scale as well as four open-ended questions. It will also ask for the 
participant’s thoughts on the potential for the group to be used as a way to encourage women to 
start their recovery journey and whether the participant would be interested in a peer moderator 
role for a future Facebook group. The TLFB will be used to assess opioid, opiate, and fentanyl 
use and MOUD use for each day since the previous TLFB assessment conducted at screening. 
We will again collect information on other OUD treatments the participant completed within the 30 
days during the intervention. Using the TLFB, we will again assess for other substance use 
including stimulant use such as methamphetamines, cocaine/crack and marijuana use. The UDS 

 
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will be conducted in-person and staff will follow the same procedures as described above for the 
screening visit.   
The Follow-Up Survey will include the same items from WHOQOL SRPB as the Baseline Survey 
to assess any changes in how their spirituality affects their Quality of Life and the K6 scale to 
assess changes in psychiatric symptoms during their participation in the Facebook group. It will 
also ask how important the participant feels it would be for Facebook groups like the pilot group 
to address spirituality from 0=not at all important to 10=very important. The study staff will assess 
adverse events (AEs) and serious adverse events (SAEs) including self-reported trips to the 
emergency department (ED), hospitalizations, and overdoses since enrollment.   
10.3.9. Phase 3 Table of Assessments 
Concept 
Assessment 
Visit 
Participant eligibility 
measures 
Screening survey   
Time 1 
 
Opioid Use Disorder diagnosis based on 
the DSM-5 checklist (American 
Psychiatric Association, 2013) 
Time 1 
 
Timeline Follow-Back interview (Sobell et 
al., 1988) to assess opioid and other 
substance use in past 30 days 
Time 1 
 
Current suicidality based on 3 items from 
the Concise Health Risk Tracking—Self 
Report (CHRT-SR) Suicidal Behavior 
Evaluation (Trivedi et al., 2011)  
Time 1 
 
Urine drug screen 
(
l; 
(https://cliawaived.com/fentanyl-rapid-
tests-20.html) 
Time 1 
Baseline 
sociodemographics  
Baseline survey using PhenX Toolkit 
items (Hamilton et al., 2011) 
Time 1 
User experience measures 
Social Media Usability scale (Lund, 2001) 
and open-ended questions 
Time 2 
Opioid use outcome  
measures 
Urine drug screen 
(
; 
Time 2 

 
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(https://cliawaived.com/fentanyl-rapid-
tests-20.html) 
 
Timeline Follow-Back interview (Sobell et 
al., 1988) to assess opioid and other 
substance use in past 30 days or since 
study enrollment 
Time 2 
MOUD retention 
Timeline Follow-Back interview (Sobell et 
al., 1988) MOUD use in past 30 days or 
since study enrollment 
Time 2 
Psychiatric symptom 
measure 
K6 scale (Kessler et al., 2002)   
Time 1, Time 2 
Spirituality measure 
Items from World Health Organization’s 
Quality of Life Spirituality, Religion, and 
Personal Beliefs measure (WHOQOL 
SRPB Group, 2006) 
Time 1, Time 2 
 
10.3.10. Data Collected by Study Staff 
Recruitment feasibility measures documented by study staff include the number of potential 
participants screened, number eligible, and number enrolled out of those eligible. Study retention 
will be defined as the proportion completing the end of intervention Follow-up Survey and a UDS.  
For intervention engagement assessment, study staff will extract data weekly from the Facebook 
application programming interface (Facebook, 2020) using an extraction program based on a 
Python module (https://pypi.org/project/facebook-scraper/) which we have utilized in prior work 
(Sinicrope et al., 2022). Standard engagement metrics for social media health promotion 
interventions (Pagato et al, 2016) include Facebook analytics of the number of posts ‘seen by’ 
group members, reactions (e.g., likes, loves), and comments. Engagement by participant includes 
the number of comments, reactions, responses to a Facebook poll or other activities, attendance 
at live events (e.g., guest speakers) and posts initiated (i.e., participant created a post with text, 
image, and/or video). A total engagement count will be calculated from these metrics. The text of 
participant-generated posts and comments will be exported into an excel spreadsheet for analysis 
of content.  Unlike many web-based platforms, Facebook analytics do not provide time spent on 
the Facebook page. 
10.3.11. End of Intervention Form 
This form tracks the participant’s status with regard to the intervention in Phase 3. It will be 
completed by a member of the study staff at the follow-up visit (for participants who complete 
study participation). 
 

 
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10.3.12. Study Completion Form 
This form tracks the participant’s status in the study. It will be completed by a member of the study 
staff at the follow-up visit or after the six-week visit window lapses for participants who do not 
complete this final follow-up. This form is used in data analyses to address variables such as 
treatment retention and completion. This form also provides a location for the site LI attestation 
of review of all study data. 

 
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11.  CLINICAL AND SAFETY ASSESSMENTS  
11.1. Adverse Events (AEs) and Serious Adverse Events (SAEs) 
In Phases 1 and 3, AEs and SAEs may be spontaneously reported to study staff at any visit 
following consent. AEs and SAEs suggesting medical or psychiatric deterioration will be brought 
to the attention of a study clinician for further evaluation and management. AE and SAE reporting 
is according to the reporting definitions and procedures outlined in the protocol and in accordance 
with applicable regulatory requirements. For purposes of this study, the following AEs do not 
require reporting in the data system but is captured in the source documentation as medically 
indicated: 
Grade 1 (mild) unrelated adverse events: This would typically include mild physical events such 
as headache, cold, etc., that were considered not reasonably associated with the use of the 
intervention. 
 
In Phase 3, study staff will assess during the follow-up visit by asking the participant if they visited 
the Emergency Department (ED), were hospitalized, or had an overdose since enrollment and to 
briefly describe the event. The study staff will inform the participant that they should contact the 
study staff immediately if they have an ED visit, are hospitalized, or have an overdose at any point 
in the study after consent.  
 
For AEs and SAEs, we considered obtaining objective information (e.g., on hospitalizations, ER 
visits, overdoses) but decided this would not be feasible for this treatment development study. 
We are recruiting women from the local community and will rely on staff referrals from (1) multiple 
addiction treatment programs, (2) community clinics and programs throughout the Metropolitan 
area, and (3) friends or colleagues affiliated with the CAC. We are not recruiting women at specific 
addictions treatment programs, or from Mayo Clinic, Hennepin Healthcare, or another health 
system, where medical record release forms and data-sharing agreements could be readily 
obtained with the permission of participants. However, through this preparatory project, we are 
building important relationships with community clinic providers and staff who will refer patients 
to the study and thus building the foundation for the next step in this research where we could 
work with specific clinics to provide such information. In this study, we will account for AEs using 
self-report as well as documenting any spontaneous reports from secondary contacts in the event 
we are not able to reach a participant for the follow-up visit. The risk of adverse events associated 
with the intervention is minimal because women are required to be currently using MOUD. 
11.2. K6 Scale  
In Phase 3, we will use the K6 scale (Kessler et al., 2002) at baseline and follow-up assessments. 
Included in the PhenX toolkit (Hamilton et al., 2011), the K6 is a screening measure that assesses 
psychological distress including depressive and anxiety symptoms over the past month. The K6 
measures distress with six questions (e.g., “How often did you feel nervous?” “How often did you 
feel hopeless?”) scored on a five-point Likert scale ranging from 0=none of the time to 4=all of the 
time. Total scores can range from 0 to 24. The K6 scale is a widely used indicator of nonspecific 
psychological distress and is highly correlated with mental illness. Moreover, studies have shown 
that having a score of 13 or greater on the K6 is a strong indicator of the presence of a DSM 

 
43 
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diagnosable psychiatric disorder with considerable disability (Furukawa et al., 2003; Kessler et 
al., 2003). The K6 has been validated in general population samples (Forman-Hoffman et al., 
2014) and among AIAN adults specifically (Mitchell & Beans, 2011). 
If a K6 score of >=13 is prevalent at baseline or follow-up, or if a substantial increase in scores 
from baseline is noted at follow-up, the LI or one of the study clinicians will follow-up with the 
participant for further assessment and initiate referral for additional mental health assessment 
and care as described in the DSMP.  
11.3.  Assessment of Suicidality at Screening  
In the Screening for study eligibility for Phase 1 (AIAN women only) and Phase 3, the study staff 
will use three items from the Concise Health Risk Tracking-Self Report (CHRT-SR) Suicidal 
Behavior Evaluation (CHRT-SR) (Trivedi et al., 2011), a self-report assessment of suicidality and 
related thoughts and behaviors. The scale assesses suicidality quickly and easily in a manner 
consistent with the Columbia Classification Algorithm of Suicide Assessment (C-CASA) (Posner 
et al, 2007). The CHRT-SR will assess high risk for suicidality by a positive response (“Agree” or 
“Strongly Agree”) on the last three questions (thoughts of, thoughts of how, and/or a specific plan 
to commit suicide) and prompt a clinician assessment for suicide risk before ending the screening 
visit. A study clinician will complete the Concise Health Risk Tracking – Clinician Rated (CHRT-
CR) (Trivedi et al, 2011) to aid in his or her assessment of symptoms and he/she will initiate 
referral for additional mental health assessment and care as described in the DSMP. 
 

 
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12. PREMATURE WITHDRAWAL OF PARTICIPANTS   
Participants in either Phases 1 or 3 may withdraw voluntarily from the study at any time. If they 
would like to withdraw from the study, they should contact the LI. They will be advised whether 
they need to complete any additional tests for their safety. 
All participants will be followed for the duration of the study CTN-0123 unless they withdraw 
consent, die, or the investigator or sponsor decides to discontinue their enrollment for any reason. 
Reasons for the investigator or sponsor terminating a participant from the study may include, but 
are not limited to 
• 
The participant becoming a threat to self or others 
• 
The participant not following instructions 
• 
The participant relapses on opioids while pregnant 
• 
Staying in the study would be harmful for the participant 
• 
Lack of funding 
• 
The study is canceled 
The participant may choose to stay in the study if they never use or discontinue their use of the 
Facebook intervention. 

 
45 
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13. STUDY HALTING RULES 
Specific stopping rules have been developed to protect the safety of our study subjects enrolled 
in Phases 1 or 3. In the case of any SAE, the study will be stopped and no further enrollment 
will take place until an investigation of the event has taken place by the LI (Dr. Patten), or a Co-
LI. 
 
If the SAE involves death or a life-threatening event, the LI, Dr. Patten, will be notified 
immediately by the study staff. Dr. Patten will telephone, fax, and/or e-mail the Mayo Clinic IRB 
with follow up notifications to the NIDA Program Official within 24 hours of when she learns of 
the event. This telephone contact will be followed up with a standardized report form submitted 
to both the IRB and NIDA within 2 working days of the study staff learning of the SAE. If the 
SAE involves something other than death or a life-threatening event, Dr. Patten will submit a 
standardized, detailed report of the event to the IRB and NIDA within 2 working days of when 
the SAE was reported. Reports of serious adverse events received by the IRB will be reviewed 
by an institutional SAE Board, (the members of these boards are not involved in this study) to 
decide of the seriousness of the event and to determine what actions, if any, will be required. If 
the SAE Board determines that suspension or termination of the study is required, this 
information will also be reported to NIDA within 24 hours. 
 
Outcome of SAEs will be reported bi-annually to NIDA or as otherwise specified by the NIDA 
Program Official. A summary of the SAEs that occurred during the previous year will be included 
in the annual progress report to NIDA and to IRB. All protocol changes and/or protocol 
amendments will be reported to NIDA, then the IRB. Additionally, a summary of all AEs will be 
reported in an annual progress report to the IRB. A determination of the association of the 
adverse event with the study intervention will be made and appropriate modifications to the 
protocol will be made if an association is suspected. If protocol modifications to ensure the 
safety of future study subjects cannot be made, the study will be terminated. 
 

 
46 
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14. PARTICIPANT REIMBURSEMENT/REMUNERATION 
Participants will be compensated for the participation in this study. Compensation will be in 
accordance with the Mayo Clinic IRB policies and procedures, and subject to IRB approval. 
Participants in all phases of the study will receive compensation via a mailed Mayo Clinic Credit 
Union cash card. The study staff will assign a cash card ID to the participant, which will be noted 
in REDCap for reference when documenting payments in Mayo Clinic’s Research Participant 
Payment Application (RPPA).  
With Research Finance, the study team will document all participant payments in RPPA and the 
study team will ask the participant for their SSN. If they decline, the study staff will mark that the 
participant does not have an SSN.  

 
47 
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15. DISSEMINATION 
With input from the CAC, the research team will create a study newsletter to share the findings in 
aggregate from both phases of the research. This will be mailed to participants in Phases 1 and 
3 who provided their permission to be re-contacted for this purpose.  
 

 
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16. TRAINING REQUIREMENTS  
16.1 Overall 
A comprehensive Training Plan will be developed to incorporate general training, study-specific 
training, mechanisms for competency assessment as well as a detailed description of training, 
supervision, and fidelity monitoring procedures. The Investigative Team is responsible for the 
development of a comprehensive Training Plan, instructional material, and delivery of the training, 
with the team comprised of the Lead Node and other participating nodes and subject matter 
experts, as applicable. 
The CTN-0123 study staff will be trained as specified in the study Training Plan. Training will 
include Human Subjects Protection (HSP) and Good Clinical Practice (GCP) as well as protocol-
specific training on assessments, the study intervention, safety and safety event reporting, study 
visits and procedures, data management, quality assurance, etc. The Lead Node is primarily 
responsible for development and delivery of study-specific training related to the study 
intervention(s) and procedures. Other parties will contribute as needed based on the subject 
matter and material to be covered. The various sub-teams will collaborate to deliver quality 
instructional material designed to prepare research staff to fully perform study procedures based 
on the assigned research roles and responsibilities. 
In addition to general and study-specific training, the Training Plan will include a description of 
the delivery methods to be used for each training module (e.g., via self-study, online, webcast, or 
teleconference). Study staff is required to complete institutionally required training per their 
research site, Institutional Review Board, and authorities with regulatory oversight. Tracking of 
training completion for individual staff as prescribed for assigned study role(s) will be documented 
and endorsed by the site LI and the Lead Node. As changes occur in the prescribed training, the 
Training Plan and training documentation tracking forms will be amended to reflect these 
adjustments. 
16.2 Protection of Human Subjects 
Key personnel have completed the required education on the protection of human research 
participants at their respective institutions. The Mayo Clinic has established a formal program 
entitled the “Mayo Investigator Training Program” (MITP). The MITP is a web-based educational 
course designed to provide all personnel involved in human subject research with training about 
human subject protection. All Mayo personnel engaged in human subject research are required 
to complete the course. MITP primary objectives are to provide historical context for human 
subject protection regulations and explore the evolving issues for human subjects research. 

 
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17.0 STATISTICAL DESIGN AND ANALYSES  
17.1 General Design 
17.1.1 Study Hypothesis 
We hypothesize that by using a CBPR approach, input from recovering AIAN participants and our 
CAC, content refinement, a comprehensive moderator exchange, and a beta test of the 
intervention with recovering AIAN participants will result in a culturally relevant Facebook 
intervention prototype to support recovery from illicit opioid use.  
17.1.2 Primary and Secondary Outcomes (Endpoints) 
Primary Outcome: A culturally relevant Facebook intervention prototype to support recovery 
from opioid use. 
Secondary Outcomes: Recruitment feasibility, study retention, level of intervention engagement, 
and intervention satisfaction. 
Exploratory Outcome Measures: Abstinence from opioid use and MOUD retention at the end 
of the intervention. 
17.2 Rationale for Sample Size and Statistical Power 
17.2.1 Projected Number of Sites 
This study will have one site. 
17.2.2 Projected Number of Participants 
17.2.2.1 Phase 1 
Using a stratified purposeful sample (Patton, 2015), we estimate up to 18 interviews with AIAN 
women participants and 12 interviews with interested parties, based on recommended guidelines 
for the number of individual qualitative interviews needed to reach data saturation (Namey et al., 
2016). Data saturation is the point at which no new information is being learned (Krueger, 2014; 
Saunders et al., 2018). Recruitment of these additional participants should be feasible within our 
study timeline. We will consult with members of our Community Advisory Committee as needed 
as several represent AIAN healthcare and community organizations, thus we do not foresee a 
need to increase the number of stakeholder interviews. 
17.2.2.2 Phase 3 
A sample of N=10 AIAN women participants is consistent with recommendations for Stage Ia 
behavioral addictions treatment development (Rounsaville et al., 2001) and beta-testing of novel 
digital and mHealth interventions (Baker et al., 2014; Nielsen, 2012). Moreover, 10 was the 
minimum number of participants for optimal Facebook intervention engagement in prior studies 
(Ramo et al., 2015).   
17.3 Statistical Methods  

 
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17.3.1 Qualitative Analyses 
17.3.1.1 Phase 1 
Content analysis (Krippendorff, 2018) supplemented with QSR NVivo software version 10 
(Doncaster, Victoria, Australia) will be used to generate interview response themes. The 
interviews will be audiotaped and professionally transcribed by a vendor approved by Mayo Clinic 
with a written transcript generated for each. If the participant was not comfortable being recorded, 
or the audio equipment was malfunctioning, the interviewer’s written notes will be imported to 
NVivo for analysis. Two study team members will review and code the data. Initially, the coders 
will read 8 transcripts from the AIAN participants to decide whether 12 AIAN participants will reach 
data saturation. Next, 6 transcripts (~20%) will be randomly selected (3 each from the AIAN 
women and interested party groups respectively). These will be independently and deductively 
coded (Saldana, 2016) to generate code lists based on the interview content domains. These 
codes will be compared and reconciled before arriving at the final set of codes and the coders are 
calibrated. A third study team member will be brought in to aid in reaching consensus if needed. 
At this point, a codebook will be developed which will describe the meaning of each code and 
include relevant key words from the transcripts that link to each code (Miles et al., 2014). To aid 
in the assessment of the “acceptability” of the postings, within each code, valence coding will also 
be employed when relevant to track whether responses to that code are positive, negative, mixed, 
or neutral. The codebook will then be reviewed by the third study team member for feedback and 
refinement. The final codes will then be applied to all data.  
Two study team members will code all interviews. The third team member will resolve 
discrepancies as needed until consensus is reached. The benefit of coding jointly is that there is 
ongoing rich discussion of the coding process, of new themes emerging from the data with 
continual updates of the codebook themes and keywords, and quality control of the coding 
process, with one person coding into NVIVO and the other person observing the coding to make 
sure errors are not made (Coffey & Atkinson, 1996; Patton, 2015; Wolff et al., 2019). As a part of 
the dual coding process, the coders will write up memos each time they meet to code. The memo-
writing will be the place where discovery of patterns across themes is recorded. Through 
discussion ideas about potential patterns and themes will be discussed and reports will be 
generated using NVIVO to further explore such themes and patterns. At the end of coding, the 
third study team member will be asked to randomly review 5 of the interviews to assess agreement 
with the coding. 
For AIAN women participants who give permission to be re-contacted, we will review her 
individual transcript (responses) and how these were interpreted (coded) (i.e., member checking). 
Responses will be entered and coded using the same methods as the preliminary analysis. 
We will conduct further qualitative analyses if there are disconfirming voices or themes where 
participants could not recognize or relate to the interpretations provided and/or to explore any 
new concepts reported.   
 
Coded data will be examined for patterns across the AIAN women and interested party groups; 
as well as among AIAN women, any patterns in themes by age group, or substance use. 

 
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The qualitative findings will be discussed with the CAC who will guide us in the interpretation and 
integration of findings and resolving any discrepancies in themes for the AIAN women and 
stakeholder groups. In the LI’s formative work to develop a social media intervention for nicotine 
use among Alaskan AIAN adults (Merculieff et al., 2021), differences were not found between 
AIAN smokers or community stakeholders in the acceptability of content (moderator postings) 
based on cultural relevance or perceived effectiveness. In addition to the feedback on the 
moderator postings, we expect the interested parties will provide unique information on how the 
intervention can best be promoted to engage AIAN women to participate in the study as well as 
factors in designing the intervention that would make the intervention appealing for sustained use 
within AIAN healthcare and community settings.  
17.3.1.2 Phase 3 
Survey: The Follow-up Survey contains four open-ended questions assessing the participant’s 
experiences with the intervention, their recommendations for improving the intervention, and their 
thoughts on using the Facebook group as a way to learn how to mentor other AIAN women who 
are engaging in illicit opioid use to start their recovery. The text of survey responses will be entered 
into an Excel spread sheet for analysis. Analyses will generally follow the procedures described 
for Phase 1. Content analysis (Krippendorff, 2018) supplemented with QSR NVivo software 
version 10 (Doncaster, Victoria, Australia) will be used to generate response themes in the data 
for each of the three survey items. Coded data will be examined for any patterns in themes by 
age group, and substance use.  
Facebook intervention group comments and postings: The text of participant-generated posts and 
comments will be exported into an excel spreadsheet for analysis of content. We will identify 
common themes of response in the data using content analysis (Krippendorff, 2018) 
supplemented with QSR NVivo software version 10 (Doncaster, Victoria, Australia). Analyses will 
generally follow the procedures described for Phase 1. We will summarize the major themes, and 
the frequency of topics discussed in participant comments and postings will be displayed 
graphically.   
17.3.2 Quantitative Analyses  
17.3.2.1 Primary Outcome: A culturally relevant Facebook intervention prototype to support 
recovery from opioid use. 
 
The cultural relevance of the Facebook group will be determined by valence coding with QSR 
NVivo software version 10. We will summarize the expected outcomes for the development of the 
intervention using descriptive statistics (frequencies, percentage) which are the development and 
refinement of the content library (yes/no), development and refinement of the Facebook 
intervention prototype (yes/no), development and refinement of the intervention moderator 
guidelines (yes/no), and intervention moderators trained (yes/no). We expect that all outcomes 
will be achieved at 100% implementation. 
 
17.3.2.2 Secondary Outcomes: Recruitment feasibility, study retention, level of intervention 
engagement, and intervention satisfaction. 

 
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We will summarize the number of potential participants screened, number eligible, reasons for 
ineligibility and number enrolled out of those eligible (i.e., participation rate) using frequencies and 
percentages. Baseline characteristics will be summarized using descriptive statistics (means, 
medians, frequencies, and percentages). We will summarize the number of enrolled women 
reporting other substance use at baseline and at follow-up. Study retention will be summarized 
as the percentage of enrolled participants completing the end of intervention survey and a UDS. 
The Social Media Usability scale (Lund, 2001) scores will be summarized using descriptive 
statistics (mean, standard deviation, median and range).   
The level of intervention engagement will be summarized using descriptive statistics (medians, 
frequencies, and percentages). The number of posts ‘seen by’ group members, their reactions, 
and comments will be summarized. We will also summarize participant-level engagement metrics 
(e.g., comments, reactions) and the total engagement count overall. The analyses will use an 
intent-to-treat approach including all 10 participants with those never having engaged in the 
Facebook group receiving a total engagement count of zero. We will describe patterns of 
engagement by age group (with age based on median split or <40 vs. >=40 years depending on 
the age distribution), substance use endorsed on the TLFB (any use: yes/no and/or median split 
of # of substances used) at baseline and follow-up, and relapse to opioid use (yes/no). We will 
summarize the total engagement count for moderator and participant-generated posts, 
respectively. 
 
17.3.2.3 Exploratory Outcomes: Abstinence from opioid use and MOUD retention at the end of 
the intervention. 
 
Descriptive statistics (percentages and frequencies) will be used to summarize the sample for 
relapse to opioids, operationalized as either a positive opiate or fentanyl UDS with missing UDS 
test imputed as positive or self-report of any illicit opioid use in the past 30 days or since study 
enrollment. Secondarily we will summarize relapse as at least seven consecutive days of self-
reported illicit opioid use in the past 30 days or since study enrollment (Nunes et al., 2018). 
Secondarily, we will also summarize outcomes considering missing UDS as missing and not 
positive (King et al., 2020).  
From the TLFB, will summarize MOUD retention as the proportion of days reporting MOUD use 
and current use using descriptive statistics (percentages and frequencies).   
17.3.3 Missing Data and Dropouts 
In Phase 1, individuals meeting the study eligibility criteria and providing informed consent will be 
enrolled and will not be replaced, even if they do not begin an interview. The analyses will include 
all enrolled participants. For some individuals in Phase 1, there may be questions that the 
participant prefers not to answer in which case the analysis will be conducted with available data 
for those questions.  
In Phase 3, individuals meeting the study eligibility criteria, providing informed consent, and 
completing the baseline assessment will be enrolled and will not be replaced. We will use an 

 
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intent-to-treat approach with the analyses including all enrolled participants. Analyses will be 
conducted considering individuals with missing self-report/TLFB and/or UDS information as (1) 
missing=relapsed and (2) missing=missing and not relapsed. 
The study team will make every effort to contact participants to complete the study tasks including 
reaching out to a secondary contact if needed. In Phase 3, participants will have a six-week visit 
window for completing follow-up study tasks including the UDS. Individuals who are not contacted 
or do not complete the follow-up study tasks will be considered lost to follow-up. 
17.3.4 Safety Analysis  
Descriptive statistics (frequencies and percentages) will be used to summarize AEs and SAEs. 
AEs, including SAEs, will be summarized by body system and preferred term using MedDRA 
codes (per The Medical Dictionary for Regulatory Activities). AEs will be presented as: (1) the 
number and proportion of participants experiencing at least one incidence of each event overall; 
and (2) the total number of each event overall in tabular form.  
17.3.5 Interim Analyses 
On a monthly basis, the occurrence of the type and number of SAEs and AEs will be summarized 
and the biostatistician will generate a report for the LI and study team for review at monthly 
research team meetings. Recruitment and study retention data will be summarized weekly. The 
Program Coordinator will generate a monthly report of the number screened, eligible, enrolled 
and completing the follow-up visit (Phase 3) for review at monthly research team meetings. 

 
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18.0 REGULATORY COMPLIANCE, REPORTING AND MONITORING 
 18.1 Statement of Compliance  
This study will be conducted in accordance with the current version of the protocol, in full 
conformity with the ethical principles outlined in the Declaration of Helsinki, the Protection of 
Human Subjects described in the International Council for Harmonisation (ICH) GCP Guidelines, 
applicable United States (US) Code of Federal Regulations (CFR), the NIDA Terms and 
Conditions of Award, and all other applicable state, local, and federal regulatory requirements. 
The LI will assure that no deviation from, or changes to the protocol will take place without prior 
agreement from the Sponsor and documented approval from the IRB, except where necessary to 
eliminate an immediate hazard(s) to the trial participants. A Manual of Operations will be provided 
as a reference guide and study quality assurance tool.   
18.2 Institutional Review Board Approval  
Prior to initiating the study, the LI will obtain written approval from the Mayo Clinic IRB to conduct 
the study, which will include approval of the study protocol. If changes to the study protocol 
become necessary, protocol amendments will be submitted in writing by the investigators for IRB 
approval prior to implementation. In addition, IRBs will approve all consent forms, recruitment 
materials, and any materials given to the participant, and any changes made to these documents 
throughout study implementation. Approval of both the protocol and the consent form(s) must be 
obtained before any participant is consented. For changes to the consent form, a decision will be 
made regarding whether previously consented participants need to be re-consented. IRB 
continuing review will be performed annually, or at a greater frequency contingent upon the 
complexity and risk of the study. The LI is responsible for maintaining copies of all current IRB 
approval notices, IRB-approved consent documents, and approval for all protocol modifications. 
These materials must be received by the LI prior to the initiation of research activities at the site 
and must be available at any time for audit. Unanticipated problems (UPs) involving risk to study 
participants will be promptly reported to and reviewed by the Mayo Clinic IRB, according to its 
usual procedures. 
18.3 Informed Consent  
The informed consent process is a means of providing study information to each prospective 
participant and allows for an informed decision about participation in the study. Informed consent 
continues throughout the individual’s study participation. The informed consent form in Phase 3 
will include all the required elements of informed consent and may contain additional relevant 
consent elements and NIDA CCTN specific additional elements. The study site must have the 
study informed consent(s) approved by the Mayo Clinic IRB. Prior to initial submission to the IRB 
and with each subsequent consent revision, the consent form(s) will be sent to the Lead Node 
(Northstar Node, Dr. 
 PI) to confirm that each consent form contains the required 
elements of informed consent as delineated in 21 CFR 50.25(a) and CFR 46.116(b), as well as 
pertinent additional elements detailed in 21 CFR 50.25(b) and 45 CFR 46.116(c) and any 
applicable CCTN requirements.  Every study participant in Phase 1 will verbally agree to 

 
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participate in the research study after listening to the study staff recite a script that includes 
language for HIPAA authorization. Every study participant in Phase 3 will be required to sign a 
valid, IRB-approved current version of the study informed consent form prior to the initiation of 
the screening UDS, screening suicidality questions, and any study related procedures. Because 
the UDS results and suicidality questions are considered PHI, the potential participant will review 
the written consent form if they qualify thus far after the initial set of screening questions. The site 
will maintain the original signed informed consent for every participant in a locked, secure location 
that is in compliance with all applicable IRB and institutional policies and that is accessible to the 
study monitors. Every study participant will be given a copy of the signed consent form.  
During the informed consent process, research staff will explain the study to the potential 
participant. In Phase 3, the study staff will provide thepotential participant with a copy of the 
consent form to read and keep for reference. All participants will receive a verbal explanation in 
terms suited to their comprehension of the purposes, procedures, and potential risks of the study 
and their rights as research participants. Extensive discussion of risks and possible benefits will 
be provided to the participants. Phase 3 participants will have the opportunity to carefully review 
the written consent form and ask questions prior to signing. The participants will have the 
opportunity to discuss the study with their family and close friends or think about it prior to agreeing 
to participate. In Phase 3, if the participant is interested in participating in the study, a qualified 
staff member will review each section of the IRB-approved informed consent form in detail and 
answer any questions the participant may pose. The person obtaining consent will also sign and 
date the consent document. A research staff member will review the consent after it is signed to 
ensure that the consent is properly executed and complete. Staff members delegated by the LI to 
obtain informed consent will be approved by the IRB. All persons obtaining consent will have 
completed appropriate GCP and HSP training, as mandated by NIDA standard operating 
procedures (SOPs). 
The informed consent form will be updated or revised whenever important new safety information 
is available, or whenever the protocol is amended in a way that may affect participants’ 
participation in the trial. The rights and welfare of the participants will be protected by emphasizing 
to them that the quality of their medical care will not be adversely affected if they decline to 
participate in this study. The participant will be informed that their participation is voluntary and 
they may withdraw from the study at any time, for any reason without penalty. Individuals who 
refuse to participate or who withdraw from the study will be treated without prejudice. The site will 
be responsible for maintaining signed consent forms as source documents for quality assurance 
review and regulatory compliance. 
The study does not preempt any applicable federal, state, or local laws which require additional 
information to be disclosed in order for informed consent to be legally effective. It is in 
conformance with 42 CFR 2.52, which allows for research-related provisions regarding to the 
disclosure of substance use disorder patient identifying information in the absence of the informed 
consent process and HIPAA authorization.” 
18.4 Quality Assurance Monitoring  
In accordance with federal regulations, the study sponsor is responsible for ensuring proper 
monitoring of an investigation and ensuring that the investigation is conducted in accordance with 

 
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the protocol. Qualified monitors will oversee aspects of site conformity to make certain the site 
staff is operating within the confines of the protocol, and in accordance with GCP. This includes 
but is not limited to protocol compliance, documentation auditing, and ensuring the informed 
consent process is being correctly followed and documented. Non-conformity with protocol and 
federal regulations will be reported as a protocol deviation and submitted to the study sponsor 
and study IRB of record, (as applicable), for further review. 
18.5 Participant and Data Confidentiality  
Participant confidentiality and privacy are strictly held in trust by the LI, participating investigators, 
their staff, the safety and oversight monitor(s), and the sponsor(s) and funding agency, and will 
be maintained in accordance with all applicable federal regulations and/or state/Commonwealth 
law and regulations. This confidentiality is extended to the data being collected as part of this 
study. Data that could be used to identify a specific study participant will be held in strict 
confidence within the research team. No personally identifiable information from the study will be 
released to any unauthorized third party without prior written approval of the sponsor/funding 
agency and the participant.  
All research activities will be conducted in as private a setting as possible.  
The study monitor, other authorized representatives of the sponsor or funding agency, and 
representatives of the Mayo Clinic IRB may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, office study records for the participants 
in this study. The study site will permit access to such records. 
Participant records will be held confidential by use of study codes for identifying participants on 
CRFs, secure storage of any documents that have participant identifiers, and secure computing 
procedures for entering and transferring electronic data. The study participant’s contact 
information will be securely stored at the study site for internal use during the study. At the end of 
the study, all records will continue to be kept in a secure location for as long a period as denoted 
in Section 18.14, Records Retention and Requirements.  
By signing the protocol signature page, the investigator affirms that information furnished to the 
investigator by NIDA will be maintained in confidence and such information will be divulged to the 
IRB/Privacy Board, Ethical Review Committee, or similar expert committee; affiliated institution; 
and employees only under an appropriate understanding of confidentiality with such board or 
committee, affiliated institution, and employees. 
18.5.1 Certificate of Confidentiality 
To further protect the privacy of study participants, the Secretary, Health and Human Services 
(HHS), has issued a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, 
behavioral, clinical or other human subjects research funded wholly or in part by the federal 
government. Recipients of NIH funding for human subjects research are required to protect 
identifiable research information from forced disclosure per the terms of the NIH Policy (see 
https://humansubjects.nih.gov/coc/index). This protects participants from disclosure of sensitive 
information (e.g., drug use). It is the NIH policy that investigators and others who have access to 

 
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research records will not disclose identifying information except when the participant consents or 
in certain instances when federal, state, or local law or regulation requires disclosure. NIH expects 
investigators to inform research participants of the protections and the limits to protections 
provided by a Certificate issued by this Policy. 
18.6 Health Insurance Portability and Accountability Act (HIPAA)   
The study site will obtain authorization from participants for use of protected health information. 
The study site will be responsible for communicating with the Mayo Clinic IRB and obtaining the 
appropriate approvals or waivers to be in regulatory compliance. Releases of participant 
identifying information that are permitted by the HIPAA regulations, but which are prohibited by 
other applicable federal regulations and/or state/Commonwealth law and regulation, are 
prohibited. 
18.7 Investigator Assurances  
The study site will have on file an active Federal wide Assurance (FWA) with the HHS OHRP 
setting forth the commitment of the organization to establish appropriate policies and procedures 
for the protection of human research subjects in alignment with 45 CFR 46, Subpart A, with 
documentation sent to NIDA or its designee. Research covered by these regulations cannot 
proceed in any manner prior to NIDA receipt of certification that the research has been reviewed 
and approved by the IRB provided for in the assurance (45 CFR 46.103). Prior to initiating the 
study, the LI will sign a protocol signature page and investigator agreement, providing assurances 
that the study will be performed according to the standards stipulated therein. 
18.8 Financial Disclosure/Conflict of Interest  
All investigators will comply with the requirements of 42 CFR Part 50, Subpart F to ensure that 
the design, conduct, and reporting of the research will not be biased by any conflicting financial 
interest. Everyone with decision-making responsibilities regarding the protocol will confirm to the 
sponsor annually that they have met their institutional financial disclosure requirements. 
18.9 Clinical Monitoring 
Investigators will host periodic visits by NIDA contract monitors who will examine whether study 
procedures are conducted appropriately, and that study data are generated, documented, and 
reported in compliance with the protocol, GCP, and applicable regulations. These monitors will 
audit, at mutually agreed upon times, regulatory documents, case report forms (CRFs), informed 
consent forms and corresponding source documents for each participant. Monitors will have the 
opportunity and ability to review any study-associated document or file. 
NIDA-contracted monitors will assess whether submitted data are accurate and in agreement with 
source documentation and will also review regulatory/essential documents such as 
correspondence with the IRB. Areas of particular concern will be participant informed consent 
forms, protocol adherence, reported safety events and corresponding assessments. Reports will 
be prepared following the visit and forwarded to the site principal investigator, the LI and NIDA 
CCTN. 

 
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Qualified node personnel (Node QA monitors) or other designated party(ies) will provide site 
management for the study site Node QA staff or other designated party(ies) will audit source 
documentation, including informed consent forms and HIPAA forms. This will take place as 
specified by the local protocol team, node LI or lead team and will occur as often as needed to 
help prevent, detect, and correct problems at the study sites. Node QA personnel will verify that 
study procedures are properly followed and that site personnel are trained and able to conduct 
the protocol appropriately. If the node personnel’s review of study documentation indicates that 
additional training of site study personnel is needed, node QA personnel will undertake or arrange 
for that training. Details of the contract, node QA and data monitoring are found in the study QA 
monitoring plan. 
18.10 Inclusion of Women and Minorities  
Phase 1 will enroll up to 18 participants reporting AIAN race and gender identity as a woman. 
Phase 1 will enroll 12 interested parties of which half (n=6) are expected to be women and about 
two-thirds (n=9) AIAN race. Phase 3 will enroll 10 participants reporting AIAN race and gender 
identity as a woman. These inclusions are scientifically justified based on the study aims and 
objectives to develop an intervention specific to AIAN women. Challenges encountered with 
recruitment will be discussed with the CAC.  
18.11 Inclusion of Individuals across the Lifespan  
The study team has extensive experience conducting research with ANAI adults at all ages and 
across the lifespan. We seek a representative distribution of adults aged 18 years and older to 
increase the applicability of our results and understanding of how the social media intervention 
can enhance recovery from opioid use among women of all adult ages. All study participants are 
expected to be 18 years of age or older. We are excluding children because social media 
interventions have been evaluated among adults, and different interventions may be warranted 
for children based on their developmental and cognitive abilities. We do not have a maximum age 
limit.  Our prior work evaluating a Facebook intervention for nicotine use found a wide age range 
among participants. In this study we will examine descriptively any patterns in intervention 
engagement by age to inform the refinement of the intervention and future research. 
18.12 Prisoner Certification 
As per 45 CFR 46 Subpart C, there are additional protections pertaining to prisoners as study 
participants. A prisoner is defined as any individual involuntarily confined or detained in a penal 
institution. The term is intended to encompass individuals sentenced to such an institution under 
a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment 
procedures which provide alternatives to criminal prosecution or incarceration in a penal 
institution, and individuals detained pending arraignment, trial, or sentencing. 
If a participant in the study becomes incarcerated or otherwise meets the 45 CFR 46 Part C 
definition of a prisoner during the study, and the relevant research proposal was not reviewed and 
approved by the IRB in accordance with the requirements for research involving prisoners under 
Subpart C of 45 CFR 46, the LI will promptly notify the IRB. All research interactions and 
interventions with, and obtaining identifiable private information about, the participant must be 

 
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suspended immediately. The lone exception to this regulation is if the LI asserts that it is in the 
best interests of the prisoner-participant to remain in the study. The LI will promptly notify the IRB 
of this occurrence. 
18.13 Regulatory Files  
The regulatory files will contain all required regulatory documents, study-specific documents, and 
important communications. Regulatory files will be checked at the study site for regulatory 
document compliance prior to study initiation, throughout the study, as well as at study closure. 
18.14 Records Retention and Requirements  
Research records for all study participants (e.g., case report forms, source documents, signed 
consent forms, audio and video recordings, and regulatory files) will be maintained by the LI in a 
secure location for a minimum of 3 years after the study is completed and closed. These records 
are also to be maintained in compliance with IRB, state, and federal requirements, whichever is 
longest. The Sponsor and LI must be notified in writing and acknowledgment from these parties 
must be received by the site prior to the destruction or relocation of research records. 
18.15 Reporting to Sponsor 
The LI agrees to submit accurate, complete, legible, and timely reports to the Sponsor, as 
required. These include, but are not limited to, reports of any changes that significantly affect the 
conduct or outcome of the trial or increase risk to study participants. Safety reporting will occur 
as previously described. At the completion of the trial, the LI will provide a final report to the 
Sponsor. 
18.16 Audits  
The Sponsor has an obligation to ensure that this trial is conducted according to good clinical 
research practice guidelines and may perform quality assurance audits for protocol compliance. 
The LI and authorized staff from the NorthStar, Northeast, Greater New York, and Southwest 
Nodes; the National Institute on Drug Abuse Clinical Trials Network (NIDA CTN, the study 
sponsor); NIDA’s contracted agents, monitors, or auditors; and other agencies such as the 
Department of HHS, the OHRP and the IRB of record may inspect research records for verification 
of data, compliance with federal guidelines on human participant research, and to assess 
participant safety. 
18.17 Study Documentation  
The study site will maintain appropriate study documentation (including medical and research 
records) for this trial, in compliance with ICH E6 R2 and regulatory and institutional requirements 
for the protection of confidentiality of participants. Study documentation includes all case report 
forms, workbooks, source documents, monitoring logs and appointment schedules, sponsor-
investigator correspondence, and signed protocol and amendments, IRB correspondence and 
approved consent form and signed participant consent forms. As part of participating in a NIDA-
sponsored study, each site will permit authorized representatives from NIDA and regulatory 

 
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agencies to examine (and when permitted by law, to copy) clinical records for the purposes of 
quality assurance reviews, audits, and evaluation of the study safety, progress, and data validity.  
Source documents include all recordings of observations or notations of clinical activities and all 
reports and records necessary for the evaluation and reconstruction of the clinical research study. 
Whenever possible, the original recording of an observation should be retained as the source 
document; however, a photocopy is acceptable provided it is a clear, legible, and exact duplication 
of the original document. 
18.18 Protocol Deviations  
This protocol defines a protocol deviation as any noncompliance with the clinical trial protocol. 
The noncompliance may be either on the part of the participant, or the study site staff. As a result 
of deviations, corrective actions will be developed by the site and implemented promptly.  
These practices are consistent with ICH GCP:  
• 
Section 4.5 Compliance with Protocol, subsections 4.5.1, 4.5.2, and 4.5.3  
• 
Section 5.1 Quality Assurance and Quality Control, subsection 5.1.1  
• 
Section 5.20 Noncompliance, subsections 5.20.1, and 5.20.2.  
 
Any departure from procedures and requirements outlined in the protocol will be classified as 
either a major or minor protocol deviation. The difference between a major and minor protocol 
deviation has to do with the seriousness of the event and the corrective action required. A minor 
protocol deviation is considered an action (or inaction) that by itself is not likely to affect the 
scientific soundness of the investigation or seriously affect the safety, rights, or welfare of a study 
participant. Major protocol deviations are departures that may compromise the participant safety, 
participant rights, inclusion/exclusion criteria or the integrity of study data and could be cause for 
corrective actions if not rectified or prevented from re-occurrence. The study site will be 
responsible for developing corrective action plans for both major and minor deviations as 
appropriate. Those corrective action plans may be reviewed/approved by the Lead Node with 
overall approval by the Mayo Clinic IRB as needed. All protocol deviations will be monitored at 
the study site for (1) significance, (2) frequency, and (3) impact on the study objectives, to ensure 
that site performance does not compromise the integrity of the trial.   
All protocol deviations will be recorded in the Electronic Data Capture (EDC) system via the 
Protocol Deviation CRF. The LI must be contacted immediately if an unqualified or ineligible 
participant is randomized into the study. 
Additionally, the study site is responsible for reviewing the Mayo Clinic IRB’s definition of a 
protocol deviation or violation and understanding which events need to be reported. The study 
sites must recognize that the CTN and IRB definition of a reportable event may differ and act 
accordingly in following all reporting requirements for both entities. 
18.19 Safety Monitoring  
The LI may appoint a Site Medical Clinician (MD, DO, NP, or PA) for this study, who will review 
or provide consultation for each Adverse Event (AE) and Serious Adverse Event (SAE) as 

 
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needed. A site licensed clinical psychologist (Dr. Patten) and site board certified psychiatrist (Dr. 
Sharma) will also be consulted with as needed. These reviews will include an assessment of the 
possible relatedness of the event to the study intervention or other study procedures. The Site 
Medical Clinician will also provide advice for decisions to exclude, refer, or withdraw participants 
as required. The study staff will determine which safety events require expedited reporting to 
NIDA and regulatory authorities. This will include events that are serious, related and unexpected. 
The study staff will be trained to monitor for and report AEs and SAEs, and participants will report 
AEs and SAEs at the follow-up visit. 
The study site has established practices for managing medical and psychiatric emergencies, and 
the study staff will continue to utilize these procedures. Treatment providers at the study site will 
be responsible for monitoring participants for possible clinical deterioration or other problems, and 
for implementing appropriate courses of action. 
Any SAE, whether or not it is related to the study intervention and for all participants, will be 
reported to the Mayo Clinic IRB and NIDA. A summary of the SAEs that occurred in the 
previous year will be included in the annual progress report to the NIDA. Any action taken by the 
respective IRBs regarding SAEs or major changes to the protocol will be reported to the NIDA. 
 
If the SAE involves death or a life-threatening event, the LI, Dr. Patten, will be notified 
immediately by the study staff. Dr. Patten will telephone, fax, and/or e-mail the Mayo Clinic IRB 
chair/vice-chair, and the NIDA Program Official within 24 hours of when she learns of the event. 
This telephone contact will be followed up with a standardized report form submitted to both the 
IRB and NIDA within 2 working days of the study staff learning of the SAE. If the SAE involves 
something other than death or a life-threatening event, Dr. Patten will submit a standardized, 
detailed report of the event to the IRB and NIDA within 2 working days of when the SAE was 
reported. Reports of serious adverse events received by the IRB will be reviewed by an 
institutional SAE Board, (the members of these boards are not involved in this study) to decide 
of the seriousness of the event and to determine what actions, if any, will be required. If the SAE 
Board determines that suspension or termination of the study is required, this information will 
also be reported to NIDA within 24 hours. 
18.19.1 Adverse Events (AEs)  
Standard definitions for adverse events and serious adverse events, their identification, 
characterization regarding severity and relationship to therapy and processing are described in 
Appendix A. 
For the purpose of this study, the following AEs will not require reporting in the data system but 
will be captured in the source documentation as medically indicated: 
Grade 1 (mild) unrelated adverse events: This would typically include mild physical events such 
as headache, cold, etc., that were considered not reasonably associated with the use of the 
intervention. 
Reportable AEs will include self-reported trips to the Emergency Department or clinical 
deterioration (based on the K6 scale score) indicated on the end-of-intervention follow-up survey. 
The study staff will follow up with the participant to determine if the AE was related to the 

 
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intervention. Participants will be asked to report any reportable AEs to the study staff if they occur 
during their active participation. 
18.19.2 Serious Adverse Events 
For the purpose of this study, the following events will not be reported as an SAE but will instead 
be reported on study-specific forms. These events will be reported to the Mayo Clinic IRB per IRB 
guidelines: 
• 
Admission for detoxification  
• 
Admission for labor and delivery 
• 
Admission for elective or pre-planned surgery 
 
The following SAEs will be reported on the 30-day follow-up survey or by the participant 
throughout their active participation: 
• 
Trips to the Emergency Department that resulted in hospitalization 
• 
Hospitalizations that are not related to the admissions above 
• 
Overdoses of any drug 
The study staff will follow up with the participant to determine if the SAE was related to the 
intervention. 
 

 
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19.0 DATA MANAGEMENT  
19.1 Design and Development  
Data will be collected and maintained by the Mayo Clinic study team via Research Electronic Data 
Capture (REDCap) software. REDCap is a secure, web-based application designed exclusively 
to support data capture for research studies. Screening data will not include any unique identifiers 
and will be used for descriptive purposes only (i.e., to characterize the population of individuals 
screened who were found to be ineligible or not interested in participating). Only the reason for 
ineligibility will be kept; all other screening data from ineligible individuals will be destroyed. Data 
entered in REDCap uses secure and certified data centers. Thus, the risk of breeching 
confidentiality is low, with numerous safeguards for confidentiality in place as described. 
The site study staff have access to computers and printers to conduct research and data analyses. 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All data elements and data transfer activities within Mayo Clinic will be strictly compliant with 
HIPAA privacy regulatory requirements.  Data shared between the study team and the study 
biostatistician at Mayo Clinic will be through a Research Electronic Data Capture (REDCap) 
database. REDCap is a secure, web-based application designed exclusively to support data 
capture for research studies. Data entered in REDCap uses secure and certified data centers. 

 
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19.2 Site Responsibilities  
The Mayo Clinic study staff will enter all data and transfer the data files electronically to the 
Mayo Clinic site biostatistician. The site statistician will oversee the transfer of electronic data 
and data storage at Mayo Clinic, correct discrepancies in REDCap, and oversee all data entry. 
19.3 Data Center Responsibilities  
Mayo Clinic study staff will develop a REDCap database that will be used to track participant flow 
such as number of individuals screened, number ineligible/eligible and reason, and participant 
completion of study assessments. 
The study staff will have the option of a printed or electronic Case Report Form (eCRF) for data 
collection. The qualitative interviews in Phase 1 will be recorded and transcribed by Landmark 
Transcription Services and the data imported to NVivo for analysis, or the interviewers’ written 
notes will be imported to NVivo for analysis. 
The Program Coordinator will create an SOP, and study staff collecting data will be trained on 
data collection and other study procedures on REDCap including monitoring of AEs.  
The study staff will monitor the safety of the subjects daily. For Phase 3 participants, this includes 
checking on the Facebook intervention group’s activities every 1-2 days. We have standard 
internal procedures to monitor the integrity of data collected. All staff will receive ongoing training 
and supervision concerning data collection and management from the Program Coordinator. Each 
day, the study staff will monitor the study binders from the previous day for completeness, 
thoroughness, accuracy, and protocol adherence. AEs will be recorded by the study staff on a 
CRF developed for each subject. The staff is then able to cross-reference data from the previous 
visits to discover any trends in existing symptoms or changes in the subject’s status. The study 
staff will check the REDCap database once a week for accuracy and completeness. If they notice 
any discrepancies, they will report them to the LI. 
The data will be reviewed by a member of the study staff. This will include gathering CRFs and 
source documents, then comparing them to entries in the database to check for accuracy before 
the database is locked. 
19.4 Data Collection  
Data collected from demographic responses prior to the interview in Phase 1 will be handled by 
the team using REDCap. As the REDCap website is being utilized to administer assessments, 
most quantitative data will be entered by those administering the interview. The baseline and 
follow-up survey data in Phase 3 will be entered by study staff into the REDCap database.  
We will have backups of the CRFs and source documents in the study team’s drive that is 
protected by Mayo Clinic’s firewall, so the study staff will be able to recreate the data if necessary.  

 
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19.5 Data Acquisition and Entry 
Study staff collecting data will have access to eCRFs and paper CRFs and will be able to enter 
data into the REDCap database. 
19.6 Data Editing  
The study statistician will correct all discrepancies in REDCap. 
19.7 Data Transfer/Lock  
The study staff will lock the data sheet in REDCap once all data has been confirmed (i.e., CRFs 
have been checked for accuracy and completeness). 
Data will be transmitted by the study staff to the NIDA Central Data Repository if requested by 
NIDA. The final raw datasets will be returned to NIDA, if requested, for storage and archiving. 
19.8 Data Training  
The SOP will outline each step in the study flow from recruitment through follow-up data entry. 
This will ensure that the study staff enters and tracks data in a consistent manner while following 
the study protocol. Training may include mock-consenting, testing out study flows, and suggesting 
improvements while abiding to the study protocol. 
 
19.9 Data Quality Assurance  
The Manual of Operations will be developed by the Program Coordinator. We will use the same 
coordination, communication and quality control procedures successfully utilized in our previous 
work. Study staff will be trained using SOPs and the quality control of the data (accuracy and 
completeness of data) will be monitored monthly by the study statistician. The quality of the data 
(data checks) including missing data and presence and frequency of outliers. The site study team 
will meet weekly discuss progress and problem solve issues related to recruitment and data 
collection.   
The interviewers for Phase 1 will be trained and certified by Dr. 
. She will listen to the 
audio-recordings of the first four interviews conducted and provide feedback to the interviewers. 
She will listen to the audiotapes for another set of four interviews at the half-way point (after 15 
are completed).   
The intervention moderators will be trained as detailed in the procedures for Phase 2. A “refresher” 
training will occur every three months after the initial training. Dr. 
 (Co-LI) and 
 
 a consultant trainer, will review moderator-participant discussions every week after the 
Facebook group has been initiated and provide additional feedback to the moderators every two 
weeks. 
The research team will develop written moderator guidelines for how often the moderator should 
log in, check-in and respond to comments/postings and other expectations for moderator 

 
66 
CONFIDENTIAL 
engagement. A potential concern about using social media for health interventions is that user 
postings may be of poor quality, for example, inconsistent with clinical practice guidelines or 
involve inappropriate or illegal activities. When participants enter the study, they will be informed 
about the policies for posting content and that any inappropriate postings will be removed. The 
moderator will be trained to handle inappropriate or misinformation, and to direct information 
content toward evidence-based information exchange and social support.  
All study staff and volunteers will be required to complete and pass the CITI HIPPA/confidentiality 
course prior to any subject contact. 

 
67 
CONFIDENTIAL 
20.0 DATA SHARING, PUBLIC ACCESS AND PUBLICATIONS  
This study will comply with the NIH Data Sharing Policy and Implementation Guidance 
(https://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm). The LI will also 
register and report results of the trial in ClinicalTrials.gov, consistent with the requirements of 
the Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials 
Registration (https://grants.nih.gov/policy/clinical-trials/reporting/ 
understanding/nih-policy.htm). 
Primary data for this study will be available to the public in the NIDA data repository, per NIDA 
CTN policy. For more details on data sharing please visit https://datashare.nida.nih.gov/. 
The primary outcome(s) publication will be included along with study underlying primary data in 
the 
data 
share 
repository, 
and 
it 
will 
also 
be 
deposited 
in 
PubMed 
Central 
http://www.pubmedcentral.nih.gov/ per NIH Policy (http://publicaccess.nih.gov/). 
The planning, preparation, and submission of publications will follow the policies of the 
Publications Committee of the CTN. Considerations for ensuring confidentiality of any shared data 
are described in Section 18.5. 
20.1 Data Sharing Plan 
Our research team fully endorses the concept data sharing as described in the National Institutes 
of Health Policy Statement on Data Management and Sharing dated October 29, 2020; notice # 
NOT-OD-21-013. Access to data generated under the project will be available for educational, 
research, and non-profit purposes. We will share and disseminate all products/resources from 
this work including surveys and intervention materials. Biospecimen samples will not be shared 
as specimen samples will be destroyed immediately following the assay tests and recording of 
results. The data emanating from research projects will be jointly owned by the researchers and 
tribal community partners. All requests for data sharing will be reviewed in a timely manner. 
Requests for materials or data sharing will be jointly reviewed and approved by the researchers 
and the established project-specific CAC with members representing different tribal communities. 
Alternatively, in the event it is not possible to hold a CAC meeting in a timely manner, requests 
for data sharing will be jointly reviewed and approved by the LI (Dr. Patten), Lead Node PI (Co-
LI, Dr. 
), and at least two community partners.   
 
 

 
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CONFIDENTIAL 
21.0 PROTOCOL AMENDMENT HISTORY 
 
Version Date 
Description of Change 
Brief Rationale 
1.4 
 
• 
Made changes to description of 
Phase 3 Facebook group 
based on interview and CAC 
feedback 
• 
Added description of the World 
Health Organization’s Quality of 
Life – Spirituality, Religion, and 
Personal Beliefs scale for 
Phase 3 
• 
Clarified that Phase 3 
participants will be allowed to 
notify study staff of reportable 
AEs, not just at follow-up 
• 
Clarified that the UDS will be 
part of the screening procedure 
and not after consent is 
obtained 
• 
Replaced Nicole Reinicke with 
Ashley Brown as additional 
study staff 
Dr. Venner noted during a 
moderator exchange that 
spirituality is important to 
consider when adapting to a 
culture. 
Several changes were made to 
reflect lessons learned during 
Phase 1. 
1.3 
06/28/2022 
• 
Removed information for 
Tremendous digital/physical gift 
cards. Will only offer Mayo 
Clinic Credit Union cash cards 
as remuneration. 
• 
Added that study staff will ask a 
question about cultural 
connectedness during baseline 
in Phases 1 and 3. 
Study staff has had consistent 
issues with Tremendous for 
another active study. The cash 
cards are ready to go. No 
participant has received 
Tremendous remuneration.  
The study team thought it would 
be useful to ask a question 
addressing cultural 
connectedness and how that 
informs the participants’ 
answers in Phase 1 and the 
Facebook group content in 
Phase 3. 
1.2 
04/15/2022 
• 
Clarified that the study staff will 
recruit up to 18 AIAN women 
• 
Added Mayo Clinic Credit 
Union cash card as an option 
Study staff found that 
Tremendous funds take several 
weeks to be added, so Mayo 
Clinic Credit Union cash card 
will be the alternative. Also 

 
69 
CONFIDENTIAL 
for remuneration, and the study 
staff will ask their preference 
• 
Added that the CAC can refer 
their friends/colleagues who 
work with AIAN women to the 
study 
wanted to expand options for 
how CAC can refer people to 
the study. 
1.1 
02/28/2022 
• 
Provided stronger rationale for 
expecting even participation 
among all adults ages 
• 
Added more details to 
qualitative analysis 
• 
Clarified that purpose of the 
UDS is to strengthen self-
reported abstinence 
• 
For Phase 3, TLFB will assess 
most commonly abused 
substances if participant 
reports them 
• 
Increased interview length to 
60-90 minutes 
• 
Fixed inconsistencies 
NIDA requested clarification 
and expansion of several 
procedures. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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23.0 APPENDIX A: ADVERSE EVENT REPORTING AND PROCEDURES  
The study site LI is responsible for study oversight, including ensuring human research subject 
protection by designating appropriately qualified and trained study personnel to assess, report, 
and monitor adverse events. 
Definition of Adverse Events and Serious Adverse Events 
An adverse event (AE) is any untoward medical occurrence in humans, whether or not 
considered study medication/intervention related which occurs during the conduct of a clinical 
trial. Any change from baseline in clinical status, ECGs, lab results, x-rays, physical examinations, 
etc., that is considered clinically significant by the site medical clinician are considered AEs.  
Suspected adverse reaction is any adverse event for which there is a reasonable possibility that 
the study medication/intervention caused the adverse event. A reasonable possibility implies that 
there is evidence that the study intervention caused the event. 
Adverse reaction is any adverse event caused by the study intervention. 
An adverse event, suspected adverse reaction, or adverse reaction is considered “serious” 
(i.e., a serious adverse event, serious suspected adverse reaction or serious adverse reaction) if, 
in the view of either the site medical clinician or sponsor, it: 
1) 
Results in death: A death occurring during the study or which comes to the attention of 
the study staff during the protocol-defined follow-up period, whether or not considered 
caused by the study intervention, must be reported. 
2) 
Is life-threatening: Life-threatening means that the study participant was, in the opinion 
of the medical clinician or sponsor, at immediate risk of death from the reaction as it 
occurred and required immediate intervention.  
3) 
Requires inpatient hospitalization or prolongation of existing hospitalization.  
4) 
Results in persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions.  
5) 
Is a congenital abnormality or birth defect. 
6) 
Is an important medical event that may not result in one of the above outcomes but may 
jeopardize the health of the study participant or require medical or surgical intervention 
to prevent one of the outcomes listed in the above definition of serious event.   
Definition of Expectedness 
Any adverse event is considered “unexpected” if it is not listed in the investigator brochure or the 
package insert or is not listed at the specificity or severity that has been observed. If neither is 
available, then the protocol and consent are used to determine an unexpected adverse event. 
Medical and Psychiatric History 
The baseline assessment will record psychiatric symptoms using the K6 scale to assist in the 
assessment of worsening in intensity or severity of these conditions that would indicate an AE.  

 
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Site’s Role in Eliciting and Reporting Adverse Events 
Appropriately qualified and trained personnel will elicit participant reporting of AEs and SAEs at 
each study visit designated to collect AEs. Adverse events (medical and/or psychiatric) 
assessment will initiate with participant consent and follow-up of ongoing adverse events will 
continue through resolution or 30 days post 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 
with the Safety Monitor/Medical Monitor as warranted.  
Standard reporting, within 7 days of our site becoming aware of the event, is required for 
reportable AEs. Expedited reporting (within 24 hours of their occurrence and/or our site's 
knowledge of the event) is required for reportable SAEs (including death and life-threatening 
events). Study staff are responsible for reporting SAEs to the IRB, per the Mayo Clinic IRB’s 
guidelines. 
Study staff are required to enter reportable AEs and SAEs in the Advantage eClinical system. 
The AE form is used to capture reportable AEs and SAEs (as defined in the protocol). Additional 
information may need to be gathered to evaluate SAEs and to complete the appropriate CRFs 
and the summary. This process may include obtaining hospital discharge reports, medical 
records, autopsy records or any other type records or information necessary to provide a complete 
and clear picture of the serious event and events preceding and following the event. If the SAE is 
not resolved or stable at the time of the initial report or if new information becomes available after 
the initial report, follow-up information must be submitted as soon as possible. 
Reportable adverse events will be followed until resolution, stabilization or study end. Any serious 
adverse reactions will be followed until resolution or stabilization even beyond the end of the 
study.  
Site’s Role in Assessing Severity and Causality of Adverse Events 
Appropriately qualified and trained study personnel will conduct an initial assessment of 
seriousness, severity, and causality when eliciting participant reporting of adverse events. A study 
medical clinician will review reportable AEs for seriousness, severity, and causality on at least a 
weekly basis.  

 
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Guidelines for Assessing Severity 
The severity of an adverse event refers to the intensity of the event: 
 
Grade 1 
Mild 
Transient or mild discomfort (typically < 48 
hours), no or minimal medical 
intervention/therapy required; hospitalization not 
necessary (non-prescription or single-use 
prescription therapy may be employed to relieve 
symptoms, e.g., aspirin for simple headache, 
acetaminophen for post-surgical pain). 
Grade 2 
Moderate 
Mild to moderate limitation in activity, some 
assistance may be needed; no or minimal 
intervention/therapy required, hospitalization 
possible. 
Grade 3 
Severe 
Marked limitation in activity, some assistance 
usually required; medical intervention/ therapy 
required, hospitalization possible. 
 
Guidelines for Determining Causality 
The site medical clinician will use the following question when assessing causality of an adverse 
event to study intervention where an affirmative answer designates the event as a suspected 
adverse reaction: 
Is there a reasonable possibility that the study intervention caused the event?  
Site’s Role in Monitoring Adverse Events 
Local quality assurance monitors will review respective study data on a regular basis and will 
promptly advise the study staff to report any previously unreported safety issues and ensure that 
the reportable safety-related events are being followed to resolution and reported appropriately. 
Staff education, re-training or appropriate corrective action plan will be implemented at the 
participating site when unreported or unidentified reportable AEs or serious events are 
discovered, to ensure future identification and timely reporting by the site.  
Regulatory Reporting for a non-IND study 
If an SAE meets the expedited reporting criteria (serious and unexpected suspected adverse 
reactions), the sponsor will submit a volunteer MedWatch report to the FDA. The Safety 
Monitor/Medical Monitor will prepare an expedited report (MedWatch Form 3500 or similar) for 
the FDA and other regulatory authorities.   
Participant Withdrawal 
The site medical clinician must apply his/her clinical judgment to determine whether or not an 
adverse event is of sufficient severity to require that the participant be withdrawn from further 
study intervention. If necessary, a site medical clinician may suspend any trial treatments and 
institute the necessary medical therapy to protect a participant from any immediate danger. A 
participant may also voluntarily withdraw from treatment due to what he/she perceives as an 

 
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intolerable adverse event or for any other reason. If voluntary withdrawal is requested, the 
participant will be asked to complete an end-of-intervention visit to assure safety and to document 
end-of-intervention outcomes and will be given recommendations for medical care and/or referrals 
to treatment, as necessary.  

 
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Adverse Event Reporting (Chart) 
1.0  
 

 
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24.0 APPENDIX B: DATA AND SAFETY MONITORING PLAN (DSMP) 
Data and Safety Monitoring Plan Template 
1.0 
BRIEF STUDY OVERVIEW 
In this project, we will develop and beta-test the Facebook intervention. We formed a study-
specific CAC to review intervention content, measures, and recruitment messaging and provide 
advice on all study activities. Members are health care providers, AIAN community partners, and 
AIAN women, with some being former opioid users. 
2.0 
OVERSIGHT OF CLINICAL RESPONSIBILITIES 
A. Site Lead Investigator 
The site’s LI (LI) is responsible for study oversight, including ensuring human research subject 
protection by designating appropriately qualified, trained research staff and medical clinicians to 
assess, report, and monitor adverse events.  
All adverse events (AEs) occurring during the course of the study will be collected, documented, 
and reported by the investigator or sub-investigators according to the Protocol.  
The occurrence of AEs and serious adverse events (SAEs) will be assessed in the follow-up 
survey via self-report questions on trips to the Emergency Department, hospitalizations, and 
overdoses. Serious adverse events will be followed until considered resolved or stable.  
B. Safety Reporting 
The LI (LI) may appoint a Site Medical Clinician (MD, DO, NP, or PA) or utilize the Mayo Clinic 
on-call physician for this study, who will review or provide consultation for each Adverse Event 
(AE) and Serious Adverse Event (SAE) as needed. These reviews will include an assessment of 
the possible relatedness of the event to the study intervention or other study procedures. The Site 
Medical Clinician will also provide advice for decisions to exclude, refer, or withdraw participants 
as required. A site clinical psychologist or psychiatrist may also review AEs and SAEs as needed. 
The study staff will determine which safety events require expedited reporting to NIDA and 
regulatory authorities. This will include events that are serious, related, and unexpected. The 
study staff will be trained to monitor for and report AEs and SAEs, and participants will report AEs 
and SAEs at the follow-up visit. 
The study site has established practices for managing medical and psychiatric emergencies, and 
the study staff will continue to utilize these procedures. Treatment providers at the site will be 
responsible for monitoring participants for possible clinical deterioration or other problems, and 
for implementing appropriate courses of action. 
Voluntary Regulatory Reporting in non-IND Trials: 
For non-IND trials, if an event meets expedited reporting criteria (serious, related and unexpected) 
the Safety Monitor/Medical Monitor or designee will voluntarily report to FDA/Regulatory 
Authorities using the MedWatch Form 3500 or similar.  

 
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C. Data and Safety Monitoring 
We will use the FDA definition of adverse events (AEs) and serious adverse events (SAEs). The 
FDA guidelines for anticipated or unanticipated SAEs will be followed. Regarding monitoring 
participant safety, any SAE, whether or not it is related to the study intervention, will be reported 
to the IRBs and NIDA. The Program Coordinator, study staff and intervention moderators located 
at the site, will evaluate for the presence of both SAEs and AEs at each scheduled contact, 
regardless of whether conducted in person, via telephone, or online. Drs. Patten and/or Bart and 
will meet with the research staff via teleconference on a bi-weekly basis to review any new or 
continuing SAEs and AEs. 
D. Quality Assurance (QA) Monitoring 
The Manual of Operations will be developed by the Program Coordinator. We will use the same 
coordination, communication and quality control procedures successfully utilized in our previous 
work. Study staff will be trained using the SOP and the quality control of the data (accuracy and 
completeness of data) will be monitored on a monthly basis by the study statistician. The quality 
of the data (data checks) including missing data and presence and frequency of outliers. The site 
study team will meet weekly discuss progress and problem solve issues related to recruitment 
and data collection.   
The intervention moderators will be trained as detailed in the Phase 2 procedures. A “refresher” 
training will occur every three months after the initial training. Collen Young, a consultant trainer, 
will review moderator-participant discussions every week after the Facebook group has been 
initiated and provide additional feedback to the moderators every two weeks. 
The research team will develop written intervention moderator guidelines for how often the 
moderator should log in, check-in and respond to comments/postings and other expectations for 
moderator engagement. A potential concern about using social media for health interventions is 
that user postings may be of poor quality, for example, inconsistent with clinical practice 
guidelines or involve inappropriate or illegal activities. When participants enter the study, they will 
be informed about the policies for posting content and that any inappropriate postings will be 
removed. The moderator will be trained to handle inappropriate or misinformation, and to direct 
information content toward evidence-based information exchange and social support. All study 
staff and volunteers will be required to complete and pass the CITI HIPPA/confidentiality course 
prior to any subject contact. 

 
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E. Management of Risks to Participants 
Confidentiality 
Confidentiality of participant records will be secured by use of study codes for identifying 
participants on CRFs, and secure storage of any documents that have participant identifiers on 
site, as well as secure computing procedures for entering and transferring electronic data. The 
documents or logs linking the study codes with the study participant on site will be kept 
locked/securely stored separately from the study files and records. No identifying information will 
be disclosed in reports, publications, or presentations.  
Information That Meets Reporting Requirements 
The consent form will specifically state the types of information that are required for reporting and 
that the information will be reported as required. These include suspected or known sexual or 
physical abuse of a child or elders or threatened violence to self and/or others. 
Participant Protection 
The site’s study clinician or other designated and qualified individual will evaluate all pertinent 
screening and baseline assessments prior to participant enrollment to ensure that the participant 
is eligible and safe to enter the study. AEs will be assessed and documented at each study visit. 
Individuals who experience an AE that compromises safe participation in a study will be 
discontinued from further intervention and provided referrals for other treatment or to specialized 
care. Study personnel will request that the participant complete an end-of-intervention visit to 
assure safety and to document end-of-intervention outcomes. 
A detailed plan is in place for clinical management of psychiatric or medical problems that might 
arise. The study staff will monitor any reports or observations of medical problems or psychiatric 
symptoms based on the K6 scale in participants which is administered at the baseline and follow-
up visits. In the event of such an occurrence, they will set into motion procedures for referral of 
the participant for mental health assessment and care. Study staff will contact the LI or one of the 
study clinicians for further assessment of the participant’s symptoms and current clinical care.  
Subjects who are patients at Mayo Clinic will be referred for additional mental health assessment 
and treatment at Mayo Clinic. However, study participants will not likely be Mayo Clinic patients. 
Thus, in the event of an emergency (e.g., suicidal plan), staff physicians will be consulted to refer 
the subject to Hennepin Healthcare or a local tribal medical facility in Minneapolis or St. Paul for 
further assessment and clinical care.  Also, individuals who report suicidal intent or other severe 
psychiatric or medical problems will be referred to Hennepin Healthcare or a local tribal medical 
facility and followed throughout the study period. Drs. Patten, Sharma, and/or Bart (licensed 
clinical psychologist, board certified psychiatrist, and a physician) or the Mayo Clinic on-call site 
physician will be consulted by study staff as needed. Continued participation with the study will 
be voluntary and in cooperation with the health care professional treating the subject’s psychiatric 
or medical condition. 
 
Study Specific Risks 
Participants may feel inconvenienced by completing study assessments and providing urine 
samples. They may feel uncomfortable in front of the study staff if their urine is positive for any 

 
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drugs. Facebook posts and comments may cause emotional discomfort for the participants 
depending on what other members and moderators post. There is a chance that the participants 
experience withdrawal symptoms as they continue to abstain from opioids, but this risk is minimal 
because they would have already abstained from illicit opioid use for at least 30 days at screening. 
What symptoms may occur are expected to be mild and may consist of nausea, abdominal 
discomfort, muscle and joint pain, perspiration, runny nose and eyes, yawning, irritability, and 
anxiety. Since this FB intervention is not anonymous, confidentiality of health information could 
be compromised. However, the intervention group moderators will emphasize that all information 
shared in the group should stay in the group, and any samples and identifiers outside of the 
intervention will be destroyed. 
3.0 
DATA MANAGEMENT PROCEDURES 
Data will be collected and maintained by the Mayo Clinic study team via REDCap software. 
REDCap meets requirements set by the Federal Information security management Act of 2002, 
the Health Insurance and Accountability Act, and the Health Information Technology for Economic 
and Clinical Health Act.  
4.0 
DATA AND STATISTICS CENTER RESPONSIBILITIES 
Mayo Clinic study staff will develop a REDCap database that will be used to track participant flow 
such as number of individuals screened, number ineligible/eligible and reason, and participant 
completion of study assessments. 
The study staff will have the option of a printed CRF or eCRF for data collection. The qualitative 
interviews in Phase 1 will be recorded and transcribed by Landmark Transcription Services and 
the data imported to NVivo for analysis. If the participant is not comfortable being recorded, or the 
audio equipment is malfunctioning, the interviewer will take detailed, written notes that will be 
imported to NVivo for analysis. 
Study staff will create a SOP and study staff collecting data will be trained on data collection and 
other study procedures on REDCap including monitoring of AEs.  
The study staff will monitor the safety of the subjects daily. For Phase 3 participants, this includes 
checking in on the intervention group’s activity every 1-2 days. We have standard internal 
procedures to monitor the integrity of data collected. All staff will receive ongoing training and 
supervision concerning data collection and management from the program coordinator. Each day, 
the study staff will monitor the study binders from the previous day for completeness, 
thoroughness, accuracy, and protocol adherence. AEs will be recorded by the study staff on a 
CRF developed for each subject. The staff is then able to cross-reference data from the previous 
visits to discover any trends in existing symptoms or changes in the subject’s status. The study 
staff will check the REDCap database once a week for accuracy and completeness. If they notice 
any discrepancies, they will report them to the LI. 
The data will be reviewed by a member of the study staff. This will include gathering CRFs and 
source documents, then comparing them to entries in the database to check for accuracy before 
the database is locked. 
5.0 
DATA COLLECTION AND ENTRY 

 
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As the REDCap website is being utilized to administer assessments, most quantitative data will 
be entered by those administering the interview. Discrepancies will be corrected by the study site 
statistician who will oversee all data entry. 

 
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6.0 
DATA MONITORING, CLEANING AND EDITING 
The study staff will monitor the safety of the subjects daily. For Phase 3 participants, this includes 
regularly checking on the Facebook group’s activity. We have standard internal procedures to 
monitor the integrity of data collected. All staff will receive ongoing training and supervision 
concerning data collection and management from the program coordinator. Each day, the study 
staff will monitor the study binders from the previous day for completeness, thoroughness, 
accuracy, and protocol adherence. AEs will be recorded by the study staff on a CRF developed 
for each subject. The staff is then able to cross-reference data from the previous visits to discover 
any trends in existing symptoms or changes in the subject’s status. The study staff will check the 
REDCap database once a week for accuracy and completeness. If they notice any discrepancies, 
they will report them to the LI. 
The data will be reviewed by a member of the study staff. This will include gathering CRFs and 
source documents, then comparing them to entries in the database to check for accuracy before 
the database is locked. 
7.0 
DATABASE LOCK AND TRANSFER 
The study staff will lock the data sheet in REDCap once all data has been confirmed (i.e., CRFs 
have been checked for accuracy and completeness). 
Data will be transmitted by the study staff to the NIDA Central Data Repository if requested by 
NIDA. The final raw datasets will be returned to NIDA, if requested, for storage and archiving.