Tough Talks: A Disclosure Intervention for HIV+ Young Men Who Have Sex With Men
Phase: NA
Conditions: Hiv, HIV/AIDS, Disclosure
Sponsor: University of North Carolina, Chapel Hill

STUDY PROTOCOL 
 
Tough Talks: Virtual Support for Difficult Conversations: Using 
Artificial Intelligence to Increase HIV Disclosure among Young Men 
Who Have Sex with Men 
 
 
NCT number NCT03414372 
Document Date 05/13/2021 
 

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Tough Talks  
Virtual Support for Difficult Conversations: Using Artificial Intelligence to Increase HIV Disclosure Among 
Young Men Who Have Sex With Men  
 
 
Funding Sponsor:  
National Institutes of Health (NIH) 
 
 Funding Mechanism:  
Small Business Innovation Research Program  
 
Study Sponsor and Principal 
Investigator:  
 
Lisa Hightow-Weidman, MD, MPH 
Associate Professor of Medicine  
Director, Behavior and Technology Lab (BATLab) 
130 Mason Farm Road  
Bioinformatics Building CB 7030 
Chapel Hill, North Carolina 
Phone: 919-843-0033   
E-mail: lisa_hightow@med.unc.edu 

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Co-Investigator(s):  
 
Margo Adams Larsen, PhD 
Research Psychologist 
Virtually Better, Inc. 
2440 Lawrenceville Hwy, Suite 200 
Decatur, Georgia 
Phone:404-634-3400  
E-mail: adamslarsen@virtuallybetter.com 
 
 
 

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Table of Contents 
PROTOCOL TEAM ROSTER ............................................................................... 5 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................. 6 
STUDY ABSTRACT ............................................................................................. 9 
PHASE 2 (RCT) STUDY SCHEMA ..................................................................... 11 
1.0 INTRODUCTION ........................................................................................... 12 
1.1. 
Background .............................................................................................................................................. 12 
1.2. 
Rationale .................................................................................................................................................. 12 
2.0 STUDY OBJECTIVES .................................................................................. 14 
2.1 
Primary Outcome ..................................................................................................................................... 14 
2.2  
Secondary Outcomes ............................................................................................................................... 14 
2.3 
Hypothesis ............................................................................................................................................... 15 
3.0 
STUDY DESIGN ........................................................................................ 15 
3.1  
Study Population ...................................................................................................................................... 15 
3.2  
Sample Size ............................................................................................................................................. 16 
3.3 Study Randomization, Stratification, or Description of Non-Random Assignment Procedures .................... 16 
4.0 
SELECTION AND ENROLLMENT OF PARTICIPANTS ........................... 16 
4.1 
Inclusion Criteria ..................................................................................................................................... 16 
4.2 
Exclusion Criteria .................................................................................................................................... 17 
4.3 
Recruitment ............................................................................................................................................. 17 
4.4  
Informed Consent .................................................................................................................................... 17 
4.5  
Screening ................................................................................................................................................. 19 
5.0 
STUDY PROCEDURES ............................................................................. 20 
5.1  
Enrollment Procedures ............................................................................................................................. 20 
5.2  
Locator/Contact Information ................................................................................................................... 22 
5.3  
Randomization Procedures ...................................................................................................................... 23 
5.4 
 Intervention/Investigation Procedures .................................................................................................... 23 
6.0  
EVALUATIONS AND MEASURES ......................................................... 25 
6.1 
Screening ................................................................................................................................................. 25 
6.2 
Enrollment ............................................................................................................................................... 25 
6.3 Two-Week Follow Up (Arm 2 only) ............................................................................................................. 26 
6.4 One-Month Assessment (Immediate Post Intervention) ................................................................................ 26 
6.5 Three-Month Assessment .............................................................................................................................. 27 
6.6 Six-Month Assessment .................................................................................................................................. 27 

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7.0  
DATA COLLECTION AND SITE MONITORING .................................... 28 
7.1  
Development of Protocol and Case Report Forms ................................................................................... 28 
7.2  
Data Records ............................................................................................................................................ 28 
7.3    Data Collection ........................................................................................................................................ 28 
7.4    Data Submission ...................................................................................................................................... 30 
7.5  
Data Quality Assurance ........................................................................................................................... 32 
7.6  
Role of Data Management ....................................................................................................................... 32 
7.7  
Study Site Monitoring and Record Availability ...................................................................................... 33 
8.0  
PARTICIPANT MANAGEMENT ............................................................. 33 
8.1   
 Tracking Participants / Follow-up .......................................................................................................... 33 
8.2   
 Compensation ......................................................................................................................................... 33 
8.3   Intervening on “Social Harms" .................................................................................................................... 33 
8.4   
Criteria for Premature Study Discontinuation ......................................................................................... 35 
9.0  
MONITORING UNTOWARD EFFECTS ASSOCIATED WITH OR RESULTING 
FROM STUDY .................................................................................................... 36 
10.0  
STATISTICAL/ANALYTIC CONSIDERATIONS ..................................... 37 
10.1    Overview of analytic strategy .................................................................................................................. 37 
10.2    Power Estimates ....................................................................................................................................... 37 
10.3    Statistical Analysis Plan ........................................................................................................................... 38 
10.4    Missing Data ............................................................................................................................................ 40 
11.0   HUMAN SUBJECTS ................................................................................. 40 
11.1    Participants’ Confidentiality .................................................................................................................... 40 
11.2    Certificate of Confidentiality ................................................................................................................... 41 
11.3    Risks and Benefits ................................................................................................................................... 41 
11.4    Institutional Review Board (IRB) Review and Informed Consent .......................................................... 43 
11.5    Waiver of the Requirement for Parental Permission for Special Circumstances .................................... 44 
11.6  Waiver of the Requirement for Signed Consent Form ............................................................................. 44 
11.7    Prisoner Participation ............................................................................................................................... 44 
11.8 45 CFR Parts 160 and 164 Standards for Privacy of Individually Identifiable Health Information ("Privacy 
Rule" Pursuant to the Health Insurance Portability and Accountability Act - HIPAA) ....................................... 45 
11.9    Study Discontinuation............................................................................................................................... 45 
12.0 PUBLICATION OF RESEARCH FINDINGS ............................................... 45 
Schedule of Events .............................................................................................................................................. 45 
13.0 REFERENCES ............................................................................................ 48 
 
 
 
 

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Protocol Team Roster 
Kathryn Muessig, Ph.D. 
Co-Investigator 
Gilling’s School of Global Public Health – Health Behavior 
University of North Carolina, Chapel Hill 
306 Rosenau Hall, CB #7440 
Chapel Hill, NC 27599-7440  
Phone: (919) 962-5059 
Fax: (919) 962-2921 
E-mail: kmuessig@email.unc.edu  
 
 
Kimberly Powers, Ph.D. 
Co-Investigator  
Gillings School of Global Public Health – Epidemiology 
University of North Carolina, Chapel Hill 
2105D McGavran-Greenberg Hall CB #7435 
Chapel Hill, NC 27599-7435  
Phone: (919) 962-0076 
Fax: (919) 962-2921 
E-mail: powersk@email.unc.edu 
 
 
 
Sara Levintow, MSPH 
Graduate Research Assistant 
Gillings School of Global Public Health – Epidemiology  
University of North Carolina, Chapel Hill 
2101 McGavran-Greenberg Hall, CB #7435 
Chapel Hill, NC 27599-7435 
Phone: (919) 966-7430 
Email: levintow@email.unc.edu 
 
Zachary Soberano 
Research Assistant 
Institute for Global Health & Infectious Diseases 
University of North Carolina, Chapel Hill 
130 Mason Farm Road 
Chapel Hill, NC 27599 
Phone: (919) 962-5018 
Fax: (919) 962-2921 
Email: zach_soberano@med.unc.edu 
 
Andrew Pyles McGee 
Research Assistant 

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Institute for Global Health & Infectious Diseases 
University of North Carolina, Chapel Hill 
130 Mason Farm Road 
Chapel Hill, NC 27599 
Phone:  
Fax: (919) 962-2921 
Email: andrewpy@live.unc.edu 
 
Rebecca Marino 
Finance Associate 
Institute for Global Health & Infectious Diseases 
University of North Carolina, Chapel Hill 
130 Mason Farm Road 
Chapel Hill, NC 27599 
Phone: (919)-966-0378 
Fax: (919) 962-2921 
 
 
List of Abbreviations and Definitions of Terms  
AE 
AI 
Adverse event 
Artificial Intelligence  
AIDS 
Acquired Immunodeficiency Syndrome 
ART 
ASSIST 
Antiretroviral treatment 
The Alcohol, Smoking, and Substance Involvement Screening Test 
BSI 
CAI 
Brief Symptom Inventory 
Condomless Anal Intercourse 
CASI 
CDC 
Commuter Assisted Self-Interview 
Centers for Disease Control and Prevention 
CLIA 
Clinical Laboratory Improvement Amendments 
CRF 
Case report form 
DAIDS 
Division of AIDS 
GCP 
Good Clinical Practices 

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HIV 
Human Immunodeficiency Virus 
ICH 
IGHID 
IRB 
International Conference on Harmonization 
Institute for Global Health & Infectious Diseases 
Institutional Review Board 
MSM 
Men who have sex with men 
NIH 
National Institutes of Health 
NIMH 
National Institute of Mental Health 
PI 
Principal Investigator 
PrEP 
Pre Exposure Prophylaxis 
OHRP 
Office of Human Research Protection 
RCT 
Randomized controlled trial 
RNA 
SAE 
SCT 
Ribonucleic acid 
Serious adverse event 
Social cognitive theory 
SID 
Study ID number 
SMART 
Study Management and Retention Tool 
SOC 
Standard of care 
SRV 
Study Recruitment Venue 
SSL 
Secure Socket Layer 
UNC 
US 
VAS 
University of North Carolina 
United States 
Visual analogue scale 
VBI 
Virtually Better, Inc.  
VL 
Viral Load 

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VR 
Virtual Reality 
YMSM 
Young men who have sex with men 
 
 
 

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Study Abstract 
Protocol Title  
 
Tough Talks - Virtual Support for Difficult Conversations: Using Artificial 
Intelligence to Increase HIV Disclosure Among Young Men Who Have Sex With 
Men  
Design 
 
This study includes 2 phases: 
Phase 1: a technical pilot to optimize functionality and technical performance; 
and  
Phase 2: a three-arm RCT to evaluate efficacy and effectiveness of Tough Talks 
among HIV-positive YMSM. 
Intervention 
Description 
Tough Talks is an application (app) for smartphones or tablets for young men 
living with HIV to learn about and practice HIV disclosure in a safe space.   
Tough Talks helps young men living with HIV to think about and practice 
disclosing. The app includes four sections (Understanding disclosure; Should I 
disclose? How do I disclose?; Preparing for the outcome) with information 
about disclosure, activities to encourage YMSM to think about their own 
disclosure values and style, choose your own adventure style games, and 
virtual reality scenarios for them to practice disclosing their status safely.  
Protocol Duration 
24 weeks for Phase 2 
Sample Size  
 
We will recruit approximately 210 YMSM (8-16 in Phase 1; 198 in Phase 2) 
across 6 study sites (Chapel Hill, NC; Houston, TX; Tampa, FL; Bronx, NY; 
Atlanta, GA; Charlotte, NC) that have extensive experience engaging, enrolling 
and retaining HIV-positive YMSM. For Phase 2, we will also recruit and enroll 
YMSM nationwide to participate remotely.  
Population 
1) age 16-29 years; 2) assigned male sex at birth; 3) male-identified; 4) HIV 
positive; 5) owns and has reliable access to a mobile device (smartphone) or 
tablet; 6) able to understand, read, and speak English; 7) reports ≥1 episode of 
anal intercourse with a male partner in past 6 months OR reports a sexually 
transmitted infection (STI) diagnosis in the last six months; 8) For RCT only: 
have a viral load measurement within 12 months prior to enrollment (or on 
day on enrollment). As this is a minimal risk study, we will use a waiver of 
parental consent for YMSM under age 18. 
Data Collection 
During the piloting and RCT stages, YMSM will complete computer-assisted 
self-interviews (CASI). Pilot trial participants and a sub-set of RCT intervention 
participants will complete a post-intervention qualitative interview. During the 
RCT, data will also be collected via chart review.  Audio recorders will be used 
to record the content of the discussions during the qualitative interviews. 
 

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The data collected from individuals will be stored using a numerical system to 
identify each subject. Only the staff working on this study will have access to 
the records and identities of the subjects. This includes the Principal 
Investigators, Co-Investigators, and additional members of the research team. 
 
Objectives 
1. A technical pilot to optimize functionality and technical performance. 
2. A three-arm RCT to evaluate efficacy and effectiveness of Tough Talks 
among HIV-positive YMSM. 
Outcomes  
Primary outcome: Viral load (VL) suppression defined as HIV RNA < the lower 
limit of detection as per the laboratory at each clinical site.  
Secondary outcomes: We will also assess intervention efficacy on a panel of 
self-reported outcomes including sexual risk, STI infections, disclosure 
behaviors, intentions and self-efficacy.  
Number of sites  
6 in-person (Houston, TX; Bronx, NY; Tampa, FL; Chapel Hill, NC; Atlanta, GA; 
Charlotte, NC); nationwide recruitment for remote procedures 
Clinical Samples  
 
Viral load suppression: Viral loads will be assessed through chart review, blood 
draw, or participant shared documentation at baseline, 3 and 6 months. 
Participants with no VL result in their medical record in the 2 months prior to 
or 3 months after their 6-month follow up visit will have one drawn for the 
study. Participants may also self-report viral load at 6 month. Viral load 
suppression will be defined as HIV RNA < lower limit of detection as per the 
laboratory processing the sample. 
 
 
 

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Phase 2 (RCT) Study Schema 
 
 
 

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1.0 INTRODUCTION 
1.1. 
Background  
Men who have sex with men (MSM) account for nearly two-thirds all of new HIV diagnoses in the United 
States (US) and young MSM (YMSM) continue to be disproportionately affected1. Among youth living 
with HIV, 67 percent report not disclosing to their first-time sex partners2. Disclosing of one’s HIV status 
is important for accessing support which can lead to improved medication adherence and retention in 
care. Those who disclose are more likely to use condoms with HIV-negative sex partners3 and 
mathematical modeling estimates that increased HIV status disclosure to sex partners may reduce 
transmissions by 40-60%4,5. Further, disclosure may motivate HIV-negative sex partners to seek testing 
and reduce their own HIV transmission behaviors. Given the potential benefits and challenges 
associated with disclosure, there is a need for sophisticated interventions that can assist MSM with the 
disclosure process. Virtual reality provides a unique environment for users to practice HIV disclosure. 
Artificial intelligence (AI) driven disclosure may offer advantages over in-person role play through the 
use of realistic avatars that represent potential romantic partners, and probabilistic settings where users 
envision having disclosure conversations. Users have the opportunity to practice disclosing and 
experience a variety of responses and outcomes. During Phase I of this project we developed an iPad-
based virtual reality system that features three avatars, two virtual locations and three disclosure 
scenarios which represent a variety of common disclosure experiences and contexts experienced by 
YMSM6. In Phase II, we will further enhance Tough Talks and develop a full-feature automated version 
to test via a multi-site, randomized controlled trial (RCT). 
1.2. 
Rationale 
HIV status disclosure is a stressor in the lives of many HIV-positive persons7. Failure to disclose HIV 
status can negatively impact health, impeding adherence to care or medications and hindering reduction 
of sexual risk behaviors8,9. Moreover, individuals who fail to disclose miss the positive effects of post-
disclosure support9,10. Disclosure to sexual partners, friends, and family can lead to social support, closer 
relationships, antiretroviral therapy (ART) initiation, adherence, and improved psychological well-
being9,11. Notably, one study of 373 HIV-positive patients in Seattle found an independent association 
between disclosure of HIV and increased CD4 T-cell counts over time12. A study by Kalichman et al. 
found that among 538 sexually active HIV+ MSM, engaging in sex without a condom with undisclosed 
non-concordant partners was associated with worse ART adherence and greater likelihood of 
unsuppressed HIV13. 
Among MSM, many studies have found that disclosure of HIV status leads to a reduction in sexual 
risk14,15 and increased social support9,10. Most data show that individuals who can communicate with sex 
partners about sexual health topics, including disclosure of HIV status, are more likely to engage in 
condom use behaviors14-17. Furthermore, disclosure may motivate sex partners to seek HIV testing and 
reduce their own HIV transmission behaviors, as well as influence other risk-reduction strategies such as 
strategic positioning (choosing insertive or receptive anal intercourse based on serostatus), serosorting 
(limiting sexual partners to those of the same serostatus) and the use of pre-exposure prophylaxis 
(PrEP)18-20. 

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Stand-alone eHealth interventions are potent tools for public health. Unlike traditional in-person 
interventions, stand-alone eHealth interventions are not limited by cost or availability of interventionists 
to deliver them. Further, eHealth interventions are scalable and accessible, especially for youth who 
engage with technology on a regular basis and are early adopters21. In addition, eHealth interventions 
have the potential to be customizable to the unique participant based on user input. 
Virtual Reality (VR) has great potential as an educational tool by offering participants a safe, situated 
learning space where they can learn-by-doing and problem solve in a realistic environment that enables 
the transfer of skills learned in VR into real life22-24. VR allows participants to practice disclosing to 
realistic virtual characters that represent potential romantic partners, as well as in realistic settings. 
Participants have the opportunity to practice disclosing using a variety of strategies and experience 
different outcomes including acceptance, confusion, lack of HIV knowledge, and rejection.  
VR is a technological tool that can be used to enhance learning by eliciting participant emotions and 
invoking affective experiences through interaction with its contents. It provides several key advantages 
over current methods of delivering HIV prevention interventions, such as role-play and video vignettes25. 
Specifically, the sensory-rich, immersive environments of VR (virtual characters, visual ambience, 
directional audio, culturally specific content) provide a realistic avenue for YMSM for mental rehearsal 
and performance of HIV disclosure behaviors in a controlled environment where new challenges can be 
gradually introduced. Further, VR environments provide a standardized setting that can be controlled 
and replicated to deliver the intervention in a systematic manner. Additionally, incorporating 
interactivity and game mechanics (e.g. customizable virtual characters, virtual conversations) is highly 
innovative and will provide participants with a compelling, engaging experience that will motivate and 
support behavior change. 
Scientific Premise: Disclosure impacts adherence in care, viral suppression, HIV transmission and mental 
and physical health. There are no stand-alone sexual partner disclosure interventions, much less any 
that can be delivered wholly online. Tough Talks, a VR HIV disclosure intervention, shows the potential 
for theoretically backed VR interventions to work as a tool to build self-efficacy. A similar strategy could 
be applied to other topics that impact an individual’s health and wellbeing - from coming out about 
one’s sexual or gender identity, to training doctors to improve delivery of difficult diagnoses, and to 
helping their patients learn to talk with their families about a variety of medical conditions.  
Table 1: Description of Tough Talks application 
Module 
Description 
List of Activities 
Understanding 
Disclosure  
Participants go through activities that set up 
what it means to disclose your HIV status, 
while reminding them that they are not 
defined by their status and that disclosure is 
a choice.  Activities in this module include 
exercises about disclosure laws across the 
country, thinking about different situations 
in which you may have to disclose or not (to 
an employer? To a roommate? To a sex 
partner? Etc.), and a mock texting activity 
• 
Choose your own adventure: It’s 
Like Coming Out…Again 
• 
What is disclosure? (video) 
• 
Disclosure and the Law 
• 
Do I have to disclose if… 
• 
HIV doesn’t change who I am 
• 
Disclosure Advice 
• 
Virtual Disclosure Practice  

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where they give advice about disclosure to a 
friend.  
Should I 
disclose? 
Participants are led through a series of 
activities that model different ways to think 
about and decide if they want to disclose to 
someone. Activities in this module include 
reviewing a list of items and assigning them 
as pros or cons of disclosing, and thinking 
about the right time and place to disclose. 
• 
Choose your own adventure: 
Learning the Ropes 
• 
Past Disclosure Experiences 
• 
To disclose, or not to disclose? 
• 
Disclosure experience videos 
• 
Right Time, Right Place 
• 
Virtual Disclosure Practice  
How do I 
disclose? 
Participants are presented with different 
ways to disclose to someone and 
encouraged to think about what ways feel 
best to them. Activities in this module 
include reviewing different ways to go 
about disclosure, and what disclosure can 
look like depending on what feels right to 
the participant.  
• 
Choose your own adventure: He 
Likes Me…He Likes Me Not 
• 
Ways to Tell Someone 
• 
Texting Disclosure 
• 
Would I say that? Conversation 
Starters 
• 
How to Deal with Someone 
Finding Out 
• 
Virtual Disclosure Practice 
Preparing for 
the outcome 
Participants explore activities that help 
them think about the outcome after 
disclosure, from receiving support, to how 
to handle a poor reaction. Participants are 
reminded that they aren’t responsible for 
how others respond. Activities in this 
module include reviewing a list of 
commonly asked questions and answers (ex. 
Is there anything I can do to protect myself? 
What does undetectable mean?) and 
thinking about what they feel comfortable 
answering.  
• 
Choose your own adventure: 
Worst Case Scenario 
• 
Are You Prepared for the 
Questions? 
• 
After you tell them. What are 
you willing to answer? 
• 
How Would YOU answer? 
• 
What am I most afraid of? 
• 
How to exit “gracefully” if things 
go awry 
• 
Virtual Disclosure Practice 
 
2.0 STUDY OBJECTIVES  
2.1 
Primary Outcome 
The primary outcome is viral load (VL) suppression. Viral load suppression will either be obtained by 
chart review, or drawn for the study. Viral load suppression will be defined as HIV RNA < the lower limit 
of detection as per the laboratory processing the sample.  
2.2  
Secondary Outcomes 
 

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We will also assess intervention efficacy on a panel of self-reported outcomes including condomless anal 
intercourse (CAI), STI infections, and disclosure behaviors, intentions and self-efficacy. For binary 
outcomes, we define intervention efficacy as a difference in proportions, while for continuous 
outcomes, we define efficacy as a difference in means. (See Table 2 on page 45) 
2.2.1 Cost Outcomes and Cost Effectiveness 
To compare costs between the intervention arms, we will collect information on (1) time spent by study 
staff for training and supervision of delivering the clinic VR intervention; (2) time participants spend in 
the clinic sessions; and (3) costs associated with the delivery of both home and clinic arms.  The 
procedures we will use to quantify the resources required to deliver the interventions will be organized 
in standard expenditure categories: personnel, supplies, equipment, services, space, and overhead. 
Incremental cost effectiveness ratio between the 2 intervention arms will be defined as ΔC/ΔE, where 
ΔC denotes the estimated difference in mean costs of the intervention and ΔE reflects the estimated 
difference in mean effectiveness of proportion suppressed between the interventions. 
2.3 
Hypothesis 
We have the following hypotheses:  
A. Participants in both intervention arms will be more likely to be virally suppressed at 6 months 
compared to participants in the SOC arm. 
B. Participants in both intervention arms will report less CAI with potentially susceptible partners 
at six months compared to participants in the SOC arm. 
C. Participants in Arm 2 (clinic) will report greater intervention satisfaction and immersion but Arm 
2 will be costlier. 
3.0 
STUDY DESIGN  
This study includes 2 phases: 
1) A technical pilot to optimize functionality and technical performance of the intervention; and  
2) A three-arm RCT to evaluate efficacy and effectiveness of Tough Talks among HIV-positive 
YMSM. 
3.1  
Study Population 
The total study sample is approximately 210 YMSM, of which the following will be enrolled for each 
phase: 1) a technical pilot will be conducted with 8-16 HIV+ YMSM in North Carolina; 2) and an RCT will 
be conducted with 198 HIV+ YMSM by study staff at 6 study sites (Houston, TX; Bronx, NY; Tampa, FL, 
Chapel Hill, NC; Atlanta, GA; Charlotte, NC). For the RCT phase, participants may also be enrolled 
remotely from any state in the United States. 

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3.2  
Sample Size  
We will recruit approximately 210 YMSM (8-16 in Phase 1; 198 in Phase 2).  To ensure inclusion of 
diverse youth who are representative of the US epidemic, we will attempt to oversample YMSM of 
color, with a goal of enrolling two-thirds of the cohort YMSM of color. 
3.3 Study Randomization, Stratification, or Description of Non-Random Assignment 
Procedures 
 
Technical Pilot: Participants will be recruited from UNC-Chapel Hill. We will enroll 8-16 participants. 
After participants are consented, they will complete a web-based computer assisted survey instrument 
(CASI) using Qualtrics software. Participants will be randomized to either use Modules 1 and 2 or 
Modules 3 and 4. Participants will receive a short orientation to the program before use. Participants 
will be provided with a notebook to take notes on each activity, as well as take a survey on each activity. 
At the end of each module, participants will do a short qualitative semi-structured interview. At the end 
of the second module, they will take a post survey. They will receive $75 for their participation in this 
aim of the study. Participants can choose to re-enroll and complete the other two Modules of Tough 
Talks as well.  
 
RCT: Participants will be recruited from across the country. We will enroll a total of 198 participants. 
After participants are consented, they will complete a baseline web-based computer assisted survey 
instrument (CASI) survey using Qualtrics software and be randomized in a 1:1:1 fashion into one of three 
arms: 1) the Tough Talks fully-online intervention, 2) the Tough Talks clinic-based intervention or 3) the 
SOC control condition, based on a randomization sequence developed by UNC and administered 
through REDCap. The randomization sequence will be stratified by study site. Participants may enroll in-
person or remotely via video teleconferencing system.  
4.0 
SELECTION AND ENROLLMENT OF PARTICIPANTS 
4.1 
Inclusion Criteria 
 
Inclusion Criteria for All Aims 
• 
Age 16-29 years 
• 
Assigned male sex at birth 
• 
Born male and male-identified 
• 
Able to understand, read, and speak English 
Additional Criteria for Technical Pilot: 
• 
Reports ≥1 episode of CAI with a male partner in past 6 months 
• 
HIV-positive (self-report) 
Additional Criteria for RCT:  

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• 
HIV-positive (medical chart review) 
• 
Viral Load measure within 12 months of screening date (assessed by chart review, blood draw, 
or shared by participant via video teleconferencing or Qualtrics) 
• 
Owns and has reliable access to a smartphone or tablet 
• 
Has reliable internet access  
• 
Reports ≥1 episode of anal sex with a male partner in past 6 months (self-report) OR reports STI 
diagnosis (urethral/rectal gonorrhea or chlamydia or syphilis) in the last six months (self-report 
OR medical chart review) 
 
As this is a minimal risk study, we will seek a waiver of parental consent for YMSM under age 18 (see 
Human Subjects section).  
4.2 
Exclusion Criteria 
Exclusion Criteria for All Aims:  
• 
Under 16 years of age 
• 
Over 29 years of age 
• 
Assigned female at birth 
• 
HIV negative 
• 
Reports 0 episodes of anal sex with a male partner in the last 6 month AND reports no new STI 
diagnosis (urethral/rectal gonorrhea or chlamydia or syphilis) in last 6 months. 
• 
Currently enrolled in another HIV behavioral intervention study; previous or future enrollment 
in another HIV behavioral intervention study is permissible, as is participation in any standard of 
care intervention(s) within the clinical study site.  
4.3 
Recruitment 
We will recruit approximately 210 YMSM (8-16 in Phase 2; 198 in Phase 3) across six in-person study 
sites that have extensive experience engaging, enrolling and retaining HIV-positive YMSM. Participants 
will be recruited through a variety of strategies, including online and via social media strategies (e.g. 
Craigslist, Grindr and Facebook ads); distributing posters, flyers, and palm cards about the study; and 
direct outreach at local venues frequented by YMSM, including community-based organizations and 
clinics providing care and services to HIV-positive youth. YMSM will also be recruited to participate 
remotely; site staff will enroll people from anywhere in the country to complete all study procedures 
online.   
For the RCT, we will also follow respondent-driven sampling (RDS) methods and use a long-chain referral 
method to supplement recruitment, especially with the adolescents (15-17) who may be harder to reach 
than young adults (18-24).   
4.4  
Informed Consent 
 

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Informed consent/assent: Individuals interested in screening for study participation will be 
consented/assented for screening after reading information about the study and screening procedures. 
Those who meet initial eligibility criteria and schedule an enrollment visit will undergo a detailed 
informed consent/assent process where study staff will explain all study procedures and answer 
questions concerning the study and consent/assent process. The research staff member will give the 
participant as much time as needed and will address any questions or concerns they may have. The 
research staff member will ask the participant questions to gauge comprehension. The consent/assent 
form describes all study procedures, including confidentiality and privacy; information about potential 
risks, discomforts, and benefits of participation; a section on HIPPA consent for medical chart 
abstraction; and information regarding who they can contact with further questions. It also states that 
participation is voluntary, that participants may decide to not take part or to withdraw from the study at 
any time without penalty or loss of any benefit to which they might otherwise be entitled, and that 
study participation is in no way related to being able to access or continue getting care or services at any 
participating study site. Participants can refuse to answer any question and can withdraw from the study 
at any time. The PIs, Co-PIs, or designee at each site will review all informed consents and assents.   
 
Assessing for decisional capacity: Study staff will review the informed consent/assent to make a formal 
assessment of the youth’s decisional capacity and ability to provide consent/assent prior to signing, 
using a 2-step process. First, the study staff determines if the person understands the study goals by 
asking “Can you tell me what this study is about?” In step 2, potential participants will be asked 
questions designed to assess their capacity to understand, appreciate, reason with, and express a choice 
about participation in our specific protocol. We will use a modified version of the widely used Evaluation 
to Sign Consent Form in which participants are asked to: 1) name things they will be expected to do 
during the study; 2) explain what they would do if they no longer wished to participate in the study; 3) 
explain what they would do if they experienced distress during the study; and 4) identify potential risks 
for participating in the study. Potential participants will be enrolled only if they are able to provide clear 
and correct answers to each of these items, without prompting or correction. If the enrollment process 
occurs online, research staff will talk with potential participants via phone or HIPAA compliant video 
teleconferencing to assess for decisional capacity and to address any questions or concerns the person 
may have. 
 
Waiver of parental consent:  We will request that the UNC-CH IRB as the central IRB (IRB of Record) 
grant a waiver of parental consent to participate in this research study for youth participants who are 16 
to 17 years of age. The research team has been granted waivers of parental permission for prior studies 
with sexual minority youth. Under 45 CFR 46.408 (c), an IRB has the authority to waive parental 
permission if it determines that “a research protocol is designed for conditions or a subject population 
for which parental or guardian permission is not a reasonable requirement to protect the subjects” and 
“an appropriate mechanism for protecting the children who will participate as research subjects is 
substituted” and “that the waiver is not inconsistent with Federal, State, or local law.” A waiver of 
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that do not involve greater than minimal risk is a common practice among researchers working in the 
area of gay and lesbian health/mental health. This is done to avoid the selection biases operating in only 
recruiting youth whose parents are both aware of and comfortable with their sexual orientation. 
Commonly these youth have explored their sexual orientation without their parents’ knowledge as the 
youth struggle with issues of disclosure and its consequences within the social, religious, and economic 
context of their families. A requirement for parental permission in this type of study could not only 
affect a person’s willingness to participate, but could also potentially impact the ability of researchers to 
engage in this type of research with sexual minority youth. Additionally, minors can often seek sexually 
transmitted infection (STI) and HIV prevention services without parental/legal guardian permission, 
depending on each site’s state laws. 
 
If the purpose of requiring parental permission as stated in CFR is to protect the minor subject, then 
requiring parental permission for youth in these circumstances is not a reasonable requirement.  
Additional privacy protections are provided in that all assessments, notes, reports, and other records 
will be identified by only a coded number to maintain participant confidentiality. These records and any 
forms that do contain identifying information will be kept in a locked, limited access area (such as a 
locked file cabinet) at the participating site. A waiver of signed consent will be requested from UNC-CH 
IRB.  
Once all eligibility is confirmed, study details will be discussed, and questions answered during the 
informed consent process. Informed consent/assent will be obtained before any study-related 
procedures are performed 
For the technical pilot, consent/assent may be obtained up to 30 days prior to or on the day of 
enrollment, prior to implementing any study activities. If more than 30 days has elapsed, consent/assent 
must be reaffirmed on the day of enrollment. 
For the RCT, consent/assent must be obtained on the day of enrollment, prior to implementing any 
study activities.  
4.5  
Screening 
 
Potential participants recruited in any of the aforementioned ways will be directed to the study 
screening webpage. The webpage will include information about the study. Those who express interest 
in the study will be asked to provide informed consent/assent for eligibility screening. Those who 
provide consent/assent will view the eligibility screener. The webpage can be viewed on participants’ 
own device (smartphone, tablet, or computer) or on a computer or tablet located in a confidential room 
at the study site to determine if they meet eligibility criteria (technical pilot, RCT).  
 
For those who meet eligibility criteria and express interest in participating, we will ask for and record the 
first name, e-mail, and phone number of the individual via the online screener. We also collect preferred 
means of contact (e.g. call, text, email) and permission to leave a message. We use SSL encryption for 

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transfers of information online and data will be stored in the secure, HIPPA-compliant servers of the 
University of North Carolina at Chapel Hill.  The CASI data will be stored in a secure database at 
Qualtrics.   
Qualtrics uses Transport Layer Security (TLS) encryption (also known as Hypertext Transfer Protocol 
Secure (HTTPS)) for all transmitted data.  Survey data are protected with passwords and HTTPS referrer 
checking.  The data is hosted by third party data centers that are Statement on Standards for Attestation 
Engagements (SSAE)-16 Service Organization Control (SOC) II certified.  All data at rest are encrypted, 
and data on deprecated hard drives are destroyed by U.S. Department of Defense methods and 
delivered to a third-party data destruction service. 
Qualtrics deploys the general requirements set forth by many Federal Acts including the Federal 
Information Security Management Act (FISMA) of 2002.  They meet or exceed the minimum 
requirements as outlined in Federal Information Processing Standards (FIPS) Publication 200. 
Health Insurance Portability and Accountability Act (HIPAA) Statement: With some restrictions, Qualtrics 
may be designated as a Business Associate when the Qualtrics BA Agreement is signed with a Covered 
Entity—those organizations that are required to comply with HIPAA privacy rules.  All client data are 
considered confidential, and treated as such. 
Related to HIPAA, Health Information Technology for Economic and Clinical Health Act (HITECH) are 
updated assessment rules to ensure that data are properly protected and best security practices are 
followed.  By using secure and certified data centers, Qualtrics ensures the highest protection and 
testing as per HITECH requirements. 
Individuals may first screen eligible either through medical chart review or via responses to the eligibility 
screener mentioned above. The study recruitment venue (SRV) staff will contact individuals who screen 
eligible for the study and schedule them for an enrollment visit using the Study Management and 
Retention Tool (SMART).  SMART Web, a study management and retention database managed by UNC, 
will aid study staff in ensuring retention. SMART Web maintains participant follow-up timelines, tracks 
participant communications, and automates sending of e-mail, text reminders, and calendar invites to 
participants for follow-up survey and visit completion.  Eligibility for all participants will be confirmed at 
enrollment visit based on confirmation of VL in the last year up to the date of enrollment.  
 
 
5.0 
STUDY PROCEDURES 
5.1  
Enrollment Procedures  
 
Technical Pilot 
We will enroll 8-16 participants. The technical pilot only consists of one in-person session. After being 
consented, all participants will be given brief instructions on the purpose of Tough Talks and an 
overview of how to use the program. They will complete an online assessment at baseline and a paper 
assessment at the end of using the program.  Participants will also be asked to provide feedback during 

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interviews conducted by study staff about intervention content, technical performance, errors and bugs 
encountered, overall experiences using Tough Talks, and feedback for further refinement. Participants 
will receive $75 for participation.  
 
RCT 
We will enroll a total of 198 participants. Study staff will review the consent in person or over Zoom (or 
another HIPPA compliant system) and if the participant decides to enroll, he can sign the paper copy or 
electronic copy programmed in Qualtrics. After participants are consented, they will complete the 
baseline web-based CASI survey using Qualtrics software and then be randomized into the Tough Talks 
online/at-home intervention (Arm 1), the Tough Talks clinic-based intervention (Arm 2) or the SOC 
control condition (Arm 3).  At this visit, those randomized to the online intervention (Arm 1) will 
download the Tough Talks app onto their personal mobile phone or tablet, have their unique App ID 
recorded by study staff, set up their preferred email login and password information, and receive 
information on how to contact study personnel for any technical issues. Arm 1 participants will have 
access to all of the intervention features upon download. Participants randomized into this arm are 
expected to proceed through the entire intervention within 30 days. Arm 1 participants who have not 
completed the app around 2 weeks after enrollment, around 3 weeks after enrollment, and during week 
after enrollment will be reminded via text or email via SMART to use the Tough Talks app.    
 
Those randomized to the in-clinic condition (Arm 2) at this visit will download the Tough Talks app onto 
their personal mobile phone or tablet, have their unique App ID recorded by study staff, set up their 
preferred email login and password information, and immediately begin using the program. At this in-
person or remote visit, they will complete both Modules 1 and 2, which includes completion of four 
virtual reality practice scenarios. These scenarios will be conducted with the assistance of research staff 
controlling the avatar responses (e.g. clinic-assisted sessions). For the remote visits, staff will do this 
privately while on video teleconference. During the in-person visits, the staff would control the avatar 
responses from a separate room. After completion of both Modules 1 and 2 of the program, participants 
will schedule their follow-up visit for approximately two weeks and receive information on how to 
contact study personnel for any technical issues when using the first half of the program at home. For 
those completing the modules remotely, they will receive a list of national resources for mental health 
support. Their two-week visit can happen anywhere during week 2 or week 4 of the study period. At 
their follow-up visit, participants will complete the second half of the program (Modules 3 and 4), which 
also includes completion of the virtual reality practice scenarios as described above (clinic-assisted 
sessions). Research staff will also be available to troubleshoot with participants in person or for the 
remote visits they will be on video teleconference and available via text if need be. 
Those randomized to the SOC control arm (Arm 3) at this visit will receive an informational, paper or 
electronic packet of information on disclosure based on available CDC guidance.  
Participants will be allowed to enroll in-person at the site or remotely via Zoom or another HIPPA 
compliant system. All participants who enroll remotely will be asked to download the necessary app to 
aid the enrollment process. They will receive all forms via text or email. Participants who enroll from 
across the country (in states where there are no SRVs) will be assigned to an SRV by region. For example, 
the Houston site staff may enroll the participants from western states, whereas the Tampa site staff may 
enroll participants from the southern states. The regional division of enrollments is subject to update 

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depending on volume of enrollments from each state, so that no site is enrolling significantly more 
remote participants than another.  
One month after study enrollment, all participants will complete an online survey to assess intervention 
acceptability as well as to assess social cognitive framework (SCT) model constructs related to 
disclosure. Three months after study enrollment, all participants will complete a second online survey. 
Study staff will perform a chart abstraction to record any VL measures in the six weeks prior to the 
three-month study visit, or any measures since BL. Six months after study enrollment, all participants 
will complete a third online survey. Study staff will perform a chart abstraction to record any VL 
measures since the 3-month assessment and in the 2 months before the six-month study visit. If a 
current VL is not documented in the medical record (2 months prior to 6-month mark, or 3 months 
after), participants will be asked to have blood drawn to ascertain a VL measure as part of the study.   
All participants will receive $50 after their baseline visit, and Arm 2 participants will receive $50 for 
completing the baseline modules, and $50 for attending their follow-up visit. All participants will receive 
$25 after completing the online CASI given at one month, $25 after completing the online CASI given at 
three months, and $50 for completing their 6-month CASI and VL measure. All participants asked to 
attend the clinic site as part of the study will also receive a travel reimbursement based on their location 
and site standards. A subset of participants in the intervention arms will do a qualitative exit interview 
($50) beginning at the one-month follow up. For participants who refer members of their social network 
to participate in the study, for each person they recruit who screens eligible and completes initial 
enrollment steps, they will receive an incentive of $10 for up to 3 referrals for a maximum of $30. If a 
participant completes all study-related procedures, they can earn up to between $200-$300 dollars, 
depending on the study arm; if a participant completes all referrals in addition to study procedures, they 
can earn between $230-$330, depending on their study arm.  
5.2  
Locator/Contact Information 
 
Once a participant has been consented and enrolled, designated site study staff will collect 
Locator/Contact Information from the participant. Participants will be asked to provide a working phone 
number or valid email address through which they can be reached. Participants will also be asked to 
provide valid contact information for a family member and/or friend who can be called in the event the 
participant cannot be reached by phone or email. Participants will be asked if messages can be left at 
the numbers provided. Participants will also be asked to provide their physical address and whether 
they can receive mail related to their study participation at that address. Study staff will not leave 
messages or send mail unless expressly permitted to do so by the participant, which also will be 
documented on this form. If permission is given to leave messages or send mail, site staff will assure 
participants that messages only ask the participant to contact study staff and will not include any 
protected health information or information related to study participation. This information may be 
entered directly into SMART or collected on the Locator/Contact Information form first and then 
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The Contact Information Form will not contain any study data and will be maintained under double locks 
at the study site, separate from all study records, with access limited to designated site research 
personnel. 
5.3  
Randomization Procedures  
 
Participants will be randomized in a 1:1:1 ratio into either the Tough Talks fully online intervention, the 
Tough Talks clinic-based intervention, or the SOC control condition, based on a robust randomization 
sequence developed by UNC. The randomization sequence will be stratified by study site. 
 
The randomization sequence will be setup in REDCap such that study staff may use the randomization 
feature to determine study arm assignment for each participant. Staff will not be aware of the 
randomization sequence, and therefore will not know what preceding or subsequent assignments will 
be.  
 5.4 
 Intervention/Investigation Procedures 
5.4.2 Technical Pilot  
After development is complete and internal beta testing performed, both the Tough Talks intervention 
and intervention procedures will be evaluated and revised during a technical pilot with a small group of 
YMSM participants (8-16) at one site (Chapel Hill, NC). All participants will be given brief instructions on 
the purpose of Tough Talks and an overview of how to use the program. They will complete an online 
assessment at baseline and a post survey after using the program. Participants will also be asked to 
provide feedback during qualitative interviews conducted by study on intervention content, 
functionality, technical performance, errors and bugs encountered, overall experiences using Tough 
Talks, and feedback for further refinement. We will solicit feedback about the acceptability and utility, 
and assess how the intervention components could be strengthened, identifying areas needing 
improvement for future iterations. Participant feedback will be specifically sought on the subjective 
impact of the intervention on HIV disclosure, engagement in care and ART adherence. Participant 
feedback will also be solicited on the acceptability of the assessments with respect to duration and 
relevance. Both the qualitative and quantitative data from the technical pilot will be used to refine the 
Tough Talks program, the intervention protocol and the assessment tools prior to the RCT pilot (Aim 3) 
using a concurrent triangulation approach, taking advantage of the strengths of both data types to cross 
validate results.62 These data will be used to further refine the intervention protocol and instruments to 
be tested in the pilot RCT (Aim 3). 
5.4.3 RCT 
Recruitment for the RCT will occur from the 6 study sites (Tampa, FL; Houston, TX; Bronx, NY; Chapel 
Hill, NC; Atlanta, GA; Charlotte, NC), as well as through online channels such as social media. Identifying, 
screening and enrolling potential participants for the RCT will proceed as described in sections 4.3, 4.4, 
4.5, and 5.1. After eligibility is confirmed, and consent/assent is obtained, participants will be assigned a 
study ID, complete the baseline CASI survey, and then be randomized to a study arm. Next, participants 
will be walked through a brief description of their study arm (clinic, at home, control). Participants will 
be compensated $50-$100 at the conclusion of the enrollment visit (depending on arm) and reminded 

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that they will be asked to complete follow up assessments online at one, three, and six months, in 
addition to a two week visit after enrollment for the in-clinic arm only.  
 
The study team will conduct a combined efficacy/effectiveness trial to compare the intervention 
delivered online, in the clinic or SOC disclosure materials. Primary and secondary outcomes will be 
assessed at intervention completion (one month), three months, and at six months, and will include HIV 
VL information (abstracted via chart review, shared by participant via Qualtrics, or blood draw), self-
report data based on the CASI surveys and staff completion of costing tools and CRFs. Mathematical 
modeling will estimate transmissions averted and costs of each arm. 
 
A sub set of participants in both intervention arms will complete a qualitative exit interview to evaluate 
the program in-depth and document a more nuanced understanding of intervention acceptability and 
impact. Participants in both interventions will be eligible to participate in an interview after completion 
of their one-month follow-up survey.  The interviews will be conducted in person or online using a 
HIPAA-compliant, IRB-approved videoconferencing software program. Online interviews will be 
recorded by the software program and back-up recorded using an external digital audio recorder. In-
person interviews will be recorded using two digital audio recorders.  Interviews will last 45-60minutes 
and will be transcribed by an IRB-approved, HIPAA-compliant transcription service. Transcripts will be 
checked for quality control by study staff against original recordings. Participants can opt to include 
video chat, but no video will be recorded. Interviews will be semi-structured and focus on participants' 
evaluation of the program (e.g. likes, dislikes, technical problems), how they used the program over the 
course of the month, what impact (if any) they perceive using the program had or would have on them 
(probing for status disclosure, HIV care and medication adherence, social support and sexual behavior 
choices), and suggestions for changes to the program. We aim to interview 20-30 participants (10-15 in 
each arm, with approximately even distribution across the 4 study sites). Based on previous similar study 
designs, we are confident that we can recruit a sufficient number of interviewees from the pool of 112 
possible intervention participants (112 = 66 in each of the two intervention arms, less 15% attrition). 
Participants will receive an additional $50 for completing a qualitative exit interview. Transcribed exit 
interviews will be analyzed thematically for both a priori and emergent themes using Dedoose 
qualitative data analysis software, or an equivalent program. We will follow similar analytic procedures 
used in the Technical Pilot in order to identify possible areas for program improvement in the RCT and to 
provide additional context for interpreting the intervention's quantitative results.  
5.4.4 Research and Training Staff 
All proposed study staff have participated in the required trainings in participation and conduct of 
studies that involve human subjects, and any future study staff will do so upon hiring. Research staff at 
individual SRVs who interact with participants at assessments do not need to be clinicians.  A research 
assistant (RA) level position should be sufficient to verify eligibility during both study aims, obtain 
informed consent, be available for questions during the CASI, abstract viral load information via chart 
reviews, take a blood sample for viral load, control the AI during clinician assisted virtual reality sessions, 
and explain the Tough Talks intervention. Research staff at SRVs will be trained in person and/or via 
videoconferencing on the intervention components and will be given a script and checklist to review 
with participants. If a participant asks a question that study staff do not feel equipped to answer, SRV 
study staff will contact research staff at the University of North Carolina at Chapel Hill and/or Duke 
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5.4.5 Intervention Monitoring/Quality Control 
Because the Tough Talks intervention is an app, intervention fidelity is assured for all activities, except 
for the virtual reality activities (i.e., all participants will receive the intervention in the same way and 
have access to all of the same resources). For the virtual reality activities, Arm 1 participants will have 
the avatar controlled by the AI and Arm 2 participants will have the avatar controlled by staff. However, 
for both VR activities, the same utterance database is being used so while we anticipate that the staff 
controlled avatar may perform better, the types of conversations and specifics on what words/phrases 
can be said in both arms will be the same. To maintain quality control the study team will train and score 
practice VR scenarios and retrain if needed prior to enrollment visits. The UNC study team will also 
review the first 10 VR session transcripts performed at each SRV site, and then 20% of the sessions on an 
ongoing basis. Site staff with issues will be re-trained.  
6.0  
EVALUATIONS AND MEASURES  
THIS SECTION CONTAINS RELEVANT EVALUATIONS AND MEASURES FOR THE RCT ONLY 
Overviews of the administration of clinical and behavioral measures are shown in the Schedule of 
Evaluations with a full list of study measures. Presented below is additional information on visit-specific 
measure administration and procedures.  
6.1  
Screening 
Online, phone-based, and in-person screeners will be used to determine if individuals meet initial 
eligibility criteria. Individuals may be screened for eligibility by accessing the study’s online screener 
using their own laptop or mobile device (e.g., if responding to online or community recruitment) or may 
complete the online screener on a local clinic tablet or computer. The online screener may also be 
administered by study staff to potential participants in person or over the phone.  All potential technical 
pilot participants who meet the initial eligibility criteria (based on the screener) must arrange an in-
person enrollment visit to confirm eligibility.  Potentially eligible RCT participants can select an online 
visit if needed. Eligibility will be confirmed at the enrollment visit based on the confirmation of screener 
completion in past 30 days, and VL measure within the past year of screener completion (or up until the 
enrollment visit date).  
6.1.1 
Administrative and Behavioral Procedures 
• 
Screening assessment, in-person, by phone, or online 
 
6.2 Enrollment  
 
Participants must be scheduled for an enrollment visit within 30 days of online, phone, or in-person 
screening; otherwise they will need to be re-screened. Individuals who meet initial eligibility criteria 

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based on the online screener will be scheduled for an enrollment visit, where screener completion, 
including recent VL measure will be confirmed. 
6.2.1 
Administrative and Behavioral Procedures 
• 
Informed Consent/Assent 
• 
Randomization to Arm 1 (online), Arm 2 (clinic delivery) or Arm 3 (SOC) 
• 
Baseline CASI Assessment  
• 
Introduction and orientation to Tough Talks 
• 
For Arm 1 and Arm 2 participants, unique Tough Talks account creation, download and set up of 
Tough Talks on participant’s mobile device  
• 
For Arm 2 participants, completion of 1st half of Tough Talks program  
• 
Remuneration for enrollment completion (including BL survey) 
6.3 Two-Week Follow Up (Arm 2 only) 
 
Participants in the clinic arm (Arm 2) will be scheduled for a two-week follow up to complete the second 
half of the program. The eligible window for completing the two-week follow up is any time during week 
2 to week 4 of their intervention.  
6.3.1 Administrative and Behavioral Procedures 
• 
Completion of 2nd half of Tough Talks program 
• 
Remuneration for completion 
6.4 One-Month Assessment (Immediate Post Intervention) 
 
The intervention will last for 1 month. The 1-month assessment should occur as soon after their 1-
month enrollment period as possible. However, given that the one-month assessment is the only one 
that includes measures of overall intervention acceptability, the assessment may occur up to 160 days 
after the ideal 1-month assessment time point (e.g. up until the end of follow-up period). SMART will aid 
study staff in ensuring retention. SMART maintains participant follow-up timelines, tracks participant 
communications, and automates sending of e-mail, text reminders, and calendar invites to participants 
for follow-up survey and visit completion. An appointment for the 1-month assessment visit will be 
scheduled to complete the following procedures listed below.  
At one month, all participants will complete an online survey to assess intervention acceptability as well 
as to assess SCT model constructs. Participants will receive $25 for completion.  
A sub-set of participants (20-30 total) in both intervention arms (10-15 in each arm) will complete a 
qualitative exit interview to evaluate the program in-depth and document a more nuanced 
understanding of intervention acceptability and impact. Participants in both interventions will be eligible 
to participate in an interview after completion of their one-month follow-up survey. The interviews will 
be conducted in person or online using a HIPAA-compliant, IRB-approved videoconferencing software 
program. Online interviews will be recorded by the software program and back-up recorded using an 

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external digital audio recorder. In-person interviews will be recorded using two digital audio recorders. 
Interviews will last 45-60 minutes and participants will receive an additional $50 for completing a 
qualitative exit interview.  
6.4.1 Behavioral Evaluations 
• 
One-month CASI assessment 
• 
Qualitative exit interview (for subgroup of participants) 
• 
Remuneration for survey completion 
• 
Updates to contact/locator information 
6.5 Three-Month Assessment  
 
A second assessment should occur 90 days (3 months) after study enrollment. However, the assessment 
may occur 15 days prior to or 30 days after the ideal three-month assessment time point. SMART will aid 
study staff in ensuring retention. SMART maintains participant follow-up timelines, tracks participant 
communications, and automates sending of e-mail, text reminders, and calendar invites to participants 
for follow-up survey and visit completion. At three months, all participants will complete a second online 
survey and staff will conduct a medical chart abstraction for VL results in the week window surrounding 
the three-month follow up visit (both before and after). Participants will complete the 3-month follow 
up survey remotely and will receive $25 for completion. Payment is not contingent upon having a VL 
result in the required window. Participants who miss their 1-month follow up are eligible to complete 
their 3-month visit. 
6.5.1 Behavioral Evaluations 
• 
Three-month CASI assessment 
• 
Remuneration for online survey completion 
6.5.2 Clinical Procedures 
• 
Viral load measure, taken from chart (if within six weeks prior to or following three-month 
follow up) 
6.6 Six-Month Assessment  
The final assessment should be conducted 6 months after study enrollment.  However, the assessment 
may occur two weeks prior to or 30 days after the ideal final assessment time point. At six months, all 
participants will complete a third online survey and undergo a medical chart review to abstract VL data. 
If participants have had a viral load taken in the two months prior to their six-month follow up 
appointment, they can complete the six-month follow-up survey remotely and receive their follow-up 
incentive. If they do not have a VL result from the prior two months, they can still complete their survey 
remotely but will be asked to provide a blood sample  to assess viral load within three months of 
completing the six-month survey. Participants will receive $50 for completion. Participants must 
complete both their survey and have an eligible viral load (either through chart review in last two 
months, self-report, or blood sample within three months after survey) to receive their incentive. 

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Participants who miss their one and/or three-month follow up are eligible to complete their final six-
month visit. 
6.6.1 Administrative and Behavioral Procedures 
• 
Six-month CASI assessment 
• 
Remuneration for visit completion (dependent on both survey and viral load) 
• 
Documentation of viral load measure (blood draw, self-report or chart review) 
6.6.2 Clinical Procedures 
• 
Viral load measure, abstracted from medical chart or blood sample 
6.6.3. Laboratory Procedures 
• 
Blood specimen analysis for viral load (if not in chart review) 
7.0  
DATA COLLECTION AND SITE MONITORING 
7.1  
Development of Protocol and Case Report Forms 
 
The protocol team is responsible for the development of this protocol as well as the Case Report Forms 
(CRFs) needed to collect the information required to implement this protocol. All Case Report Forms are 
input in REDCap, where study staff will complete all relevant fields.   
7.2  
Data Records  
 
Participant-related study information will be identified through a study ID number (SID) and participant 
code on all participant CRFs, audio files, transcripts, and CASI files. Participant names or other 
personally-identifying information will not be used on any study documents other than the Contact 
Information Worksheet (stored in double-locked office separate from other study information only 
accessible by designated study staff) and informed consent form and will be redacted from usability and 
field trial interview transcripts. All study-related information will be kept in double-locked, limited 
access areas at each study site. Participant names and their SID and participant code will be stored in in 
SMART Web, accessible only to designated study staff, and representatives from the NICHD. SIDs will 
not be entered into the mobile app and instead a unique app ID will be assigned to each participant and 
used when setting up the app. These unique App IDs will be provided by the UNC Study Team and 
recorded into the Intervention Delivery Form during enrollment.  Original source documents (e.g., 
Contact Information Worksheet) for individual participants will be maintained at the respective SRV and 
will be accessible only to the study staff. Data from original source documents will be transcribed with 
SMART or on CRFs in REDCap as applicable. Electronic data will be stored on a secure server at UNC.      
7.3    
Data Collection  
7.3.1   CRFs 
Study monitoring data, including information about eligibility, demographic data, and monitoring 
untoward effects will be collected on CRFs. All CRFs for this study must be entered into REDCap. Hard 
copies will be made available for download from a UNC-run secure cloud management platform, to be 
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7.3.2   CASI Survey Data 
Technical Pilot: Self-administered surveys will be completed by participants at the baseline and 1-month 
assessment time points. Participants will complete an online computer assisted self-interview (CASI) via 
survey hosts on Qualtrics.  
RCT: Self-administered surveys will be completed by participants at the baseline, 1-month, 3-month and 
6-month assessment time points. Participants will complete an online computer assisted self-interview 
(CASI) via survey hosts on Qualtrics.  
Data collected using a CASI method at the clinic sites will be entered on a portable computer or mobile 
phone via an internet-based application. All data collected using CASI will remain confidential; no 
personal identifying information will be collected during the computer session.  The participant’s unique 
SID number will be used in order to link the interview responses to the participant’s CRF data. This 
unique SID will also be used to link participant completed follow-up Qualtrics surveys  
7.3.3 CASI Data Security 
CASI Data Security 
Only authorized users with a login name and password will be able to access and open the online HIPPA-
compliant online CASI platform administered survey.  
7.3.4 Video Platform Description 
A HIPPA-compliant video platform will be used for this study. Either Zoom or a comparable platform 
may be used to conduct qualitative interviews remotely and/or to enable remote enrollments. For the 
qualitative interviews, participants will have the option to conduct face-to-face video chat, video chat in 
which they can see the interviewer, but the interviewer cannot see them, or audio chat only. In order to 
ensure privacy, participants will be asked to complete the interview within a private room. Zoom is 
compatible on PCs, tablets, and smartphones; as well as maintains the option to conduct an audio 
conference without the video component.   
End-to-end encryption: Zoom encrypts all presentation content at the application layer using the 
Advanced Encryption Standard (AES) 256-bit algorithm. Zoom end-to-end (E2E) chat encryption allows 
for a secured communication where only the intended recipient can read the secured message. Zoom 
uses public and private keys to encrypt the chat session with Advance Encryption Standard (AES256), 
and session keys are generated with device unique hardware ID to avoid data being read from other 
devices. This ensures that the session cannot be eavesdropped on or tampered with. 
Cloud Control Infrastructure: A distributed network of low-latency multimedia routers (software) 
resides on Zoom’s communications infrastructure. With these low-latency multimedia routers, all 
session data originating from the host’s device and arriving at the participants’ devices is dynamically 
switched — never stored persistently through the Zoom communications infrastructure. Zoom’s 
communications infrastructure for real-time video, audio, and data communications resides on Zoom 
dedicated servers, which are housed in SSAE 16 SOC2 compliant datacenters on opposite sides of the 
US. Zoom sessions are completely temporary and operate analogously to the popular mobile 
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communications infrastructure also enables an extremely scalable and highly available meeting 
infrastructure unrestricted by the limitations of physical data centers. 
The Zoom client communicates with the multimedia router to establish a reliable and secure 
connection. At the time of instantiation, the Zoom client will determine the best method for 
communication, attempting to connect automatically using udp and tcp port 8801, 8802 and 8804 or 
HTTPS (port 443/TLS). 
The Zoom sessions will contain identifying information, but this information will be stripped from the 
recorded Zoom sessions by the study team immediately post completion.  
7.3.5 Back Up Recording 
All qualitative interviews may also be recorded using a back-up digital audio recorder. Audio files will be 
erased after being transcribed and transcripts will be de-identified. All audio files will be kept 
confidential and stored in a locked/limited access folder on secured servers, which is only accessible to 
designated study staff. All members of the research team will be trained in confidentiality and have 
signed confidentiality agreements. A professional transcription service, experienced in the handling of 
confidential data, will be used to fully transcribe verbatim all audio files. Prior to receipt of the first 
audio file, the transcription service will be instructed to exclude from the typed transcript identifying 
information (e.g., a name) that may have been verbalized during the course of the interviews.  
7.4    
Data Submission 
7.4.1   CRFS 
Although Tough Talks will involve substantial online follow-up, forms on REDCap will be used to collect 
key study visit data (e.g., enrollment and randomization assignment), study milestones such as 
completion or discontinuation, study laboratory results, and adverse events (AE). During active study 
conduct, the study sites will maintain the CRFs within REDCap and any hard-copy CRFs will be stored in 
secured locations and later entered into REDCap.  
7.4.2   Audio-recorded Data 
Audio recorded data from the technical pilot exit interviews will initially be stored as a digital file on a 
secure encrypted UNC server. Exit interviews will be transcribed verbatim from the digital audio 
recording and de-identified by assigning unique numerical codes. After transcripts are verified by the 
research team and one year after the study is over, audio files will be destroyed.  
All CASI data will only be identified with a unique SID and stored on a secure encrypted server by the 
UNC team. Only study site research staff and the research team at the University of North Carolina/Duke 
will have access to the data. 
7.4.3   CASI Data Transmission 
Only authorized users with a login and password will be able to access and open the survey through the 
internet site. Survey data will be stored in secured databases on a UNC server.  

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7.4.4   Retention Data 
The study will use a HIPAA-compliant web-based platform entitled Study Management and Retention 
Toolkit (SMART), which is a SaaS (Software as a Service) based mobile application aiding studies with 
various aspects of participant recruitment, study implementation, and retention. The application has the 
ability to securely manage participant information across multiple studies and customers 
simultaneously, stratifying participant information by study and site. SMART includes an admin web 
portal and a participant facing mobile app (optional), which allows for secure messaging, study calendar 
management, self-scheduling by participants, secure photo uploads, and longitudinal tracking of 
participants from screening to study completion. The ability to designate specific roles to all SMART 
users allows for greater control around permissions and accessibility to participant information. Users 
can even be limited to a reporting only role, which allows for study oversight through real time 
aggregate reporting, but no access to PHI. SMART is a licensed service of the Center for AIDS Research 
(CFAR) at Emory University, Prevention Science Core. Utilization of the mobile app is optional and the 
admin web portal will fully function without it.  
The following information outlines the security of the three SMART components: (1) the admin web 
portal, (2) the participant app, and (3) a web service that acts as a liaison between the mobile app and 
the study database.  
Admin Web Portal: The admin web portal is a web-based application developed using Microsoft .NET 
technologies. It uses SQL server as backend database. The application requires two servers to host: (1) 
Web server [Windows server with IIS] and (2) SQL server [Standard or Enterprise version]. Both these 
servers are to be placed behind a firewall. Web server will have a public IP to access the server using 
VPN. SSL certificate is to be installed on the web server. The admin website will be rendered over SSL 
(https). The application uses form authentication (no integrated authentication such as AD). All 
passwords are stored encrypted within the database. The system will also be using database level 
encryption, which will prevent any copying of information from one database to another. The web 
application also uses an automatic logout feature after a certain period of inactivity. By default, the 
inactivity duration is set to three minutes.  
Study staff can only first gain access to the admin web portal if granted by a study or site administrator. 
Their assigned user role will determine their permissions to perform different actions and even view PHI. 
Email notifications are sent from the system (without the need to login) when: (1) a staff member 
requests to reset their password, (2) role assignments to a study are made, (3) an event/visit that staff 
are scheduled to work is nearing, (4) a new task is assigned to a staff member, or (5) they are designated 
as a staff member to receive alerts of positive test results. All participant communications are 
performed using secure messaging through the message center (inbox) implementation within the 
mobile app. If the mobile app is not utilized by a study, communications are sent as standard email or 
text messages to participants.  
Mobile App: The mobile app, developed natively for iOS and Android platforms and available for free in 
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communication, photo uploads, and updating contact information. The study will indicate during the 
initial setup within the admin web portal whether the participant mobile app is utilized or not. If the app 
is utilized, participants will receive download instructions after their information is entered into the 
admin web portal. Only participants listed in an active study who validate their email or phone number 
against the contact information listed in the admin web portal will be able to proceed into the app. For 
validation, the app uses both traditional form authentication as well as social login (Facebook and 
Google). The social login feature will only work if the email associated with either social account 
matches the contact information within the admin web portal. The app does not request anything other 
than basic information from these authentication services. Participants cannot “remember” their 
password on the mobile device for automatic logins to ensure privacy. All participant data and activity 
status is maintained within a secure and encrypted SQL Server database. To create the connection 
between the admin web portal and the mobile app, each participant is assigned a unique ID within the 
application, which is associated with their login credentials. When a participant has been successfully 
authenticated through the mobile app, the admin web portal will send their specific information to their 
phone through the established secure session (web APIs using SSL). The app will not store the 
information presented locally on the phone. Local data storage is used only for storing some minimal 
non-PHI information, such as app settings. The mobile app implements an automatic logout when there 
is inactivity for more than three minutes. If a participant should need to re-download the app on a new 
device, login and password authentication will be required again.  
The mobile app has push notifications that are primarily used for reminders and notifications of new 
messages. Push notifications displayed on the participant’s phone will be generic in nature and not 
contain any PHI. Reminders and notifications within the mobile app inbox will also be generic in nature, 
with any message containing sensitive information requiring a pin, established during registration as a 
secondary authentication, to open within the mobile app. Firebase cloud-messaging service is used as a 
communication channel for these notifications. No PHI is passed through Firebase. Push notifications are 
customizable in the study setup, and samples of system notifications include: “You have a new message 
in your inbox,” “You have an upcoming event for March 7, 2018,” and “You have a pending task.”  
Web Service: A web service will also be hosted on the web server. This service is used by the mobile 
application to retrieve and store data. The service will utilize secure socket layer (SSL) for 
communication. 
7.5  
Data Quality Assurance 
 
Investigators receiving federal funding must adhere to the Code of Federal Regulations (CFR) to protect 
research participants and produce reliable study information. Sites participating in research sponsored 
by the NIMH need to have an internal quality assurance (QA) plan that will identify problems and correct 
errors in research study records.  
7.6  
Role of Data Management 
 

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UNC will provide instructions concerning the recording of study data on CRFs, and the entry and 
transmission of the data, and administration and transmission of CASI data.  
7.7  
Study Site Monitoring and Record Availability 
 
Site monitors at UNC may visit participating study sites to review a selected portion of the individual 
participant records, including assent/consent forms, CRFs, and supporting source documentation to 
ensure the protection of study subjects, compliance with the protocol, and accuracy and completeness 
of records. Regulatory files, as required, will also be inspected to ensure that regulatory requirements 
are being followed. 
 
The site investigator will make study documents (e.g., assent/consent forms, case report forms) and 
pertinent hospital or clinic records readily available for inspection by the local IRB, the central IRB, the 
site monitors, the NIMH, the Office for Human Research Protections (OHRP), or the sponsor’s designee 
for confirmation of the study data. 
8.0  
PARTICIPANT MANAGEMENT 
8.1   
 Tracking Participants / Follow-up 
 
All subjects will be contacted before each follow-up study visit/assessment (i.e., enrollment, 2-week visit 
for Arm 2 participants, one-month, three-month, and six-month time points). Multiple contact methods 
will be used for youth who are difficult to reach (e.g., mail, alternate phone numbers, e-mail, text 
message, Facebook). Doximity, a HIPAA compliant app, may be used to call participants.   Subjects will 
be asked whether or not messages can be left for each of the phone numbers that they provide.  They 
will be informed that messages will not contain any information regarding the nature of the project. The 
SMART participant management system will be used. 
8.2   
 Compensation 
 
Technical pilot participants:  Compensated with $75 for participation.  
 
RCT participants:  Compensated with $50 at enrollment visit, $50 for completing baseline modules (Arm 
2 participants only), $50 for the 2-week visit (Arm 2 participants only), $25 at the one-month visit, $25 at 
the 3-month visit, and $50 at the six-month visit. Participants who do a qualitative interview will receive 
an additional $50. ($200-300 total). Compensation will be provided in person, sent digitally or can be 
mailed to subjects, if allowed by the SRV. 
8.3   Intervening on “Social Harms"  
We identified the following items as possible risks to subjects and describe how we plan on addressing 
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1) Breach of Confidentiality: A potential risk to participants is violation of confidentiality. We will 
take the utmost caution to protect the confidentiality of all responses. We will minimize this risk 
by maintaining confidentiality and discretion throughout the usability testing, field testing and 
RCT. Files – audio, paper and electronic– will not have any identifying information about the 
study participants and will be tracked through a unique SID. All audio recordings will be 
downloaded and stored on a password-protected, encrypted computer in locked offices at UNC-
CH and subsequently transferred to UNC encrypted servers. Transcription of audio files will be 
conducted using a HIPAA-compliant transcription service. Any names mentioned in the audio 
files will be redacted during transcription. Interview transcripts will be kept on UNC secure 
servers. Analysis of transcripts will be conducted on a password-protected, encrypted computer. 
Hard copies will be kept in locked files. This research specifically targets a vulnerable population, 
children (YMSM ages 16-17). We will take every available step to minimize the risk of 
identifying/linking data being subpoenaed, stolen, or inadvertently released. First, the Tough 
Talks has acquired a Certificate of Confidentiality from the NIH.. Second, the study will safeguard 
against the risk of the linking information being stolen by keeping such information in a locked 
Excel spreadsheet on a secure server at UNC to which only essential study personnel who have 
completed CITI certification for human subjects research ethics training (http://citiprogram.org) 
will have access. We have also included numerous features to ensure app security and privacy. 
All relevant app communications (e.g. those between participants or those between participants 
and staff) will be secured via industry standard encrypted SSL communications links. These 
connections will ensure that all communications are inaccessible to unauthorized third parties. 
Furthermore, the app can be updated regularly to address any unforeseen security updates to 
the software libraries underlying the secured communication links. Beyond encrypting 
communication, we users will need to log in with a username and password to access the app, 
even if the use of their phone is “unlocked”. This will allow the user to share their phone 
generally with others without granting access to Tough Talks. These software security solutions 
will provide the layers of both communications security and physical access security to ensure 
that only authorized users have access to the information stored on the phone as well as the 
information being shared over communications links. We will take special care to ensure that 
Tough Talks addresses participant privacy. We have chosen the app name, Tough Talks, because 
it does not relate to health care and is therefore designed to be non-stigmatizing and un-
interpretable by anyone observing a participant using the app on their mobile phones. During 
app onboarding, study staff will assist youth in choosing a discreet and anonymous username. 
Moreover, mobile phone screens themselves are also constructed to prevent surreptitious 
observation. 
 
2) Emotional discomfort: It is possible that the study may precipitate discomfort and/or an 
emotional response when YMSM answer questions about potentially sensitive topics such as 
HIV disclosure. Further, participants may feel embarrassed about discussing sensitive issues. All 
participants will be told during the informed consent process that their participation is voluntary 
and that they can chose to stop participating at any time without any consequences. Based on 
our experiences using similar data collection methods with YMSM in past studies, the likelihood 
and seriousness of this risk is minimal and we will strive to create a safe and comfortable 
environment for all study participants. 
 

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3) Discomfort during collection of blood specimen: The risk of discomfort due to blood sample 
collection is considered minimal. Physical harms are minimal. Blood samples will be collected 
based on best clinical practices in each of the SRV sites by trained staff. Subjects could 
experience dizziness, diaphoresis and nausea associated with the procedure but in prior clinical 
studies using blood sample collection, adverse events have been rare. 
 
All sites have specific policies governing the treatment of human subjects. These policies specify that 
medical and psychological assistance will be available in the immediate environment in the event a 
participant should experience any adverse reactions resulting from study procedures.  
While participants will be informed that they may refuse to answer any question at any time, responses 
or reactions to certain questions may indicate distress on the part of the participants. If at any time 
during the study a participant divulges that they are at risk for harm, including but not limited to being 
abused or experiencing violence, if harm is suspected or likely, or if the participant states they are 
suicidal/homicidal, measures will be taken to ensure their safety. Reporting will be done as appropriate 
to the situation and the legal statutes, including reporting to child protection agencies or other 
appropriate agencies, and referrals will be provided to appropriate support, counseling, or treatment 
resources. 
8.4   
Criteria for Premature Study Discontinuation 
 
The principal investigator has the authority to withdraw any participant at any time if in their opinion it 
would be in the best interest of the participant. The participant will be informed of this withdrawal and 
explained the rationale. Withdrawal will be documented in the study tracking system. 
Subjects will be prematurely discontinued from the study if any of the following occurs:  
• 
The subject withdraws consent/assent;  
• 
The study is cancelled by the NIH; 
• 
The study is cancelled for other administrative reasons;    
• 
The subject becomes incarcerated or placed in detention during the study; or  
• 
Death of the subject. 
 
Participants may end their participation in the study at any time. No further data collection will occur 
from the date the decision is made to permanently discontinue the subject from the study. Participants 
who experience distress during the study while in the study site clinic will be offered counseling on site. 
Participants who experience distress during the study and do not come to the clinical site for a visit will 
be provided a list of community referrals via phone or e-mail. Any unexpected adverse events that meet 
the new safety information reporting criteria will be immediately reported to the UNC-CH IRB and the 
respective sites’ IRBs if applicable. The Study Stop and Adverse Event Forms will be completed at this 
time.  

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9.0  
MONITORING UNTOWARD EFFECTS ASSOCIATED WITH OR RESULTING 
FROM STUDY  
 
Site research staff must first follow both the UNC IRB and their own IRB’s procedure for reporting and 
managing untoward effects.  
 
There are three types of untoward effects to be identified: 1) those related to the participant, 2) those 
related to the study staff, and 3) those related to the neighborhood/community (if applicable). 
 
First, the study will catalogue any untoward effect related to the participant. Reporting is required for 
occurrences including social harms, psychological distress, and serious life-threatening events such as 
suicide attempts. These may be immediately apparent to the study staff, such as the participant’s 
emotional upset state requiring referral for counseling; or they may be delayed and reported later to 
study staff, such as physical harm to an individual for having participated in the study.  Study staff will 
notify the UNC/Duke teams via secure email with a subject line stating that immediate response is 
necessary. Study staff will be briefed with best practices and trainings on the scope of possible untoward 
effects and how to report events.  
 
Second, study staff may encounter untoward events during sessions that personally affect them. 
Training and guidance will seek to minimize this risk. Nonetheless, an assessment of the cost of 
conducting this study must include cataloguing these events as well. The UNC/Duke team will be 
notified of these events so that they may be immediately addressed, evaluated, and then modify 
guidance or expanded to minimize similar risk to other study staff. 
 
Third, a critically important area that any community-based study intends to evaluate is the impact, 
including untoward effects, of the project on the community. This will be done informally for this 
protocol with untoward events being reported to the protocol team. 
 
All untoward effects/adverse events/unanticipated problems will also need to be reported to the UNC 
IRB if they meet all three of the following criteria: 
“Unanticipated problems involving risks to subjects or others” (UPIRSO) refers to any incident, 
experience, or outcome that:  
1) is unexpected (in terms of nature, severity, or frequency) given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the subject 
population being studied;  
2) is related or possibly related to a subject’s participation in the research; and  
3) Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized.  
 
Events that meet the criteria for an UPIRSO and are also serious adverse events should be reported to 
the UNC IRB within one (1) week of the investigator becoming aware of the event. Any other events that 
meet the criteria for a UPIRSO should be reported to the IRB within two (2) weeks of the investigator 
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If the report cannot be completed in its entirety within the required time period, a preliminary report 
should be submitted. The report should be amended once the event is resolved and/or more 
information becomes available. 
10.0  STATISTICAL/ANALYTIC CONSIDERATIONS 
10.1    Overview of analytic strategy 
10.1.2   Technical Pilot  
To evaluate the functionality, technical performance, errors and bugs encountered, overall experiences 
using Tough Talks, and provide feedback for further refinement. 
10.1.3   RCT  
Conduct a combined efficacy/effectiveness trial to compare the intervention delivered online, in the 
clinic, or SOC clinic disclosure messaging. The primary outcome of HIV viral suppression will be assessed 
at six months. We will also assess intervention efficacy on a panel of self-reported outcomes including 
CAI, STI infections, disclosure behaviors, intentions and self-efficacy assessed at baseline, 3 months, and 
6 months. Cost effectiveness of both intervention arms will also be assessed. 
 
The primary analysis will be based on intention-to-treat principles, where all participants are assumed to 
have followed their randomized assignment; secondary analyses will account for observed intervention 
completion. Additionally, we will develop a mathematical model to estimate secondary HIV 
transmissions and potential transmissions averted as a result of the intervention’s effect on viral 
suppression and CAI with susceptible partners.  
10.2    Power Estimates 
10.2.2   Technical Pilot Power Considerations 
Power is not a concern for the technical pilot as it is performed to collect feedback from a small number 
of members from the target population about the functionality of the near final version of the 
intervention. 
10.2.3   RCT Power Considerations 
Power and sample size. The sample size calculation is based on the primary aim examining a change in 
the probability of viral load suppression from baseline to six months of follow-up between the standard 
of care arm and each of the two intervention arms. Using data from previous work, we estimate the 
probability of viral load suppression to be 0.66 in each of the three trial arms at baseline, and a change 
in this probability to 0.88 in each of the two intervention arms at six months of follow-up. Assuming this 
absolute change of 0.22, a two-sided alpha level of 0.05, and 15% loss to follow-up over the six-month 
study period, we estimate we will need 66 participants in each of the 3 study arms (n=198) to achieve 
80% power to detect this change in the probability of viral load suppression between SOC and the two 
intervention arms. While our sample size is not powered to detect a difference between the two 
intervention arms, precise estimates of the efficacy for each arm are critical for subsequent costing 
analyses. 
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10.3    Statistical Analysis Plan 
10.3.2   Technical Pilot Analysis Plan 
All data collected during Phase 1, the Technical Pilot, will be qualitative in nature and therefore not have 
a statistical analysis plan.  
10.3.3   RCT Primary Analysis Plan 
The study is a multi-site randomized 3-arm parallel group, longitudinal trial. The primary 
analysis will be based on intention-to-treat principles where we assume that all participants have 
followed their randomized assignment. The primary outcome is the probability of viral load suppression 
at six months, defined as less than the lower limit of detection as per the laboratory at each clinical site. 
At baseline, the most recent viral load will be abstracted from participants’ medical records, within a 
specified time window (per trial eligibility criteria). At six months, participants’ most recent viral load will 
be abstracted if one is available in the 2-month window prior to the six-month follow-up visit; if none is 
available within that window, a blood draw will be done for the study to ascertain viral load, or 
participant can have viral load measure as part of normal care within three months after six-month visit. 
We will use a binomial regression model (with identity link) for the risk difference (RD) in 6-month viral 
suppression, comparing each of the intervention groups with the SOC group. Due to random 
assignment, we expect that the probability of viral suppression at baseline will be balanced between the 
intervention and control groups. However, if baseline differences occur by chance, we will use inverse 
probability of treatment weights to correct imbalances in baseline viral suppression. Additional baseline 
covariates may be included in the model to increase the precision of treatment effects. The treatment 
weights may be combined with censoring weights if loss to follow-up exceeds 15% or if there is evidence 
of differential censoring by treatment group. 
All analyses will be conducted using R (R Foundation for Statistical Computing, Vienna, Austria). 
10.3.3 RCT Secondary Analysis Plan 
The occurrence of CAI with a potentially susceptible partner in the last three months will be assessed at 
baseline, three-months, and six-months following the intervention. At each time point, participants will 
complete the web-based CASI survey that will include items on sexual risk behaviors over the prior three 
months. These items will ask about frequency of insertive and receptive anal intercourse, condom use, 
and number and HIV status of partners. CAI with a potentially susceptible partner will be defined as ≥1 
act of condomless anal intercourse with a partner who is not known to be HIV-positive. To assess 
intervention effect at the time point of primary interest (six months), we will use a binomial regression 
model (with identity link) for the RD in any CAI with a susceptible partner (vs. none) at six months, 
comparing the intervention groups to the control group. Similar to viral suppression, we expect that the 
probability of CAI with a susceptible partner will be similar for intervention and control groups at 
baseline. We will use inverse probability of treatment weights to correct any imbalances in baseline CAI 
with a susceptible partner. In addition, baseline covariates may be included in the model to improve 
precision of treatment effects. Censoring weights may also be included if loss to follow-up exceeds 15% 
or if there is evidence of differential censoring by treatment group. 
 

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In addition to the main six-month CAI outcome (any CAI with a potentially susceptible partner in the last 
3 months), we will conduct a separate analysis in which “potentially susceptible partner” is defined as a 
partner who is not known to be HIV-positive or taking HIV medications (including PrEP). Additionally, we 
will compare the intervention and control arms with respect to the number of CAI acts in the last three 
months according to partner HIV and PrEP status (known HIV-positive, HIV-negative and not on PrEP, 
HIV-negative and on PrEP, unknown HIV status). Finally, linear mixed models will be fitted to all 
continuous outcome measures (i.e., self-regulation, self-efficacy to disclose, disclosure outcome 
expectations, consequences of disclosure, and intentions to disclose) to estimate the relative change in 
mean response from baseline to 6 months between intervention and SOC groups. Before fitting all 
models we will look for balance between treatment arms to assess the success of randomization, and 
we will adjust for possible confounding variables to improve precision and validity where needed. In the 
event that loss to follow-up is differential across treatment arms, we will employ inverse probability 
weighting to correct for this selection bias. We will test hypotheses using the likelihood ratio test, and 
goodness-of-fit among models will be assessed using the likelihood-ratio test, AIC and BIC criteria. 
Intervention completion and acceptability will be assessed at 1 month, and sensitivity analyses will 
evaluate how our findings for primary outcomes are influenced when we account for observed 
intervention completion. 
 
Transmission Model 
We will use a modified Bernoulli process mathematical model26 to estimate the expected number of 
secondary sexual HIV transmission events for study participants. The estimated number of transmissions 
expected from each participant in each three-month interval (months -3 to 0, months 1 to 3, months 4 
to 6) will be based on his viral load, specific risk behaviors, reported numbers of partners and acts within 
those partnerships, and partner HIV/PrEP status in that interval. In addition to the study data, we will 
review the literature to obtain model parameters for per-act HIV transmission probabilities, the effect of 
viral load and condom use on transmission probabilities, and expected HIV prevalence among partners 
whose HIV status was unknown. To account for uncertainty in model input parameters, we will run 
10,000 simulations of the model, varying the input values for parameters obtained from the literature. 
The main output of each model run is the expected number of secondary transmissions for each 
participant over the six months after baseline, which will be summarized as the mean value (with 95% 
credible interval) in that period across all simulations. We will compare the estimated transmission 
events for the intervention and control groups to estimate transmissions averted due to the Tough Talks 
approach. 
10.3.4. Program cost data collection 
We will use the program costing approach described by Kim and colleagues (2014)27 combined with 
standard cost weights derived from the analysis of Medicaid or other archival billing data sources, if 
needed. Detailed resource use for the interventions will be collected for both the intervention groups 
and the usual treatment group28. These data will be assigned standard cost weights developed using the 
data collection framework provided by Kim and colleagues (2014)27. We will use the individual site data 
collected by the Excel model from Kim, combined with study contract and expenditure records to 
estimate the intervention costs and of resource use differences by treatment. The Kim Excel model is a 
standardized instrument that is used to capture the economic cost treatment programs (e.g., personnel, 
facilities, supplies) to calculate a cost per visit or other type of service27. Study case flow and expenditure 
data will be used to determine the average cost/subject for each service type, average cost per 
technology-related resource used, and overall cost of technology to be amortized over the interventions 

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in the study. We will examine the effect of software amortization and market uptake assumptions on 
the ICERs estimated by the model. 
10.3.5 Qualitative exit interviews  
Transcribed exit interviews will be analyzed thematically for both a priori and emergent themes using 
Dedoose qualitative data analysis software (or equivalent). We will follow similar analytic procedures 
used in Phase 1 in order to identify possible areas for program improvement in Phase 2 and to provide 
additional context for interpreting the intervention’s quantitative results. 
10.4    Missing Data 
 
Several procedures will be used to conduct data analysis when data for either outcomes or covariates 
are missing. The first step will be to assess the extent and pattern of missing data. If data are missing for 
only a few cases, then data analysis will be conducted only on study participants with complete data. 
However, when such a strategy would result in loss of data from a substantial proportion of participants, 
or if this approach would lead to biased or inaccurate results, then some form of imputation will be 
performed. The form of imputation used will depend on the nature of the data that are missing. For 
example, data that are collected repeatedly might be imputed using the “last value carried forward” 
method; and in some instances, interpolation between neighboring points might also be used.  
When the primary endpoint is missing, one data analysis will be conducted using only cases with the 
endpoint. Subsequent analysis will be done where missing endpoints are imputed. Hot-deck imputation 
or regression imputation may also be used in this context. 
11.0   HUMAN SUBJECTS 
 
This study will be conducted in compliance with the protocol, ICH Good Clinical Practice (GCP) 
guidelines, and 45 CFR Part 46. 
11.1    Participants’ Confidentiality 
 
All laboratory specimens, questionnaires, evaluation forms, reports, transcripts, and other records will 
be identified by SID and participant initials only, to maintain participant confidentiality. All paper records 
with personally-identifying information will be kept in a locked file cabinet in a limited secure access 
area at each study site. All computer entry and networking programs will be done with coded numbers 
only. Clinical information will not be released without written permission of the participant, except as 
necessary for monitoring by the protocol team or NICHD. Every effort will be made to ensure that study 
participants are protected from risks.  
 
Breach of Confidentiality:  A potential risk to participants is violation of confidentiality. We will take the 
utmost caution to protect the confidentiality of all responses. We will minimize this risk by maintaining 
confidentiality and discretion throughout all research procedures and data management and analysis.  
Participants may be concerned about the security of their data, particularly since it is collected and 
stored electronically. UNC and Duke have significant experience developing security protocols for 

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Internet-based studies, and we will take a variety of steps to ensure participant security, including using 
a dedicated server behind a firewall, encryption of data, separation of identifiers from responses, and 
password-protected access to data. Therefore, we believe that this risk will be minimal.  
For both Tough Talks intervention arms, participants will create a unique username that does not 
contain any identifying information but will be their username on the app. Participants will not be able 
to privately communicate with each other on the app. Trained research staff at the University of North 
Carolina will monitor the website daily to ensure violations to privacy.  
11.2    Certificate of Confidentiality 
 
This research specifically targets a vulnerable population, children – YMSM ages 15-17. We will take 
every available step to minimize the risk of identifying/linking data being subpoenaed, stolen, or 
inadvertently released. First, the Tough Talks has secured a Certificate of Confidentiality from the NIH. 
Second, all research staff members are required to complete ethical clearance certification regarding 
protection of human subjects through their relevant IRBs. Third, all studies will have documented 
procedures to safeguard against the risk of the linking information being stolen by keeping such 
information in locked spaces to which only essential study personnel who have completed CITI 
certification for human subjects research ethics training (http://citiprogram.org) will have access.  
Per Section 2012 of the 21st Century Cures Act as implemented in the 2017 NIH Certificates of 
Confidentiality Policy, all ongoing or new research funded by NIH as of December 13, 2016 that is 
collecting or using identifiable, sensitive information is automatically issued a CoC.  As noted on the NIH 
website (http://grants.nih.gov/grants/policy/COC/faqs.htm#187), a Certificate of Confidentiality will 
help the research team “...avoid compelled ‘involuntary disclosure’ (e.g., subpoenas) of names and 
other identifying information about any individual who participates as a research subject (i.e., about 
whom the investigator maintains identifying information) during any time the Certificate is in effect.”  
11.3    Risks and Benefits 
11.3.1   Risks 
To minimize the risk of participants feeling uncomfortable about answering personal questions, we will 
use Computer Assisted Self Interview (CASI) methods for the study's assessments. In CASI, participants 
read assessment questions on a laptop computer or mobile phone and use a combination of mouse click 
and keyboard/touchscreen entry to input the answers themselves. Study staff may be available to assist 
participants with questions or technical difficulties on the CASI. Participants will also be able to refuse to 
answer any question that makes them uncomfortable. In-depth interviews will be conducted face-to-
face or online.  
To minimize risks to confidentiality, we will secure study data with all appropriate physical, electronic 
and operational protections. Data will be stored in a physically secure environment. All data files will 
have encryption and strong password protection. Any identifiable data will either be stored on UNC 
secure servers or will be on fully encrypted laptops. CASI assessments and online eligibility screening will 
take place on Qualtrics. Access to data will be on a role-based standard; only those study staff who 
require access to each type of data to complete their study-related roles will be allowed access. All study 
staff will be trained in security and confidentiality procedures, and will sign a confidentiality agreement 
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We will also develop procedures to minimize indirect disclosure that a participant is participating in an 
HIV- related research study, or a study that enrolls MSM. For each mode of contact information, we will 
ask specifically whether anyone else potentially has access to that mode of communication, and if it is 
acceptable to leave a non-specific message about participation in a health study. No study-related 
messages will ever mention HIV prevention or the nature of the research study.  
We use SSL encryption for transfers of information online, and Qualtrics has a business partner HIPAA 
agreement with UNC. Qualtrics is HIPAA compliant.  
UNC will use Dedoose software to perform all qualitative analyses. Dedoose is a web-based application 
for organizing and analyzing textual, audio, and video data (qualitative) along with outstanding 
functionality for their integration with survey, test score, ratings, and demographic data (quantitative). 
Dedoose employs the highest levels of data encryption available for a web application in all data 
storage, back up, and transmission. Dedoose allows for project specific encryption feature.  
In addition to a Certificate of Confidentiality, we will protect participants in the following ways (which 
correspond to the potential risks described in A.3): 
 
1) Breach of confidentiality. We will take every precaution to minimize risks to study participants. 
All research staff members are required to complete ethical clearance certification regarding 
protection of human subjects through UNC-CH and Duke University or at their participating 
study site. We also have a strong data and safety monitoring plan in place to protect 
participants. Adverse events will be reported to the UNC-CH and Duke University and study site-
specific IRBs using the Adverse Event Reporting Forms. Reports will be sent within 24 hours of 
notification by the PIs. Annual updates on enrollment and retention will also be sent to the IRBs. 
 
All data collection will take place in secure and supervised clinical settings. All study personnel 
names on this protocol have completed training and received certification in Human Subjects 
Research Protection (CITI Program) and HIPAA regulations. They will continue to renew this 
training in compliance with institutional policies. Participants will be asked to provide informed 
written consent to audio recording (usability testing, field testing) and HIV testing, and medical 
chart abstraction. To assure confidentiality and protection of the participants during audio 
recording, all files and transcripts will be stored on a password protected, encrypted computer 
in a locked file cabinet in a secured office. To additionally preserve confidentiality, we will only 
use participants’ SIDs and names will not be used in data analysis. Informed consent forms, 
audio files, and transcripts will be kept in locked files and password-protected databases in a 
locked office accessible only to investigators. Audio files will be destroyed within one year of 
study completion. 
 
2) Emotional discomfort during the assessment and/or while using the mobile app. While 
participants will be informed that they may refuse to answer any questions at any time, 
responses or reactions to certain questions may indicate distress on the part of the participants. 
If at any time during the study, a participant divulges that he is at risk for harm, including but 
not limited to being abused or experiencing violence, if harm is suspected or likely, or if the 
participant states he is suicidal/homicidal, measures will be taken to ensure his safety locally. 
Reporting will be made as appropriate to the situation and the legal statutes, and referrals will 
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3) Discomfort during collection of blood specimen. Whenever possible, we will conduct a medical 
chart review in order to minimize the need for blood sample collection for participants. There 
are only two time points in the study that require a potential blood draw if VL is not provided in 
the participants’ medical chart (enrollment and 6-month assessment). All necessary blood 
sample draws will be executed by trained professionals within the SRV sites or independent 
laboratory.  
 
In addition to a Certificate of Confidentiality, we will protect participants in the following ways:  
We will take every precaution to minimize risks to study participants. Adverse events will be reported to 
the UNC-CH IRB, individual research PI institutional IRBs, and STUDY site-specific IRBs per each 
institution’s IRB reporting requirements using Adverse Event CRF. When possible, reports will be sent 
within 24 hours of notification by the PIs. Annual updates on enrollment and retention will also be sent 
to the IRBs.  
All data collection will take place in secure and supervised clinical settings. All study personnel have 
completed training and received certification in Human Subjects Research Protection (CITI Program) and 
HIPAA regulations. They will continue to renew this training in compliance with the UNC IRB policy as 
well as their individual institutional policies.  
11.3.2   Benefits 
 
The risk to individual participants is small and the potential benefit to both the individual and society is 
substantial. The main benefit of the proposed study to society is the development of a potentially 
feasible and acceptable mobile app that improves HIV disclosure. Participants may experience 
improvements in their own experiences disclosing their HIV status, thereby potentially reducing their 
risk for transmitting HIV and risks and costs to society. Therefore, the risk/benefit ratio is favorable. 
Study participants will be compensated for their time. 
 
YMSM account for nearly two thirds of all new HIV infections in the US and YMSM are the only risk 
group experiencing a significant increase in HIV incidence. If successful, our intervention will improve 
these outcomes in our subject population. Given this high potential impact and low potential hazards to 
participants, we find that a clear examination of these research questions outweighs the previously 
mentioned risks. The effectiveness of a novel, scalable, technology driven, intervention to address HIV 
disclosure is understudied with this population. Given the significant health outcomes associated with 
HIV infections, and the paucity of intervention programs for this population of young adults, the 
knowledge to be gained from this research is significant. The risks to participants are reasonable in 
relation to the importance of the knowledge to be gained. 
11.4    Institutional Review Board (IRB) Review and Informed Consent 
 
This protocol, the informed assent/consent documents, and any subsequent modifications will be 
reviewed and approved by the UNC IRB who is responsible for the oversight of the study. The informed 
assent/consent will describe the purpose of the study, the procedures to be followed, and the risks and 

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benefits of participation.  Consent/assent will be obtained to explain the nature, significance, and risks 
of the study. Sample informed consent/assent forms are included. 
11.5    Waiver of the Requirement for Parental Permission for Special Circumstances 
 
The site IRBs and the UNC IRB as the central IRB will be requested to grant a waiver of parental 
permission to participate in this research study for youth participants under (not inclusive of) the age of 
18.   
Under 45 CFR 46.408 (c), an IRB has the authority to waive parental permission if it determines that “a 
research protocol is designed for conditions or a subject population for which parental or guardian 
permission is not a reasonable requirement to protect the subjects” and “an appropriate mechanism for 
protecting the children who will participate as research subjects is substituted” and “that the waiver is 
not inconsistent with Federal, State, or local law.” 
A request for a waiver of the requirement for parental permission is requested for 2 reasons:  1) many 
youth would be reluctant to participate in this study – which focuses on HIV and risks for poorer 
medication adherence – if they are required to get parental permission; and 2) many of the youth in our 
study are likely to be gay, bisexual, or have an attraction to persons of the same gender, but may not be 
out to their parents; requiring parental permission may place participants at risk for outing themselves 
as part of the LGBT community or having HIV. For these reasons, we believe it is important to be granted 
a waiver for parental permission for this study population. 
11.6  Waiver of the Requirement for Signed Consent Form  
11.6.1 For Eligibility Screening 
An online consent process for the eligibility screening is proposed. The introduction to the screening 
interview includes all the required elements for consent (45 CFR 46.116). No identifying information on 
volunteers is recorded during the online screening until a participant is determined eligible (i.e., by 
marking “I do consent to be screened for eligibility”). Therefore, there will be no identifying link of who 
agreed to be screened or not screened for the study. In addition, the screening presents minimal risk to 
participants and involves no procedures that would require written consent outside of a research 
context. Under these conditions the IRB is authorized to modify the requirements to obtain a signed 
consent form for some or all subjects (45 CFR 46.117 [c]). 
11.7    Prisoner Participation  
 
NIMH has concluded that this protocol does NOT meet Federal requirements governing prisoner 
participation in human subjects research and should NOT be considered by local IRBs for the 
recruitment of prisoners. Subjects enrolled who subsequently become incarcerated or are placed in 
detention may not continue study participation. Study visits cannot be conducted during the period of 
incarceration or detention.  

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11.8 45 CFR Parts 160 and 164 Standards for Privacy of Individually Identifiable Health 
Information ("Privacy Rule" Pursuant to the Health Insurance Portability and Accountability 
Act - HIPAA) 
 
Each site is responsible for adherence to their individual institution’s HIPAA policies and procedures. 
11.9    Study Discontinuation 
 
This study may be discontinued at any time by the UNC IRB, NICHD, or other government agencies as 
part of their duties to ensure that research participants are protected.  
12.0 PUBLICATION OF RESEARCH FINDINGS 
 
Any presentation, abstract, or manuscript will be made available for review by the study sponsor(s) prior 
to submission.   
 
Schedule of Events  
Table 2: Schedule of Study Evaluations and Outcomes  
 
 
BL 
One-
month  
Three-
months 
Six-
Months 
Primary Outcomes 
Viral load 
suppression 
Viral load suppression will be 
defined as HIV RNA < lower limit 
of detection as per the laboratory 
at each clinical site. 
Medical 
Chart 
review or 
blood 
draw for 
study 
X 
 
X 
X 
Secondary Outcomes 
Condomless anal 
sex (CA) with 
potentially 
susceptible 
partner 
 ≥1 act of CAI with a partner who is 
not known to be HIV-positive in 
the last 3 months. 
CASI 
X 
 
X 
X 
Disclosure Self-
Regulation 
(Behaviors) 
Measure of desire and actual 
disclosure behaviors to family, 
peers and sex partners 
CASI 
X 
X 
X 
X 
Self-efficacy to 
disclose 
Adapted version of disclosure self-
efficacy measure for MSM (6 
items)14. 
CASI 
X 
X 
X 
X 

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Disclosure 
outcome 
expectations 
Adapted version of disclosure 
outcome expectations measure 
for MSM  (2 domains: self-
evaluative expectancies - 6 items, 
and hedonistic outcome 
expectancies – 3 items)14. 
CASI 
X 
X 
X 
X 
Intentions to 
disclose 
Adapted version of disclosure 
intentions measure for MSM (1 
item)14. 
CASI 
X 
X 
X 
X 
Consequences of 
disclosure  
Measure indicating how important 
each of a list of possible 
consequences concerning 
disclosure was to them when 
considering disclosing to a specific 
person29. 
CASI 
X 
X 
X 
X 
Potential Moderators 
Brief Symptom 
Inventory (BSI)  
The BSI yields nine primary 
symptom scales and global indices 
and has norms for adolescents and 
adults30. 
CASI 
X 
 
X 
X 
The Alcohol, 
Smoking, and 
Substance 
Involvement 
Screening Test 
(ASSIST)  
Individuals respond to eight items 
assessing the frequency and 
consequences of drug and alcohol 
use31. 
CASI 
X 
 
X 
X 
Other Outcomes of Interest  
Retention in Care 
# missed and scheduled visits over 
last 6 months 
CASI 
X 
 
X 
X 
STIs 
New diagnosis of rectal/urethral 
gonorrhea or chlamydia or syphilis 
in last 6 months. 
Medical 
Chart 
abstraction 
CASI 
X 
 
X 
X 
Adherence 
A visual analogue scale (VAS) will 
be used to assess antiretroviral 
therapy adherence over the last 3 
months32. 
CASI 
X 
 
X 
X 
PrEP uptake in 
serodiscordant 
partners 
Participants will be asked to report 
on any known PrEP use among 
their serodiscordant partners. 
CASI 
X 
 
X 
X 
Feasibility/Acceptability and Cost 

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Feasibility 
(participants) 
Records on recruitment, retention 
(missed assessments) and follow-
up attempts will be kept. 
Intervention usage will include: # 
of times participant accessed the 
intervention, average time spent 
on the site, and # of activities 
completed. 
App 
Metrics 
 
X 
 
 
Acceptability 
Both a scale adapted from Horvath 
et al33. and The System Usability 
Scale is a validated 10-measure 
scale that assesses subjective 
usability of a system. It is scored 
from 0 to 100, and a score of 68 or 
greater indicates that the online 
intervention is acceptable34,35. 
CASI 
 
X 
 
 
TT specific 
Acceptability 
Features liked, disliked with some 
write in questions, avatar specific 
acceptability 
CASI 
 
X 
 
 
Cost  
Resources used to provide 
standard of care visits, installation 
and orientation to Tough Talks, 
clinic visits, and any unexpected 
consequences of the two 
intervention approaches recorded 
as part of the feasibility data 
collection.  
CRFs, staff 
tools 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 

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