A Multidimensional Digital Approach to Address Vaccine Hesitancy and Increase COVID-19 Vaccine Uptake Among African American Young Adults in the South (Tough Talks COVID)
Phase: NA
Conditions: COVID-19, Vaccine Uptake
Sponsor: Florida State University

 
 
 
      
TITLE OF RESEARCH STUDY: A MULTIDIMENSIONAL DIGITAL APPROACH TO 
ADDRESS VACCINE HESITANCY AND INCREASE COVID-19 VACCINE UPTAKE 
AMONG AFRICAN AMERICAN YOUNG ADULTS IN THE SOUTH (TOUGH TALKS 
COVID) 
 
NCT05490329 
 
DOCUMENT DATE: 07APR2023LATE PROTOCOL 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 1 of 32 
HRP-503 Revised: October 25, 2022 
 
 
PROTOCOL TITLE: 
A Multidimensional Digital Approach to Address Vaccine Hesitancy and Increase 
COVID-19 Vaccine Uptake among African American Young Adults in the South (Tough 
Talks COVID) 
 
PRINCIPAL INVESTIGATORS: 
Lisa Hightow-Weidman, MD MPH 
College of Nursing 
Phone: 850-644-5260 
E-mail: lhightowweidman@fsu.edu 
 
Henna Budhwani, PhD MPH 
College of Nursing 
Phone: 850-644-5260 
Email: hbudhwani@fsu.edu 
 
VERSION NUMBER/DATE: 
Modified from UNC Version 3.0 08/02/2022 
FSU Version 1.1 01/06/2023 
 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
1 
01/06/2023 
Update randomization schema to include 
balanced assignment within given study states 
N 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 2 of 32 
HRP-503 Revised: October 25, 2022 
 
 
Table of Contents 
1.0 
Study Summary ....................................................................................................... 3 
2.0 
Objectives ................................................................................................................ 7 
3.0 
Background ............................................................................................................. 7 
4.0 
Study Endpoints .................................................................................................... 10 
5.0 
Investigational Test Articles or Products .............................................................. 11 
6.0 
Procedures Involved .............................................................................................. 11 
7.0 
Data and Specimen Banking ................................................................................. 16 
8.0 
Sharing of Results with Subjects ........................................................................... 16 
9.0 
Study Timelines..................................................................................................... 16 
10.0 
Inclusion and Exclusion Criteria ........................................................................... 17 
11.0 
Vulnerable Populations ......................................................................................... 18 
12.0 
Local Number of Subjects ..................................................................................... 18 
13.0 
Recruitment Methods ............................................................................................ 18 
14.0 
Withdrawal of Subjects ......................................................................................... 19 
15.0 
Risks to Subjects ................................................................................................... 20 
16.0 
Potential Benefits to Subjects ................................................................................ 22 
17.0 
Data Management and Confidentiality ...................................................................22 
18.0 
Provisions to Monitor the Data to Ensure the Safety of Subjects ......................... 27 
19.0 
Provisions to Protect the Privacy Interests of Subjects ......................................... 28 
20.0 
Compensation for Research-Related Injury ...........................................................29 
21.0 
Economic Burden to Subjects ................................................................................29 
22.0 
Consent Process .................................................................................................... 29 
23.0 
Process to Document Consent in Writing ............................................................. 30 
24.0 
Setting ................................................................................................................... 30 
25.0 
Resources Available .............................................................................................. 30 
26.0 
Multi-Site Research ............................................................................................... 30 
 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 3 of 32 
HRP-503 Revised: October 25, 2022 
 
 
1.0 
Study Summary 
 
Study Title 
A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among 
African American Young Adults in the South (Tough Talks 
COVID) 
Study Design 
Hybrid type 1 effectiveness implementation 2-arm RCT with 
360 AA-YA from AL, NC, and GA 
Primary Objective 
The overall objective of the research study is to adapt and test 
the efficacy of the Tough Talks-COVID (TT-C) app among 
360 AA-YA ages 18-29 recruited from community partners in 
AL, GA, and NC. The primary outcome is COVID vaccine 
uptake and series completion. 
Secondary 
Objective(s) 
Secondary outcomes are VH, confidence, and knowledge, 
attitudes, and beliefs. 
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
Tough Talks COVID (TT-C) Mobile Application 
IND/IDE # 
(see section 5) 
N/A 
Study Population 
Aim 1 (online survey and DST workshops) (complete): 
1) YA aged 18-29 
2) identify as AA 
3) English proficient 
4) access to a personal smartphone 
5) current resident of AL, GA or NC. 
Aim 2 (focus group) (complete): 
1) YA aged 18-29 
2) identify as AA 
3) English proficient 
4) access to a personal smartphone 
5) express COVID vaccine hesitancy (VH) 
6) reside in one of the six intervention communities in AL, 
GA, and NC. 
Aim 3 (2-arm randomized controlled trial): 
1) YA aged 18-29 
2) identify as AA 
3) English proficient 
4) access to a personal smartphone 
5) express COVID vaccine hesitancy (VH) 
6) reside in AL, GA, and NC 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 4 of 32 
HRP-503 Revised: October 25, 2022 
 
 
 
Not eligible: having received full series of COVID vaccine 
doses (including vaccines plus booster or prior participation 
in a vaccine trial). 
Sample Size 
Total study sample is ~544 of which the following will be 
enrolled for each aim: 1) online survey with 150 participants; 
up to 24 of whom will be selected to participate in the DST 
workshops; 2) focus groups with up to 16 participants, beta 
testing with community and YAB members; 3) 2-arm RCT 
conducted with 360 participants. The TT-C remote and 
standard of care arms will each include 180 participants. 
Study Duration for 
individual 
participants 
Study duration for participants in Aim 1 is up to four weeks 
for those participating in the DST workshops. Study duration 
for participants in Aim 2 is up to 2 months. The duration of 
study for RCT participants is 3 months. 
Study Specific 
Abbreviations/ 
Definitions 
AA 
African American 
AA-YA African American Young Adults 
ACTG 
AIDS Clinical Trials Group 
ACASI 
 Audio Computer Assisted Self Interview 
AE 
Adverse Events 
AES 
Advanced Encryption Standard 
AIDS 
 Acquired Immunodeficiency Syndrome 
AL 
Alabama 
ATN 
Adolescent Medicine Trials Network for 
HIV/AIDS Interventions 
CASI   Computer assisted self-interview 
CBPR Community Based Participatory Research 
CDC Center for Disease Control and Prevention 
CFR   Code of Federal Regulations 
CoC 
Certificate of Confidentiality 
COVID  SARS-CoV-2 
CRF 
Case Report Form 
CYOA 
Choose Your Own Adventure 
DHHS 
 U.S. Department of Health and Human Services 
DHIs 
Digital Health Interventions 
DSW 
Digital Storytelling Workshop 
E2E 
End-to-End 
EC 
Ethics Committee 
EUA 
Emergency Use Authorization 
FISMA  Federal Information Security Management Act 
FIPS 
Federal Information Processing Standards 
GA 
Georgia 
GCP 
Good Clinical Practices 
HBCU 
Historically Black Colleges and Universities 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 5 of 32 
HRP-503 Revised: October 25, 2022 
 
 
 
HIPAA Health Insurance Portability and Accountability 
Act 
HITECH Health Information Technology for Economic and 
Clinical Health Act 
HIV 
Human Immunodeficiency Virus 
ICH 
 International Conference on Harmonization 
IRB 
Institutional Review Board 
NC 
North Carolina 
NICHD  National Institute of Child Health and 
Development 
NIDA 
National Institute on Drug Abuse 
NIH 
 National Institutes of Health 
NIMHD National Institute on Minority Health and Health 
Disparities 
PI 
Principal Investigator 
OHRP 
 Office of Human Research Protection 
QNS 
Query and Notification System 
RCT 
Randomized Control Trial 
RDC 
 Remote data capture 
RDS 
Respondent-Driven Sampling 
SAGE 
 Strategic Advisory Group of Experts 
SID 
Study ID Number 
SOC 
Standard of Care 
SSAE 
Standards for Attestation Engagements 
SSL 
 Secure Sockets Layer 
TLS 
 Transport Layer Security 
TT-C 
Tough Talks COVID 
UNC 
University of North Carolina 
UPiRSO Unanticipated Problem involving Risk to Subjects 
or Others 
VH 
Vaccine Hesitancy 
YA 
Young Adults 
YAB 
Youth Advisory Board 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 6 of 32 
HRP-503 Revised: October 25, 2022 
 
 
 
RCT Schema: 
 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 7 of 32 
HRP-503 Revised: October 25, 2022 
 
 
2.0 
Objectives 
2.1 The overall objective of the research study is to adapt and test the 
efficacy of the Tough Talks-COVID (TT-C) app among 360 AA-YA 
ages 18-29 recruited from community partners in AL, GA, and NC. 
The primary outcome is COVID vaccine uptake and series 
completion. 
Secondary outcomes are VH, confidence, and knowledge, attitudes, 
and beliefs. 
2.2 We hypothesize that the intervention arm will be more effective than 
the control arm at increasing vaccine uptake 
3.0 
Background 
3.1 Young Adults (YA) are a key “super-spreader” population 
transmitting SARS-Co-V2, the causative agent of COVID-19 
(COVID). Interventions to increase the uptake of COVID 
vaccination among YA are central to ending the pandemic.1 Given 
their high rate of asymptomatic infection2 compounded by 
transmission rates that are being fueled by behaviors that run 
contrary to physical distancing and face covering regulations, YA 
represent a priority population upon which to focus efforts to ensure 
high levels of COVID vaccine uptake.1 Indeed across the Southern 
US, increases in positive SARS-CoV-2 test results among YA were 
found to precede increases among older adults (aged ≥60 years) by 
4–15 days, providing evidence for the significant contribution YA 
play in sustaining community transmission.3 YA have been 
implicated in local COVID outbreaks and infection clusters4 linked 
to bars,5 parties6,7 and college campuses.8 High rates of employment 
in public facing essential jobs often do not allow YA to work 
remotely.9,10 Further, YA who identify as African American (AA- 
YA) often have the social capital to influence health behaviors in 
older family and community members who are at high risk for 
COVID morbidity and mortality.11 
Digital Health Interventions (DHIs) can reach large numbers of YA 
regardless of geographic location and empower them to make 
informed decisions about their health using a familiar modality that 
YAs value and trust. Our collaborative team developed the theory 
informed DHI Tough Talks to assist YA with HIV disclosure 
decision making, specifically by considering the social, ethical and 
behavioral implications of their choices and the consequences that 
follow. In response to NOT-MD-21-008: Research to Address 
Vaccine Hesitancy, Uptake, and Implementation among Populations 
that Experience Health Disparities, we propose to leverage lessons 
learned from the HIV epidemic among YA and AA-YA and apply a 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 8 of 32 
HRP-503 Revised: October 25, 2022 
 
 
community-based participatory research (CBPR) approach to adapt 
and test Tough Talks to address COVID vaccine hesitancy, Tough 
Talks-COVID (TT-C).12 Our CBPR approaches are grounded in 
equitable communities partnerships, and strive to be mutually 
beneficial throughout the life of a project, from inception to 
dissemination. Attention to equity is critical for research within AA 
communities, who face a legacy of misrepresentation, 
discrimination, and exploitation in clinical research which has 
engendered understandable mistrust of vaccines, medicine, and 
research.13 
The TT-C intervention will enable AA-YA to actively make 
autonomous decisions about COVID vaccine receipt using non- 
stigmatizing and YA-tailored messaging. Through engaging 
activities and narrative communication, TT-C will address the 
structural contexts (e.g. emotionally charged, issues of confidence 
and distrust in medicine, stigma), mis-information (e.g. vaccination 
knowledge), environmental barriers (e.g., access to care, health 
insurance) and potential consequences (e.g. outcomes related to 
accepting or refusing vaccination).14 Using CBPR methods to co- 
create TT-C with AA-YA will promote personal agency, bolster 
resilience in the face of the pandemic, strengthen intervention 
quality, and increase intervention relevance and engagement.15-17 We 
will employ CBPR methods to assess multi-level factors identified 
within the NIMHD Research Framework at the individual 
(knowledge, attitudes, and normative beliefs), interpersonal (peer 
and family influence), institutional (provider communication, health 
care system) and structural level (stigma, discrimination) that 
inﬂuence COVID vaccine hesitancy (VH) and refusal. We will 
leverage novel data collection methods to reach and engage AA-YA 
through the conduct of our multiphase, implementation science 
randomized controlled trial (RCT). 
3.2 Vaccine Hesitancy (VH) is complex, influenced by factors at the 
individual, community, provider, health care system, and societal 
levels.20 A cross-sectional online survey of US adults (n=2,650) 
conducted in December 2020 found that respondents who reported 
experiences of racial discrimination had 21% increased odds of 
higher VH compared to those who did not report such experience.21 
Thus, as espoused by the WHO Strategic Advisory Group of Experts 
(SAGE), individual/social group influences, contextual influences, 
and vaccine-specific issues must be identified and then targeted 
through multi-component and tailored interventions to increase 
vaccine uptake within relevant populations.22 We therefore utilize 
the NIMHD Research Framework, informed by the SAGE Working 
Group (Figure 1) to provide a model for depicting the determinants 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 9 of 32 
HRP-503 Revised: October 25, 2022 
 
 
relevant to understanding and addressing VH in AA-YA and to 
guide our intervention development.23 
Building capacity and promoting AA-YA agency through co- 
creation of the intervention will foster resilience in the face of the 
pandemic, strengthen intervention quality, and increase engagement 
with intervention content.15-17,24 COVID has exacerbated disparities 
experienced by AA-YA, particularly those residing in the 
underserved US South. AA face significantly more morbidity than 
other races. From May-August 2020 Black individuals accounted for 
18.7% of overall deaths despite making up just 12.5% of the US 
population.25 COVID continues to disrupt economic resources, social 
networks, and healthcare services26 across socioecological levels, 
disproportionately affecting disparity populations such as AA-YA.27 
Stigma, discrimination, and distress due to COVID are widely 
evident,28 and highest among those with intersectional identities 
(e.g., AA, YA, rural, etc.),29 reinforcing health inequities.30,31 
Comprehensive multi-component interventions, situated in the 
existing contexts of racial disparities and discrimination, that are 
responsive to the diverse needs of AA-YA, and address both the 
structural and psychosocial barriers to COVID vaccination are 
critically needed. To this end, our project is rooted in community- 
based participatory research (CBPR) methods as an innovative way 
to partner with communities most impacted by the pandemic.12,32-34 
Our approach explicitly engages with the social and ethical 
implications of research with AA communities, who face a history of 
misrepresentation, discrimination, and exploitation which has 
engendered valid and understandable mistrust of medicine and 
research.13 
Digital Health Interventions (DHIs) are well-suited for YA given the 
ubiquity of technology use and their suitability for delivering content 
tailored to each user’s unique needs. DHIs can increase knowledge, 
self-efficacy, and motivation for behavior change while ameliorating 
distrust, fear, and stigma across a variety of health conditions.35-40 
YA already rely on digital technologies to build their social 
networks, receive social support, and obtain health 
information.37,41,42 Access to credible online resources is critical 
given the majority of YA access COVID information from online 
news and social media sites.43 Likewise, misinformation via social 
media can increase behaviors that perpetuate COVID VH.44 Our 
team in on the forefront of designing stand-alone, preventative health 
DHIs that hold promise for engaging AA-YA to address COVID VH 
and uptake.37,45-49 Specifically, the Tough Talks DHI (R43/R44 
MH104102) was developed to assist youth living with HIV with 
disclosure decision making by considering the social, ethical and 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 10 of 32 
HRP-503 Revised: October 25, 2022 
 
 
behavioral implications of their choices and the consequences that 
follow.50-52 Tough Talks was informed by Social Cognitive Theory 
(SCT); the inclusion of emotionally engaging scenarios, interactivity, 
and automation promotes observational learning, social modeling, 
and reinforcement of behavioral skills (Figure 2). Feasibility and 
acceptability of the platform for AA-YA males has been established; 
early results from a national RCT appear promising for impacting 
disclosure decisions (see Section C.5). For these reasons, we have 
chosen to adapt Tough Talks, a culturally tailored and theoretically 
informed DHI to increase COVID vaccine uptake in stigmatized 
AA-YA in three southern states. 
3.3 Acceptance of COVID vaccination is lowest among YA and African 
Americans (AA). Two highly effective vaccines for COVID were 
given Emergency Use Authorization (EUA) by the FDA in 
December, the Moderna and Pfizer, mRNA vaccines. The Moderna 
vaccine showed 94% and Pfizer 90% efficacy in phase 3 trials. Both 
vaccines require 2 doses about 3-4 weeks apart. Despite the high 
efficacy, the rapid development and testing of these vaccines has 
resulted in public concern around safety of the vaccines. This built 
on a history of medical mistrust has result in low levels of 
willingness to take up a vaccine in surveys done among AA 
populations in the US. Rates of COVID-19 vaccination are currently 
at 61.8% in Alabama, 64.3% in Georgia, and 82.2% in North 
Carolina, with rates continuing to be lower among African American 
populations in southern states. A recent 2022 Health Resources and 
Services Administration (HRSA) report found that only 54.5% of 
African American residents in surveyed Georgia clinics accepted 
their first vaccine dose, 10% lower than the overall state rate and 
only 34.1%, 34.9%, and 25.1% of Alabama, Georgia, and North 
Carolina residents, respectively, have accepted a booster. Those who 
remain unvaccinated may be highly resistant toward accepting 
vaccination or are overwhelmingly apathetic. Further, lower vaccine 
acceptance was associated with younger age (18-49 years) in a 
nationally representative survey conducted in October 2020 among 
US residents (n=525).19 
All aims of this study have been previously reviewed and approved 
by the University of North Carolina at Chapel Hill IRB. Aims 1 and 
2 were completed while the research team was at UNC-CH. By 
submitting this protocol to Florida State University, we are seeking 
IRB approval for the RCT (Aim 3) and analysis activities only. The 
original protocol, study documents, and approval letters are 
appended in the IRB submission. 
4.0 
Study Endpoints 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 11 of 32 
HRP-503 Revised: October 25, 2022 
 
 
4.1 The primary study endpoint is COVID vaccine uptake and series 
completion. The secondary study endpoint is change in vaccine 
hesitancy, vaccine confidence, and change in knowledge, attitudes, 
and beliefs. 
4.2 N/A 
5.0 
Investigational Test Articles or Products 
 
5.1 The Tough Talks COVID intervention is a mobile app co-created with AA- 
YA using CBPR methods. The application enables AA-YA to actively make 
autonomous decisions about COVID vaccine receipt using non-stigmatizing 
and YA-tailored messaging. It includes engaging activities and narrative 
communication, and seeks to address structural contexts, misinformation, 
environmental barriers, and potential consequences. 
5.2 N/A 
5.3 N/A 
5.4 N/A 
 
6.0 
Procedures Involved 
6.1 This study will consist of three distinct aims to develop and test the 
TT-C intervention for COVID vaccine hesitant AA-YA. Aims 2 and 
3 procedures are premised on the formative data collected in Aim 1. 
Aim 3: Conduct a hybrid type 1 effectiveness implementation 2-arm 
randomized controlled trial with 360 AA-YA from AL, NC, and GA. 
6.2 Enrollment: After screening eligible and agreeing to be contacted, 
eligible responses will be reviewed individually by study staff to 
determine authenticity and legitimacy. In addition to eligibility 
criteria, staff will review bot detection values as well as location 
based on IP address & latitude/longitude. If determined eligible, staff 
complete the Verification CRF and REDCap will email the 
individual with a unique consent form link to complete. Once 
completed, REDCap will send the baseline survey linked to their 
unique ID in REDCap. 
After the baseline survey is complete, study staff will randomize the 
participant with the Randomization CRF to either the intervention or 
control group. Based on the study arm, study staff will either email 
the participant with the developed SOC materials or email the 
participant with a unique link to create their account for the TT-C 
app. If SOC, the participant will be compensated at this time. 
If participant is randomized to intervention arm, they will be 
prompted to create their account with the provided link, then will be 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 12 of 32 
HRP-503 Revised: October 25, 2022 
 
 
directed to download and login to the TT-C app. Once account 
creation is confirmed in the administrator portal, study staff will 
compensate the participant for enrolling. 
Randomization: RCT participants will be randomized via block 
randomization into the control condition and TT-C (remote), each 
with a balanced 180 participants. Assignment will be stratified by 
state to achieve balance between intervention and control 
participants within a given study state. 
Locator/Contact Information Collection: Once consented and 
enrolled, designated site study staff will collect contact information 
from the participant. Participants will be asked to provide contact 
information through which they can be reached. Participants will 
also be asked to provide valid contact information for two family 
members and/or friends 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. Study staff 
will not leave messages unless expressly permitted to do so by the 
participant which also will be documented. If permission is given to 
leave messages, site staff will assure participants that messages left 
with a family member or friend will only ask the participant to 
contact study staff and will not include any protected health 
information or information related to study participation. 
The Contact Information Worksheet 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. 
Optional Monkeypox Module: Participants will also be given the 
opportunity to complete an optional set of questions about 
Monkeypox immediately following the baseline survey. 
TT-C arm: Once enrolled, participants will be emailed a unique link 
to create their TT-C account and instructions on how to download 
the TT-C (remote) app from the iOS or Google Play store. They will 
be asked to complete the intervention within one month. Participants 
will be compensated for completing the baseline survey and 
reminded that they will be asked to return (virtually) in 1 and 3 
months for follow-up. 
Standard of Care arm: Research staff will provide COVID vaccine 
materials from the CDC to those participants in the SOC arm. 
Participants will be compensated for completing the baseline survey 
and reminded that they will be asked to complete 1 and 3-month 
follow-up surveys. To provide the maximum benefit through this 
trial, after the completion of the data collection associated with the 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 13 of 32 
HRP-503 Revised: October 25, 2022 
 
 
primary RCT, those randomized to the control arm who still report 
VH will be offered the opportunity to accept the TT-C intervention 
delivered remotely. These participants will be asked to use the app 
for one month and complete follow-up surveys at their 4- and 6- 
month time points (same surveys used for 1 and 3M). These 
participants will be compensated for survey completion. 
Participants will also be asked to complete exit interviews to discuss 
their experience with the intervention and/or their knowledge, 
attitudes, and perceptions of COVID-19 vaccination. 
6.3 Research Staff Training: 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. Training for all research staff includes (but is not limited to): 
an overview of the study; study procedures and human subjects 
issues (informed consent process, confidentiality); a demonstration 
of all technology components; methods for establishing comfort with 
the sensitive issues that may arise in the course of the focus groups 
or assessments; Human Subjects Protection; Good Clinical Practice; 
informed consent; quality management; confidentiality; and 
reporting of adverse events. 
Intervention Monitoring/Quality Control: Because the TT-C 
intervention is an app, intervention fidelity is assured for all 
activities except for the reflection activities and facilitation of 
vaccination appointments. 
Data Platform Security: We use SSL encryption for transfers of 
information online and data will be stored in the secure, HIPAA- 
compliant servers of the Florida State University. The CASI data 
will be stored in a secure database at Qualtrics and REDCap. 
Qualtrics and REDCap use 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 and REDCap deploy 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. 

MOD00003318 
FSU IRB Approved 
7 April 2023 
PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
Page 14 of 32 
HRP-503 Revised: October 25, 2022 
 
 
Health Insurance Portability and Accountability Act (HIPAA) 
Statement: With some restrictions, Qualtrics and REDCap may be 
designated as Business Associates when the Qualtrics and REDCap 
BA Agreements are 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 and 
REDCap ensure the highest protection and testing as per HITECH 
requirements. 
Zoom Platform Description: The Zoom platform may be used to 
conduct qualitative interviews remotely. 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. Zoom is compatible on PCs, tablets, and smartphones; as 
well as maintains the option to conduct an audio conference without 
the video component. Zoom offers HIPAA-compliant versions of its 
platform. Study staff will use HIPAA-compliant version of Zoom for 
study activities. 
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 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 conversation over the 
public mobile network. In addition to unique security beneﬁts, 
Zoom’s communications infrastructure also enables an extremely 

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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, as in VSee 
above, but this information will be stripped form the recorded Zoom 
sessions before they are sent to the analysis team for content 
analysis. 
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. 
6.4 The study 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. 
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 (if used, stored in double-locked office 
separate from other study information only accessible by designated 
study staff) and will be redacted from focus group and exit 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 separate tabs in 
REDCap, accessible only to designated study staff, site monitors, 
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 logging into the app. These unique App 
IDs will be provided by the developer and recorded into REDCap 

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during enrollment. Original source documents (e.g., Contact 
Information Worksheet) for individual participants will be 
maintained at the respective site and will be accessible only to the 
study staff. Data from original source documents will be transcribed 
on CRFs as applicable. Electronic data will be stored in Box, 
OneDrive or on a secure server at FSU. 
Audio-Recorded Data: Audio recorded data from the focus group 
sessions will initially be stored as a digital file on a secure encrypted 
FSU server. Focus groups 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. 
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 
FSU-run secure cloud management platform, to be used if needed. 
CASI Survey Data: Data collected using a CASI method at the 
community partner 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 personally identifying 
information will be collected during the computer session. The 
participant’s unique SID number will be used in order to link the 
participant to the responses. 
CASI Data Security: Only authorized users with a login name and 
password will be able to access and open the online HIPAA- 
compliant online CASI platform administered survey. 
6.5 N/A 
6.6 N/A 
7.0 
Data and Specimen Banking 
7.1 N/A 
7.2 N/A 
7.3 N/A 
8.0 
Sharing of Results with Subjects 
8.1 After completion of analyses, overall study results will be shared 
with participants in the form of a lay summary and/or infographic. 
This information will be sent to participants via the email they 
consented to using for study purposes. 

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Any manuscripts for academic publication or other publicly 
available materials generated as a result of this work will not 
individually identify participants in this study. 
9.0 
Study Timelines 
9.1 
Participants in the TT-C arm will be asked to complete the 
intervention within one month. They will also be asked to complete 
follow-up surveys up to 3-months post-baseline. Participants in the 
SOC arm will also be asked to complete study activities up to 3- 
months post-baseline. Of note, those in the SOC arm who decide to 
access the TT-C app after the 3-month follow-up survey will be 
asked to complete additional surveys at 4- and 6-months post- 
baseline. 
Recruitment of subjects is expected to be completed within 9 
months of study launch. Primary outcome analyses are expected to 
be completed with 6 months of end of data collection. 
10.0 Inclusion and Exclusion Criteria 
10.1 All potential participants (whether recruited online or in-person) will 
complete an online screening survey via Qualtrics and REDCap to 
obtain consent to be screened and verify all inclusion criteria. 
Screening may occur on the same day as enrollment or beforehand. 
The online screening survey will begin with a script that will be read 
by participants to explain the purpose of screening and clarify that if 
they are eligible, they will be invited to participate in the study. The 
script will also provide general information about the research study, 
the nature of the screening questions and related potential risks, the 
approximate length of the screening (~5 minutes), the confidentiality 
of the screening information, the use of any screening information 
obtained, the ability to skip any questions or withdraw at any time 
and contact information of key study personnel. After reading this 
screening script, participants will be asked if they are interested in 
participating and agree to voluntarily complete the screening 
procedure. Participants will electronically indicate their agreement 
and then take the survey. 
Those who meet eligibility criteria will be asked to record the first 
name, e-mail, and phone number if interested in participating; those 
disinterested in participating can decline by exiting the website. 
Potential participants who do not meet eligibility criteria will be 
asked if they would like to be contacted about other research studies 
and, if so, to provide contact information. 
10.2 Inclusion Criteria: 
• Ages 18-29, inclusive 

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• Identify as African American/Black 
• Able to speak and read English 
• Has access to personal smartphone 
• Current resident of AL, GA, NC 
 
Exclusion Criteria: 
• Aged younger than 18 years or older than 29 years 
• Does not identify as African American/Black 
• Non-English speaking 
• Does not live in AL, GA, NC 
• Unable to provide informed consent 
• Receipt of full COVID vaccine series (including vaccination and 
booster or prior participation in a vaccine trial) 
10.3 Special populations: 
• This study will not include adults unable to consent 
• This study will not include individuals who are not yet adults 
(infants, children, teenagers) 
• This study may include pregnant people as they are not 
specifically excluded. Their status as pregnant should not affect 
their ability to complete any of the outlined study activities, nor 
should the outlined study activities affect their pregnancy 
• This study will not include prisoners 
11.0 Vulnerable Populations 
11.1 NICHD has concluded that this protocol does NOT meet Federal 
requirements governing prisoner participation in human subject 
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 
12.0 Local Number of Subjects 
12.1 N/A 
12.2 N/A 
13.0 Recruitment Methods 
13.1 Our recruitment strategy includes: 1) free and paid advertising and 
posting on social media sites; 2) advertising through targeted patient 
recruitment companies; 3) distribution through national 
organizations working with AA-YA, including HBCUs; and 4) 

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distribution through our community partners and other network 
collaborations. 
13.2 Participants will be sourced from 1) social media sites; 2) targeted 
recruitment companies; 3) distribution through national 
organizations working with AA-YA, including HBCUs; and 4) our 
community partners and other network collaborations in AL, GA, 
NC. 
13.3 We will use methods successfully deployed in our prior studies to 
recruit through social media sites frequented by AA-YA and rely on 
our strong network of community and academic partners for 
additional dissemination. Recruitment procedures may vary slightly 
depending on the community organization and study phase, which 
will be negotiated prior to the beginning of each phase of the study. 
For the focus groups and RCT, we will also follow respondent- 
driven sampling (RDS) methods and use a long-chain referral 
method to supplement recruitment. 
13.4 We will use text and photos in combination for the Tough Talks - 
COVID research study recruitment campaign. One or more text 
elements will be combined with photos to create engaging 
advertisements. The language, photos and graphics might be used 
alone or with text statements on a variety of online platforms 
including but not limited to, websites, social media, online news 
outlets, mobile phone apps, social networking sites, micro-blogging 
outlets, photo sharing portals, etc. The language and images may 
also be used for printed materials, including but not limited to 
buttons, stickers, palm cards, flyers, and print advertisements. All 
ads will identify Tough Talks - COVID as a research study. A 
detailed recruitment plan providing example advertising text and 
images is appended to the IRB submission. 
13.5 TT-C arm participants are compensated (using an e-gift card) for 
completion of baseline ($50), 1-month ($50), and 3-month surveys 
($50), $50 for completing 75% of the app activities, and $50 for exit 
interviews (up to $250 in total). These participants will also be given 
the opportunity to complete an optional module of questions about 
Monkeypox as part of the baseline survey for an additional $10. In 
total, TT-C arm participants could be compensated up to $260. 
SOC arm participants are compensated (using an e-gift card) for 
completion of baseline ($50), 1-month ($50), and 3-month surveys 
($50) (up to $150 in total). These participants will also be given the 
opportunity to complete an optional module of questions about 
Monkeypox as part of the baseline survey for an additional $10. If an 
SOC arm participant decides to engage with the TT-C app when 
offered after the 3-month follow-up, they could complete an 

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additional survey at 4- and 6-months post-baseline, for $50 each, and 
$50 for exit interviews. These participants will also receive a $50 
completion incentive if they complete at least 75% of the app 
activities. In total, SOC arm participants could be compensated up to 
$360. 
13.6 N/A 
14.0 Withdrawal of Subjects 
14.1 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: 
a. The subject withdraws consent/assent 
b. The study is cancelled by the NIH (or other administrative entity) 
c. The study is cancelled for other administrative reasons 
d. Death of the subject 
14.2 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 at the community 
partner organization will be offered counseling on site. Participants 
who experience distress during the study and do not come to the 
partner organization for a visit will be provided a list of community 
referrals via phone or e-mail. Any unexpected adverse events that 
meet the unanticipated problem (UP) reporting criteria will be 
immediately reported to the IRB of record and the respective sites’ 
IRBs if applicable. A Study Stop Form will be completed at this 
time. 
14.3 No further data collection will occur from the date the decision is 
made to permanently discontinue the subject from the study. 
15.0 Risks to Subjects 
15.1 We identified the following as possible risks to subjects and describe 
below how we plan to address those 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 aims of the 

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study. Files – audio, paper and electronic– will not have any 
identifying information about the study participants and will be 
tracked through a unique SID and participant code. All audio 
recordings will be downloaded and stored on a password-protected, 
encrypted computer in locked offices at FSU and subsequently 
transferred to FSU 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 FSU secure 
servers. Analysis of transcripts will be conducted on a password- 
protected, encrypted computer. Hard copies will be kept in locked 
files. We will take every available step to minimize the risk of 
identifying/linking data being subpoenaed, stolen, or inadvertently 
released. First, the Tough Talks-COVID study team 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 FSU 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, 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 TT-C app. 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 TT-C addresses participant privacy. 
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. 
Emotional discomfort: It is possible that the study may precipitate 
discomfort and/or an emotional response when AA-YA answer 
questions about potentially sensitive topics such as medical mistrust. 
Further, participants may feel embarrassed about discussing sensitive 
issues. All participants will be told during the informed consent 

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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 youth 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. 
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 he or she 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 
or she is suicidal/homicidal, measures will be taken to ensure his or 
her 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. 
15.2 N/A 
15.3 N/A 
15.4 N/A 
15.5 N/A 
15.6 N/A 
16.0 Potential Benefits to Subjects 
16.1 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 promotes autonomy and 
improves COVID-19 vaccine uptake amongst AA YA and their 
social networks. This study is poised to reduce COVID morbidity 
and mortality among AA YA and their social networks, including 
peers and older adults. Therefore, the risk/benefit ratio is favorable. 
16.2 Participation in this study may result in no direct benefit to 
participants. 
17.0 Data Management and Confidentiality 

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17.1 Sample Size Considerations: Sample size calculations were 
conducted using simulation methods. The simulations: a) Step One: 
specify probabilities of vaccination and sample sizes for the three 
treatment groups and draw random samples of the specified sizes 
from binomial distributions with the specified probabilities treated as 
binomial parameters; b) Step Two: compare the outcome rates in the 
three samples using logistic regression and record whether the 2 
degree-of-freedom test for differences is statistically significant; c) 
Step Three: make pairwise comparisons treatment arms using 
logistic regression; and d) Step Four: Repeat process 1,000 times and 
calculate power as the proportion of data sets (of 1000) generating 
statistically significant results. 
Power calculations were conducted assuming that dropout would be 
equivalent across arms, and that approximately 15% would be loss to 
follow-up; therefore, assuming 250 306 participants will complete 
the primary endpoint assessment (125 153 per arm). Exhibit 1 
depicts graphically the estimated detectable effect sizes (as a 
difference in proportion receiving any COVID vaccine) we will have 
80% power to detect given a sample size of 250306, range of control 
arm rates of vaccine uptake, and assuming two-sided α=0.05. If the 
rate of COVID vaccination in the control arm is between 10-20%, 
we will have 80% power to detect a difference in vaccination of 
1312-146% between arms. If the rate of vaccination in the control 
arm is higher (30%), we will have 80% power to detect a 1715.5% 
difference in vaccination rate between arms. The detectable effect 
size is lowest highest when the control proportion is closer to 50%, 
but we will still have 80% power to detect a difference of 17.616% if 
the rate of vaccination in the controls is 50%. We anticipate 
vaccination rate in the control arm will be low given that vaccines 
have been available for some time. Therefore, we expect a total 
sample size of 300 360 will provide sufficient power to detect a 
clinically meaningful difference in vaccine uptake. 
 

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Effectiveness Outcomes: Primary effectiveness outcomes are 
COVID vaccine uptake and completion of series; secondary 
effectiveness outcomes are VH20, confidence53, and knowledge, 
attitudes, and beliefs.54 We will also collect implementation 
outcomes, SCT constructs targeted by TT-C, COVID-specific risks 
and behaviors and pertinent constructs that have been validated in 
the extant literature on AA-YA (Table 5). 
Analyses of Effectiveness Data: We will use logistic regression to 
determine the effect of treatment arm on the probability of 
vaccination uptake (yes/no) and COVID vaccine series completion 
(yes/no) at month three . We will determine whether the overall 2- 
degree-of-freedom test for differences among treatments is 
statistically significant. If so, we will examine the parameter 
estimates and standard errors to determine where difference lie 
between the three arms. We will focus on the odds ratios for 
comparing the probability of infection in each of the two treatment 
groups with the probability in the controls. The secondary outcomes 
of VH20, vaccine confidence53 and vaccine knowledge, attitudes and 
beliefs54 will all be assessed using previously validated scale scores, 
each of which will consist of the continuous sum of responses to a 
series of questions with Likert scale responses. We will use linear 
regression models with treatment group as the exposure to determine 
whether secondary outcomes vary among treatment groups. Lastly, 
we use the causal mediation framework proposed by Valeri and 
Vanderweele to understand mechanisms for any intervention effects 
through each of our hypothesized mediators.55-58 We will use the 
gformula command in Stata which uses the mediational g-formula to 
estimate the controlled direct, natural direct, and natural mediated 
(indirect) effects.59 
Implementation Outcomes and Analysis: We will conduct qualitative 
interviews with a group of purposively selected AA-YA participants 
(est. n=12-16) and site staff (est. n=6-8) to assess barriers and 
facilitators to TT-C intervention implementation. We will conduct 
12-16 in-depth exit interviews (~4-6 per state) on a rolling basis after 
participants have concluded the 3-month study cycle. All interviews 
will be audio-recorded and transcribed verbatim. Qualitative 
analyses will be conducted in the NVivo coding program. From AA- 
YA, we will ask questions on how sociocultural non-intervention 
contexts affected the likelihood of vaccine acceptance, vaccine series 
completion, and VH. From staff, we will collect qualitative data on 

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the inner and outer contexts affecting implementation with ongoing 
fidelity such as on policies, environment, funding, and social 
conditions that could influence intervention scale-up and 
sustainment. Due to the urgency of addressing COVID VH, we will 
use Rapid Content Analysis that is routinely leveraged in 
implementation science to assess and disseminate results quickly and 
accurately.60 Findings will be explored as a function of participant 
age, sex, state, and setting. Qualitative findings will provide a direct 
line into real-world implementation considerations. 
Note: Any deviations from the analysis plans outlined above or in 
the sections that follow will be documented and justified in the 
Statistical Analysis Plan developed for this protocol. 
Qualitative Data Analysis: FSU will use NVivo software to perform 
all qualitative analyses. NVivo 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). 
NVivo employs the highest levels of data encryption available for a 
web application in all data storage, back up, and transmission. 
NVivo allows for project specific encryption feature. 
Missing Data: In sensitivity analyses, we will also use inverse 
probability of treatment weights (IPTW) to account for missing data 
and potential differential retention between study arms over the 
study period. We will weight outcome models using stabilized 
inverse probability-of-censoring weights that include treatment arm 
as a predictor to account for differential loss to follow up. Pooled 
logistic regression models will be used to estimate the numerator and 
denominator of censoring weights, and weights will be multiplied 
over time.15,16,61 The denominator will be calculated using a logistic 
regression model for loss to follow up, including treatment arm. 
Weights will be stabilized to reduce potential bias from extreme 
weights. Numerator weights for the stabilized IPTW will be 
estimated using a logistic regression model for loss to follow up 
without covariates. Distributions will be examined to ensure weights 
have a mean of 1; extreme weights that may introduce bias will be 
trimmed by cutting the top or bottom 1%. Analogous weight will be 
calculated for missing data, including relevant covariates, and will be 
multiplied by censoring weights. 
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 

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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. 
17.2 We will monitor recruitment and retention rates, site compliance 
with study procedures, and provide technical assistance for queries 
and concerns. Encrypted data will be saved on an FSU server, with 
password protection. We will examine data quality weekly (e.g., 
missing data, assessment of distributional assumptions, identification 
of outliers) and before statistical analysis is conducted. 
Comparability between participants across all three arms will be 
reviewed. Missing scale data will not be estimated. Comparability 
between sites and states will be examined. Data will be aggregated 
for general analysis purposes; however, if significant differences 
emerge, separate analyses comparing outcomes between sites or 
states detailing differences will be conducted. 
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 NICHD need to have an internal quality assurance 
(QA) plan that will identify problems and correct errors in research 
study records. 
Site monitors 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., consent 
forms, case report forms) and pertinent hospital or clinic records 
readily available for inspection by the local IRB, the site monitors, 
the NICHD, the Office of Human Research Protection (OHRP), or 
the sponsor’s designee for confirmation of the study data. 

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17.3 We will take every available step to minimize the risk of 
identifying/linking data being subpoenaed, stolen, or inadvertently 
released. First, 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 participant (i.e., about whom the investigator maintains 
identifying information) during any time the Certificate is in effect.” 
We have applied for and received Certificates of Confidentiality for 
other NIH-funded research projects, and given the sensitive nature of 
the data collected for this project, do not foresee difficulty securing 
one for this study. Second, all research staff members are required to 
complete ethical clearance certification regarding protection of 
human’s 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. 
17.4 N/A 
17.5 N/A 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
18.1 Site staff must first follow 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. 
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 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 team of these 
untoward effects using a query system. Study staff will be briefed 

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during the training on the scope of possible untoward effects and 
instructed to report events. 
Second, study staff may encounter untoward events during study 
visits 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 protocol chairs should be notified of these events so that they 
may be immediately addressed, evaluated, and guidance modified or 
expanded to minimize similar risk to other staff. 
Third, a critically important area 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 FSU 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: 
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; 
is related or possibly related to a subject’s participation in the 
research; and 
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 FSU 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 becoming aware of the 
problem. 
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 
19.0 Provisions to Protect the Privacy Interests of Subjects 

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FSU IRB Approved 
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PROTOCOL TITLE: A Multidimensional Digital Approach to Address Vaccine 
Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
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19.1 All questionnaires, evaluation forms, reports, and other records will 
be identified by a coded number and initials only, to maintain 
participant confidentiality. All records with personally-identifying 
information will be kept in a locked, limited access area (such as a 
locked file cabinet). All computer entry and networking programs 
will be done with coded numbers and initials only. Every effort will 
be made to ensure that study participants are protected from risks. 
The main risk breach of confidentiality. 
19.2 Participants may be concerned about the security of their data, 
particularly since it is collected and stored electronically. Research 
staff at FSU have significant experience developing security 
protocols for 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. 
For the Tough Talks intervention arm, 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 Florida Stata University will monitor the website daily to 
ensure violations to privacy. 
19.3 N/A 
20.0 Compensation for Research-Related Injury 
20.1 N/A 
20.2 N/A 
20.3 N/A 
21.0 Economic Burden to Subjects 
21.1 Participants should not incur any costs for their involvement in the 
activities described in this protocol. 
22.0 Consent Process 
22.1 Informed consent will be obtained from participants prior to 
completion of any study activities. Study staff will follow HRP-090 
(SOP: Informed Consent Process for Research). The informed 
consent process will occur online prior to completing any study 
procedures. Eligible participants will receive the electronic consent 
delivered via email. Once they have electronically signed the consent 
form, they will be sent the online survey hosted by REDCap. 
Non-English Speaking Subjects 

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• 
N/A 
 
Waiver or Alteration of Consent Process (consent will not be 
obtained, required information will not be disclosed, or the 
research involves deception) 
• 
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]). 
Subjects who are not yet adults (infants, children, teenagers) 
 
• 
N/A 
 
Cognitively Impaired Adults 
 
• 
N/A 
 
Adults Unable to Consent 
 
• 
N/A 
23.0 Process to Document Consent in Writing 
23.1 Study staff will follow HRP-091 (SOP: Written Documentation of 
Consent) by ensuring participants electronically sign the consent 
document (via REDCap eConsent). 
23.2 N/A 
23.3 The consent document to be completed by participants is appended 
to the IRB submission. 
24.0 Setting 
24.1 This is a fully remote (virtual) study. Qualitative interviews will be 
completed via a HIPAA-compliant teleconferencing software (e.g. 
Zoom). 
25.0 Resources Available 

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FSU IRB Approved 
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Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
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25.1 The study team has significant experience with the conduct of 
internet-based recruitment and virtual/remote enrollment and 
completion of study activities. All staff will be adequately trained on 
the protocol and will practice assigned study activities before 
engaging with prospective or enrolled participants. Study team 
members will meet regularly (with the Lead PI present) to ensure 
proper implementation of study procedures, as outlined in the 
protocol. A study coordinator will be designated to coordinate all 
study staff, training, and activities. 
26.0 Multi-Site Research 
26.1 A total of 360 participants will be enrolled in the RCT phase of this study. 
26.2 All sites will follow the recruitment procedures outlined above. There will 
be no modification of materials per site. 
26.3 The following are responsibilities of the Reviewing IRB: 
• Documenting IRB determination and provision to relying sites 
• Provision of IRB-approved materials to lead study team 
• Provision of consent form templates to relying site study teams 
• Provision of relevant IRB policies to lead study team 
The following are responsibilities of the Relying IRB: 
• Conflict of interest management for relying site staff 
• Study team training/qualification provision to reviewing IRB 
• Provision of local context information to reviewing IRB 
• Incorporation of site-specific consent language 
The following are responsibilities of the Lead Study Team: 
• Preparation and submission of study-wide application 
• Preparation and submission of site-specific application(s) 
• Provision of IRB-approved documents to relying sites study 
teams 
• Provision of consent form templates to relying site study teams 
• Collection and submission of information for continuing 
review 
• Reporting of reportable events (unanticipated problems, 
noncompliance, subject complaints, etc.) 
• Provision of information necessary for study closure 
The following are responsibilities of the Relying Study Team: 

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FSU IRB Approved 
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Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young 
Adults in the South (Tough Talks COVID) 
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• Conflict of interest management for relying site staff 
• Incorporation of site-specific consent language 
26.4 N/A