iThrive WI - A Smartphone Intervention for Overdose and Risk and COVID-19 Among People Who Use Drugs
Phase: NA
Conditions: Substance Use Disorders, Overdose, COVID-19
Sponsor: University of Wisconsin, Madison

 
 
 
 
 
iThrive WI – A smartphone intervention for 
overdose and risk and COVID-19 among people who 
use drugs 
 
NCT05518461 
8/8/2024 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
Page 1 of 42 
Revised: October 18, 2022 
PROTOCOL TITLE: 
iThrive WI – A smartphone intervention for overdose and risk and COVID-19 among 
people who use drugs 
 
LEAD RESEARCHER: 
Rachel Gicquelais, PhD, MPH 
University of Wisconsin - Madison 
Departments of Medicine & Population Health Sciences  
School of Medicine and Public Health  
Warf Office Bldg Office 603 
610 Walnut St,  
Madison, WI 53726 
      
          (410) 212-0787 
gicquelais@wisc.edu  
 
CO-INVESTIGATOR:  
Ryan Westergaard, MD, PhD, MPH 
University of Wisconsin - Madison 
Departments of Medicine & Population Health Sciences  
5223 UW Medical Foundation Centennial Bldg 
1685 Highland Avenue, Madison, WI 53705  
608-265-7927 
rpw@medicine.wisc.edu  
 
VERSION NUMBER/DATE: 
Version 1.0 – 07/06/2022 
Version 2.0 – 07/29/2022 
Version 3.0 – 08/06/2022 
Version 4.0 – 08/24/2022 
 
Version 5.0 – 10/18/2022 
 
Version 6.0 – 05/21/2023 
 
Version 7.0 – 08/08/2024 
 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
1 
07/29/2022 
Addressed comments from pre-review by 
Jennifer Fenne 
Yes 
2 
08/06/2022 
Addressed comments from pre-review by 
Jennifer Fenne 
Yes 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
Page 2 of 42 
Revised: October 18, 2022 
3 
08/24/2022 
Adjusted to reflect a Certificate of 
Confidentiality has been obtained. Fixed minor 
typos.  
Yes 
4 
10/18/2022 
Updated study team personnel 
No 
5 
5/21/2023 
Updated study team personnel 
No 
6 
08/08/2024 
Updated data storage location and Dr. 
Gicquelais position to SMPH 
No 
 
 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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Revised: October 18, 2022 
Table of Contents 
1.0 
Study Summary 
 
 
 
 
 
 
 
3 
2.0 
Background 
 
 
 
 
 
 
 
 
5 
3.0 
Study Objectives and Endpoints 
 
 
 
 
 
8 
4.0 
Number of Participants 
 
 
 
 
 
 
9 
5.0 
Inclusion and Exclusion Criteria 
 
 
 
 
 
9 
6.0 
Special Populations 
 
 
 
 
 
 
 
11 
7.0 
Recruitment Methods  
 
 
 
 
 
 
12 
8.0 
Consent/Assent Process 
 
 
 
 
 
 
13 
9.0 
Process to Document Consent in Writing 
 
 
 
 
15 
10.0 
Setting  
 
 
 
 
 
 
 
 
17 
11.0 
Study Intervention 
 
 
 
 
 
 
 
17 
12.0 
Study Timelines 
 
 
 
 
 
 
 
18 
13.0 
Procedures Involved  
 
 
 
 
 
 
18 
14.0 
Comparison of usual care and study procedures 
 
 
 
26 
15.0 
Withdrawal of Participants 
 
 
 
 
 
 
26 
16.0 
Data Management and Confidentiality 
 
 
 
 
27 
17.0 
Provisions to Protect the Privacy Interests of Participants 
 
 
29 
18.0 
Sharing of Results 
 
 
 
 
 
 
 
30 
19.0 
Data and Specimen Banking  
 
 
 
 
 
31 
20.0 
Study Analysis 
 
 
 
 
 
 
 
32 
21.0 
Potential Benefits to Participants 
 
 
 
 
 
33 
22.0 
Risks to Participants  
 
 
 
 
 
 
33 
23.0 
Provisions to Monitor the Data to Ensure the Safety of Participants  
35 
24.0 
Economic Burden to Participants 
 
 
 
 
 
36 
25.0 
Resources Available  
 
 
 
 
 
 
37 
26.0 
Multi-Site Research  
 
 
 
 
 
 
37 
27.0 
References 
 
 
 
 
 
 
 
 
38 
28.0 
Appendices 
 
 
 
 
 
 
 
 
41 
 
 
 
 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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Revised: October 18, 2022 
 
1.0 
Study Summary 
Study Title 
iThrive WI – A mobile health intervention to lower overdose 
risk and promote COVID-19 vaccine education amongst 
people who use drugs  
Brief Summary 
This study will examine if the use of a smartphone 
application called Thrive4Life Connect can help people who 
use drugs lower their risk of overdose and learn more about 
COVID-19 vaccines.  
Number of study sites 
3 – Vivent Health offices located in the cities of Milwaukee, 
Eau Claire, and Appleton, WI 
Study Design 
The mobile health system used in this study, called 
Thrive4Life Connect, has been developed for use in harm 
reduction settings by our team with prior funding from the 
National Institute on Drug Abuse. Thrive4Life Connect is 
based on the Addiction Comprehensive Health Enhancement 
Support System (A-CHESS) and facilitates brief, behavioral 
interventions targeting knowledge gaps, motivation, and 
social connectedness. This app is being used in another IRB-
approved study at UW-Madison (Study ID: 2017-0866). In 
the proposed study, we will develop new intervention content 
for assessing and increasing vaccine confidence and lowering 
overdose risk. We will test the feasibility and preliminary 
effectiveness using a pilot, pre-post study design with 60 
people who have injected drugs in the past week and used 
opioids in the past 30 days. We will examine feasibility 
outcomes based on study recruitment, retention, and 
intervention completion. We will also examine changes in 
knowledge about COVID-19 and overdose, motivation to 
reduce risk, and behavioral outcomes including overdose risk 
behaviors and vaccine uptake to establish preliminary 
effectiveness. 
Primary Objective 
To test the feasibility of a mobile health application, 
Thrive4Life Connect, to deliver an intervention 
focused on reducing overdose risk and supporting 
COVID-19 vaccine uptake among people who use 
drugs in Wisconsin.  
Secondary 
Objective(s) 
To understand overdose risk, COVID-19 vaccine uptake, and 
related attitudes and behaviors before and after the mobile 
health intervention. 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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Revised: October 18, 2022 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
COVID-19 and overdose-related content contained within 
Thrive4Life Connect, a mobile health application  
Drugs/devices used on 
study (including any 
IND/IDE #)  
N/A 
Study Population 
Adults who have used opioids in the past 30 days and 
injected drugs in the past week, primarily recruiting among 
clients of Vivent Health 
Sample Size 
60 people 
Study Duration for 
individual 
participants 
6 months 
 
Study Specific Abbreviations/ Definitions: 
HIV 
Human immunodeficiency virus 
PN 
Prevention Navigator 
PS 
Prevention Specialist 
PWID 
People who inject drugs 
ROI 
Rural Opioid Initiative 
SSP 
Syringe service programs 
UW 
University of Wisconsin 
 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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2.0 
Background 
2.1 We are now approaching the third year of the COVID-19 pandemic, 
which collided with a worsening, ongoing overdose epidemic that 
killed 9,260 people in Wisconsin from 2000-2019 from opioid 
overdose alone. Consistent with national and state-level trends 
indicating increases in fatal and nonfatal overdoses,1,2 overdose 
mortality in Wisconsin increased by 27% during 2020 relative to 
20193 Unfortunately, provisional 2021 data suggest it will be the 
deadliest year for drug overdose deaths in Wisconsin and the US.3 
Beyond exacerbations to overdose mortality, prior studies also 
suggest that COVID-19 itself has disproportionately impacted people 
who use drugs, and that low vaccine confidence may continue to 
drive poor outcomes. Studies have shown that people who use drugs 
are at increased risk for COVID-19 infection, hospitalization, and 
death.4 Regarding vaccination, a survey of people who inject drugs 
in Wisconsin conducted by our team in March-May 2021 indicated 
that 50% of respondents were hesitant to be vaccinated for COVID-
19, consistent with prior studies.5 
 
Our team is well-positioned to support people who inject drugs 
(PWID), during the collision of a worldwide COVID-19 pandemic 
and the US overdose epidemic as we have conducted multiple prior 
studies in collaboration and partnership with Vivent Health, the 
state’s primary network of syringe services programs. Our research 
will describe how mHealth interventions can reduce overdose and 
COVID-19 risk at a critical time of climbing overdose mortality in 
Wisconsin.  
 
2.2 Preliminary studies - Mobile health Interventions with PWID: 
Dr. Westergaard and his research team have conducted several 
mobile health (mHealth) interventions among individuals with active 
substance use disorders that provide a strong theoretical basis for the 
proposed work and highlight our team’s ability to use mobile phones 
to collect rich behavioral health data from this population. Hep-Net, 
a UW-ICTR-funded pilot study designed to increase readiness to be 
tested for hepatitis C and respond to an overdose,6,7 showed the 
feasibility of a brief, computerized intervention involving 
individualized goal setting in the syringe services setting. We then 
studied the benefits of the Addiction Comprehensive Health 
Enhancement Support System (A-CHESS)8 within multiple 
treatment settings, including opioid use disorder treatment9 and HIV 
treatment (DP2DA042424).10 A-CHESS is guided by self-
determination theory,11,12 which identifies three supports for intrinsic 
motivation for behavior change derived from basic psychosocial 
needs: relatedness (meaningful relationships with others; a sense of 
connectedness), competence (ability to deal with challenges), and 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
Page 7 of 42 
Revised: October 18, 2022 
autonomy (sense of being in control of one’s own behavior and 
goals). A-CHESS also operationalizes the situated Information-
Motivation-Behavioral Skills (sIMB) Model,13 by providing 
Information (e.g., available community resources), Motivation (e.g., 
a weekly survey about health goals), and Behavioral Skills (e.g., 
messaging with a counselor). 
 
Existing Research Infrastructure to be Leveraged in The 
Proposed New Research: 
WI Rural Opioid Initiative - Formative Phase (UW-Madison 
IRB Study ID: 2017-0866): The Rural Opioid Initiative is a 
national, multi-site research consortium funded by NIDA, CDC, 
SAMHSA, and the Appalachian Regional Commission. The 
Wisconsin node of the consortium (grant numbers UG3DA044826 
and UH3DA044826, R. Westergaard and D. Seal, MPI) is built on an 
academic-community partnership with Vivent Health. In 2018-19, 
during the initial, formative (UG3) phase of this study, we enrolled 
991 PWID from six rural counties in Wisconsin using the best 
available methods to ascertain a population-representative, cross-
sectional sample of a hard-to-reach population.14-16 We included 
individuals aged 15 or above, who injected drugs within the past 30 
days, and resided in Brown, Outagamie, La Crosse, Marathon, 
Douglas, or Eau Claire counties. Through Audio Computer-Assisted 
Self-Interviews,17 participants reported sociodemographic 
characteristics, substance use behaviors, overdose history and risk 
behaviors, and were tested for HIV, viral hepatitis, and sexually 
transmitted infections. 
 
WI Rural Opioid Initiative - Intervention Phase (UW-Madison 
IRB Study ID: 2017-0866): We are currently in the intervention 
(UH3) phase of the WI Rural Opioid Initiative, which involves a 
clinical trial of a short-term intervention, “prevention navigation,” to 
increase use of preventive health services and reduce risks from 
injecting drugs for PWID utilizing syringe services programs. 
Prevention navigation is based on Project START, an evidence-
based, six-session, individualized case management intervention that 
was found to reduce HIV risk among recently incarcerated men 
using motivational interviewing techniques and a harm reduction 
framework.18,19 Our current trial adapted the Project START model 
for syringe services program settings. Clients receiving the 
intervention build skills and set goals to reduce their overdose, HIV, 
and hepatitis C risk, increase their readiness to engage in addiction 
and hepatitis C treatment, and address other areas of concern such as 
smoking and self-stigma. We are currently enrolling PWID in a non-
randomized, clinical trial in the same syringe services program 
offices that participated in the formative phase of the study. Over 12 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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weeks, intervention recipients complete 4 sessions lasting 50-70 
minutes each wherein a “prevention navigator” uses strategies 
including linkage-to-care case management, peer navigation, 
motivational enhancement, formative decision making, and harm 
reduction to help participants develop an individualized risk 
reduction plan related to their injection drug use. Outcomes at 3 and 
6 months among the 270 total intervention participants will be 
compared with data from 135 control participants, all of whom are 
recruited from the same sites involved in the formative phase. 
Analyses will compare two primary outcomes between intervention 
and control participants: confidence in ability to access addiction 
treatment services when participants are ready for treatment and 
engagement in addiction treatment services.  
 
An additional activity supported by the intervention phase of the WI 
Rural Opioid Initiative is the development of Thrive4Life Connect, a 
novel harm reduction mHealth application that adapts A-CHESS for 
PWID accessing syringe services programs at Vivent Health. 
Thrive4Life Connect is guided by similar theoretical frameworks as 
A-CHESS (i.e., self-determination theory11,12 and the sIMB13). The 
Thrive4Life Connect app will be used by all participants to complete 
study surveys moving forward. 
 
2.3 COVID-19 exacerbated a worsening overdose epidemic,20-22 
resulting in a 27% increase in overdose deaths in Wisconsin in 2020 
relative to 2019.23 Factors hypothesized to contribute to increased 
overdose mortality during the pandemic include an unsafe illegal 
drug supply contaminated with illicitly manufactured fentanyl,24 
increasing drug use while alone (i.e., away from potential overdose 
responders) due to physical distancing,25 and deteriorating mental 
health.26 These data indicate a need for targeted overdose risk 
reduction efforts to reduce the behavioral health impacts of COVID-
19. 
 
2020 and 2021 are the deadliest years for overdose on record 
nationally and in Wisconsin. Consistent with national trends,22,24-26 a 
COVID-19 impact survey conducted by our team among PWID in 
Wisconsin between March and May, 2021 found that increases in 
overdose risk behaviors may be driving overdose mortality upwards. 
In total, 52% of PWID used alone more often (i.e., away from 
potential overdose bystanders who could respond), 52% were 
concerned about the safety of the drug supply, 27% overdosed, and 
>75% reported greater depression, anxiety, and loneliness during the 
pandemic. 
 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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COVID-19 vaccine hesitancy may exacerbate health disparities 
among PWID. People who use drugs, especially those with an opioid 
use disorder and racial/ethnic minorities, are at increased risk for 
COVID-19 infection and poor outcomes (e.g., hospitalization, 
death).27 Unfortunately, like other studies,28 50% of PWID we 
recently surveyed were hesitant to be vaccinated for COVID-19. 
PWID are also under-vaccinated for other infections (e.g., hepatitis 
A and B29) and lack access to preventive services.30 To address 
disparities, interventions targeting upstream social determinants of 
health (i.e., stigma, social isolation, distrust in healthcare, food and 
housing insecurity) are needed. These may improve use of 
preventive services and change behaviors that ultimately cause 
health disparities, including those from COVID-19 and overdose. 
 
3.0 
Study Objectives and Endpoints 
3.1 The primary objective of this study is to understand the feasibility of 
using a smartphone application to deliver an intervention focused on 
overdose and COVID-19. The secondary objective is to understand 
overdose risk, COVID-19 vaccine uptake, and related attitudes and 
behaviors before and after the intervention. 
 
3.2 We hypothesize that an intervention to increase COVID-19 
vaccination and reduce overdose risk will be feasible to deliver via a 
smartphone based on intervention completion rates. We also 
hypothesize that engaging with intervention content may increase 
knowledge about COVID-19 and overdose and reduce risk 
behaviors.  
 
3.3 Study Endpoints: 
● Baseline: At the beginning of the study, participants will complete a 
baseline survey to assess their pre-study overdose and COVID-19 
risk behaviors, attitudes, beliefs, and knowledge. These data will be 
used as a basis to assess change at 3 months and 6 months. 
 
● 3-Months: After the 12-week Thrive4Life Connect mobile 
intervention, participants will complete the same survey questions 
from baseline at 3 months to assess any changes in their overdose 
and COVID-19 risk behaviors, attitudes, beliefs, and knowledge. We 
will also examine the percentage of participants who completed 
intervention content each week, and the percentage of skipped 
intervention content questions to examine feasibility. 
 
● 6-Months: 3 months after the 12-week mobile intervention, 
participants will again complete the same survey at 6 months to 
assess any changes in their overdose and COVID-19 risk behaviors, 
attitudes, beliefs, and knowledge. The 6-month survey will help us to 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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understand whether any behavior changes from 3-months were 
sustained. 
 
3.4 Participants who express any type of mental or other distress (e.g., 
thoughts of self-harm, harm to others, reports of child or elder abuse) 
based on any communications with the study team (e.g., by private 
message through Thrive4Life Connect, on the Thrive4Life Connect 
discussion board, via text or phone call with the study team, or any 
other way) will be engaged by study staff and connected with 
resources through Vivent Health or other means (e.g., National 
Suicide Prevention Hotline). The participant will be reminded that 
they can stop study participation at any time. Participants in 
significant distress may be removed from the study by research team 
staff. 
 
4.0 
Number of Participants 
4.1 This study will include 60 participants in total across 3 Vivent 
Health syringe services locations in Wisconsin – Milwaukee, 
Appleton, and Eau Claire.  
- 
Milwaukee: 30 participants 
- 
Appleton: 15 participants 
- 
Eau Claire: 15 participants 
 
4.2 In a prior longitudinal study with Vivent Health (WI Rural Opioid 
Initiative - Intervention phase), we have experienced up to 50% 
attrition at 3 months and 6 months. Because of this, we may enroll 
up to 90 participants in this study. 
 
4.3 Enrolled participants are individuals who complete the baseline 
survey. Participants who leave the study early (i.e., before 
completing the 3-month study assessment) may be replaced.  
 
5.0 
Inclusion and Exclusion Criteria 
5.1 Individuals interested in participating in the study will complete a 
brief screening survey via REDCap during a visit to a Vivent Health 
study site. Participants meeting the eligibility criteria described 
below will be invited to participate in the study and asked to provide 
multiple types of contact information. The screening survey will ask 
for participant names, which will be stored confidentially on HIPAA 
compliant drives, for the duration of study recruitment. The names of 
ineligible participants and those not interested in participating in the 
study will be kept and used to ensure that ineligible participants do 
not screen again.  
 
We will retain screening data at an aggregate level to describe the 
number of people who screened as eligible or ineligible, as the 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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percentage eligible will be important in examining the feasibility of 
the intervention and study. For participants that screen as ineligible, 
choose to not participate, or do not consent to participating, only 
their name will be retained from the screening data. As in this study 
participants are only permitted to screen once, the names of 
ineligible participants will be kept to ensure they do not screen 
again. These names will be stored on secure HIPAA-compliant 
servers at the UW      School of Medicine and Public Health as well 
as HIPAA-compliant Vivent Health Microsoft Teams. All the names 
of people who screen as ineligible will only be kept for the duration 
of participant recruitment for this study and will be destroyed after.  
 
If a participant screens as eligible and then schedules an enrollment 
appointment with the intent to participate (enrollment will occur one 
week after screening), but then decides to not consent or not 
participate at that time, their screening data, except for their name, 
will be destroyed. Only their name will be kept to ensure they do not 
screen again.  
 
We will retain all screening data for people who consent to 
participating in the study. For these participants who consent to 
participating in the full study, screening data will not be deidentified 
until recruitment and study analyses are complete and banking 
occurs (described later in this protocol). Once recruitment and 
analysis procedures are complete for this study, all data collected 
during screening will be deidentified.  
 
Interested and eligible participants will complete a locator form 
(which is a part of the screening survey) containing individually 
identifiable data, including participant name and age, address, and 
contact information. Individually identifiable data will be stored 
separately from study-related data collected as part of the screening 
survey. Ineligible participants or those not interested in participating 
in the study will not complete the locator form. 
 
5.2 Inclusion Criteria: To be considered eligible to participate, clients 
must meet all the following criteria on the screening survey: 
● Be 18 years old or older 
● Willing to attend in person study encounters at any of the 
following Vivent Health locations: Milwaukee, Appleton, 
and Eau Claire  
● Used opioids to get high in the past 30 days 
● Injected drugs at least 2 times in the past 7 days 
● Express interest in reducing their overdose risk 
 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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COVID-19 vaccination status will not be considered when assessing 
participant eligibility. Information regarding COVID-19 vaccination 
status will still be collected using the eligibility survey to 
approximate COVID-19 vaccination rates among our population of 
interest and to customize content delivered in the study intervention.  
 
5.3 Exclusion Criteria: None in addition to the inclusion criteria   
 
If a client initially screens as ineligible to participate in the study, 
they cannot screen again. Eligibility and screening will continue 
until a total of 60 participants is reached across the three Vivent 
Health sites. The distribution of participants between the sites will be 
as follows: 30 participants in Milwaukee, 15 participants in Eau 
Claire, and 15 participants in Appleton. 
 
6.0 
Special Populations 
6.1 ☒ Individuals who are receiving inpatient or outpatient services for 
mental illness, developmental disability, or alcohol and other drug 
abuse (AODA).  
 
Justification: Our target study population involves people who 
inject drugs, who are at risk of overdose, necessitating the inclusion 
of these individuals in our study. Some of our participants may be in 
treatment programs, and others may be using drugs but not in 
treatment. We chose to target this population as our proposed 
intervention centers around lowering overdose risk, which requires 
engagement with individuals who engage in overdose risk-related 
behaviors. 
 
Safeguards: To minimize the risks to people receiving treatment for 
substance use or who are using substances, participants will be 
provided with a paper or electronic copy of the informed consent 
when they initially screen as eligible to participate in the study. The 
informed consent process will be completed at the enrollment visit 
by either watching a video of the informed consent highlights then 
discussing with a Prevention Specialist OR by discussing the key 
areas of the informed consent with a Prevention Specialist. Vivent 
Health prevention specialists will be available to answer any 
questions that participants may have. Participants will be informed 
that their participation is voluntary, they can stop participating at any 
time, and they can skip any survey questions they are uncomfortable 
answering. We will also inform participants that study participation 
(and stopping study participation) will not affect their access to 
services at Vivent Health or any treatment they are receiving. We 
also have a Certificate of Confidentiality to ensure that the research 
team cannot be forced to disclose information that may identify 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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participants, even by a court subpoena, in any federal, state, or local 
civil, criminal, administrative, legislative, or other proceedings. 
16.0  
7.0 
Recruitment Methods 
7.1 Recruitment will occur out of the following Wisconsin Vivent 
Health locations: Milwaukee, Eau Claire, and Appleton. Previous 
participants from other Thrive4Life-related studies may also be 
included in recruitment efforts. Previous participants from prior 
studies at Vivent Health will be recruited using the same methods as 
other prospective participants if they attend an SSP visit at one of the 
study sites. They may also be recruited via phone call, text message, 
or other contact methods they shared in Thrive4Life, if they 
indicated previously that such outreach is acceptable.  
 
7.2 Recruitment will occur out of Wisconsin Vivent Health locations in 
Milwaukee, Eau Claire, and Appleton.  
Prospective participants will be made aware of our study opportunity 
according to the discretion of Vivent Health Prevention Specialists 
who identify prospective participants that express interest in 
lowering their overdose risk.  
 
General flyers providing introductory information about our study 
may also be handed out to prospective participants or posted at 
participating Vivent Health locations.  
 
If an individual shows interest in enrolling in our study, they will be 
made fully aware of the study process and expectations prior to 
screening for eligibility. Prospective participants will watch a brief 
overview video discussing the study, read through a one-page flyer 
that provides a study timeline and expectations, and discuss any 
remaining questions with Vivent Health Prevention Specialists. If 
clients still express interest afterwards, they will be given a Vivent 
Health iPad to complete the eligibility survey. 
 
7.3 Described in section 7.2.  
 
7.4 Recruitment Materials:  
● General flyer: This flyer will provide introductory 
information about our study and will encourage interested 
individuals to ask staff at their local Vivent Health office 
about this opportunity.  
● One-pager and FAQs flyer: This flyer will be provided to 
individuals who have already expressed interest in 
participating in our study. This handout will have more 
specific information about enrollment and picking up the 

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COVID-19 among people who use drugs 
 
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study-provided iPhone, the study timeline, surveys, 
compensation, study expectations, and answers to FAQs.  
● Overview video: This video will be provided to people who 
have expressed interest in participating in our study. This 
video will cover the same information in the one-pager but 
in a video format. The video will include audio and 
PowerPoint slides that will provide an overview of study 
information.  
 
7.5 Participants will receive cash compensation for completing specific study 
surveys. The maximum value for compensation for one participant in this 
study will be $150. Participants will also receive an iPhone (model SE) as 
part of their participation in the study. An unlimited phone service plan will 
be provided to participants for the duration of their participation in the study 
(6-7 months). Phone service will end after study completion, but participants 
will be able to keep their iPhone. If participants lose their iPhone, up to one 
replacement will be provided after the participant informs Vivent Health and 
UW research staff of their need for a new phone. Cash compensation and 
iPhones will be provided to participants in person at their Vivent Health 
location (Milwaukee, Eau Claire, or Appleton). Venmo, Paypal, or mailing 
remuneration will be alternative methods for providing compensation to 
participants as needed (E.g., If a participant moves locations). Compensation 
will be provided to participants after confirmed completion of the study 
surveys (see below).  
 
Survey compensation:  
● Baseline survey: $20 
● First set of daily check-ins: After the baseline survey, three 
daily check-in surveys will be made available. The 
completion of one daily check-in will be remunerated at 
$10, for a total of up to $30 for completing all three check-
ins.  
● 3-month survey: $20 
● Second set of daily check-ins: After the 3-month survey, 
three daily check-in surveys will be made available. The 
completion of one daily check-in will be remunerated at 
correlates to $10 in compensation, for a total of up to $30 
for completing all three check-ins. 
● 6-month survey: $20 
● Third set of daily check-ins: After the 6-month survey, 
three daily check-in surveys will be made available. The 
completion of one daily check-in will be remunerated at 
correlates to $10 in compensation, for a total of up to $30 
for completing all three check-ins. 
 
8.0 
Consent/Assent Process 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
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8.1 This study will involve individuals who are using drugs, who may 
also be receiving inpatient or outpatient services for mental illness, 
developmental disability, or alcohol and other drug abuse (AODA). 
To minimize the risks to this population, participants will be 
provided with a paper or electronic copy of the informed consent 
when they initially screen as eligible to participate in the study. The 
informed consent process will be completed at the enrollment visit 
by either watching a video of the informed consent highlights then 
discussing with a Prevention Specialist OR by discussing the key 
areas of the informed consent with a Prevention Specialist. 
Participants will be informed that their participation is voluntary, 
they can stop participating at any time, and they can skip any survey 
questions they are uncomfortable answering. After watching the 
informed consent video or walking through the consent with a 
Prevention Specialist, participants will be prompted to ask the 
research team any questions. We also obtained a Certificate of 
Confidentiality from the National Institutes of Health, which 
participants will be made aware of. 
 
Walkthrough of Study Informed Consent Process: 
Participants will first complete a screening survey to determine their 
eligibility. This screener will be completed with Prevention 
Specialists at participating Vivent Health locations. Eligible 
participants who are interested in participating in the study will be 
invited to complete a locator form with Prevention Specialists asking 
for multiple contact methods, which will be utilized for follow-up 
throughout the study. Participants that express interest in enrolling in 
the study will be invited back to Vivent Health in one week for an 
enrollment and informed consent appointment. Participants will be 
given a paper or electronic copy of the study consent form and asked 
to review this information in the week before their enrollment 
appointment. 
 
During the week between the screening encounter and enrollment 
encounter, study iPhones and Thrive4Life Connect accounts will be 
activated for the prospective participants. The participant’s name and 
enrollment appointment time will be inputted into a secure Vivent 
Health Microsoft Teams spreadsheet. This spreadsheet will be used 
to keep track of participant enrollment appointments and determine 
when participant iPhones will need to be activated. Participants will 
be reminded of their enrollment appointment through their preferred 
contact method from the locator form.  
 
The informed consent process will take place at the enrollment 
appointment at Vivent Health locations in Milwaukee, Eau Claire, 
and Appleton. Participants will be provided with detailed 

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information about study procedures by reading the consent document 
on paper or electronically. Additional copies of the consent 
document will be available in the private room at the Vivent Health 
prevention offices. 
 
Participants will either watch a video of the informed consent 
highlights then discuss with a Prevention Specialist OR discuss the 
key areas of the informed consent with a Prevention Specialist. 
Participants will be able to watch the consent video OR walkthrough 
the consent with a Prevention Specialist, and review the full text of 
the consent document. Participants will then be able to provide their 
electronic agreement to participate in the study on their study iPhone 
in the Thrive4Life Connect mobile application (by checking a box, 
rather than signing their name). Participants may also provide verbal 
consent to participate instead, with documentation of consent being 
kept on the HIPAA-compliant secure Vivent Health Microsoft 
Teams. Agreement documentation will also be stored with study data 
on the Thrive4Life Connect platform. In alternative circumstances, a 
paper version (no video) of the consent form will be reviewed and 
provided by research staff at Vivent Health before proceeding with 
any study procedures. Participants will then be able to affirm 
participation verbally if needed after reviewing paper consent if, for 
example, Wi-Fi is down, or another situation arises. 
 
During the informed consent process, participants will be reminded 
that their participation is voluntary, and they can withdraw at any 
time during the study. Participants will be notified that the data 
collected from this study may be banked in a secure location and 
utilized by researchers for future studies about improving harm 
reduction.  
 
9.0 
Process to Document Consent in Writing 
9.1 We are requesting a waiver of written documentation of consent. We 
will provide participants with a paper or electronic copy of the 
informed consent information and provide an iPad and headphones 
so they can watch a video walking them through the informed 
consent during their in-person enrollment appointment at a 
participating Vivent Health location. Participants will also be able to 
talk through the informed consent document with a Prevention 
Specialist instead of watching the video. During this appointment, 
participants will be able to ask the Vivent Health Prevention 
Specialist, who is facilitating their appointment, any questions about 
the study and consent information. Then, participants will be asked 
to agree or not agree to participate in this study in the Thrive4Life 
Connect app (they can also elect to take time to think about it and get 
back to us at a later date). Therefore, participants will be provided 

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with consent information via oral, written, and electronic methods.  
 
After consent is verbally affirmed, participants will open their 
account in Thrive4Life Connect app. The first thing they see will be 
a screen containing the text from the informed consent document. At 
the bottom of this screen, there will be a checkbox asking 
participants to select here if they agree to participate in this study. 
Participants will be unable to access content in the Thrive4Life 
Connect app unless they agree to the consent checkbox in the app. 
The Thrive4Life Connect app is limited in its ability to collect a 
‘true’ signature from participants. Specifically, creating an actual 
signature (via stylus or finger) is not a functionality that currently 
exists in the app. Additionally, there is no mechanism to provide a 
validated electronic signature on Thrive4Life Connect.  
 
The study meets the criteria for a waiver of signed consent through 
criteria set #1 on HRP-411. The research involves explaining a written 
script of the informed consent through a pre-recorded video that covers 
the elements of consent in HRP-314. Participants will also be able to 
talk through the informed consent document with a Prevention 
Specialist if they prefer. Prevention Specialists will be provided with a 
written script of the informed consent as well. Participants will have the 
opportunity to ask questions and will receive a paper or electronic 
copy of the consent to review during the video or discussion and 
afterwards. The research proposed in this study presents no more 
than minimal risk of harm to prospective subjects. Regarding the risk 
to participants, the primary risks include being identified as a 
participant in this study and distress caused by answering questions 
about sensitive topics, such as substance use. These risks have been 
minimized by the study team by having a Certificate of 
Confidentiality, ensuring that participants are encouraged to 
password-protect their study iPhone, and ensuring participants do not 
include any identifiable information in their Thrive4Life Connect 
public usernames. Study data will also be stored on HIPAA 
compliant servers at the UW      School of Medicine and Public 
Health. Participants are also free to skip questions they are 
uncomfortable with answering and can reach out to study staff as 
needed.  
 
This study also involves no procedures for which written consent is 
normally required outside of the research context, as we ask 
participants to download an app available through the app store and 
participate in self-help type activities.  
 
9.2 Participants will be provided with a paper or electronic copy of the 
informed consent detailing the study procedures, risks, and benefits. 
They will be asked to review this information during the week 

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between their screening and enrollment encounters. Then during the 
enrollment appointment, participants will review the study 
procedures and informed consent document by either watching a 
video of the informed consent highlights then discussing with a 
Prevention Specialist OR by discussing the key areas of the informed 
consent with a Prevention Specialist. During this process, 
participants will be encouraged to ask any questions they may have 
about the study. Agreement to participate in the study will be 
collected via electronic agreement on the Thrive4Life Connect 
mobile application. Participants may also provide verbal consent to 
participate instead, with documentation of consent being kept on the 
HIPAA-compliant secure Vivent Health Microsoft Teams. 
 
10.0 Setting 
10.1 This research will primarily be conducted remotely utilizing a 
smartphone application, Thrive4Life Connect, and study provided 
iPhone. Participant recruitment, screening, enrollment, consent, and 
remuneration will occur in person at Milwaukee, Eau Claire, and 
Appleton Vivent Health locations. Additionally, participants will be 
able to come into their local Vivent Health location to ask any 
questions they may have throughout the study. Data analysis will 
occur at the UW-Madison      School of Medicine and Public Health.  
 
If a participant loses their study-provided iPhone and backup phone, 
they will be able to complete the study surveys on the online browser 
version of Thrive4Life Connect. If needed, participants may be able 
to go to a Milwaukee, Appleton, or Eau Claire Vivent Health 
location to complete their study surveys on the study iPad.   
 
11.0 Study Intervention 
11.1 Participants will be asked to complete a series of intervention modules using 
the Thrive4Life app on a smartphone provided by the study. These modules 
are meant to simulate the format and style of the WI Rural Opioid 
Initiative’s in-person interaction with a prevention navigator and are focused 
on overdose risk and vaccine hesitancy. Participants will answer a series of 
questions and receive immediate, tailored feedback within the intervention 
modules based on their responses to module activities and questions. The 
options and responses to module questions and activities were created 
collaboratively with Vivent Health staff and by reviewing intervention 
materials (i.e., worksheets used during the intervention) from our prior study 
involving in-person prevention navigation intervention sessions.  
 
The FDA Policy for Device Software Functions and Mobile Medical 
Applications states (in section V.B, page 12) states that mobile health 
applications that help patients self-manage their disease or conditions 
without providing specific treatment or treatment suggestions fall under a 

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category for which FDA intends to exercise enforcement discretion. The 
Thrive4Life Connect app and our intervention meet this criteria based on 
prior consultations with Jake Rome at UW-Madison ICTR. 
 
Data from this study are not planned for use and are not being held in 
support of a future submission to the FDA for approval of the app. 
 
12.0 Study Timelines 
12.1 The duration of an individual participant’s participation in the study 
will last approximately 6 months. We aim to enroll all 60 study 
participants within 8 months. Initial analyses for this study will be 
completed by the end of the funding period, August 31st, 2023, but 
may continue beyond that time. We anticipate completing analyses 
by August 31, 2024. 
 
13.0 Procedures Involved 
13.1 We will use a pilot pre-post comparison study with 60 PWID from 
three Vivent Health syringe services programs in Milwaukee, Eau 
Claire, and Appleton. Participants will complete baseline surveys, a 
12-week intervention and will repeat surveys 3 months and 6 months 
after baseline. We will primarily examine feasibility outcomes 
(percentage of participants who complete each component of the 12-
week intervention). We will also compare overdose risk behaviors 
and COVID-19 vaccine confidence at 3 and 6 months to baseline.  
 
13.2 Schedule of Procedures and Study Outline 
This study will involve required and optional procedures.  
 
Required activities include:  
● Thrive4Life Connect  
● Surveys  
o Baseline survey  
o 12 weekly check-in intervention surveys about 
overdose prevention 
o 3-month survey  
o 9 daily check-in surveys   
o 6-month survey 
● Surveys will collect information about: Name, age, gender 
identity, ZIP code, race and ethnicity, education, marital 
status, alcohol and drug use, types of health care received, 
mental health, and other related items. 
● Private messaging: Study staff will send participants 
messages in Thrive4Life Connect to remind participants 
about when surveys open, send personalized resources, and 
answer any questions.  

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● Data linkage to databases like the Wisconsin Immunization 
Registry, Medicaid, and Wisconsin hospitalization, 
emergency medical services, and infectious disease 
surveillance registries.  
 
Optional activities include:  
● Interactive modules about COVID-19 vaccines 
● Sharing thoughts on discussion boards and private 
messaging others 
● Engaging with online and local resources in the app 
● Logs for motivation and thoughts of gratitude 
● Using UW-Madison study team contact information. 
 
See the study timeline/flowchart below for a detailed overview of when 
various activities will occur.  

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13.3 After recruitment, study participants will be involved in the 
following procedures: eligibility screening, informed consent and 
study enrollment, baseline surveys, 12-week intervention session, 3-
month follow-up surveys, and 6-month follow-up surveys.  
 

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Recruitment, screening for eligibility, and informed consent and 
enrollment will follow the procedures previously described (See 
“Recruitment” and “Informed Consent” sections).  
 
During the initial enrollment appointment and after providing 
informed consent, participants will complete the baseline survey and 
first of three daily check-ins (ecological momentary assessments). 
The baseline survey will involve multiple choice questions about 
overdose and COVID-19 infection and vaccine knowledge, attitudes, 
and risk behaviors. The daily check-ins will ask clients to report drug 
use risk behaviors during drug using events in the prior day through 
Thrive4Life Connect. Participants will be asked to complete two 
additional daily check-ins about their drug use in the prior day over 
the course of the week following the enrollment appointment. 
Participants will be notified through an in-app notification and/or 
private message that a new survey is available. This event-level data 
will provide a detailed picture of co-occurring overdose risk 
behaviors beyond what can be captured in surveys with longer recall 
periods. We will specifically assess the setting of use and whether 
the participant was alone, had naloxone nearby, tested drugs for 
fentanyl, or mixed drug classes. 
 
During the 12-weekly intervention session, participants will 
complete weekly check-in surveys focused on 1) risk reduction 
planning tailored to their needs and motivation to change their 
overdose risk behaviors and COVID-19 vaccination status, and 2) 
goal setting and outlining steps they will take to achieve their 
overdose and COVID-19 health goals. All participants will choose 
goals related to overdose prevention, but choosing goals related to 
COVID-19 will be an optional activity.  
 
The 3- and 6-month follow-up surveys will collect the same data as 
the baseline survey and daily check-ins. Three months after 
beginning the study, participants will complete another survey 
assessing their overdose and COVID-19 infection and vaccine 
knowledge, attitudes, and risk behaviors. They will then be asked to 
complete the second set of three total daily check-ins. This process 
will be repeated for the 6-month timepoint. A total of nine daily 
check-ins (ecological momentary assessments) will be completed by 
each participant over the duration of the study.  
 
Throughout the study, participants will have access to and be 
encouraged to engage with a list of local resources and information 
about overdose risk and COVID-19. Participants will be regularly 
reminded that they can contact project staff if they need referrals or 
supplies. Discussion boards and private messaging functions within 

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the Thrive4Life Connect app will also be available to participants. 
Participants’ general usage (i.e., clicks) of resources or pages on the 
app are tracked within the Thrive4Life Connect app. Actions such as 
the frequency of participant engagement with resources in the 
Thrive4Life Connect app, posting on discussion boards, and sending 
private messages may be analyzed as data for the study. Participant 
discussion board and private message text will be monitored 
regularly by specific study staff approved to interact with 
participants via Thrive4Life Connect data exports to ensure that no 
illegal or inappropriate activity is occurring in these areas and that 
participants are not expressing thoughts of harm to themselves or 
others, or any other signals of distress. All participants and study 
staff will be able to publicly post and view other discussion board 
posts. To protect participant confidentiality, participants are 
encouraged to choose anonymous public usernames (which are 
viewable by other participants and study staff on discussion boards) 
and avoid posting identifiable information. All participants and study 
staff will also be able to utilize the private messaging function. 
Private messaging will primarily be used by study staff to send 
participants resources that are specific to their 12 weekly 
intervention goals. Participants will also be able to message each 
other and study staff. When messaging with other participants, the 
same guidelines for discussion boards to ensure confidentiality will 
apply.  
 
Referrals to community resources (e.g., housing assistance) and 
sterile injecting supplies or other resources (e.g., naloxone) are 
provided as part of the regular care that participants may receive at 
Vivent Health. A majority of the resources available to participants 
in this study focus on general education that is publicly available 
online and/or in suggesting topics or supplies that participants may 
want to ask about as part of their usual care in the future (e.g., 
picking up a naloxone supply if they don’t already have one). Once 
participants are connected with in-person resources or supplies at 
Vivent Health locations, that will be considered as part of regular 
Vivent Health care.  
 
Throughout the study, all resources provided in any survey or in the 
Thrive4Life Connect app will be continuously updated to reflect the 
most current information. All resources and any links will be 
updated as information changes or becomes available. 
 
We may use identifiable information from participants to link their 
information to databases like the Wisconsin Immunization Registry, 
Medicaid enrollment and claims data managed by the UW-Institute 
for Research on Poverty (IRP), and Wisconsin hospitalization data 

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from the Wisconsin Hospital Association Info Center, emergency 
medical services from the Wisconsin Ambulance Run Data System, 
and infectious disease surveillance registries capturing COVID-19, 
hepatitis C, and HIV infections. The purpose of this linkage is to 
understand how people who inject drugs use health care resources as 
well as to gather outcome data such as COVID-19 infection or 
vaccination status, overdose events, and substance use or other 
treatment utilization.  To accomplish this, we will link multiple 
datasets using individual identifiers (name, date of birth, address, 
sex, race, phone number).  
 
The UW-Institute for Research on Poverty (IRP) will assist in 
constructing the Medicaid study dataset. The IRP has longstanding 
technical expertise in the construction and secure use of integrated 
person-level electronic datasets that combine State of Wisconsin 
administrative data. Specifically, the IRP maintains the Multi-
Sample Person File (MSPF) dataset which combines data for the 
universe of individuals interacting with several WI state agencies, 
including the Department of Health Services (home of the Medicaid 
program) and the Department of Corrections, at the person-level 
dating back to the late 1990’s through the present. The MSPF is 
structured at the person-level, and each individual has a unique ID 
over time and across state agencies (e.g., a person who is 
incarcerated in a WI state prison and later enrolled in WI Medicaid) 
which supports longitudinal analysis. We will provide the UW IRP 
programming staff with our sample selection criteria (i.e., identifiers 
listed above for individuals enrolled in the study). They will query 
the MSPF dataset with these criteria to identify possible linkages to 
our study. In addition to basic program participation information 
(e.g., dates of participation), the MSPF includes identifying variables 
for each unique person including Social Security number, date of 
birth, name, and the individual’s identification number for each state 
agency that contributes to the MSPF in which s/he receives or has 
received services. The IRP will submit a finder file with the relevant 
identification information to each entity that is providing person-
level data for the study. Upon receipt of these data, the IRP will then 
merge data from all sources at the person level, assign a unique, 
study number to each subject, and remove the personal identifying 
information used to match data across sources from the analytic 
dataset that is provided to the investigators. The exchange of data 
between the IRP and state agencies is governed by the Data Use 
Agreements between the IRP and the respective agencies and 
follows a strict data security protocol to protect the confidentiality of 
individuals. The DUA between the IRP and the WI Medicaid 
program will be obtained for this study once recruitment has ended. 
 

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The remaining dataset owners are housed at the Wisconsin 
Department of Health Services (DHS) or with affiliated 
organizations (e.g., WHAIC) for whom DHS provides assistance 
with linkage projects. The process for gaining approval for linkage 
projects involves putting together a formal request for review by the 
DHS Data Governance Board, which we will do upon completing 
recruitment. After approval from the board is obtained (including a 
review of proof of IRB approval for this protocol), we will work 
with the data owners and University HIPAA privacy officers to draft 
a Data Use Agreement. Once all stakeholders are in agreement on 
the DUA elements and there is a draft ready, the DUA is routed for 
institutional signature, which will facilitate getting all of the 
appropriate persons to review and approve the document. Once DUA 
approval is obtained, the research team will work with the specific 
data owners at DHS, who perform the data linkage based on 
identifiers provided. No study data beyond identifiers will be shared 
with DHS during this process (e.g., survey data about drug use). 
DHS data owners will then provide a file on matched encounters 
back to the research team, which will be identifiable via a unique 
participant ID number created for the linkage. This unique identifier 
will allow the research team to link the received DHS datasets back 
to the original study data (e.g., survey data, Thrive4Life Connect use 
data). 
 
13.4 Identifiable Data Elements: Possible participants will complete a 
screener and locator form. The screener and locator form will both 
be administered via one REDCap survey. If a participant screens as 
eligible, the survey will pause and a Vivent Health prevention 
specialist will confirm their interest in enrolling. Interested 
participants will then complete the rest of the survey by providing 
multiple methods of contact information.  
 
Identifiable Data Element 
Add an X if collecting and storing 
Names (or derivatives such as initials) 
X 
Dates (except year) 
X 
Telephone Numbers 
X 
Geographic subdivisions smaller than 
a state 
X 
Email addresses 
X 

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Thrive4Life Connect app 
account/study ID numbers 
X 
Social media contact information 
X 
Information for 2 or more points of 
contact  
X 
 
 
Other Data Elements:  
We will collect the following data directly from participants using survey 
responses in the Thrive4Life Connect app: 
● Overdose and COVID-19 health-related goals 
● Substance use and overdose risk, knowledge, attitudes, beliefs, 
concerns, and behaviors 
o Safer behaviors  
o Risk behaviors 
● Overdose perspectives and experiences 
● COVID-19 knowledge, attitudes, beliefs, concerns, and 
behaviors 
● General attitudes towards vaccines 
● COVID-19 vaccination status and history  
● Event-level information about the most recent time a 
participant used drugs  
o Daily check-ins (ecological momentary assessments)  
● Survey completion dates  
 
Source Records:  
☒ Data from outside institutions or organizations (specify: Wisconsin 
Department of Health Services and Medicaid, registries described 
above) 
☒ Other (specify: A-CHESS Thrive4Life Connect mobile app utilization 
data) 
 
Supplementary data will be collected indirectly from participants based on 
their activity in the Thrive4Life Connect app: 
● Discussion board participation  
● In-app private messaging with study staff 
● Viewing of in-app resources  
● Usage of “My Motivation” and “My Gratitude”  
“My Motivation” and “My Gratitude” are optional activities 
available in the Thrive4Life Connect app.  
 
“My Motivation” prompts participants with the following, 
“Stay motivated by keeping a list of why you want to stay well 
- and watch your list grow!” This area then provides 

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participants with an opportunity to curate a personal log of 
things (text or pictures) that motivate them to meet their goals.  
 
“My Gratitude” prompts participants with the following, 
“Awareness and appreciation of things you're thankful for may 
help brighten your day. What are you grateful for?” 
Participants can then curate a personal list of things (text only) 
that they are grateful for in “My Gratitude.”  
 
13.5 The Thrive4Life Connect mobile application does not require FDA 
regulation, as per consultation with the Administrative Director of 
the FDA Regulated Research Oversight Program.  
 
14.0 Comparison of usual care and study procedures 
14.1 Clients visiting Vivent Health may choose not to participate in the 
study. There is no alternative to participating if they choose not to 
participate. 
 
14.2 Regardless of study participation, clients at Vivent Health can 
continue to receive their usual prevention services from Vivent 
Health, including but not limited to obtaining sterile injecting 
equipment and other supplies, referrals, and hepatitis C and HIV 
testing. 
 
14.3 Study participants are provided with some overlapping information 
about overdose prevention, COVID-19, and health and social 
services via the Thrive4Life Connect smartphone application that 
could be obtained from staff working at Vivent Health. Specifically, 
the Thrive4Life Connect app contains a resources section with flyers 
and information on these topics, which are also available at Vivent 
Health. 
 
14.4 Research participation will not affect access to Vivent Health 
prevention services or any other care or treatment the participant is 
involved in. 
 
15.0 Withdrawal of Participants 
15.1 The Thrive4Life Connect application allows participants to share 
their views, opinions, photos and personal experiences. However, 
participants are prohibited to post content on the Thrive4Life 
Connect site that promotes racism, bigotry, hatred, nudity, or 
physical harm of any kind against any group or individual. If 
participants use the application in an inappropriate manner, research 
staff will delete the inappropriate messages and follow up with them. 
If the behavior continues, research staff may withdraw participants 
from the study. 

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Participants expressing severe emotional or mental distress (e.g., by 
communicating thoughts of harm to self or others) may also be 
withdrawn from the study by study staff (or by their own choice). 
Withdrawal decisions will be made jointly by the research team and 
lead researchers. 
 
If a participant is incarcerated, no research activities would occur 
during the time of incarceration. Participants can contact the study 
team when they are released to discuss participating in the study. If 
participants are under criminal justice supervision and are prohibited 
from using internet-enabled devices, it is their responsibility to 
ensure that their study participation is allowable under the terms of 
their supervision. 
 
15.2 Orderly termination will involve informing the participant that they 
are being withdrawn from the study. The study team will then have 
the ability to remove access from the study activities on the 
Thrive4Life Connect application and to deactivate the data plan on 
their study-provided smartphone. 
 
15.3 See 15.2.  
 
Participants are able to end their participation in the study at any 
time. Participants who do not complete the 12-week intervention will 
still be eligible to complete the 3-month and 6-month paid study 
surveys. This situation will be considered a partial withdrawal. These 
partial withdrawals will be reported in the same way, in continuing 
reviews, as withdrawals. Data may continue to be collected if 
partially withdrawn participants begin using the Thrive4Life 
Connect app again and if they decide to still complete the 3-month 
and 6-month surveys. If participants partially withdraw and their 
phone service is turned off, they can contact the study team to 
discuss participation and turning the service back on. All surveys can 
be completed without phone service using Wi-Fi.  
 
16.0 Data Management and Confidentiality 
16.1 To ensure quality control of participant data in the Thrive4Life 
Connect app, our study team will test the functionality of each 
survey and all intervention content. This testing procedure will be 
designed to identify any possible survey bugs, ensure correct 
memory logic between surveys, and ensure skip logic within 
surveys.  
 
A majority of the survey questions in this study utilize multiple 
choice or checkbox options and guided type in boxes with limited 

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answer ranges. All questions must be answered, but a “Prefer not to 
answer” option is always available for participants who may be 
uncomfortable answering certain questions. Instructions are also 
provided at the beginning of each survey.  
 
Survey data are stored in the Thrive4Life Connect app even if a 
participant does not complete a survey or forgets to submit their final 
answers. This function ensures data quality by limiting data loss. 
 
Research staff will periodically review completed surveys to ensure 
they are functioning properly. 
 
16.2  Steps to secure data: 
☒ Data will be coded, and the “key” linking identities to codes will 
be kept separately from the data. 
☒ Only those listed as key personnel will have access to the “key.” 
 
List of key personnel: 
▪ 
Rachel Gicquelais 
▪ 
Ryan Westergaard 
▪ 
Sarah Uhm 
▪ 
Katy Mijal 
▪ 
Rebecca Miller 
▪ 
Erika Bailey 
▪ 
Andrew Hagmeier 
▪ 
Jacob Schleicher 
▪ 
Dahlia Jones 
▪ 
Adam Hanson 
▪ 
Carmella Brown 
▪ 
Caitlin Conway 
▪ 
Theresa Zauner 
▪ 
Mikaela Becker 
▪ 
Carly Kowitz 
▪ 
Catrina Solberg 
▪ 
Janelle Moneypenny 
▪ 
Kara Lee 
 
☒ This study is in part funded by the National Institutes of 
Health. However, NIH funding only covered the 
development of the Thrive4Life Connect app platform, and 
not the development or evaluation of the intervention 
studied in this project. To ensure confidentiality for 
participants and because we will collect sensitive 
information, the research team applied for and received a 
new Certificate of Confidentiality to protect data from 

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being requested without the subject’s consent as part of a 
legal proceeding. 
 
16.1 Data storage: 
☒ Research Electronic Data Capture (REDCap) Specify which 
instance you will be using (e.g., ICTR’s, Department of 
Medicine’s): Department of Medicine 
☒ Other software option that will be stored on departmental 
server. Specify the department:      School of Medicine and 
Public Health HIPAA-compliant servers 
☒ Locked filing cabinet or drawer inside a locked room. 
Specify the building:      School of Medicine and Public 
Health WARF building 
☒ Other (describe): HIPAA-compliant Vivent Health 
Microsoft Teams – Information about study survey completion 
dates will be collected for each participant. This information 
will be used to inform whether a specific participant is eligible 
to pick up their compensation for each survey. Vivent Health 
personnel will also update the Microsoft Teams to reflect when 
a participant has picked up their compensation.  
☒ Portable devices will be used to access secure web-based 
data collection sites such as ICTR’s REDCap. No data will 
be stored locally on the device. 
 
16.2 Management of Identifiers:  
☒ Identifiers will be destroyed at study closure or at the time 
of publication. 
 
16.3 
Data will be stored on the Thrive4Life Connect mobile application 
platform, HIPAA-compliant servers at the UW School of Medicine and 
Public Health     , DOM REDCap, and HIPAA-compliant Vivent Health 
Microsoft Teams, as described above. Because data are collected 
electronically, separate data storage for each study site is not necessary and 
will not be used.  
 
The Thrive4Life Connect app was developed based on the UW-Madison 
Addiction-Comprehensive Health Enhancement Support System (A-
CHESS) platform, which has been used in several prior addiction-related 
studies. Any data stored on a participant's device are stored in an encrypted 
file and only accessible by that participant, i.e. participants don't have any 
other participant’s data on their phone. These data are only collected after 
the participant has signed into their account and are removed when the 
participant signs out of the Thrive4Life Connect A-CHESS based 

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application. Any data transferred to and from UW-Madison servers are 
done through an encrypted connection. 
 
Thrive4life Connect utilization data that will be used for study analyses of 
Thrive4Life Connect app utilization are stored on HIPAA Compliant 
servers housed at the UW-Madison Division of Information Technology 
(DoIT).  DoIT partners with the UW-Madison Office of Cybersecurity to 
ensure that our infrastructure meets the necessary security controls. 
 
16.4 Data including identifiers from this study will only be shared with 
members of the study team at UW-Madison and Vivent Health.  
 
17.0 Provisions to Protect the Privacy Interests of Participants 
17.1 Steps to protect participants’ privacy interests: 
☒ Procedures will be performed in a private area where others 
cannot see the procedures being performed or overhear the 
conversation between subjects and researchers. 
☒ All members of the study team are up to date on their institutional 
HIPAA training. 
 
We have strict rules to protect participant personal information and 
protected health information (PHI). We will limit who has access to 
participant health information, names, addresses, phone numbers, 
and other identifiable information. We will also store this 
information securely. We may publish and present what we learn 
from this study, but none of this information will identify 
participants directly without permission. Study participants will also 
be protected by a Certificate of Confidentiality.  
 
Federal or state laws may permit or require us to show information 
to university or government officials and to study sponsors 
responsible for monitoring this study. There are some situations 
when we will not keep information confidential. We will report 
information about participants to the appropriate authorities in the 
following circumstances: 
● If they tell us they are planning to harm themselves or 
another person. 
● If they tell us something that causes us to believe that a child 
or vulnerable adult is being abused 
 
17.2 This study involves collecting sensitive information about drug and 
alcohol use on surveys in the Thrive4Life Connect app. The primary 
objective of this study is to test a novel mobile health intervention to 
reduce overdose risk and support vaccine uptake with people who 
inject drugs in Wisconsin. To assess the effectiveness of this study 

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Revised: October 18, 2022 
and fulfill the study goals, the collection and analysis of this 
sensitive information is necessary.   
 
17.3 Participants will be able to stop their participation at any time 
throughout the study. Additionally, participants can refuse to answer 
any survey question(s) that may make them uncomfortable. 
Throughout the study, participants will also be encouraged to reach 
out to the study team if they have any questions. Based on a 
participant’s survey answers, they will also be connected with 
resources that are specific to their situation. We also obtained a 
Certificate of Confidentiality for the study and will explain what this 
means to participants during the informed consent process.   
 
18.0 Sharing of Results  
18.1 Results from this study will not be shared directly with participants 
or others. Individual results will not be reported in participants’ 
health records.  
 
18.2 We will only share results in an aggregate format, and we will not 
share any data that could be used to identify participants. We will 
only report summary data to individuals outside the study team. We 
expect to publish manuscripts based on information gathered in this 
study, but no participants will be identified in these shared results.  
 
19.0 Data and Specimen Banking 
19.1 Data from this pilot study will be banked for future use. Data 
banking will not be optional. Deidentified data from this study, 
specifically Thrive4Life Connect survey answers, will be stored on 
HIPAA compliant secure servers at the UW-Madison      School of 
Medicine and Public Health. 
 
Banked data will be stored indefinitely, but study ID numbers will be 
removed from data before banking. Banking will occur after all 
publications for this study are completed and published or after 7 
years (whichever comes first).  
 
Members at UW-Madison that can see and use participant 
information:  
● Members of our research team  
● Offices and committees responsible for the funding and 
oversight of research 
 
19.2 Data to be stored: 
We will collect the following data directly from participants using survey 
responses in the Thrive4Life Connect app: 
● Overdose and COVID-19 health-related goals 

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● Substance use and overdose risk, knowledge, attitudes, beliefs, 
concerns, and behaviors 
o Safer behaviors  
o Risk behaviors 
● Overdose perspectives and experiences 
● COVID-19 knowledge, attitudes, beliefs, concerns, and behaviors 
● General attitudes towards vaccines 
● COVID-19 vaccination status and history  
● Event-level information about the most recent time a participant 
used drugs  
o Daily check-ins (ecological momentary assessments)  
● Survey completion dates  
● Demographic information 
● Frequency and distribution of questions where participants chose 
“Prefer not to answer”  
 
Supplementary data may also be collected indirectly from participants 
based on their activity in the Thrive4Life Connect app: 
● Discussion board participation  
● In-app private messaging with study staff 
● Viewing of in-app resources  
● Usage of “My Motivation” and “My Gratitude”  
 
Information from participants collected from databases like the 
Wisconsin Immunization Registry, Medicaid, and Wisconsin 
hospitalization, emergency medical services, and infectious disease 
surveillance registries.  
 
All data will be deidentified prior to banking.  
 
19.3 To comply with some academic journal requirements, we anticipate 
needing a procedure to make data available to interested colleagues. 
Written requests to release deidentified data or specimens may be 
made to the lead researchers by email. Requests must specify the 
specific data requested. The lead researcher would then supply a 
deidentified dataset based on the data requested. No PHI will be 
shared in a requested dataset. 
 
19.4 Participants will not be able to withdraw their banked data for future 
research use. All data will be fully anonymized prior to banking. If a 
participant decides to withdraw from the study, no additional data 
will be collected from them after that point.  
 
20.0 Study Analysis 

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20.1 Primary Outcome Null hypothesis (feasibility): the study is feasible based 
on intervention content completion rates of at least 50%. Alternative 
hypothesis: fewer than 50% of intervention content is completed. 
 
Secondary outcome null hypothesis #1 (preliminary effectiveness of 
overdose content): there is no difference in the number of days endorsing 
overdose risk behaviors per month at baseline vs. 3 months and baseline vs. 
6 months. Alternative hypothesis: the frequency of overdose risk behaviors 
decreased from baseline to 3 months, and baseline to 6 months. 
 
Secondary outcome null hypothesis #2 (preliminary effectiveness of 
COVID-19 content): there is no difference in proportion of participants 
who have been vaccinated against COVID-19 at baseline vs. 3 months and 
baseline vs. 6 months. Alternative hypothesis: the proportion vaccinated 
will increase from baseline to 3 months, and baseline to 6 months. 
 
20.2 As a pilot feasibility study, the number of participants (n=60) reflects the 
maximum allowable participants in our budget and study timeframe. A 
formal sample size calculation was not done. 
 
20.1 All participants who enroll in the study will be included in each analysis. 
 
20.4 The average and variation in percentage of completed intervention modules 
and in the percentage completing each weekly intervention module over 12 
weeks will be calculated and examined descriptively. 
 
 
We will examine changes in the frequency of endorsing overdose risk 
behaviors and COVID-19 vaccination based on a descriptive analysis of the 
baseline, 3 month and 6 month surveys. We may also test for differences 
using appropriate statistical tests, including paired t-tests, McNemar’s test, 
and models appropriate for count outcomes and repeated measures (Poisson 
or Negative Binomial Generalized Estimating Equations). As a pilot study, 
we expect that most analyses will be descriptive rather than inferential in 
nature. 
 
20.5 We will examine weekly survey and intervention module completion rates. 
There are no stopping rules for efficacy or safety in this study. 
 
20.6 As a pilot feasibility study, we will examine missingness and survey 
completion as primary outcomes to assess engagement with intervention 
content and study feasibility. We may impute or use simple techniques such 
as last observed carried forward in analyses. We will track reported reasons 
for missing data such as loss of study phone, incarceration, withdrawal, etc. 
 
21.0 Potential Benefits to Participants 

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Revised: October 18, 2022 
21.1 
Participating in this study may be a beneficial way for PWID to get 
support from other people living with substance use problems. Thrive4Life 
Connect will also provide participants with information about local resources and 
harm reduction. The study may also benefit other people in the future by helping 
us learn more about how a smartphone app can lower overdose risk for people 
who use drugs.  
 
22.0 Risks to Participants 
22.1 Risks: 
● Information participants enter into Thrive4Life Connect can 
be viewed by UW and Vivent Health research team 
members. They may monitor discussion boards and post 
information there. Study staff will also reach out to 
participants via private messaging or other contact methods 
(texts, phone calls, social media, etc.). Information 
participants enter into Thrive4Life Connect is not stored on 
the phone, but this information is stored on the Thrive4Life 
Connect app. 
● When participants set up their Thrive4Life Connect account, 
they will be asked to create an account username. This 
username will be listed on discussion board posts and 
included in a list of participants that can receive private 
messages. To reduce the risk of being identified, we will 
require participants to choose a username that will NOT 
include any identifiable information such as their first name, 
last name, date of birth, address, etc.  
● Other participants can see what is posted to the discussion 
boards. There is a risk that other participants could identify 
each other based on the information they provide in their 
discussion board posts. 
● Answering questions on sensitive issues (like drug and 
alcohol use, mental health, etc.) in surveys may cause 
anxiety, distress, embarrassment, or feelings of sadness. 
Participants do not have to answer any questions that they do 
not want to. 
● The Thrive4Life Connect app allows participants to share 
their views, opinions, photos, and personal experiences. 
However, participants are NOT allowed to post content on 
the Thrive4Life Connect app that promotes racism, bigotry, 
hatred, nudity, or physical harm of any kind against any 
group or individual. If a participant uses the app in an 
inappropriate or illegal manner, the research staff will delete 
the inappropriate content and follow up with them. If the 
behavior continues, the research staff may withdraw the 
participant from the study. 

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COVID-19 among people who use drugs 
 
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● There is a risk that study participants may send or receive 
private messages including unwanted or inappropriate 
content. If this happens, we ask that participants report this 
information to the study team (608-294-7446).  
● Information from the internet and/or Thrive4Life Connect 
discussion boards could be wrong. However, a panel of UW 
staff review all information on the app, so this risk is 
unlikely. We will provide tips to help participants figure out 
whether they can trust the information they receive from 
these sources. 
● There is a risk that participant information could become 
known to someone not involved in this study. If this happens, 
it could result in damage to reputation, which could also 
affect relationships with family and friends, affect 
employment, or make it harder to get insurance or a job. 
● The study team may discover behavior that raises concern 
about harm to themselves or others. If we see anything that 
suggests that a participant or others face imminent risk of 
harm, we will contact appropriate parties to intervene (e.g., 
your care team and/or police). 
 
22.2 Potential participants may choose not to participate or enroll after 
learning more about the study. Participants may end their 
participation at any time and choose not to answer any questions 
they do not wish to. Participants are not required to use the app 
discussion board. They must be able to receive private messages or 
texts from study staff (with survey reminders and weekly 
intervention content feedback) but are not required to respond. 
Participants will be shown how to add a password to their study 
iPhone, and how to disable the function that shows a preview of the 
content received in messages during study enrollment to protect 
privacy. 
 
23.0 Provisions to Monitor the Data to Ensure the Safety of 
Participants 
23.1 The study team (lead researchers Dr. Gicquelais and Dr. 
Westergaard and staff including Ms. Sarah Uhm, Ms. Katy Mijal, 
and Ms. Mikaela Becker) will be responsible for monitoring the data 
to ensure the safety of participants. We will review all survey data 
collected at baseline, 3 months and 6 months for any reports of 
serious events (i.e., death, life-threatening overdose, hospitalizations 
lasting 24 hours or more). Data will be monitored on a monthly 
basis. We will also review any reports of potentially serious events 
received by participants to the study team via the Thrive4Life 
Connect app private message function or discussion board on a 
rolling basis. Given the sample size of only 60 participants and 

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planned analyses focused on feasibility, we will not be able to 
statistically examine the safety data to determine whether harm is 
occurring. We will review adverse events starting with recruitment 
of the first study participant through 30 days after the last date that 
the final participant completed their final study procedure (i.e., all 6 
months surveys). 
 
The severity of each event will be classified using the following 
guidelines adapted from the UW-Madison ICTR Trial Template: 
 
Mild (Grade 1) 
Events require minimal or no treatment and do not interfere 
with the subject’s daily activities. 
Moderate (Grade 2) 
Events result in a low level of inconvenience or concern with 
the therapeutic measures. Moderate events may cause some 
interference with functioning. 
Severe (Grade 3) 
Events interrupt a subject’s usual daily activity and may 
require systemic drug therapy or other treatment. Severe 
events are usually potentially life-threatening or 
incapacitating. 
Life Threatening 
(Grade 4) 
The subject was at risk of death at the time of the event. 
Fatal (Grade 5) 
The event caused death. 
 
The relationship of each event to study procedures will be 
classified using the following guidelines adapted from the UW-
Madison ICTR Trial Template: 
Definitely 
Related 
Clearly related to the study procedures/intervention and other 
possible contributing factors can be ruled out. 
Probably 
Related 
Likely related to the study procedures/intervention and the influence 
of other factors is unlikely. 
Possibly 
Related 
Possibly related to the study procedures/intervention and there are 
other factors that could be equally likely. 
Unlikely to be 
related 
Doubtfully related to the study procedures/intervention and there is 
another likely cause. 

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COVID-19 among people who use drugs 
 
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Unrelated 
Clearly not related to the study procedures/intervention and/or 
evidence exists that the event is definitely related to another cause. 
 
The event will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information 
previously described in the protocol, the IRB application, or the 
informed consent document.  
 
In consultation with the lead researchers, a trained member of the 
study team will be responsible for conducting an evaluation of 
adverse events or unanticipated problems and shall report these 
issues and evaluation to the reviewing Institutional Review Board 
(IRB) in accordance with the Reportable Event Reporting 
Requirements.  
 
24.0 Economic Burden to Participants 
24.1 There are no costs associated with joining or participating in this 
study. 
 
25.0 Resources Available  
Will the research be conducted outside 
School of Medicine and Public Health 
or UW Hospitals and Clinics (e.g. the 
researcher does not have an SMPH 
research feasibility attestation for this 
study)?    
☒ YES (complete 25.1) 
☐ NO (remove text below, but retain this 
section) 
 
25.1 All recruitment activities will be conducted at Vivent Health offices. 
Each Vivent Health office included in the study has a brick-and-
mortar location in the community that provides prevention services 
such as HIV and hepatitis C testing and sterile injection supplies. 
Thus, these locations provide access to our eligible population. We 
expect to devote up to 1 year to recruit participants. UW-Madison 
will provide all necessary study supplies to conduct the research. All 
persons assisting with the research will be listed on our IRB and 
have completed the appropriate human subjects research trainings. 
Trainings for the study procedures will be completed prior to starting 
recruitment and enrollment.  
 
26.0 Multi-Site Research 
26.1 This study will involve multiple sites. Three Vivent Health locations 
will be included in this study: the Milwaukee, Eau Claire, and 
Appleton Vivent Health locations. To ensure consistency in study 
operations, all Vivent Health sites will use the same procedures to 

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COVID-19 among people who use drugs 
 
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Revised: October 18, 2022 
enroll participants. At all enrollment appointments, participants will 
review the study procedures and informed consent document by 
either watching a video of the informed consent highlights then 
discussing with a Prevention Specialist OR by discussing the key 
areas of the informed consent with a Prevention Specialist. The 
content relayed regarding the study procedures and informed consent 
will be standardized across all sites, as all participating locations will 
use the same video or script and paper or electronic consent 
materials. 
 
HIPAA-compliant Vivent Health Microsoft Teams will be used to 
store participant screener, locator, and survey completion data. The 
Vivent Health Microsoft Teams will be accessible to all site 
locations. Participant information for each site will be stored within 
the same survey reports for this study.  
 
Prior to beginning enrollment, we will host training sessions for all 
site locations to provide each location with the most up to date 
information regarding the study protocol, consent, data management, 
and other study activities. All research staff who engage in the 
informed consent process will be up to date on required HIPAA and 
CITI trainings and listed as personnel on the IRB application.  
 
Because the IRB reliance protocol will not fully be in place at the 
time of writing IRB review (a Federal Wide Assurance is being 
completed as soon as possible), Vivent Health personnel will not 
engage in any research activities until the Vivent Health sites have 
been formally approved via a change of protocol and a finalized 
reliance agreement has been executed.  
 
26.2 The UW-Madison study team will consistently communicate with 
the participating Vivent Health locations to address any 
modifications to the study. Communication may occur via in-person 
or virtual meetings, email and phone communications, and Vivent 
Health Microsoft Teams for any changes related to PHI. The 
Research Supervisor at Vivent Health, who is a member of the 
research team and oversees research projects occurring at Vivent 
Health will also help to disseminate key study protocols, changes, 
problems, and information about closure of the study throughout the 
duration of the study. 
 
27.0 References 
1. Glober N, Mohler G, Huynh P, et al. Impact of COVID-19 Pandemic 
on Drug Overdoses in Indianapolis. J Urban Health Bull N Y Acad 
Med. 2020;97(6):802-807. doi:10.1007/s11524-020-00484-0 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
Page 40 of 42 
Revised: October 18, 2022 
2. Khoury D, Preiss A, Geiger P, Anwar M, Conway KP. Increases in 
Naloxone Administrations by Emergency Medical Services Providers 
During the COVID-19 Pandemic: Retrospective Time Series Study. 
JMIR Public Health Surveill. 2021;7(5):e29298. doi:10.2196/29298 
3. Ahmad F, Escobedo L, Rossen L, Spencer M, Warner M, Sutton P. 
Provisional Drug Overdose Death Counts. National Center for Health 
Statistics; 2021. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-
data.htm 
4. Wang QQ, Kaelber DC, Xu R, Volkow ND. COVID-19 risk and 
outcomes in patients with substance use disorders: analyses from 
electronic health records in the United States. Mol Psychiatry. 
2021;26(1):30-39. doi:10.1038/s41380-020-00880-7 
5. Mellis AM, Kelly BC, Potenza MN, Hulsey JN. Trust in a COVID-19 
vaccine among people with substance use disorders. Drug Alcohol 
Depend. 2021;220:108519. doi:10.1016/j.drugalcdep.2021.108519 
6. Westergaard RP, Hull SJ, Merkow A, Stephens LK, Hochstatter KR, 
Olson-Streed HK, Baker LM, Hess TM. Computerized Tailored 
Interventions to Enhance Prevention and Screening for Hepatitis C 
Virus Among People Who Inject Drugs: Protocol for a Randomized 
Pilot Study. JMIR Res Protoc. 2016 Jan 22;5(1):e15. PMCID: 
PMC4744331 
7. Hochstatter KR, Hull SJ, Sethi AK, Burns ME, Mundt MP, 
Westergaard RP. Promoting Safe Injection Practices, Substance Use 
Reduction, Hepatitis C Testing, and Overdose Prevention Among 
Syringe Service Program Clients Using a Computer-Tailored 
Intervention: Pilot Randomized Controlled Trial. J Med Internet Res. 
2020 Sep 29;22(9):e19703. PMCID: PMC7556373 
8. Gustafson DH, McTavish FM, Chih M-Y, Atwood AK, Johnson RA, 
Boyle MG, Levy MS, Driscoll H, Chisholm SM, Dillenburg L, Isham 
A, Shah D. A smartphone application to support recovery from 
alcoholism: a randomized clinical trial. JAMA Psychiatry. 2014 
May;71(5):566–572. PMCID: PMC4016167 
9. Gustafson DH, Landucci G, McTavish F, Kornfield R, Johnson RA, 
Mares M-L, Westergaard RP, Quanbeck A, Alagoz E, Pe-Romashko 
K, Thomas C, Shah D. The effect of bundling medication-assisted 
treatment for opioid addiction with mHealth: study protocol for a 
randomized clinical trial. Trials. 2016 12;17(1):592. PMCID: 
PMC5153683 
10. Hochstatter KR, Akhtar WZ, Dietz S, Pe-Romashko K, Gustafson DH, 
Shah DV, Krechel S, Liebert C, Miller R, El-Bassel N, Westergaard 
RP. Potential Influences of the COVID-19 Pandemic on Drug Use and 
HIV Care Among People Living with HIV and Substance Use 
Disorders: Experience from a Pilot mHealth Intervention. AIDS 
Behav. 2021 Feb;25(2):354– 359. PMCID: PMC7376523 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
Page 41 of 42 
Revised: October 18, 2022 
11. Ryan RM, Deci EL. Self-determination theory and the facilitation of 
intrinsic motivation, social development, and well-being. Am Psychol. 
2000 Jan;55(1):68–78. PMID: 11392867 
12. McTavish FM, Chih M-Y, Shah D, Gustafson DH. How Patients 
Recovering From Alcoholism Use a Smartphone Intervention. J Dual 
Diagn. 2012;8(4):294–304. PMCID: PMC3541672 
13. Rivet Amico K. A situated-Information Motivation Behavioral Skills 
Model of Care Initiation and Maintenance (sIMB-CIM): an IMB 
model based approach to understanding and intervening in engagement 
in care for chronic medical conditions. J Health Psychol. 2011 
Oct;16(7):1071–1081. PMID: 21459919 
14. Heckathorn DD. Respondent-Driven Sampling: A New Approach to 
the Study of Hidden Populations. Soc Probl. Oxford Academic; 1997 
May 1;44(2):174–199. 
15. Heckathorn DD. Respondent-Driven Sampling II: Deriving Valid 
Population Estimates from Chain-Referral Samples of Hidden 
Populations. Soc Probl. Oxford Academic; 2002 Feb 1;49(1):11–34. 
16. Salganik MJ, Heckathorn DD. 5. Sampling and Estimation in Hidden 
Populations Using Respondent-Driven Sampling: Sociological 
Methodology [Internet]. SAGE PublicationsSage CA: Los Angeles, 
CA; 2016 Jun 24 [cited 2020 Jun 29]; Available from: https://journals- 
sagepub-com.proxy1.library.jhu.edu/doi/10.1111/j.0081-
1750.2004.00152.x 
17. Macalino GE, Celentano DD, Latkin C, Strathdee SA, Vlahov D. Risk 
behaviors by audio computer-assisted self-interviews among HIV-
seropositive and HIV-seronegative injection drug users. AIDS Educ 
Prev. 2002 Oct;14(5):367–378. PMID: 12413183 
18. Wolitski RJ. Relative Efficacy of a Multisession Sexual Risk–
Reduction Intervention for Young Men Released From Prisons in 4 
States. Am J Public Health. 2006 Oct;96(10):1854– 1861. PMCID: 
PMC1586131 
19. CDC Division of HIV/AIDS Prevention, National Center for 
HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. Project START: 
An Individual-level Intervention for People Being Released from a 
Correctional Facility and Returning to the Community [Internet]. 2020 
[cited 2021 May 25]. Available from: 
https://www.cdc.gov/hiv/research/interventionresearch/rep/packages/st
art.html 
20. Centers for Disease Control and Prevention. Overdose Deaths 
Accelerating During COVID- 19 [Internet]. Centers for Disease 
Control and Prevention. 2020 [cited 2021 Feb 23]. Available from: 
https://www.cdc.gov/media/releases/2020/p1218-overdose-deaths-
covid- 19.html 
21. UW Health. COVID-19 Pandemic Coincides With Rise of Opioid 
Overdoses [Internet]. UW Health News and Events. 2020. Available 

PROTOCOL TITLE: iThrive WI – A smartphone intervention for overdose and risk and 
COVID-19 among people who use drugs 
 
Page 42 of 42 
Revised: October 18, 2022 
from: https://www.uwhealth.org/news/covid-19- pandemic-coincides-
with-rise-of-opioid-overdoses-w/53462 
22. Holland KM, Jones C, Vivolo-Kantor AM, Idaikkadar N, Zwald M, 
Hoots B, Yard E, D’Inverno A, Swedo E, Chen MS, Petrosky E, Board 
A, Martinez P, Stone DM, Law R, Coletta MA, Adjemian J, Thomas 
C, Puddy RW, Peacock G, Dowling NF, Houry D. Trends in US 
Emergency Department Visits for Mental Health, Overdose, and 
Violence Outcomes Before and During the COVID-19 Pandemic. 
JAMA Psychiatry. 2021 Feb 3; PMCID: PMC7859873 
23. Ahmad F, Escobedo L, Rossen L, Spencer M, Warner M, Sutton P. 
Provisional drug overdose death counts [Internet]. National Center for 
Health Statistics; 2021. Available from: 
https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm 
24. Tyndall M. Safer opioid distribution in response to the COVID-19 
pandemic. Int J Drug Policy. 2020 Sep;83:102880. PMCID: 
PMC7383133 
25. Genberg BL, Astemborski J, Piggott DA, Woodson-Adu T, Kirk GD, 
Mehta SH. The health and social consequences during the initial 
period of the COVID-19 pandemic among current and former people 
who inject drugs: A rapid phone survey in Baltimore, Maryland. Drug 
Alcohol Depend. 2021 Feb 13;221:108584. PMCID: PMC7881742 
26. Stack E, Leichtling G, Larsen JE, Gray M, Pope J, Leahy JM, Gelberg 
L, Seaman A, Korthuis PT. The Impacts of COVID-19 on Mental 
Health, Substance Use, and Overdose Concerns of People Who Use 
Drugs in Rural Communities. J Addict Med. 2020 Nov 3; PMID: 
33156181 
27. Wang QQ, Kaelber DC, Xu R, Volkow ND. COVID-19 risk and 
outcomes in patients with substance use disorders: analyses from 
electronic health records in the United States. Molecular Psychiatry. 
Nature Publishing Group; 2021 Jan;26(1):30–39. 
28. Mellis AM, Kelly BC, Potenza MN, Hulsey JN. Trust in a COVID-19 
vaccine among people with substance use disorders. Drug Alcohol 
Depend. 2021 Mar 1;220:108519. PMCID: PMC7797771 
29. Koepke R, Sill DN, Akhtar WZ, Mitchell KP, Guilfoyle SM, 
Westergaard RP, Schauer SL, Vergeront JM. Hepatitis A and Hepatitis 
B Vaccination Coverage Among Persons Who Inject Drugs and Have 
Evidence of Hepatitis C Infection. Public Health Rep. 2019 
Dec;134(6):651–659. PMCID: PMC6832086 
30. Lasser KE, Kim TW, Alford DP, Cabral H, Saitz R, Samet JH. Is 
unhealthy substance use associated with failure to receive cancer 
screening and flu vaccination? A retrospective cross-sectional study. 
BMJ Open. 2011 Apr 7;1(1):e000046. PMCID: PMC3191402 
 
28.0 Appendices 
See additional materials included in iThrive WI ARROW IRB application.