Improving Pediatric COVID-19 Vaccine Uptake Using an mHealth Tool: a Randomized, Controlled Trial
Phase: NA
Conditions: COVID-19 Vaccines, Telemedicine, Vaccine Hesitancy, Pediatric ALL
Sponsor: IDeA States Pediatric Clinical Trials Network

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 1 of 73 
Improving pediatric COVID-19 vaccine uptake using an 
mHealth tool: a randomized, controlled trial 
 
Unique Protocol Identification Number: 273761 
National Clinical Trial (NCT) Identified Number:  
Principal Investigator: Russell J. McCulloh, MD; Ellen Kerns, PhD, MPH;  
Paul Darden, MD 
Version: 10 
13 February 2023 
 
 
 
 
 
 
 
 
 
 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 2 of 73 
Summary of Changes from Previous Version: 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
 Abbreviations & 
Definitions 
 Adding definition of Participants 
 To clarify the role of parent/caregivers as 
participants in the study. To clarify the role of 
children as participants in the study. 
Known Potential Risks 
Added phrase “see definition of 
participants” 
Clarify role and definition of parent/caregiver 
participants.  
Objectives and 
Endpoints 
Endpoint for secondary objective 1 – 
deleted enrolled to describe children 
Correct mistake 
 Parent/caregiver 
Inclusion Criteria 
 Changed 18 years old to age of 
majority, as defined by the state of 
residency 
  
Initial Recruitment 
Methods 
Adding “In-person” recruitment 
This type of recruitment is possible only for 
those sites for which the research team is part 
of the clinic. 
Initial Recruitment 
Methods 
Adding opt-in letter 
Opt-out letter will function also as an opt-out 
letter 
User Acceptance Pilot 
Testing 
Added approximately to demographic 
goals 
Allow flexibility with app pilot testing 
Screening Procedures 
and Screening Failures 
Adding a sentence 
To specify that the data collected during 
screening procedure will be recorded by the 
research staff in the EDC and that data 
collection will be done before consent 
Informed Consent 
Adding language 
To request full waiver of assent for children 
eligible to be in the study. 
Informed Consent 
Process 
Adding language 
To specify that in-person consent can be done 
only by enrolling sites research staff members 
and not by clinical stuff. 
Informed Consent 
Process 
Adding language 
To specify how the consent process will be 
documented. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 3 of 73 
Sample Size 
Determination 
Minor changes 
To reply requests of DSMB 
 
Changes from Version 04 to Version 05 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
1.3.1 & 1.3.2 
Updated study-level and participant-level 
schedule of activities 
Add extra time to collect COVID-19 vaccine 
information 
7.5.2 
1st paragraph; 3rd sentence: Replaced 
enrollment site with participating clinic and 
DCOC with enrolling site 
Correct error 
7.5.3 
Removed that DCOC will send the 
caregiver the links to the Baseline, 
Midpoint, and Post assessments. 
Removed the Midpoint assessment will 
collect updated contact information. 
Changed that the enrolling site will 
schedule a video conference instead of the 
participant contacting the enrolling site to 
schedule this.   
Correct error 
9.2 
Deleted week 6 from lost to follow-up 
definition. 
Removed that the survey links will be 
emailed and changed contacted to notified 
Allow more flexibility 
12.1.6 & 12.1.7 
Clarified enrolling sites will be monitored; 
added site close-out visit; replaced site 
performance plan with site monitoring 
plan 
Correct error 
 
Changes from Version 05 to Version 06 
Affected Section(s) 
Summary of Revisions Made 
Rationale 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 4 of 73 
1 
Updated study intervention and duration 
in Synopsis, Schema, and SOAs 
 
FDA & CDC ACIP EUA approval for Pfizer 
COVID-19 vaccine in children 6 months to 4 
years. The Pfizer vaccine for this age group 
requires 3 shots for complete vaccination 
series. 
2.2 
Update age ranges for COVID-19 vaccine  
Throughout 
Included ACIP with CDC recommendations 
ACIP recommendations sometimes differ from 
FDA approvals. Since this is a pediatric study, 
the study team will use the CDC/ACIP 
recommendations. 
4 & 11.4.2  
Updated definition of complete COVID-19 
vaccination series 
FDA & CDC ACIP EUA approval for Pfizer 
COVID-19 vaccine in children 6 months to 4 
years. The Pfizer vaccine for this age group 
requires 3 shots for complete vaccination 
series.  
4 
Update name of survey in Secondary 
Objective 2 to week 16 survey 
Study design change due to FDA & CDC ACIP 
EUA approval for Pfizer COVID-19 vaccine in 
children 6 months to 4 years. The Pfizer 
vaccine for this age group requires 3 shots for 
complete vaccination series. 
5.2 
Update figure 6 to include 8 weekly push 
notifications and 2 monthly 
5.3 
Updated time participant will be in the 
study. 
6.1.1 
Changed amount of time mobile device 
must be able to run the app from 12 
weeks to 24 weeks 
6.3 
Added sentence that participants may 
contact App Team if they lose their phone 
or change operating system. 
Since study timeline is extended, there is an 
increased risk that participants may lose or 
change devices.  
7.2 
Increased participant remuneration from 
$60 to $80 to compensate participants for 
additional survey. 
Updated when push notifications will be 
sent.  
Updated when coordinators will contact 
participants about assessments  
Study design change due to FDA & CDC ACIP 
EUA approval for Pfizer COVID-19 vaccine in 
children 6 months to 4 years. The Pfizer 
vaccine for this age group requires 3 shots for 
complete vaccination series. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 5 of 73 
7.5.3 
Added subheadings 
Changed Midpoint Assessment to Week 8 
Assessment 
Changed Post Assessment to Week 16 
Assessment. Deleted bullets and refer to 
Table 1.  
Added Week 24 Assessment 
Updated Table 1 to be consistent with text 
Clarify subsection 
 
Study design change due to FDA & CDC ACIP 
EUA approval for Pfizer COVID-19 vaccine in 
children 6 months to 4 years. The Pfizer 
vaccine for this age group requires 3 shots for 
complete vaccination series. 
8.1.2 – 8.1.3 
Describe changes in push notifications and 
changes to vignettes.  
Study design change due to FDA & CDC ACIP 
EUA approval for Pfizer COVID-19 vaccine in 
children 6 months to 4 years. The Pfizer 
vaccine for this age group requires 3 shots for 
complete vaccination series. 
8.4 
Changed compliance matric from 
interaction from push notifications to 
participants allowing receipt of 
notifications 
Study design change due to FDA & CDC ACIP 
EUA approval for Pfizer COVID-19 vaccine in 
children 6 months to 4 years. The Pfizer 
vaccine for this age group requires 3 shots for 
complete vaccination series. 
Throughout 
Correction of typos or clarification of text Correct error/Clarify text 
9.2 
Deleted specific week from lost to follow-
up definition 
Allow a more flexible definition 
10.1, 11.4.2, 11.4.3 
Updated efficacy assessment procedures 
and analysis of endpoints 
Study design change due to FDA & CDC ACIP 
EUA approval for Pfizer COVID-19 vaccine in 
children 6 months to 4 years. The Pfizer 
vaccine for this age group requires 3 shots for 
complete vaccination series. 
12.1.4 
Added Medical Monitor information 
Medical Monitor added to the study 
12.1.7.1 
Deleted 5% from first paragraph 
Correction to provide more flexibility 
 
Changes from Version 06 to Version 07 
Affected Section(s) 
Summary of Revisions Made 
Rationale 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 6 of 73 
7.5.2 
Remove Nebraska App Team and use a 
more generic term as Research Team 
Correction to provide more flexibility 
7.2 
Remove Nebraska App Team and use a 
more generic term as Research Team 
Correction to provide more flexibility 
 
Changes from Version 07 to Version 08 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
7.1 
Correction of typos 
Correct error 
7.1.1 
Moved section related to “In person 
recruitment” 
Clarification of text 
To include details about methods used 
by the research team to send to 
participants the Opt-Out/Opt-In Letter 
and ICF+HIPAA 
To improve section 
 
Clarify text 
To add details 
7.4.1 
Add specific modality to record research 
staff’s signature in the ICF+HIPAA and 
Process Note 
Correction to provide more flexibility 
 
7.5.2 
Change language about how the 
research team will send the instruction 
for the app. 
Added language 
Correction to provide more flexibility 
 
Correction to provide more flexibility 
9.2 
Changed word from call to contact 
Correction to provide more flexibility 
 
Changes from Version 08 to Version 09 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
1.1 
Extended the overall study duration 
from 21 to 24 months. The enrollment 
period was extended from 6 to 8 
months. The final participants’ 
Due to slower recruitment than expected, the 
study duration has been extended.  

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 7 of 73 
completion was extended from 6 
months to 7 months. 
1.3.1 
Table with study-level activities was 
updated. 
To reflect the extended study duration. 
7.1 
Minor edits 
To clarify text 
 
Changes from Version 09 to Version 10 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
1.1 
Updated participant duration  
Reflect extended duration of vaccine status 
follow-up 
1.2 
Corrected dates without push 
notifications. Updated vaccine 
verification status 
Correction and reflect extended vaccine 
verification period 
1.3.1 
Updated all activities after participant 
recruitment. Added 3 months to study 
timeline.  
Reflect extended periods because of extended 
participant activities to include week 24 
survey and extended vaccine verification 
period.   
1.3.2 
Extended vaccine status follow-up 
period 
Reflect change that period lasts until week 29 
5.3 
Extended vaccine status follow-up 
period 
Reflect change that period lasts until week 29 
10.1 
Changed secondary endpoint #1 from 16 
weeks to 24 weeks 
Correction 
 
 
 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 8 of 73 
Table of Contents 
Abbreviations & Definitions ................................................................................................................................................ 12 
Statement of Compliance ................................................................................................................................................... 14 
1. 
Protocol Summary ...................................................................................................................................................... 14 
1.1 
Synopsis ............................................................................................................................................................ 14 
1.2 
Schema.............................................................................................................................................................. 16 
1.3 
Schedule of Activities (SoA) ................................................................................................................................ 17 
1.3.1 
Study-Level Activities ................................................................................................................................. 17 
1.3.2 
Participant-Level Activities......................................................................................................................... 18 
2. 
Introduction ............................................................................................................................................................... 19 
2.1 
Study Rationale.................................................................................................................................................. 19 
2.2 
Background ....................................................................................................................................................... 19 
2.3 
Guiding Conceptual Framework: The Health Belief Model .................................................................................. 23 
2.4 
Evidence of Capability: The Children’s COVID-19 Student Symptom Checker and mHealth Software Platform..... 25 
3. 
Risk/Benefit Assessment ............................................................................................................................................. 29 
3.1 
Known Potential Risks ........................................................................................................................................ 29 
3.2 
Known Potential Benefits ................................................................................................................................... 29 
3.3 
Assessment of Potential Risks and Benefits ........................................................................................................ 29 
4. 
Objectives and Endpoints ............................................................................................................................................ 30 
5. 
Study Design ............................................................................................................................................................... 31 
5.1 
Overall Design ................................................................................................................................................... 31 
5.2 
Scientific Rationale for Study Design .................................................................................................................. 31 
5.3 
End of Study Definition ...................................................................................................................................... 33 
6. 
Study Population ........................................................................................................................................................ 33 
6.1 
Inclusion Criteria ................................................................................................................................................ 33 
6.1.1 
Participants ............................................................................................................................................... 33 
6.1.2 
Sites .......................................................................................................................................................... 34 
6.2 
Exclusion Criteria ............................................................................................................................................... 34 
6.2.1 
Participants ............................................................................................................................................... 34 
6.3 
Lifestyle Considerations ..................................................................................................................................... 35 
7. 
Recruitment, Retention, Consent, SCREENING, & AssessmentS ................................................................................... 35 
7.1 
Recruitment ...................................................................................................................................................... 35 
7.1.1 
Initial Recruitment Methods ...................................................................................................................... 36 
7.1.2 
Recruitment Standardization ..................................................................................................................... 37 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 9 of 73 
7.2 
Retention .......................................................................................................................................................... 38 
7.3 
Screen Failures and Rescreens ........................................................................................................................... 39 
7.3.1 
Screening Procedures and screen failures .................................................................................................. 39 
7.3.2 
Rescreens .................................................................................................................................................. 39 
7.4 
Informed Consent .............................................................................................................................................. 39 
7.4.1 
Informed Consent Process ......................................................................................................................... 40 
7.4.2 
In-person Consent ..................................................................................................................................... 40 
7.5 
Assessments ...................................................................................................................................................... 41 
7.5.1 
Enrollment ................................................................................................................................................ 41 
7.5.2 
APP Registration and Usage (Adherence) ................................................................................................... 41 
7.5.3 
Baseline and Follow-Up Assessments (Week 8, 16, 24)............................................................................... 41 
8. 
Study Intervention ...................................................................................................................................................... 44 
8.1 
Software, Functionality, and Content of the Intervention ................................................................................... 44 
8.1.1 
App Software ............................................................................................................................................ 44 
8.1.2 
Control (General Health app) ..................................................................................................................... 45 
8.1.3 
Intervention exposure (Vaccine Uptake App) ............................................................................................. 45 
8.1.4 
Communication Addressing Vaccine Hesitancy in the Vaccine Uptake App ................................................. 46 
8.2 
Preparation/Handling/Storage/Accountability.................................................................................................... 51 
8.2.1 
Acquisition and accountability ................................................................................................................... 51 
8.2.2 
Appearance, Packaging, and Labeling ........................................................................................................ 51 
8.3 
Measures to Minimize Bias: Randomization ....................................................................................................... 51 
8.4 
Study Intervention Compliance .......................................................................................................................... 51 
9. 
Study Intervention Discontinuation and Participant Discontinuation/Withdrawal ........................................................ 52 
9.0 
Discontinuation of Study Intervention ................................................................................................................ 52 
9.1 
Participant Discontinuation/Withdrawal from the Study .................................................................................... 52 
9.2 
Lost to Follow-Up............................................................................................................................................... 52 
10. Study Assessments and Procedures............................................................................................................................. 52 
10.1 
Efficacy Assessments ......................................................................................................................................... 52 
10.2 
Safety and Other Assessments ........................................................................................................................... 53 
10.3 
Adverse Events and Serious Adverse Events ....................................................................................................... 53 
10.3.1 
Definition of Adverse Events (AE) .............................................................................................................. 53 
10.3.2 
Definition of Serious Adverse Events (SAE) ................................................................................................. 53 
10.3.3 
Classification of an Adverse Event .............................................................................................................. 54 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 10 of 73 
10.3.4 
Time Period and Frequency for Event Assessment and Follow-Up .............................................................. 54 
10.3.5 
Adverse Event Reporting ........................................................................................................................... 55 
10.3.6 
Serious Adverse Event Reporting ............................................................................................................... 56 
10.3.7 
Reporting Events to Participants ................................................................................................................ 56 
10.4 
Unanticipated Problems .................................................................................................................................... 57 
10.4.1 
Definition of Unanticipated Problems (UP) ................................................................................................ 57 
10.4.2 
Unanticipated Problem Reporting.............................................................................................................. 57 
10.4.3 
Reporting Unanticipated Problems to Participants ..................................................................................... 57 
11. Statistical Considerations ............................................................................................................................................ 58 
11.1 
Statistical Hypotheses ........................................................................................................................................ 58 
11.2 
Sample Size Determination ................................................................................................................................ 58 
11.3 
Populations for Analyses .................................................................................................................................... 59 
11.4 
Statistical Analyses ............................................................................................................................................ 60 
11.4.1 
General Approach ..................................................................................................................................... 60 
11.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................................................... 60 
11.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................................................... 61 
11.4.4 
Safety Analyses ......................................................................................................................................... 61 
11.4.5 
Baseline Descriptive Statistics .................................................................................................................... 61 
11.4.6 
Planned Interim Analyses .......................................................................................................................... 61 
11.4.7 
Sub-Group Analyses .................................................................................................................................. 61 
11.4.8 
Sensitivity Analyses ................................................................................................................................... 62 
11.4.9 
Tabulation of Individual Participant Data ................................................................................................... 62 
11.4.10 
Exploratory Analyses ................................................................................................................................. 62 
12. Supporting Documentation and Operational Considerations ....................................................................................... 62 
12.1 
Regulatory, Ethical, and Study Oversight Considerations .................................................................................... 62 
12.1.1 
Study Discontinuation and Closure ............................................................................................................ 62 
12.1.2 
Confidentiality and Privacy ........................................................................................................................ 63 
12.1.3 
Future Use of Stored Specimens and Data ................................................................................................. 63 
12.1.4 
Key Roles and Study Governance ............................................................................................................... 64 
12.1.5 
Safety Oversight ........................................................................................................................................ 65 
12.1.6 
Clinical Monitoring .................................................................................................................................... 65 
12.1.7 
Quality Assurance and Quality Control ....................................................................................................... 66 
12.1.8 
Data Handling and Record Keeping ............................................................................................................ 67 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 11 of 73 
12.1.9 
Protocol Deviations ................................................................................................................................... 68 
12.1.10 
Publication and Data Sharing Policy ........................................................................................................... 68 
12.1.11 
Conflict of Interest Policy ........................................................................................................................... 68 
12.2 
Additional Considerations .................................................................................................................................. 69 
13. References.................................................................................................................................................................. 70 
 
 
 
 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 12 of 73 
ABBREVIATIONS & DEFINITIONS 
Enrolling site – The institution where participants will be screened and consented to participate in the MoVeUP 
App study. In most cases, this will be the ISPCTN site. 
Participating clinic – The institution that the enrolling site works with to gather potential participants to screen 
and consent. (e.g., The institution from where the enrolling sites gets its list of potential participants for 
consecutive recruitment.) 
Participants – parent/caregiver is the participant. The child’s only participation is medical record review, and 
that all references to “the participant” apply to the parent/caregiver. 
 
AAP 
American Academy of Pediatrics 
ACIP 
 
Advisory Committee on Immunization Practices 
AE 
Adverse Event 
App 
Application 
CAPA 
Corrective And Preventative Action 
CDC 
Center for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
cIRB 
Central Institutional Review Board 
COVID-19 
Coronavirus Disease 2019 
CRF 
Case Report Form 
DCOC 
Data Coordinating and Operations Center 
DSMB 
Data Safety Monitoring Board 
DSMP 
Data Safety Monitoring Plan 
ECHO 
Environmental influences on Child Health Outcomes 
EDC 
Electronic Data Capture System 
EUA 
Emergency Use Authorization 
FDA 
Food and Drug Administration 
GCDMP 
Good Clinical Data Management Practices 
GCP 
Good Clinical Practice 
HBM 
Health Belief Model 
HIPAA 
Health Insurance Portability and Accountability Act 
HPV 
Human Papillomavirus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 13 of 73 
ISPCTN 
IdeA States Pediatric Clinical Trials Network 
ITT 
Intention-To-Treat 
mHealth 
Mobile Health 
MIS-C 
Multisystem Inflammatory Syndrome in Children 
mITT 
Modified ITT 
MMR 
Measles, Mumps, and Rubella 
MOP 
Manual of Procedures 
NCT 
National Clinical Trial 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PP 
Per-Protocol 
PROS 
Pediatric Research in Outpatient Settings 
QA 
Quality Assurance 
QC 
Quality Control 
QR 
Quick Response 
RUCA 
Rural Urban Community Area 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMART IRB 
Streamlined, Multisite, Accelerated Resources for Trials IRB 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
SUS 
System Usability Scale 
UAMS 
University of Arkansas for Medical Sciences 
UP 
Unanticipated Problem 
UPIRTSO 
Unanticipated Problems Involving Risks To Subjects Or Others 
UNMC 
University of Nebraska Medical Center 
US 
United States 
 
 
 
 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 14 of 73 
 
 
STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation Good Clinical Practice 
(ICH GCP) and the following: United States (US) Code of Federal Regulations (CFR) applicable to clinical studies 
(45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812). 
 National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible for the 
conduct, management, or oversight of NIH-funded clinical trials have completed Human Subjects Protection and 
ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be submitted to 
the Institutional Review Board (IRB) for review and approval.  Approval of both the protocol and the consent 
form must be obtained before any participant is enrolled.  Any amendment to the protocol will require review 
and approval by the IRB before the changes are implemented to the study.  In addition, all changes to the 
consent form will be IRB-approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
1. 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
Title: 
Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, 
controlled trial  
Study 
Description: 
Site-level block-randomized trial 
Objectives: 
Primary Objective: 
Determine the effect of a parent-facing, vaccination decision-
making mobile health (mHealth) tool on children’s COVID-19 
vaccine series completion 
Secondary Objective 1: 
Determine the effect of a parent-facing, vaccination decision-
making mHealth tool on children’s COVID-19 vaccine series 
initiation  
Secondary Objective 2: 
Determine the effect of a parent-facing, vaccination decision-
making mHealth tool on parental attitude toward pediatric 
COVID-19 vaccination 
Endpoints: 
Primary Endpoint: 
Proportion of children who complete COVID-19 vaccination, as 
verified in state, clinic, or participant-held records  

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 15 of 73 
Secondary Endpoint 1: 
Proportion of children who receive ≥1 dose of the COVID-19 
vaccination series, as verified in state, clinic, or participant-held 
records 
Secondary Endpoint 2: 
Change in enrolled parent/caregiver domain scores from 
baseline to immediately post-intervention on the modified WHO 
SAGE Vaccine Hesitancy Scale adapted for the COVID-19 Vaccine 
Study Population: Custodial parents/caregivers with ≥1 child eligible for COVID-19 vaccination who has not yet 
received the vaccine at the time of study enrollment.   
Phase: 
 N/A 
Description of 
Sites/Facilities 
Enrolling 
Participants: 
Enrolling sites will recruit participants. These sites will collaborate with outpatient practices 
within ECHO ISPCTN states that provide primary care services to children (<18 years old). 
Sites will serve a population base of at least 40% Medicaid/uninsured children, <60% non-
Hispanic White children, or >40% of families residing in rural communities. Sites are 
encouraged, but not required, to have a high Spanish-speaking population. 
Description of 
Study 
Intervention: 
• 
Vaccine Uptake App: 24-week (8 weeks with weekly push notifications; 2 monthly 
push notifications for 2 months [1 notification per month]; 8 weeks without) exposure 
to a mobile phone application (app) designed to improve parental knowledge, 
attitudes, and self-efficacy regarding pediatric COVID-19 vaccination. The app will 
address logistical and motivational barriers to pediatric COVID-19 vaccination. 
Participants will also receive eight weekly nudges (cues to action) regarding 
vaccinating their child that will be sent to participants via push notifications to their 
mobile devices. Through branching logic, users will access content tailored to their 
COVID-19 vaccine knowledge and confidence gaps, locality, degree of rurality-
urbanicity, primary language (English/Spanish), race/ethnicity, and child’s age.  
• 
General Health App: 24-week (8 weeks with weekly push notifications; 2 monthly 
push notifications for 2 months [1 notification per month]; 8 weeks without) exposure 
to a mobile phone app designed to provide information on general pediatric health 
and infection prevention and mitigation strategies based on recommendations from 
the American Academy of Pediatrics (AAP) and the Centers for Disease Control and 
Prevention (CDC). Nudges regarding these topics will be sent to participants via push 
notifications to their mobile devices. 
Study Duration: 
24 months (6 months study start-up; up to 8 months rolling enrollment; 7 months final 
participants’ completion; 3 months analysis) 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 16 of 73 
Participant 
Duration: 
28 weeks (8 weeks with weekly push notifications; 2 monthly push notifications for 2 months 
[1 notification per month]; 8 weeks without notifications; 4 weeks participant vaccine status 
follow-up) 
1.2 
SCHEMA 
 
 
 
Figure 1. Schema of study intervention 
 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 17 of 73 
1.3 
SCHEDULE OF ACTIVITIES (SOA) 
1.3.1 
STUDY-LEVEL ACTIVITIES 
  
 
*Recruitment ends at the end of study week 31. 
Study-Level Activities
Weeks  
-12- -9 
(M -3)
Weeks   
-8 - -5   
(M -2)
Weeks     
-4 - -1   
(M -1)
Weeks     
1-4        
(M 1)
Weeks    
5-8 (M 2)
Weeks     
9-12      
(M 3)
Weeks    
13-16    
(M 4)
Weeks   
17-20   
(M 5)
Weeks    
21-24   
(M 6)
Weeks   
25-28   
(M 7)
Weeks   
29-32   
(M 8)
Weeks   
33-36    
(M 9)
Weeks   
37-40   
(M 10)
Weeks   
41-44   
(M 11)
Weeks   
45-48   
(M 12)
Weeks   
49-52   
(M 13)
Weeks     
53-56    
(M 14)
Weeks     
57-60   
(M 15)
Weeks    
61-64      
(M 16)
Weeks   
65-68     
(M 17)
Weeks    
69-72    
(M 18)
App usability testing
Site preparation 
Participant recruitment 
enrollment/consent 
(rolling)
*
Participant assessments 
& follow-up 
Participant 
renumeration 
App push notifications
Participant app usage 
tracking
Participant vaccine 
status follow-up
Analysis & write-up
Study Months

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
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1.3.2 
PARTICIPANT-LEVEL ACTIVITIES 
Participant Activities               
Coordinator Conducted
W 1
W 15 W 16 W 17 W 18 W 19 W 20 W 21 W 22 W 23 W 24 W 25 W 26 W 27 W 28 W 29
Recruit
Enroll/consent
Randomize
Incomplete assessment follow-up
Participant renumeration 
Vaccine status follow-up
mHealth Tool Conducted
Registration
Push Notifications
Tool use recorded
Participant Conducted Assessments
Baseline
Week 8
Week 16
Week 24
W 11
W 2
W 3
W 4
W 12 W 13 W 14
W 5
W 6
W 7
W 8
W 9
W 10

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
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2. 
INTRODUCTION 
2.1 
STUDY RATIONALE 
The research objective of the current proposal is to determine the effectiveness of a vaccine communication 
mHealth app on parental decisions to vaccinate their children against coronavirus disease 2019 (COVID-19). The 
COVID-19 pandemic inflicts disproportionate harm on individuals from underserved communities, including 
those in rural settings. Maximizing vaccine uptake in these communities will decrease infection rates, severe 
illness, and death. Given that most US families from rural communities use smart phones (80% overall, 76% of 
families earning <$30,000/year) and have home internet (72% overall, 57% of families earning <$30,000/year),1 
mHealth interventions hold the promise of broad uptake to these populations. Bundling multiple proven 
mHealth vaccine-uptake interventions into a single app may maximize the impact of deploying such a tool to 
increase COVID-19 vaccination. The new knowledge gained from the completion of this study will directly inform 
future efforts to increase COVID-19 vaccination rates across diverse settings and provide an evidentiary base for 
app-based vaccine communication tools that can be adapted to future vaccine-deployment efforts. 
2.2 
BACKGROUND 
Introduction 
COVID-19 vaccines demonstrate excellent effectiveness (50-90%) against infection and symptomatic disease, 
and more importantly, almost 100% protection from severe disease and death,2,3 including from newer 
circulating variants. However, nearly 3 in 10 Americans state they probably or definitely will not get vaccinated, 
and many IdeA states have higher rates of COVID-19 vaccine refusal.4 Moreover, individuals from Black and 
Hispanic communities express higher vaccine hesitancy, despite experiencing significantly worse disease burden 
and mortality.5-8 The NIH has identified these vulnerable populations, as well as individuals from rural, medically 
underserved, and migrant communities, as high priorities for vaccination and vaccine communication efforts.9 
Key goals of vaccine communication highlighted by the NIH include: (1) providing assurance of vaccine safety; (2) 
highlighting collective and individual benefits to vaccination; (3) explaining the vaccine development and 
approval process; (4) addressing vaccine hesitancy; and (5) monitoring and countering misinformation. These 
communication objectives require tailoring to specific target audiences to be effective and must, therefore: (1) 
leverage close community partnerships to identify relevant information needs and cultural context; and (2) 
employ scalable and impactful communication strategies that encourage vaccination across diverse segments of 
the population. The proposal will also leverage the previous work of the study team and resources developed by 
the NIH Community Engagement Alliance (CEAL).10 
COVID-19 Vaccines for Children 
From December 11 through May 10, 2021, the US Food and Drug Administration (FDA) expanded the emergency 
use authorization (EUA) of the COVID-19 vaccine for individuals and adolescents as young as 12 years of age. 
Currently, the Pfizer BioNTech COVID-19 vaccine is the only vaccine authorized by the FDA for use in children in 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 20 of 73 
ages 6 months and older, which includes 2- and 3-dose series for some age groups and vaccine formulations..11 
SARS-CoV-2, the virus that causes COVID-19 disease, has infected more than 3 million children and killed more 
than 300 children. High COVID-19 vaccination coverage among children is critical to lessen the public health 
burden on children’s physical, mental, and social health.12,13 
Parents/caregivers vary in their confidence/hesitancy to vaccinate their children against SARS-CoV-2.14 
While there is a good amount of literature on adults and vaccine hesitancy, there is much less information about 
children. A recent nationally representative study of parents’ intentions and perceptions of COVID-19 
vaccination was published by Szilagyi et al.14 The survey covered February 17 to March 30, 2021. In that survey, 
a parent’s race and ethnicity were associated with the likelihood of their child getting vaccinated with 44% of 
parents who were White and 47% of parents who were Black answering somewhat or very unlikely to vaccinate 
their child versus 42% overall and 36% of parents who were Hispanic and 35% of Asian American. Age of parent 
and of their child were associated with younger ages being more likely to answer somewhat or very unlikely to 
vaccinate their child. The most trusted source of information about the COVID-19 vaccine was the child’s doctor, 
with 72% of parents indicating that they completely or mostly trust their child’s doctor. Interestingly, 50% 
indicated trust in the CDC and 48% in the AAP. No other source of information approached 50%. When these 
results were analyzed controlling for parent and child factors, parent perceptions, child receipt of influenza 
vaccine and parental receipt of COVID-19 vaccine, trust in the child’s doctor remained significant while other 
parent and child factors, including child’s age and race/ethnicity were no longer significant predictors of 
indicating very likely or likely to get a vaccine for their child. It is worth noting that, among adults, intent to 
vaccinate has changed and gotten more positive over time.14, 15 
Vaccine Hesitancy is Higher in Rural Communities and ISPCTN States, which are an Ideal Setting for Testing the 
Effectiveness of an mHealth Vaccine Uptake App 
The Environmental influences on Child Health Outcomes IdeA States Pediatric Clinical Trials Network (ECHO 
ISPCTN) includes 18 states from geographically diverse areas of the US.16 Unfortunately, most ISPCTN states 
report lower than average rates of COVID-19 vaccine uptake, as shown in Figure 2. Many ECHO ISPCTN states 
have a disproportionately high number of rural residents compared with non-ISPCTN states, and COVID-19 
vaccine hesitancy—and vaccine coverage rates—lag significantly in rural communities across the US when 
compared to their non-rural counterparts17; only 39% of rural Americans are vaccinated versus 46% of urban 
Americans. Community feedback from ECHO ISPCTN sites highlights significant vaccine hesitancy and barriers to 
COVID-19 vaccination. For example, community advisory board feedback from stakeholders in rural Nebraska 
emphasizes that access to COVID-19 vaccine among eligible children and their families, particularly those with 
low English fluency, is very low. Additionally, there is significant concern from community members regarding 
the safety of COVID-19 vaccines. In Mississippi, surveys of rural families across diverse racial and ethnic 
backgrounds demonstrate very high levels of COVID-19 vaccine hesitancy, and in some higher-risk groups such 
as rural Black families, 40% or more of respondents may be vaccine hesitant. Hesitancy among rural Black 
individuals in Mississippi aligns with findings of lower vaccine uptake nationally. Overall, 32% of Black Americans 
are vaccinated against COVID-19 versus 45% of White Americans.18  

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 21 of 73 
Based on these findings, further focus group data on COVID-19 vaccine motivators, barriers, and sources of 
hesitancy are being obtained by ECHO ISPCTN sites to identify targets for intervention, especially among Black 
and Hispanic parents from both rural and non-rural areas as well as rural White parents. The study team will use 
this information for customizing the mHealth Vaccine Uptake app, as outlined in Section 8 below. We expect the 
data from this qualitative study to be available well in advance of the start of this randomized control trial. 
Finally, the ISPCTN has established a strong record of clinical trials conduct in behavioral, clinical, and 
telemedicine-based interventions. Most relevant to this protocol, the iAmHealthy feasibility trial, whose co-
Principal Investigator (PI) is a co-investigator on the current protocol, enrolled rural children and parents into a 
24-week telemedicine-based behavioral health intervention, achieved goal enrollment of 104 parent-child dyads 
and retention rates >85% over the study period. Thus, conducting vaccine communication research within the 
ISPCTN provides a unique opportunity to determine the effectiveness of interventions in states and communities 
experiencing disproportionately low COVID-19 vaccine uptake while building upon a strong record of 
accomplishment for successfully fielding technology-based behavioral intervention trials. 
 
 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 22 of 73 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2a. Percentage of COVID vaccine initiation by state (ECHO ISPCTN sites outlined in black). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2b. COVID-19 vaccine completion rates by state (ECHO ISPCTN sites outlined in black). 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 23 of 73 
2.3 
GUIDING CONCEPTUAL FRAMEWORK: THE HEALTH BELIEF MODEL 
Many factors contribute to an individual’s decision to engage in a health promotion or disease prevention 
activity. The Health Belief Model (HBM), first developed in the early 1950s, provides an organizing framework to 
understand people’s health behavior decisions.19 The HBM relies on the assumption that individuals’ health 
decisions stem from a desire to avoid and/or recover from illness and an individual’s belief that they can take 
specific actions to prevent, cure, or reduce the severity of illness. The HBM has been used to assess vaccine 
hesitancy for other vaccines, including influenza and human papillomavirus (HPV) vaccines.20,21 Specific 
components of the HBM are summarized in Figure 3.  
The HBM provides an 
organizational framework 
for understanding the 
considerations of parents 
and caregivers in deciding 
whether to vaccinate their 
children against COVID-19. 
HBM constructs as applied 
to parental COVID-19 
vaccine decision making 
include: 
1. Perceived susceptibility 
of their children being 
infected with SARS-CoV-2. 
2. Perceived severity of COVID-19 disease or multisystem inflammatory syndrome in children (MIS-C) in their 
children.  
3. Perceived benefits that their children may experience from receiving a COVID-19 vaccine. 
4. Perceived barriers (both attitudinal and logistic) that parents/caregivers may have to obtaining COVID-19 
vaccination for their children. 
5. Cues to action (personal stories/vignettes, advice, and prompts received from others, including social 
norms) to trigger a parent/caregiver to vaccinate their children against COVID-19. 
6. Self-efficacy or belief in one’s own capacity to complete the steps necessary to vaccinate their children 
against COVID-19 (e.g., identifying a vaccination site, scheduling an appointment, arranging transportation, 
being able to pay, etc.). 
Other individual and community-level factors may influence the above elements, including race, ethnicity, and 
education level, among others. mHealth vaccine communication apps can address multiple domains of the 
Health Belief Model simultaneously and hold the potential for customization to incorporate relevant 
Figure 3. Health Belief Model components. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 24 of 73 
community, cultural, and/or individual factors,22 which should improve the effectiveness of the app to increase 
COVID-19 vaccination rates among app users.  
mHealth Tools Can Increase Vaccine Confidence and Vaccination Rates  
mHealth tools such as mobile apps and decision support tools demonstrate the potential to positively affect 
vaccination rates.23-26 In an Italian study of a smartphone app to increase parents’ knowledge and empowerment 
when deciding to vaccinate their child against measles, mumps, and rubella (MMR), use of the smartphone app 
increased parental knowledge and confidence in choosing MMR vaccination and increased parental reported 
intention to vaccinate. However, actual immunization actions taken after the intervention period were not 
measured. Similarly, in a cluster-randomized trial of a web-based decision aid for informing parental decision-
making about MMR vaccination, the web-based tool, when compared to a leaflet intervention, was associated 
with lower parental-reported decisional conflict and higher vaccination rates among parents deciding whether 
to give the first dose of MMR vaccine to their child. A follow-up study of the web-based tool also found it more 
cost-effective than traditional approaches.  
Cues to action, which can include behavioral nudges, are a proven effective means of increasing vaccine uptake 
in various settings.27,28 Text messages and voice phone calls can serve as effective prompts to action, and such 
prompts maximize their impact when they include customized information relevant to the individual recipient. 
In a large field experiment conducted in the US, text message nudges alone increased flu vaccination rates 
among 49,000 participants by 5%. Nudges were most effective when they were phrased as there being a vaccine 
reserved for a participant’s child and when they used language that would be expected to come from their 
healthcare provider.  
Narrative messaging and vignettes can also serve as prompts to action. Narrative messaging can present 
information to users in a culturally congruent context and has been shown to increase vaccination rates, 
particularly in HPV vaccination.29,30 A systematic review of educational interventions for increasing HPV 
vaccination identified two interventional trials that evaluated the impact of narrative stories on vaccination 
outcomes at up to 2 months. In one study, adolescent participants who viewed narrative videos featuring peers 
and experts were twice as likely to be vaccinated as those viewing other message formats.31  
Tailored messaging, including culturally congruent storytelling, can provide information to users in a less 
threatening and more relatable format by using likable characters with similarities to the end-user. Such 
messaging can engender an emotional connection, which may help persuade individuals to engage in 
recommended health behaviors.32 Another example of using narrative interventions to promote vaccine uptake 
is the CANImmunize app, originally piloted as ImmunizeCA.24,33 The CANImmunize app, used in Canada to assist 
in tracking of vaccination status and to deliver information on vaccines to users, includes video education and 
personal endorsements for vaccines, combined with push notifications, medical records keeping, and self-
directed learning to increase vaccination uptake. Initial reports suggest high usage of the tool, including 
narrative elements, but controlled trials of the CANImmunize app on vaccination rates are lacking. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 25 of 73 
In summary, prior research highlights the potential impact of several mHealth interventions to increase vaccine 
acceptance and uptake. However, findings from these studies may not be directly applicable to COVID-19 
vaccination. Prior mHealth-based interventional and large-scale clinical trials assessing the effectiveness of 
mHealth vaccine-uptake tools are generally lacking. Given that national efforts to use mHealth tools to increase 
vaccine uptake have been deployed in other countries,33 establishing an evidentiary base for their effectiveness 
may have major public health program development and implementation implications. Additionally, prior 
interventions focus on vaccines that had been licensed through the standard FDA approval process following 10 
to 15 years of research and development. By contrast, COVID-19 vaccines are only available to some US age 
groups under FDA EUA to facilitate the availability of unapproved medical treatments during public health 
emergencies. EUA for the first COVID-19 vaccines came after an unprecedented 1 year of development and 
testing. Multiple surveys demonstrate that the newness of these vaccines raises safety concerns for many 
individuals. Finally, many mHealth interventions lack customization for specific community- and/or individual-
level factors that may influence vaccine decision-making, such as race, ethnicity, or geography (such as rurality). 
Our mHealth Vaccine Uptake app uniquely combines several proven effective methods for increasing 
vaccination rates with user customization to increase pediatric COVID-19 vaccination rates across diverse 
settings. 
 
 
2.4 
EVIDENCE OF CAPABILITY: THE CHILDREN’S COVID-19 STUDENT SYMPTOM CHECKER AND 
MHEALTH SOFTWARE PLATFORM 
The co-Pis of this protocol have extensive experience developing and deploying customizable mHealth clinical 
decision support apps for healthcare providers. These apps have been used by >50,000 users and incorporate 
user analytics that enable assessment of engagement with the app.34-36 We have also created customizable 
mHealth apps for COVID-19 infection response decision-making for parents (COVID-19 Student Symptom 
Checker) that, in partnership with community stakeholders and school districts, have been translated into 
multiple languages, including Spanish and Nepali (Figure 4).  

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 26 of 73 
These apps were built using software 
and data infrastructure developed at 
and owned by the University of 
Nebraska Medical Center (UNMC). The 
important functionalities of the 
previous two apps that will also be 
deployed for the Vaccine Uptake app 
in the current protocol are:  
1. Customization at both the local 
institution and individual user 
levels for an experience that is 
uniquely tailored to each user’s 
local context and personal 
background. 
2. A development environment that 
enables content viewing in multiple languages. 
3. A content management interface that enables rapid content modification and updates. 
4. Push notifications to participants to trigger app usage. 
5. Back-end analytics to measure user interactions with app components.  
Further details of the functionality of our mHealth tool are outlined in Section 8 below.  
 
Figure 4. Screenshot of the Children’s COVID-19 Student Symptom 
Checker. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 27 of 73 
Preliminary data since release of the COVID-19 
Student Symptom Checker app in August 2020 
shows that these tools demonstrate broad 
uptake and use across diverse racial and 
ethnic backgrounds, with more than 85% of 
eligible households having registered for the 
tool. The median weekly number of students 
screened by the app was 7,000 (Figures 5a & 
b). User feedback demonstrated that parents 
used the app to make decisions on whether to 
obtain SARS-CoV-2 testing and whether to 
send their children to school. Feedback from 
school districts showed that school nurses and 
principals used the app to help them counsel 
parents regarding school attendance and to 
review components of school response plans 
included within the app.  
Finally, members of our team have experience 
developing and testing the effectiveness of 
vaccine communication interventions. 
Specifically, Dr. Paul Darden has assessed the 
impact of text messaging interventions on 
HPV vaccination rates37; conducted 
prospective clinical trials of multi-modal, 
clinic-based interventions to increase HPV 
vaccination rates38; and assessed parental 
perceptions of barriers to vaccination through 
the Pediatric Research in Outpatient Settings 
(PROS) Network, a national practice-based 
research network.39  
In summary, our team has the expertise in mHealth tool development and deployment, clinical trials conduct, 
and vaccine communication to conduct the proposed study. 
 
 
 
 
Figure 5a. Sample dashboard of enrollment metrics generated from 
data provided by users of the Student Symptom Checker. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 28 of 73 
 
 
Figure 5b. Sample dashboard of enrollment metrics generated from data provided by users of the Student Symptom 
Checker. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 29 of 73 
3. 
RISK/BENEFIT ASSESSMENT 
3.1 
KNOWN POTENTIAL RISKS 
This study poses minimal risk to participants (see definition of participants in Abbreviations & Definitions). 
Participants (in both the Vaccine Uptake app and General Health app arms) will provide protected health 
information (PHI) (e.g., children’s names, dates of birth, and dates of vaccination) to the study team. While the 
study team will make every effort to store this electronic information in secure electronic databases and 
physical documents in secure facilities, there remains a risk of accidental as well as mandated disclosure of PHI. 
Participants will view content and answer questions related to the COVID-19 pandemic that may provoke some 
emotional stress or anxiety relating to the pandemic and/or COVID-19 vaccination. 
The study will expose participants to content providing guidance in accordance with the most current 
recommendations from the CDC/ACIP. This information is subject to change. While educational content for both 
arms will undergo revisions in real time, participants may not always choose to access updated information after 
the study team posts it. In addition, app content will likely recommend vaccination with the COVID-19 vaccine 
while it is still available under FDA EUA rather than FDA approval for some of the participants based on their 
age. 
3.2 
KNOWN POTENTIAL BENEFITS 
Participants who receive the Vaccine Uptake app will receive self-directed, multi-format education on the 
COVID-19 vaccine, which may reduce participant stress and/or anxiety in decision making regarding whether 
their child should receive the COVID-19 vaccine and increase their knowledge about vaccination.  
Caregiver participants who receive the Vaccine Uptake app will receive information on local resources for 
vaccinating their children against COVID-19, which may result in increased vaccination uptake among 
participants’ children. 
Caregiver participants who receive the General Health app will receive general health and infection prevention 
education, which may improve their own knowledge and risk reduction behaviors, which may decrease their 
own, and their children’s risk of contracting an infection and suffering the negative consequences from the 
infection. 
There is also potential for benefit to other parents and their children in the future if the study demonstrates that 
the intervention provides an effective means of educating parents about and increasing pediatric uptake of 
COVID-19 vaccine. 
3.3 
ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
We do not anticipate significant health risks to participants and will make every effort to minimize the possible 
risks described in Section 3.1. The benefit of understanding the effect of a vaccine-education mHealth tool on 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 30 of 73 
promoting pediatric COVID-19 vaccination uptake outweighs the risks. Standards of medical care provided to 
participants’ children will not be altered based on participants’ study-related activities.  
This protocol minimizes risks to participants by (a) correctly and promptly informing participants about risks 
(Section 3.1, above) so that they can join in partnership with the researcher in recognizing and reporting harms; 
(b) having staff properly trained in administering study procedures that may cause psychological distress, such 
as survey administration; and (c) providing safety monitoring.  
If the FDA issues new warnings or precautions or withdraws EUA/approval for any of the COVID-19 vaccines for 
any of the included pediatric age groups during the study, the study team will take responsive action. Actions 
will include prompt notification of participants via at least one of the following methods: app push notification, 
text message, phone call, email, registered mail, as well as possibly study termination depending on the severity 
of the concern, as determined by the PIs and data safety monitoring board (DSMB). 
 
4. 
OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Primary 
Objective 1: Determine the 
effect of a parent-facing, 
vaccination decision-making 
mHealth tool on children’s 
COVID-19 vaccine series 
completion 
Proportion of children who 
complete COVID-19 
vaccination, as verified in state, 
clinic, or participant-held 
records  
The intended goal of the intervention is to 
increase the number of children receiving a 
complete COVID-19 vaccine series since series 
completion provides children with maximal 
protection afforded by vaccination. Self-report of 
vaccination will not be used, only verified 
vaccination records, to avoid introduction of recall 
and social desirability biases in the assessment of 
the endpoint. The study team will define vaccine 
series completion as per the current Advisory 
Committee on Immunization Practices (ACIP) 
guidance for the vaccine product. For children who 
receive a product that requires more than 2 doses 
for the primary series, receipt of up to 3 doses will 
be considered complete. 
Secondary 
Objective 1: Determine the 
effect of a parent-facing, 
vaccination decision-making 
mHealth tool on children’s 
Proportion of children who 
receive ≥1 dose of the COVID-
19 vaccination series, as 
Some COVID-19 vaccines require completion of a 
multiple-dose series to achieve intended 
immunity. A necessary precursor to our primary 
endpoint of vaccine series completion is vaccine 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 31 of 73 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
COVID-19 vaccine series 
initiation 
verified in state, clinic, or 
participant-held records 
series initiation (i.e., receipt of first dose). As more 
individuals initiate vaccine series than complete it, 
vaccine series initiation may be a more sensitive 
indicator of the intervention’s effect. 
Objective 2: Determine the 
effect of a parent-facing, 
vaccination decision-making 
mHealth tool on parental 
attitude toward pediatric 
COVID-19 vaccination 
Change in enrolled 
parent/caregiver domain 
scores from baseline to week 
16 on the modified SAGE 
Vaccine Hesitancy Scale 
adapted for the COVID-19 
Vaccine 
Vaccine hesitancy contributes to vaccination 
decisions. Measuring any changes in vaccine 
hesitancy in association with use of the Vaccine 
Uptake app will provide further insight into the 
impact of the app on parent/caregiver decision-
making. 
 
5. 
STUDY DESIGN 
5.1 
OVERALL DESIGN 
This multi-site, parallel, randomized, controlled trial will assign parents/caregivers of children eligible to receive 
COVID-19 vaccine seen at participating clinics to receive either the mHealth Vaccine Uptake app or the General 
Health app containing general infection and child health topics. Randomization will be stratified by site using a 
permuted block design with varying block size. Outcome is receipt of COVID-19 vaccine by the 
parents’/caregivers’ children. 
5.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
Rationale for a randomized trial: Based on the Health Belief Model and prior evidence, factors contributing to 
individuals’ vaccine hesitancy, confidence, and/or refusal likely are multi-factorial and vary widely across 
individuals. Randomization of participants to the Vaccine Uptake or the General Health app study arms, outlined 
further below, is designed to minimize selection bias of individuals with specific attitudes or beliefs into a single 
study arm. For example, individuals who have lower vaccine hesitancy may be at baseline more interested/open 
to participating in the Vaccine Uptake study arm, whereas individuals with greater hesitancy may be more likely 
to decline.40 This potential bias ideally will be minimized by having participants consent to engaging in whatever 
study arm to which they are randomly assigned.  
Rationale for using the mHealth app platform developed at UNMC in the intervention and control study arms: 
Most parents/caregivers, including those in rural areas, have access to a mobile device and the internet (see 
Section 2.1, Background). Prior studies support the feasibility of deploying app-based interventions aimed at 
increasing vaccination rates. Based on community feedback and our team’s experience deploying app-based 
interventions for COVID-19 symptom screening, ensuring that the app imposes a low data burden is important 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 32 of 73 
to maximizing uptake. Consequently, the platform developed at the UNMC uses data at only four time points: 1) 
initial download/registration (approximately 200-300 megabytes), 2) recording of sessions (2-3 
kilobytes/session), 3) push notifications (2-3 kilobytes/notification), and 4) periodic updates (20-30 
kilobytes/update). Thus, our mHealth app platform incurs a very low data demand, which minimizes the barrier 
to use for participants. 
Rationale for use of a control mHealth app: Participants in the General Health app arm will receive access to an 
mHealth app to ensure similarity in access to intervention materials (e.g., sending out of a link to register for app 
access via the same platforms) and barriers to access (e.g., low technology literacy, lack of an internet-capable 
device). The goal is to compare the impact of the customized, targeted content over generic information on an 
app, not the ability to access content on an educational app. 
 
Figure 6. Comparison of functional and content elements of the Vaccine Uptake app and General Health app. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 33 of 73 
Limitations of using a mHealth control: App content, even if not customized or vaccine-related, may still elevate 
vaccination rates above what they would be with no intervention due to reducing barriers to accessing general 
information about infection control and prevention. 
5.3 
END OF STUDY DEFINITION 
The study will end for the participant after they have reached 29 weeks of enrollment and either completed 
their 24-week assessment or failed to complete it by week 29. 
6. 
STUDY POPULATION 
6.1 
INCLUSION CRITERIA 
6.1.1 
PARTICIPANTS 
For this study, there will be two sets of inclusion/exclusion criteria: 
1. Parents/caregivers who will receive either the Vaccine Uptake app or General Health app 
2. Children of the above-mentioned parents/caregivers who are eligible to receive COVID-19 vaccine in 
their state 
Parent/caregiver inclusion criteria:  
• 
Age of majority, as defined by the state of residency 
• 
Access to a mobile device that can store and run the study app for 24 weeks. Devices that can run the 
app include mobile phones and tablets running Android or iOS operating systems 
• 
Able to speak and read in English or Spanish 
• 
Be a parent/caregiver with primary medical decision-making and legal authority to consent to 
vaccination decisions for at least one child who meets the child inclusion criteria 
Child inclusion criteria:  
o Age 6 months to less than age of majority, as defined by the child’s state of residence 
o Has not received any doses of COVID-19 vaccine based on parent/caregiver report 
o Eligible to receive COVID-19 vaccine 
o Patient at a participating clinic 
Rationale for parent/caregiver inclusion criteria: Parent/caregiver vaccine confidence/acceptance will vary 
widely, ranging from those who firmly refuse the COVID-19 vaccine to those who strongly endorse the COVID-19 
vaccine for their children. All parents/caregivers, regardless of baseline vaccine hesitancy/confidence, are 
eligible to participate in the study. Subject randomization is intended to balance the proportion of vaccine 
refusing/vaccine endorsing participants. Parental vaccine hesitancy will not be assessed prior to enrollment. 
Such assessment may bias enrollment towards those individuals with greater vaccine acceptance through social 

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desirability bias. Unlike vaccine-hesitant individuals, baseline vaccine refusing parents/caregivers are unlikely to 
be willing to participate in vaccine communication efforts and, therefore, will likely decline study participation 
during recruitment or informed consent.40 
Due to evolving COVID-19 EUAs by age categories and variable availability of vaccine by state, the study team 
may rescreen parents who do not meet enrollment criteria at initial screening. 
6.1.2 
SITES 
Participating clinics must meet all the inclusion criteria:  
• 
Provide primary pediatric general healthcare to at least 100 unique pediatric patients in the last 12 
months; this can include family medicine clinics. Given that primary pediatric care in rural settings often 
occurs in family medicine clinics, including these clinics as potential performance sites will increase the 
generalizability of the findings 
• 
Have electronic health record (EHR) or billing database infrastructure to identify potential participants 
by reviewing the medical records of children within the study inclusion criterion of child-age range 
• 
Have ability to access their state’s COVID-19 vaccination registry 
• 
Meet at least one of the following diversity, equity, and inclusion criteria for the patient population 
served: 
o <60% non-Hispanic White; 
o >40% from a rural zip code as defined by rural-urban community area (RUCA) code ≥4; or  
o >40% on Medicaid/Medicare or uninsured. 
• 
Sites are encouraged, but not required, to have a high Spanish-speaking population. 
Sites are not required to stock and administer pediatric COVID-19 vaccines to serve as enrolling sites. 
6.2 
EXCLUSION CRITERIA 
6.2.1 
PARTICIPANTS 
Parent/caregivers exclusion criteria: 
• 
Has only a child or children with known contraindication to all COVID-19 vaccines 
• 
Has only a child or children whose other parent/caregiver is already a current or past participant in the 
study 
• 
Has a child or children enrolled in any other COVID-19 vaccine study of any kind 
• 
Past or present participation in a COVID-19 vaccine or behavioral trial 
• 
Has cognitive impairment that limits their ability to engage with the app content and/or make medical 
decisions regarding vaccination, based on the site investigator’s assessment and local human subjects 
research policies 

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Child exclusion criteria: 
• 
Not a patient of a participating clinic 
• 
Prior receipt of least one dose of COVID-19 vaccine 
• 
Receiving or scheduled to receive COVID-19 vaccination at the time of parental consent 
• 
Known medical contraindication to all COVID-19 vaccines 
• 
Ineligible to receive COVID-19 vaccine 
• 
Prior or current participation in a COVID-19 vaccine study of any kind 
 
Rationale for parent/caregiver exclusion criteria: One or multiple parents/caregivers may have decision-making 
authority for a child’s vaccinations. Our primary outcome is the proportion of children who complete COVID-19 
vaccination, not individual parental decision-making. Additionally, although only one parent/caregiver is 
enrolled, it is likely that information to which they are exposed during the course of the trial will be shared with 
another parent/caregiver who has decision-making authority if present. 
6.3 
LIFESTYLE CONSIDERATIONS 
Participants will require sufficient access and literacy in technology to operate a mobile device and to download 
and interact with apps typically used on such devices. If participants have barriers in accessing sufficient Wi-Fi or 
mobile data bandwidth for initial app download (the only portion of app use anticipated to incur use levels 
above 1 mb), the enrollment visit will be arranged to take place somewhere with Wi-Fi to which the participant 
can freely connect. 
If participants change or lose their phone or change operating systems, participants can contact the App Team 
for technical support.  
 
7. 
RECRUITMENT, RETENTION, CONSENT, SCREENING, & ASSESSMENTS 
7.1 
RECRUITMENT 
The target population will include all parents/caregivers meeting the inclusion criteria listed in Section 6.1. 
Please see Section 11.2 for enrollment numbers. Recruitment methods will prioritize enrolling participants from 
rural and underrepresented racial and ethnic communities, as these communities have experienced 
disproportionately lower vaccination rates and greater hardship due to the COVID-19 pandemic. To address the 
issue of potentially underperforming sites and clinics, we will ask ISPCTN sites to identify at least two clinics that 
can participate in the trial to achieve a goal of 24 participating clinics. In addition, enrolling sites will over-recruit 
by 15% to account for participant withdrawals. We will also allow competitive enrollment across clinics to 
enable high-performing sites to contribute maximally to achieving goal overall study enrollment.  

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Based on sample size estimates and weekly minimum recruitment goals, the goal accrual is 60 parent/caregiver 
participants per site across 15 enrolling sites with approximately 2 participating clinics per site. The anticipated 
accrual rate is a minimum of 7-8 participants per week per enrolling site over an 8-week recruitment period.  
Recruitment for all enrolling sites will be competitive; there is no initial enrollment cap per enrolling site. 
Because of the compressed nature of recruitment, potential poor performance of enrolling sites must be 
addressed early in the recruitment process.  
Site investigators and coordinators will meet weekly to review accrual. Sites will also receive weekly reports of 
enrollment performance, and high-performing sites will provide insights and support/mentorship for lower-
performing sites with the help of Data Coordinating and Operations Center (DCOC) and protocol leadership. 
Sites will be prompted to share best practices as well as issues with recruitment during the weekly meetings. As 
part of recruitment, we will record how many subjects were approached, how many declined and the reason for 
declining (e.g., out of age range, non-rural zip code, or declined) using a log developed by the enrolling site 
research staff. These logs will be monitored overall and by site. 
At the end of each week of recruitment, the study team will assess accrual and make an explicit decision about 
adjusting recruitment strategies. Additional strategies to achieve goal recruitment will include: 
1. Extend the recruitment window for all sites beyond the initial 8-week period. 
2. Targeted supplemental advertising through social media and local media outlets 
Stopping rule: The project goal is to recruit at least 892 parents/caregivers during the recruitment period. At 3 
months after study start, 20% of participants must be recruited. If recruitment does not meet this milestone, 
then the study PIs will report enrollment progress to the DSMB and obtain recommendations.  
7.1.1 
INITIAL RECRUITMENT METHODS 
For efficiency, identification of potential participants will rely on several methods to capitalize on existing 
electronic health record databases and clinical workflows at study recruitment sites. Proposed identification 
methods include retrospective lists of recently seen patients and traditional advertisements for self-referral.  
• 
Retrospective. Site coordinators (or other designated personnel) can identify potential participants by 
reviewing a list of consecutively seen patients provided by participating clinics. The practice will develop 
the list from 12 months of patient-visit data (e.g., billing records). The site coordinator/designee will 
organize this list from more to less recent clinic visit dates and remove duplicate patients. The generated 
list will include patient zip code, race/ethnicity, and gender. Sites will be instructed to contact non-
White and/or rural participants first to help ensure diverse participant enrollment. DCOC will provide a 
list of rural (RUCA≥4) zip codes based on the 7/13/2019 revision of the 2010 RUCA Codes crosswalk.41 
• 
Traditional. Sites may engage in traditional clinical trial recruitment methods focused on participant 
self-identification. Sites can recruit participants through various methods, including, but not limited to, 
provider recommendation at appointment visits, electronic health record messaging systems, and quick 

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response (QR) codes. DCOC will provide a menu of options from which sites can choose, such as flyers, 
email, or advertisements on social media in English and Spanish. The DCOC will obtain IRB approval for 
all recruitment materials. Recruitment materials will provide information to contact the site 
coordinator/designee for more information. During the consent process, site coordinators will ask 
participants recruited through the traditional method how they learned of the study. 
• 
In person recruitment. This type of recruitment is possible only for those sites for which the research 
team is part of the participating clinic. The enrolling site research staff must be employed by the 
Institution under which the participating clinic is affiliated, before engaging in any research-related 
activities.  Refer to section 7.4.2 for more details about this type of recruitment. The staff of the 
participating clinics cannot be involved in any research-related activities. 
 
Based on ECHO ISPCTN clinics’ recent experience with patient recruitment, we expect that the retrospective 
list method will have the highest yield. To allow research staff to contact potential participants, enrolling 
sites will send an opt-out/opt-in letter to potential participants, which will have the participating clinics’ logo 
and letterhead, and if possible, be signed by the lead clinicians. This letter will describe the study and inform 
families that research staff collaborating with the participating clinic will contact them. If families do not 
wish the research team to contact them, the letter will ask participants to contact the enrolling site or 
participating to opt out of being contacted about the study. The letter sent to potential participants will 
include the following documents: 
• 
Opt-out/opt-in letter 
• 
Informed consent form (ICF) with detailed description of the study and with Health Insurance 
Portability and Accountability Act (HIPAA) language embedded (ICF+HIPAA) 
The research team will send the Opt-Out/Opt-In Letter and ICF+HIPAA by postal mail, e-mail, or other 
methods. 
7.1.2 
RECRUITMENT STANDARDIZATION 
To ensure participant safety and consistent and high-quality data submission in compliance with protocol and 
study operations, the DCOC and study team will train enrolling site study staff. The DCOC expects all enrolling 
site study staff to take responsibility for learning the study, primarily by studying the protocol and manual of 
procedures (MOP), to ensure compliance with the protocol and GCP. The enrolling site study staff will receive 
training through the following methods: a mandatory training session in the form of an Investigator Meeting, 
and as needed training in the form of one-on-one enrolling site-specific training and/or other targeted training. 
DCOC personnel will train all enrolling site study staff on the protocol, reporting procedures for study deviations, 
potential study deviations, and noncompliance, as well as essential documentation for study conduct. The DCOC 
will train enrolling site study staff on in-person and tele informed consent processes and documentation.  

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Date: 02/13/2023 
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Enrolling site study staff must document all training and provide the DCOC with this training documentation. The 
DCOC will train enrolling site study staff on any relevant study electronic data capture (EDC) system(s) to ensure 
that staff understand how to utilize the system to perform study-specific data collection and other necessary 
processes. 
7.2 
RETENTION 
User Acceptance Pilot Testing  
Prior to the start of participant enrollment, the apps for the Vaccine Uptake and General Health app arms will 
undergo pilot testing to optimize user acceptance. There will be approximately 5 testers from each of the 
following groups (total: 15): 
1. Self-identified rural (English-speaking) 
2. Self-identified non-rural (English-speaking) 
3. Spanish-speaking 
We will ensure that approximately 5 testers among the two English-speaking groups will not be non-Hispanic 
White.  Each testing session will last one hour and will involve reviewing user workflow and formative feedback 
on app content, including appropriateness of customizations by race, ethnicity, and rurality. User acceptance 
testing participants will receive $20 per test in which they participate.  
Participant Remuneration. Participants in the randomized trial will receive $20.00 for each assessment that is 
completed. There are four assessments, these will occur at baseline and weeks 8, 16, 24. The total 
compensation that participants may receive is $80.00. 
Study team activities to maximize participant retention include the following: 
• 
Enrolling site coordinators will instruct participants to register in the app and will be available to refer 
participants to the Nebraska App Team if assistance is needed  
• 
Research Team members will contact participants to confirm completion of app registration  
• 
Scheduled push notifications during weeks 1-8 and then monthly for 2 months will prompt participants 
to engage with in-app content 
• 
Ad hoc push notifications regarding national and local updates to vaccine availability/eligibility will 
prompt participants to engage with in-app content 
• 
Enrolling site coordinators will contact participants at weeks 8, 16, and 24 for follow-up assessments 
• 
Enrolling site coordinators will perform follow-up contact attempts for participants who do not 
complete their assessments at weeks 8, 16, or 24 
• 
Contact methods for communicating with study participants will comprise multiple modalities, including 
(but not limited to): email, phone call, and/or text messages 

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7.3 
SCREEN FAILURES AND RESCREENS 
7.3.1 
SCREENING PROCEDURES AND SCREEN FAILURES 
For potential participants recruited with the retrospective method, site coordinators will contact (by phone or 
other methods) potential participants to briefly introduce the study. If potential participants are interested in 
learning more about the study, site coordinators will review the inclusion and exclusion criteria with potential 
participants to ensure they qualify. These data will be recorded by the research staff in the EDC.  If potential 
participants are eligible, the site coordinator will perform the consent process as described in section 7.4.1. 
Potential participants should have received the ICF+HIPAA, and they should have had time to read the 
documents. 
For potential participants recruited with the traditional method, site coordinators will ask participants if they 
would like to have a copy of the ICF+HIPAA form sent to them before discussing the study. If potential 
participants agree to discuss the study without a hard or electronic copy of the ICF+HIPAA, site coordinators will 
review the inclusion and exclusion criteria with potential participants to ensure they qualify. If potential 
participants are eligible, site coordinators will perform the consent process, as described in section 7.4.1.    
The study team will consider participants who undergo screening but do not enroll or consent to participate in 
the trial as screen failures, such as participants contacted by the research team but who do not meet inclusion 
and/or exclusion criteria.  
Site coordinators must document and retain the following information for screen failures: basic demography, 
screen failure details, inclusion and/or exclusion criteria the participant did not meet, and other details as 
required. The data collected will be recorded by the research team in EDC. This data collection will be done 
before obtaining consent from the potential participants. 
7.3.2 
RESCREENS 
Site coordinators may rescreen parents/caregivers who initially do not meet enrollment criteria that are likely to 
change over time. Examples include parents/caregivers of children who age into the CDC/ACIP-recommended 
COVID-19 vaccination minimum age limit or who gain vaccination access due to progressing state prioritization 
schemes.  
7.4 
INFORMED CONSENT 
This research study does not involve more than minimal risk of harm to participants and does not involve 
procedures for which written consent is normally required outside of the research context. The research study 
has been designed to perform all the study related procedures remotely, and study personnel will not interact in 
person with potential participants during the intervention.  The potential participants will be provided with a 
written statement regarding the research (ICF+HIPAA) before the consent process. A waiver of consent 
documentation has been granted for adult participants (parents/caregivers). 

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Moreover, a full waiver of assent has been requested/granted. Children will not have to sign an assent and/or 
verbally agree to be part of this study. The ethical justification for requesting a waiver of assent is that this 
research study does not involve more than minimal risk of harm to participants and does not involve procedures 
for which written consent is normally required outside of the research context. Children participating in the 
study involves only medical chart review or access to the state registry to collect COVID-19 vaccination record.  
7.4.1 
INFORMED CONSENT PROCESS 
After determining that participants meet all inclusion criteria and none of the exclusion criteria, site 
coordinators or research team members will conduct the informed consent process to obtain a verbal consent. 
The study team anticipates that site coordinators/research team members will remotely conduct most consent 
processes (e.g., via telephone, or video conference platform, etc.). However, some in-person consenting could 
occur. The in-person consent will be done only by enrolling sites research staff members. Eligible potential 
participants should have received a copy of the ICF+HIPAA before being contacted by site coordinators or 
research team members. This will allow potential participants to follow the information presented by the site 
coordinators/research team members on their copy of the documents.  
Informed consent is a process that starts before a participant agrees to participate in the trial and continues 
throughout the individual’s trial participation. Site coordinators/research team members will inform participants 
that participation is voluntary, that they may withdraw from the trial at any time without prejudice, and that 
nonparticipation will not adversely affect their medical care.  
Site coordinators/research team members will explain the study to participants in terms participants can 
understand and answer any questions that may arise. The explanation will state the purposes, procedures, and 
potential risks of the study and describe participants’ rights as research participants. Participants will have the 
opportunity to carefully review the ICF+HIPAA and ask questions before consenting. Site coordinators/research 
team members will give participants the opportunity to discuss the study with their family or surrogates or think 
about participating in the study before agreeing to participate. 
The enrolling site coordinators/research team member that performed the consent process must sign and date 
the ICF+HIPAA. Moreover, the research team member will have to document the informed consent process, 
following the current University of Arkansas for Medical Sciences (UAMS) Institutional Review Board policy. The 
consent process will be documented in a “Process Note.” ICF+HIPAA and the “Process Note” forms will either be 
hand-signed or signed via electronic means such as DocuSign. 
7.4.2 
IN-PERSON CONSENT 
Enrolling site coordinators/research team members will coordinate with participating clinic staff to schedule a 
series of days to complete screening and consenting processes with previously contacted potential participants. 
If uncontacted, potentially qualifying participants visit the clinic during these days, site coordinators/research 
team members may screen and consent these individuals in person at the time of the visit or schedule a later 
time to do so. Site coordinators/research team members will ask participants how they learned of the study. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
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If clinic staff identify potential participants during a regular clinic or telemedicine visit, clinic staff can give, fax, or 
email potential participants study information (e.g., study pamphlet) and can give, fax, or email the potential 
participants’ contact information to the site coordinators/research team members. The site 
coordinators/research team members may contact potential participants to describe the study and, if 
participants agree, complete the consent process, including verifying eligibility. 
7.5 
ASSESSMENTS 
7.5.1 
ENROLLMENT 
At the end of the consent process, the enrolling site research team will complete the enrollment survey with 
participants. This survey will ask for the contact information of the participant (name, phone number, physical 
address, and email address) and self-identified rurality. The survey will ask for the name, race/ethnicity, sex, 
name of children’s primary care clinic and physician, and birthday of the participant’s children. The site 
coordinator/research team will record this information in the EDC. 
7.5.2 
APP REGISTRATION AND USAGE (ADHERENCE) 
During enrollment, site coordinators/research team members will ask participants if they would like assistance 
downloading and registering with the app. If participants request assistance, they will be scheduled with a 
Research Team member for technical assistance. After enrollment, caregiver participants will be block-
randomized within their participating clinic by the enrolling site to either the Vaccine Uptake or General Health 
app study arms (see Section 8.2 for complete details on randomization). A Research Team member will then 
register the caregiver in the assigned app using their assigned study number as well as the caregiver 
participant’s self-identified race, ethnicity, gender identity, rurality, and clinic of recruitment collected at 
enrollment.  The Research Team will send caregiver participants the instructions on how to download their 
assigned app. Once downloaded, participants will enter their email address to retrieve their registration. The 
Research Team will follow up with participants who have not used the app within one week of 
registration/instructions successfully sent via telephone, email, or video conference to confirm the completion 
of app registration. Each time the app is opened, every selection made within the app will be tagged and 
recorded with both the caregiver participant’s study number and a time date stamp. This data will be tracked 
throughout the caregiver participant’s 24-week intervention to determine adherence (Section 8.3). 
7.5.3 
BASELINE AND FOLLOW-UP ASSESSMENTS (WEEK 8, 16, 24) 
BASELINE ASSESSMENT 
After enrollment and app registration, caregiver participants will be sent a link to the baseline survey with 
questions regarding their vaccine hesitancy, intent to vaccinate, perceived risks and benefits of the vaccine, who 
they trust for vaccine information, and disease avoidance behaviors. The survey will also ask some household-
level questions, including:  

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
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Version #: 10 
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• 
highest education achieved by their children’s mother, 
• 
insurance status, 
• 
household members, 
• 
vaccination status of household members, 
• 
COVID-19 infection status of household members, 
• 
increased infection vulnerability status (e.g., chronic health condition or other circumstances increasing 
vulnerability) of household members, and 
• 
experience of household members with any one of a set of common challenges (e.g., lack of food, 
housing, etc.).  
All these questions, aside from vaccine hesitancy, will come from the RADX-Up Common Data Elements.42 To 
assess vaccine hesitancy, caregiver participants will answer questions derived from the WHO SAGE Vaccine 
Hesitancy Scale that will be adapted to COVID-19 vaccines.43  
WEEK 8 ASSESSMENT 
At the week 8 time point, the caregiver participants will be sent a link to an assessment that asks for the 
following topics:  
1. Vaccine status of eligible children 
The surveys will ask caregiver participants for the dates, brands, and administrators for all COVID-19 
vaccinations that any of their children received since enrollment, if any. For each vaccinated child, the 
survey will ask participants to upload a photo of the vaccination card. If a participant is unable to upload the 
photo or the writing on a card is illegible, the enrolling site personnel will contact the participant to schedule 
a time for a video conference to view and verify the card information.  
2. Usability of the app 
Surveys will include a systems usability assessment measured by the System Usability Scale (SUS). The SUS 
is a simple, ten-item scale giving a global view of subjective assessments of usability.44 SUS instructions will 
ask caregiver participants to record their immediate response to each item, rather than thinking about 
items for a long time. Responses range from Strongly Agree to Strongly Disagree. The SUS yields a single 
number representing a composite measure of the overall usability of the system. SUS scores have a range 
of 0 to 100, with 100 representing a perfect score. 
WEEK 16 ASSESSMENT 
Caregiver participants will complete an assessment at or around week 16. Table 1 lists the content of this 
assessment.  
WEEK 24 ASSESSMENT  

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At week 24, participants will be sent a link to an assessment that asks for the vaccine status of eligible children. 
PARTICIPANT VACCINE STATUS FOLLOW-UP 
Study staff will assess COVID-19 vaccination status as noted above. For any child who is not card-verified at the 
8-, 16-, or 24-week assessment, site coordinators/study team members will review the child’s vaccination 
records in their clinic’s electronic medical record system and/or the state immunization registry beginning at 
Week 25 to determine COVID-19 vaccine status. 
 
Table 1. Details the content covered in each assessment 
 
Assessments 
Information Collected 
Enrollment 
App Baseline  Week 
8 
Week 
16 
Week 
24 
Children 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Vaccine Status 
 
 
 
X 
X 
X 
Participant (Parent/Caregiver) 
 
 
 
 
 
 
Contact Information 
X 
 
 
X 
 
 
Consent 
X 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Vaccine hesitancy 
 
 
X 
 
X 
 
Intent to vaccinate 
 
 
X 
 
X 
 
Perceived Benefits of Vaccination 
 
 
X 
 
X 
 
Perceived Risks of Vaccination 
 
 
X 
 
X 
 
Trusted organizations 
 
 
X 
 
X 
 
Disease avoidance behaviors 
 
 
X 
 
X 
 
Perceived app usability 
 
 
 
X 
 
 
Adherence 
 
X 
 
 
 
 
Household/Family 
 
 
 
 
 
 
Maternal Education 
 
 
X 
 
 
 
Insurance 
 
 
X 
 
 
 
Vulnerable Household Members 
 
 
X 
 
 
 
COVID-19 Status 
 
 
X 
 
X 
 
COVID-19 History 
 
 
X 
 
X 
 
Challenges 
 
 
X 
 
X 
 
 

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8. 
STUDY INTERVENTION 
8.1 
SOFTWARE, FUNCTIONALITY, AND CONTENT OF THE INTERVENTION 
Overview: Participants in the Vaccine Uptake and General Health app arms will receive access to different 
mobile apps designed to provide health information. Content of the Vaccine Uptake app will focus on vaccine 
uptake, while content of the General Health app will focus on infection prevention and general child health.  
8.1.1 
APP SOFTWARE  
The Nebraska App Team will build the Vaccine Uptake and General Health apps using custom software created 
by Drs. Ellen Kerns and Russell McCulloh (protocol chairs) as a decision-support tool. The software creates 
pathways (i.e., decision trees) by linking together a series of question cards in which the user’s response 
determines the next step. For the Vaccine Uptake App, the decision trees will be customized according to the 
user’s demographic information entered at registration, language preference (English or Spanish), and local 
context (state vaccination program stage/tier by age, local vaccination sites’ contact information, vaccination 
endorsement by local leaders and clinic staff, etc.). After the initial use session in which users complete their 
registration, the app will remember their registration characteristics and renders the pathways accordingly for 
every subsequent use. Figure 7 outlines how individual user and site data contribute to the presentation of 
customized app content. 
 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
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Version #: 10 
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Figure 7. Schema of how individual user and site data contribute to the presentation of customized content in the 
Vaccine Uptake app. 
 
8.1.2 
CONTROL (GENERAL HEALTH APP)  
Specific elements of the General Health app will include:  
• 
Push notifications: The app will deliver messages directly to participants’ mobile devices prompting 
them to vaccinate their child and directing them to view specific app content (8 weeks with weekly push 
notifications; 2 monthly push notifications for 2 months [1 notification per month]). 
• 
Content areas: Specific topics presented as pathways are outlined in the schedule of push notifications 
(Table 2), but the general categories of topics included are: 
o 
General infection prevention and mitigation measures 
o 
General child health topics 
o 
General COVID-19 information from the “How to Protect Yourself & Others” page for COVID-19 
on the CDC website: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-
sick/prevention.html. 
o 
Table 2 shows the schedule of push notifications during the study period (intervention topics 
may change according to qualitative interview feedback) 
 
8.1.3 
INTERVENTION EXPOSURE (VACCINE UPTAKE APP)  
The intervention app will consist of 3 pathways: 1) step-wise decision support with narrative vignettes, 2) self-
directed learning on each selected topic area, 3) area-specific vaccine access information and corresponding 
push notifications. The Health Belief Model (Section 2.3) will drive topics for the vignettes and self-directed 
learning. Specific content will be guided by the qualitative interviews being conducted in an ongoing study and 
will include (among others identified): Safety; Effectiveness and personal/family susceptibility/vulnerability; 
Benefits (personal, family, community); Trust, decision-making/autonomy; Availability/accessibility. The list 
below provides specifics of the pathways and push notifications: 
• 
Step-wise decision support with narrative vignettes: Using this pathway, participants will view 
information about COVID-19 vaccination in the form of short stories that include images of children, 
healthcare providers, and family members, as appropriate. The study team will tailor images and text 
content of the narrative vignettes to participant registration demographics. For instance, rural White 
adult participants with teenage children will mostly view vignettes featuring rural, White parents, teens, 
and healthcare providers discussing issues noted in the qualitative study to be of interest to this 
demographic group. Similarly, Hispanic participants of infants will mostly view vignettes featuring 
Hispanic parents, infants, and healthcare providers discussing issues of interest to this demographic 
group, etc. As everyone benefits from gaining input from diverse sources, pathways will not exclusively 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 46 of 73 
feature messengers with complete demographic concordance. Participants can review other vignettes of 
interest to them or explore different questions within vignettes through in-app navigational buttons. 
• 
Step-wise self-directed learning: Using this pathway, the app will give participants a menu of topics. 
Clicking on any of these will provide the participant general information on the topic and external links 
derived from the CDC and local health authorities, including hyperlinks that will open an internet 
browser window within the app. Unlike a website frequently asked question page, users will access 
information through branching logic based on topic area. 
• 
Vaccine access: Using this pathway, the app will give participants local vaccine availability, 
recommendations for vaccination (e.g., at what age children can receive the vaccine locally), links to 
sign-up for a vaccination appointment locally, and resources for traveling to vaccination sites, etc.  
• 
Push notifications: The app will deliver messages directly to participants’ mobile devices through 8 
weekly and 2 monthly push notifications. These messages will direct participants to view specific app 
content (scheduled once weekly and once monthly, see Table 2 for topic schedule) and alert participants 
to local or national changes to vaccine availability or vaccination recommendations (as necessary, up to 
once weekly). 
• 
Content areas: The study team will use the Health Belief Model (Section 2.3, Figure 3) to derive general 
content, and the qualitative study interviews will guide specific content, including (among others 
identified): 
• 
Vaccine Safety 
• 
Vaccine Effectiveness 
• 
Personal/family susceptibility/vulnerability to COVID-19 disease morbidity and mortality 
• 
Benefits of vaccination (personal, family, community) 
• 
Trust in government, healthcare systems regarding vaccination; decision-making/autonomy in 
choosing vaccination for children 
• 
Vaccination Availability/accessibility 
8.1.4 
COMMUNICATION ADDRESSING VACCINE HESITANCY IN THE VACCINE UPTAKE APP 
The qualitative project will use focus groups of specific sociodemographic groups in four states to understand 
the communication sources people rely on and misinformation influencing COVID-19 vaccine decision-making. 
The mHealth app will use principles outlined by NIH CEAL as we construct the pathways (Table 2).10,45 The focus 
groups will identify key misinformation, which will be used in each pathway. For example, in the vignettes there 
will be testimonials from their clinic staff, and the step-wise decision making will present accepted facts without 
reinforcing misinformation.46,47 
Table 2: Example vaccine uptake app components and HBM domains/vaccine hesitancy issues addressed 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 47 of 73 
Vaccine Uptake App 
Component 
Example Component* 
HBM domain 
NIH CEAL Known 
Barrier/Concern 
Push Notifications, to 
include: 
-Behavioral nudges 
-Alerts to information 
about the vaccine in 
general 
-Clinic-specific 
information on 
vaccine issues 
“Your child’s COVID-19 
vaccine is available at 
[insert clinic name]. To 
schedule your 
appointment, touch here.” 
Links to local clinic’s 
appointment making 
resource. 
 
“Did you know that over 
xx million children have 
received the COVID-19 
vaccine? Hear from 
parents why they chose to 
vaccinate their children.” 
(Links to Vignette) 
 
“More than xx children 
have received the vaccine 
at your clinic. Click here to 
schedule your child’s 
vaccine appointment 
today.” 
 
“[Organization] is 
providing free rides to 
[insert vaccination site]. 
Click here for more 
information.” 
 
“COVID cases in children 
in your area are 
increasing. Protect your 
Perceived barriers to 
vaccination 
 
Cues to action 
 
 
 
 
Psychological characteristics 
(peer group pressure) 
Perceived benefits 
Susceptibility to disease 
Access 
issues/questions 
Do I need to pay for 
a COVID-19 
vaccine? 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 48 of 73 
child with the vaccine 
today. Click here to 
schedule your 
appointment.” 
Vaccine Access Pathway 
(“Find your child’s COVID-
19 vaccine”) 
Information about local 
events for vaccination; 
information about free 
rides to a vaccination site; 
links to schedule vaccine 
visits 
Perceived barriers to 
vaccination 
Cues to action 
Access to care 
Psychological characteristics 
Do I need an ID to 
get COVID-19 
vaccine for my 
child? 
 
Do I (my child) have 
to be a legal 
resident to get 
COVID-19 vaccine? 
 
Do I need proof of 
insurance to get the 
COVID-19 vaccine 
for my child? 
 
Do I need to 
provide personal 
identifying 
information 
(address, phone 
number, etc.) to get 
my child 
vaccinated? 
Vignettes/step-wise 
decision support. Will 
include: 
-Relatable storytelling 
-Testimonials from local 
staff/leaders 
 
Vignette: Taking your 
teenager to get 
vaccinated. 
 
 
Vignette: Why I vaccinated 
my child. 
Health motivation 
Safety/perceived severity of 
effects from the vaccine 
 
Psychological characteristics 
Perceived benefits 
Does the COVID-19 
vaccine impact 
fertility? 
 
 
How effective is the 
COVID-19 vaccine? 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 49 of 73 
 
 
Vignette: Parent of child 
with COVID-19/MISC. 
Their story. 
 
 
 
Vignette: Provider 
testimonial (trusted 
messenger) on long 
COVID/MISC and the 
choice to vaccinate their 
own children 
 
 
 
Vignette: School outbreak, 
from the perspective of 
teachers/students/parents 
 
 
 
 
Vignette: Student athlete 
who got COVID 
 
 
Vignette: Protecting a 
vulnerable family member 
 
Perceived susceptibility 
 
Perceived susceptibility 
Perceived severity of SARS-
CoV-2 
Psychological characteristics 
 
Perceived susceptibility 
Perceived severity of SARS-
CoV-2 
Perceived benefits of the 
vaccine 
Health motivation 
Cues to action 
 
Perceived susceptibility 
Perceived severity of SARS-
CoV-2 
Perceived benefits of the 
vaccine 
Cues to action 
 
Perceived susceptibility 
Perceived severity of SARS-
CoV-2 
Perceived benefits of the 
vaccine 
 
Psychological characteristics 
 
 
Does COVID-19 
cause disease in 
children? Is it worse 
than the flu? 
 
 
Are COVID-19 
vaccines safe? 
 
How were COVID-
19 vaccines 
developed? 
 
 
Does COVID-19 
infect children 
aren’t they too 
healthy to get sick?  
 
 
 
Is natural immunity 
just as good as 
getting vaccinated? 
 
 
 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 50 of 73 
 
 
 
Perceived benefits of the 
vaccine 
Health motivation 
Cues to action 
 
Does receiving the 
vaccine give you 
COVID-19? 
If you are 
vaccinated, then 
why do I have to get 
vaccinated? 
 
 
Customization for clinic 
site 
Clinic logos/colors 
 
Clinic location/contact 
information 
 
Links to clinic’s website 
and appointment-making 
tools 
 
Clinic-specific vaccination 
events (when applicable) 
Perceived barriers to 
vaccination 
 
Psychological characteristics 
 
Cues to action (trusted 
organization) 
 
Health motivation (trusted 
organization) 
Questions around 
trust and trusted 
messengers. 
Customization for 
participant socio-
demographics 
Vignette pictures/content 
adjusted for race, 
ethnicity, language, 
and/or rurality 
Psychological characteristics 
 
Susceptibility to disease 
 
Benefits of vaccination 
 
Health motivation 
Does the vaccine 
work for people like 
my child?  
 
Has the vaccine 
been tested in 
people like my 
child? 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 51 of 73 
Self-directed learning 
pathways 
COVID-19 by the numbers 
(stats and pictographs) 
 
 
Natural immunity vs 
vaccination 
 
 
 
Frequently asked 
questions about COVID-19  
Susceptibility/severity of 
infection 
Benefits of vaccination 
 
Benefits of vaccination 
Susceptibility/severity of 
infection 
 
Potentially multiple 
avenues, depending upon 
user motivation to access 
information 
Various questions, 
concerns, and 
misinformation 
topics, with focus 
on topics from 
CEAL, CDC, and 
qualitative 
interviews. 
*Specific content may vary based on user acceptance testing and qualitative study results; HBM=health belief 
model 
 
8.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
8.2.1 
ACQUISITION AND ACCOUNTABILITY 
 N/A 
8.2.2 
APPEARANCE, PACKAGING, AND LABELING 
 N/A 
8.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION 
Randomization: The study will use a 1:1 parallel design at the caregiver level to assign caregivers to the 
intervention (Vaccine Uptake app) or the control (General Health app) arm. The study team will stratify 
randomization by participating clinic and in varying block of participants using a permuted design. 
Randomization will occur after enrollment and before the baseline assessment. 
8.4 
STUDY INTERVENTION COMPLIANCE 
The study team will measure and monitor compliance using app usage analytics. The study team will summarize 
app usage measures as follows: 
• 
Cumulative number of times app was accessed (sessions) to determine total content exposure 
• 
Average session duration 
• 
Median weekly app sessions to determine rate of engagement over time 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 52 of 73 
• 
Number of unique content areas are accessed within the app 
• 
Whether participants allowed receipt of push notifications  
To be compliant to the intervention, participants must have at least one app session in which they access 
content from at least one app pathway. 
 
9. 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
9.0 
DISCONTINUATION OF STUDY INTERVENTION 
See Sections 3.3 and 5.3 
9.1 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
The study team will consider the following to be an early-terminated participant: any participant who completes 
the informed consent process and enrolls in the study but later withdraws their consent, or the site investigator 
removes the participant from the study. The study team will not replace early terminated participants; instead, 
sites will over recruit to account for early-terminated participants.  
Participants may withdraw from the study at their own request, or the site investigator, DSMB, and/or DCOC can 
withdraw a participant. If a participant withdraws from the study, site coordinators or investigators can ask the 
participant why they chose to withdraw. Site coordinators will document the reasons for withdrawal. 
9.2 
LOST TO FOLLOW-UP 
The study team will consider participants lost to follow-up if they do not have vaccination status confirmed by 
the end of the vaccine follow-up period (either survey/self-report or via EMR/registry check).  
To minimize the number of participants lost to follow-up, the study team will send survey links and notify 
participants beforehand, asking participants to respond to the survey link. Survey reminders will be sent to non-
respondents daily for 3 days. Site coordinators will then contact any remaining non-respondents. 
10. 
STUDY ASSESSMENTS AND PROCEDURES 
10.1 
EFFICACY ASSESSMENTS 
The primary endpoint is child initiation and completion of COVID-19 vaccination by the end of week 24 post 
caregiver randomization. Verification of vaccine receipt will occur by any of the following methods: 
1. Photograph of the child’s vaccine card, furnished by the caregiver 
2. Medical records documentation of child vaccine receipt 
3. Recorded vaccine receipt in the appropriate state vaccine registry 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 53 of 73 
Secondary endpoint #1 is child receipt of ≥1 dose of the COVID-19 vaccination series by the end of week 24 post 
caregiver randomization. Verification of vaccine receipt will be the same as for the primary endpoint. 
Secondary endpoint #2 is enrolled caregiver domain scores on the modified SAGE Vaccine Hesitancy Scale 
adapted for the COVID-19 Vaccine from baseline and the end of week 16 post caregiver randomization. 
Caregiver participants will complete this survey electronically. 
10.2 
SAFETY AND OTHER ASSESSMENTS 
Because this study is of an educational intervention and poses minimal risk, adverse events (AEs) and serious 
adverse events (SAEs) are not expected. The study team will not solicit AEs or SAEs but will provide all 
participants with a site-specific telephone number to report AEs/SAEs. The study team will track severe and 
serious AEs that are potentially study related. 
10.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
10.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
An AE is defined as any untoward occurrence associated with the use of an intervention in humans, whether or 
not considered intervention related (21 CFR 312.32 [a]). Section 10.3.3.3 includes a list of potential AEs; 
however, the study team will not solicit AEs or SAEs but will provide all participants with a site-specific 
telephone number to report AEs/SAEs. The study team will document severe AEs and SAEs and will track SAEs.  
10.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
We will consider an AE or suspected adverse reaction “serious” if, in the view of the PIs, medical monitor, DSMB, 
or sponsor, it results in any of the following outcomes:  
• 
Death 
• 
Life-threatening AE 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
Persistent or significant incapacitation or substantial disruption of the ability to conduct normal life 
functions 
• 
Congenital anomaly/birth defect  
Important medical events that may not result in death, be life-threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and 
may require medical or surgical intervention to prevent one of the outcomes listed in the SAE definition. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias, or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 54 of 73 
10.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
10.3.3.1 SEVERITY OF EVENT 
These are the guidelines to describe the severity of AEs: 
Mild. Events require minimal or no treatment and do not interfere with the participant’s daily activities.  
Moderate. Events result in a low level of inconvenience or concern with the therapeutic measures. Moderate 
events may cause some interference with daily functioning. 
Severe. Events interrupt a participant’s usual daily activity and may require systemic drug therapy or other 
treatment. Severe events are usually potentially life threatening or incapacitating. Of note, the term “severe” 
does not necessarily equate to “serious.” 
10.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
All severe AEs and SAEs must have their relationship to trial intervention assessed by the clinician who examines 
and evaluates the participant based on temporal relationship and her/his clinical judgment. We will grade the 
degree of certainty about causality by using the categories below. 
Related. We know the AE occurred with the trial intervention, there is a reasonable possibility that the trial 
intervention caused the AE, or there is a temporal relationship between the trial intervention and event. 
Reasonable possibility means that there is evidence to suggest a causal relationship between the trial 
intervention and the AE. 
Not Related. There is not a reasonable possibility that the administration of the trial intervention caused the 
event, there is no temporal relationship between the trial intervention and event onset, or there is an 
established alternate etiology. 
10.3.3.3 EXPECTEDNESS 
The site investigators will be responsible for determining whether a severe AE or SAE is expected or unexpected. 
A severe AE or SAE will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described for the trial intervention. 
Potential events could include the following.  
• 
Anxiety 
• 
Depression 
• 
Feeling stigmatized or threatened 
10.3.4 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The study team will provide participants with a site-specific telephone number to report severe AEs or SAEs. 
Since this study will not administer the COVID-19 vaccine or any other intervention beyond the app, the study 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 55 of 73 
team will not actively solicit AEs or SAEs or monitor any events related to COVID-19 vaccination. When site 
coordinators or site investigators learn of a severe AE or SAE, they will refer participants to their primary care 
physician and will record the severe AE or SAE into the EDC and will track the SAE.  
Site coordinators/research team members will record severe AEs as described in the next section and in the 
(MOP). Severe AE data collection typically includes event description, time of onset, if available, resolution time 
and day, if available, and the site investigator’s assessment of severity, relationship to study participation or 
intervention (assessed only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. Site coordinators/research team members must appropriately document 
severe AEs occurring during the trial, regardless of relationship to the trial. The study team will track severe AEs 
until one of the following criteria are met: resolution, the condition stabilizes, the event is otherwise explained 
or is judged by the site investigator to be no longer clinically significant, or the participant withdraws from the 
study. The study team will track all SAEs by asking site coordinators/research team members about the SAE 
every 14 days until resolution or until the site investigator determines the event is chronic or until the 
participant is stable. The DCOC may request other supporting documentation of the event, and site investigators 
or site coordinators should provide this documentation as soon as possible.  
Site coordinators/research team members will document changes in a severe AE in the source document and 
EDC to allow for an assessment of the duration of the event. Severe AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
Participants may report severe AEs for seven days after completing all study procedures and SAEs for 30 days 
after completing all study procedures. Site coordinators and/or DCOC safety personnel will record and track 
according to this protocol and DCOC standard operating procedures (SOPs).  
10.3.5 ADVERSE EVENT REPORTING 
Severe AEs will be included in the statistical analysis, and site coordinators/research team members will 
document severe AEs in the EDC system and follow the reporting procedures outlined in the MOP. The MOP 
section on documenting severe AEs will encompass the requirements of the: 
1. cIRB policies and procedures 
2. SOPs for the Streamlined, Multisite, Accelerated Resources for Trials IRB Reliance platform (SMART IRB) 
3. ICH E6(R2), GCP: Integrated Addendum to ICH E6(R1): Guidance for Industry  
4. local IRB policies and procedures, when applicable. If there are discrepancies between the procedures, 
the most stringent of the procedures will be followed.  
The DCOC will report severe AEs to the cIRB for its yearly continuing review. The DCOC will report to the central 
IRB (cIRB), as specified in the study-specific IRB communication plan, based on recommendations of the SMART 
IRB. Sites will also report severe AEs to the local IRB, per local IRB policies and procedures, and make them 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 56 of 73 
available to the sponsor (DCOC) on a continuing basis through the EDC system. The study team will report to the 
DSMB, per the DSMB charter.  
The trial-specific MOP will describe the details of the reporting structure and additional details related to 
timelines for reporting.  
The specific regulations of the FDA do not apply to this protocol because this is not an FDA-regulated trial. 
10.3.6 SERIOUS ADVERSE EVENT REPORTING 
Site coordinators/research team members will document all SAEs in the EDC, and the DCOC will report SAEs, per 
Table 3 below. The DCOC will notify monitoring personnel (e.g., medical monitor) and monitoring bodies (e.g., 
DSMB), per the DSMB charter.  
Table 3. SAE Reporting. 
Report to 
Timing 
Notes 
cIRB (SMART IRB definition) 
Yearly (minimum)/at continuing review 
For continuing review; 
Submitted to IRB via DCOC 
Local IRB 
Per local IRB policies and procedures 
 
DCOC (Sponsor, per SMART IRB 
definitions, and lead trial team) 
Immediately, but no later than 48 hours after 
finding out about the event 
CO-SOP-012.v1.0/SOP 
Overall PIs (per SMART IRB 
definitions) 
Immediately, but no later than 24 hours after 
finding out about the event 
 
Medical Monitor 
Per DSMB charter 
 
DSMB 
Per DSMB charter 
 
 
The study team will track all SAEs until satisfactorily resolved or the site investigator deems the event is chronic 
or the participant is stable. The DCOC/trial sponsor may request other supporting documentation, and sites 
should provide this as soon as possible. 
The DCOC will ensure the summary is accurate and will report of SAE data to the cIRB in time for consideration 
at the next continuing review. The DCOC will also create and provide any SAE data summaries requested by the 
monitors or specified in the DSMB charter. The site investigators will be responsible for following their local 
institution’s requirements. 
The MOP has additional details. 
10.3.7 REPORTING EVENTS TO PARTICIPANTS 
The study team will notify participants of those trial-related (or potentially trial-related) SAEs that may affect 
their willingness to continue with the trial or their future health. Any of the following can determine if study 
personnel should contact participants: the IRB, the medical monitor, the DSMB, or the PIs. The person or 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
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Date: 02/13/2023 
Page 57 of 73 
oversight body that makes the determination will inform the DCOC, which will instruct the site investigators and 
site coordinators to contact the participants consented through their site. 
Site coordinators/research team members will record any contact with participants, if necessary, in the EDC 
and/or trial log. 
10.4 
UNANTICIPATED PROBLEMS 
10.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to subjects 
or others (UPIRTSOs) to be any problem, event, or new information that is: 
• 
Unanticipated or unexpected; 
• 
Related to the research; and  
• 
Involves new or increased risks to subjects or others.  
A UPIRTSO is not necessarily an AE or an SAE. For example, a breach of confidentiality is a potential UPIRTSO 
that is not an AE or SAE. 
The MOP provides additional details. 
10.4.2 UNANTICIPATED PROBLEM REPORTING 
Site coordinators/research team members must report potential UPIRTSOs, per this protocol, to the cIRB, via the 
method(s) specified in the MOP, and directly to the DCOC. If the cIRB determines the issue is, indeed, a 
UPIRTSO, the DCOC will notify persons and entities as required by cIRB policies and procedures, the study-
specific communication plan, and the DSMB charter. Site coordinators/research team members must also report 
these events to their local institutions according to the rules and regulations of the local institution. The cIRB will 
report the issue to OHRP, per the policies of the cIRB. The cIRB required reporting times are provided in the 
contemporaneous version of 10.2, Information that must be reported to the IRB and IRB actions, which is 
available via http://irb.uams.edu/irb-policies/current-irb-policies/principal-investigator-responsibilities/. The 
reporting times, at the time of the approval of this protocol, are in the table below.  
Table 4. Unanticipated Problem Reporting (per UAMS IRB policy at time of approval of this protocol). 
Unanticipated Problem 
Required Reporting Time to cIRB 
Death or life-threatening 
Immediately to IRB office or IRB Chair 
All other events 
Within 10 days of event or notification of event if non-local 
 
10.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS 
For reporting UPIRTSOs to participants, we will follow the same procedures as described in Section 10.3.7, 
Reporting Events to Participants.  

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
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Date: 02/13/2023 
Page 58 of 73 
 
11. 
STATISTICAL CONSIDERATIONS 
11.1 
STATISTICAL HYPOTHESES 
Our hypothesis for our primary endpoint is that unvaccinated children of caregivers assigned to the Vaccine 
Uptake app will be more likely to achieve COVID-19 vaccine series completion than those children whose 
caregivers are assigned to the General Health app. The null hypothesis is that the vaccination series completion 
rate among children of caregivers assigned to the Vaccine Uptake app will not differ from the vaccine series 
completion rate among children of caregivers assigned to the General Health app.  
11.2 
SAMPLE SIZE DETERMINATION 
The primary outcome for this study is the proportion of unvaccinated children who complete the COVID-19 
vaccine series during the study period. The underlying assumption, based on available data for ISPCTN site 
states, is that without the mHealth intervention, the COVID-19 vaccine uptake would occur in 30% of children. 17 
Justification of primary outcome effect size. Table 5 summarizes vaccination rates among children 12-17 years 
old through July 31, 2021, as published by the CDC.48 Based on these data, we see that vaccination rates decline 
with decreasing age and that ECHO ISPCTN states demonstrate a trend toward lower overall and by-age 
vaccination rates.  When excluding Vermont, Rhode Island, and New Hampshire (states that are part of the 
highest regional vaccine uptake rates in the US), the other 15 ECHO ISPCTN states have vaccination rates 
significantly lower than non-IDeA states. Assuming that cumulative vaccination rates continue to increase over 
time and that vaccination rates for children <12 years old will continue the trend toward lower vaccination rates, 
we anticipate that 30% overall vaccination rates among eligible children at the time of study launch is 
reasonable. 
Table 5. Proportion of Children 12-17 yrs. old who completed COVID-19 vaccination by July 31, 2021  
 
12-17 Med[IQR] 
16-17 years old 
14-15 years old 
12-13 years old 
Overall  
30% [25%-42%] 
40% [32%-51%] 
29% [24%-41%] 24% [19%-34%] 
IDeA State Residents  
24% [20%-37%] 
33% [26%-49%] 
23% [19%-35%] 20% [14%-32%] 
IDeA State Residents 
(excluding New England)  
23% [19%-36%]* 
31% {26%-45%] 
22% [18%-29%] 19% [14%-31%] 
Non-IDeA State Residents  
32% [25%-42%] 
41% [32%-51%] 
29% [24%-41%] 25% [19%-34%] 
*Difference from non-IDeA state residents (p=0.028)  
 
We based the 10% increase in vaccination rates on the cumulative estimated effects of intervention components 
within the Vaccine Uptake app. As discussed in the Background, behavioral nudges such as text messages (i.e., 
push notifications within the app) are associated with a 5% increase in vaccination rates.49 App-based education 
and communication has shown variable increases in vaccination rates and intent to vaccinate, up to 8-10%.50,51 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
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Thus, a combined 10% increase in vaccination rates is reasonable to expect from the Vaccine Uptake app since it 
combines multiple approaches in the same intervention.   
Public Health Impact. In this study, we are estimating that using the Vaccine Uptake app will result in a 10% 
increase in the proportion of children who will complete COVID-19 vaccination. When looking at the impact of a 
10% increase in pediatric vaccination rates, based on a US population of 53.7 million children 5-17 years of age,52 
such an increase would result in an additional 5 million vaccinated children. Previous research has shown that 
app-based vaccine uptake interventions are less costly than more traditional methods, such as paper handouts 
and communication tools. We estimate a cost of $10,000 dollars for the first year of a customized version of the 
Vaccine Uptake app per state. Deployment of the Vaccine Uptake app nationally would cost a little as $500,000 
dollars per year, or 10 cents per additional child who completes COVID-19 vaccination. 
In determining sample size, each caregiver is considered to be a cluster with an average of 2 unvaccinated 
children. To demonstrate an improvement in the proportion of unvaccinated children of caregivers who 
complete the COVID-19 vaccination series due to the mHealth intervention from 30% to 40%27,53,54 would require 
758 caregivers (379 per arm), at the two-sided 0.05 significance level with power of 0.90 and an intraclass 
correlation coefficient of 0.60. The table below shows the sample size needed to have 90% power to detect a 
10-percentage point increase in the proportion of children who complete the vaccination series using the 
Vaccine Uptake app with varying levels of intraclass correlation. To ensure that there are at least 758 caregivers, 
the primary analysis population, we expect to randomize 892 caregivers to account for up to 15% of randomized 
participants who do not use the Vaccine Uptake app or General Health app after downloading it during 
enrollment. 
Intraclass 
Correlation 
Coefficient 
Sample Size 
0.40 
331 per arm (662 total) 
0.50 
355 per arm (710 total) 
0.60 
379 per arm (758 total) 
0.70 
402 per arm (804 total) 
0.80 
426 per arm (852 total) 
 
11.3 
POPULATIONS FOR ANALYSES 
This study will have three analysis populations: 
1. ITT population – This population will include all participants randomized into the study. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 60 of 73 
2. Modified ITT (mITT) population – This population will include all participants who are randomized into 
the study, were eligible for the study, and completed at least one session in the app involving the use of 
at least one pathway. 
3. Per-protocol (PP) population - This population will include all participants in the mITT population who 
were maintained in the study for the full 27 weeks. 
The primary population for analysis will be the ITT population. Study statisticians will perform additional 
analyses on the PP and mITT populations. 
11.4 
STATISTICAL ANALYSES 
11.4.1 GENERAL APPROACH 
Following finalization of the protocol, but prior to data lock, the DCOC statistical team will issue a Statistical 
Analysis Plan (SAP) as a separate document, which will provide detailed analytical plans for the set of analyses 
outlined below. The statistical team will conduct all statistical analyses following the statistical principles for 
clinical trials as specified in ICH Statistical Principles for Clinical Trials (ICH Topic E9). The study team will describe 
and justify any deviations from the planned analyses in the final integrated clinical study report. The study team 
will present all study data and summary tables for the overall study and by study sites. 
The statistical team will summarize descriptive statistics for continuous data by using mean and standard 
deviation or median and interquartile range, as appropriate. The team will also summarize categorical data by 
using frequency and percent, and they will investigate any outliers detected during data review and will define 
in the SAP methods for handling outliers or data transformation. 
11.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
COVID-19 Vaccine Series Completion. For each vaccine-eligible child, the primary endpoint will be whether or 
not the child initiates and completes the COVID-19 vaccine series during the 24 weeks of the intervention 
period. The study team will define vaccine series completion as per the current ACIP guidance for the vaccine 
product. For children who receive a product that requires more than 2 doses for the primary series, receipt of up 
to 3 doses will be considered complete. Vaccine doses will only be valid for study purposes if given within the 24 
weeks of study participation. Additional doses, when required for primary series completion, will only be valid if 
they are in accordance with ACIP-recommended interval minus a 4-day grace period, in accordance with 
recommendations of the ACIP. Also, per ACIP, there will be no maximum interval between valid doses. Incorrect 
second vaccine product (i.e., mixed series) will be invalid for study purposes. The statistical team will use a 
mixed model with the binomial distribution and the logit link to compare the two intervention groups with 
respect to the proportions of children who complete COVID-19 vaccination, using a site random effect and 
controlling for clustering by caregiver.   

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 61 of 73 
11.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Vaccine Series Initiation. For each vaccine-eligible child, this secondary endpoint will be defined as whether or 
not the child initiates the COVID-19 vaccine series during the 16 weeks of study participation. Vaccine series 
initiation will be receipt of at least 1 valid dose of any COVID-19 vaccine product. Vaccine doses for series 
initiation will only be valid for study purposes if given within the 16 weeks of study participation. The statistical 
team will use a mixed model with the binomial distribution and the logit link to compare the two intervention 
groups with respect to the proportions of children who initiate COVID-19 vaccination, using site as a random 
effect and controlling for clustering by caregiver.  
Parental attitude toward pediatric COVID-19 vaccination. The study team will evaluate parental attitude 
toward pediatric COVID-19 vaccination by using the vaccine hesitancy questionnaire that includes ten 
statements with ordinal responses using a 5-point Likert scale. At baseline and week 16, the study statisticians 
will generate summary statistics for each of the 10 questions for the two intervention groups. Similarly, the 
change in responses from baseline to end of study will be determined for each intervention group. The study 
statisticians will use the general linear mixed model to evaluate the intervention effect on responses to each 
measure at baseline and end of study, and they will use this model to evaluate the change in each measure by 
using site as a random effect. Within each intervention arm and for each statement, the study statisticians will 
use the Wilcoxon signed rank test to determine if the change in response from baseline to end of study is 
significantly different from zero. 
11.4.4 SAFETY ANALYSES 
The DCOC will detail reported intervention-related severe AEs and SAEs experienced by participants and will 
summarize these by the intervention arm. The DCOC will present summary statistics for overall and by sites. 
11.4.5 BASELINE DESCRIPTIVE STATISTICS 
The statistical team will summarize baseline and demographic characteristics by intervention group and will 
apply summary statistics for both continuous and categorical variables. For continuous variables, descriptive 
measures will include number of non-missing values, mean, standard deviation, median, minimum, and 
maximum. For categorical variables, descriptive statistics will include frequency counts and percentages by 
category. 
11.4.6 PLANNED INTERIM ANALYSES 
There are no planned interim analyses of efficacy for this study.  
11.4.7 SUB-GROUP ANALYSES 
If there are enough study participants in specific racial/ethnic categories and or urban/rural and/or age group 
categories, the study team will perform the planned analyses for the primary efficacy analyses within subgroups. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
Page 62 of 73 
11.4.8 SENSITIVITY ANALYSES 
While some participants may choose not to use the app beyond the initial download session, their outcomes will 
still be assessed and used to determine efficacy of the intervention. App interactions—or lack thereof—will be 
informative to understanding how participants engage with delivered content and how those interactions—or 
lack thereof—correlate with primary and secondary endpoints. The statistical team will use logistic regression 
analyses to determine the association between mHealth usage levels and completion or initiation of COVID-19 
vaccine series. 
11.4.9 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
The statistical team will provide a detailed description of participant disposition, will tabulate the number of 
enrolled participants overall and by study site, and will present this data as counts and percentages. 
Additionally, the statistical team will summarize the number of participants either completing or discontinuing 
the study using counts and percentages. 
11.4.10 EXPLORATORY ANALYSES 
The statistical team will use logistic regression analyses to determine the association between demographic 
factors including rurality and completion or initiation of COVID-19 vaccine series. 
 
12. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
12.1 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
12.1.1 STUDY DISCONTINUATION AND CLOSURE 
The trial may be suspended or stopped per any stopping/suspension specifications in the DSMB charter. The 
cIRB may also stop or suspend the trial. Early termination of the study may be permanent if there is sufficient 
cause. 
The suspending or terminating party will provide, directly or indirectly, written notification documenting the 
reason for trial suspension or termination to the following, as applicable: trial participants, PIs, site investigators, 
cIRB, local IRBs, NIH, DCOC, and OHRP. Persons and offices notified will include those specified in the trial MOP, 
the cIRB’s policies and procedures, and the SMART IRB policies and procedures.  
The suspending or terminating party will also contact trial participants and inform them of any changes to the 
trial visit schedule. Circumstances that may warrant trial termination or suspension include, but are not limited 
to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol requirements 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
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• 
Data that are not sufficiently complete and/or evaluable 
If the trial is temporarily suspended, it may resume once concerns about safety, protocol compliance, and data 
quality are addressed and are satisfactory to the DSMB, the cIRB, the local IRB(s) (when applicable), the funding 
agency, and the DCOC. 
12.1.2 CONFIDENTIALITY AND PRIVACY 
The study team will record data from the software to a HIPAA-compliant cloud PostGres Azure database. Sites 
and study team members will conduct all trial activities in as private a manner as possible.  
Records will be maintained as required by the privacy and security rules promulgated by the HIPAA (Title 45 of 
the CFR Part 164). 55,56  
During the trial, site investigators and/or site coordinators will keep all trial records in secure locations that only 
authorized personnel can access. Examples of secure locations include but are not limited to: 1) locked file 
cabinet(s) in a limited (badge or key) access room, or 2) password-protected computer systems. Study personnel 
may only transmit records that contain PHI, as defined by HIPAA, through an open email system if the personnel 
encrypt the data. Password protection alone is insufficient for data transmission through an open email system 
(e.g., Outlook). After trial completion, access to trial records will be limited (see next section).  
Certain bodies/institutions may need to review information, including the participant information, for any of the 
following reasons: to process information or to ensure compliance with the protocol and other applicable 
requirements (such as the policies and procedures of the cIRB). Institutions/bodies that may have access to the 
participants’ information include:  
• 
UAMS IRB (cIRB) and other oversite offices 
• 
IRB for the site through which the participant is consented 
• 
OHRP 
• 
DCOC  
• 
NIH 
Individuals with access to trial records will be: 
• 
Study PIs 
• 
Site investigators 
• 
Site coordinators 
• 
Data managers at enrolling site(s) 
12.1.3 FUTURE USE OF STORED SPECIMENS AND DATA 
No specimens will be collected or stored for this trial. Regarding stored data, site investigators, site coordinators, 
and study team members will document all trial interactions, and these will be password protected in a secured 
facility/location.  

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
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The study team will place participant’s de-identified data and other limited information, such as race and ethnic 
group, into one or more centralized database(s). The study team will share this data in compliance with the NIH 
data sharing policy.  
For future studies using any procedures or analysis not specified in this protocol, IRB approval is required.  
If another investigator/collaborator has a meaningful purpose for accessing the data retrieved in this protocol, 
the DCOC must consult the PIs and the cIRB must approve. 
12.1.4 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigators 
Russell J. McCulloh, MD 
University of Nebraska Medical Center 
physical work address 
402-955-5400 
rmcculloh@childrensomaha.org  
Ellen Kerns, PhD, MPH 
University of Nebraska Medical Center 
8404 Indian Hills Drive, Omaha, NE 68114 
(402)-955-6038 
Ellen.kerns@unmc.edu 
Paul Darden, MD 
University of Arkansas for Medical Sciences 
13 Children’s Way, Slot 842, Little Rock, AR 72202 
(501) 364-5020 
PMDarden@uams.edu  
Operational Principal Investigator 
Jessica Snowden, MD 
University of Arkansas for Medical Sciences 
13 Children’s Way, Slot 512-35, Little Rock, AR 72202 
501-364-4693 
jsnowden@uams.edu 
Medical Monitor 
Rebecca Latch, MD 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
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University of Arkansas for Medical Sciences 
13 Children’s Way, Slot 512-35, Little Rock, AR 72202 
+1 (501) 364-1050 
LatchRebeccaL@uams.edu  
 
The clinical trial outlined in this protocol is part of the ECHO ISPCTN, a branch of the program supported by the 
NIH. 
The data coordination, technical instruction, data standards, quality control (QC) and quality assurance (QA), 
and operational coordination for the clinical trial protocol outlined here (and for the ECHO ISPCTN overall) is 
provided by the DCOC. 
The Steering Committee governs the ECHO ISPCTN and includes representatives from all site awardees, as well 
as representatives from the DCOC and the NIH. Overseeing the work of the Steering Committee is the NIH ECHO 
office, as well as an executive Leadership Committee.  
A team of content experts and DCOC staff completed this protocol, and the ECHO ISPCTN Steering Committee 
reviewed it. The NIH Protocol Review Committee and the DSMB further reviewed the protocol.  
12.1.5 SAFETY OVERSIGHT 
Ensuring participant safety is the responsibility of all study team members, especially the PIs, site investigators, 
site coordinators, and monitors. A medical monitor and the DSMB will provide oversight.  
The medical monitor will be a pediatrician with expertise in infectious disease and vaccinations and will be 
independent of the trial. The NIH will convene the DSMB, and it will meet regularly, according to its charter.  
The entities that will receive reports include, but are not limited to, the DCOC and the NIH. The DSMB charter 
will provide additional information. 
12.1.6 CLINICAL MONITORING 
We will conduct enrolling site monitoring to ensure that site investigators and site coordinators are protecting 
the rights and well-being of trial participants, that the reported trial data are accurate, complete, and verifiable, 
and that the conduct of the trial complies with the currently approved protocol/amendment(s), with ICH GCP, 
and with applicable regulatory requirement(s).  
• 
A DCOC team member or designee will remotely monitor enrolling sites to ensure data quality and 
integrity via weekly phone meetings and queries of EDC entries.  
• 
On-site monitoring visits will also be performed at each site, per the Site Monitoring Plan, if needed for 
cause. 
• 
The DCOC will conduct an enrolling site close-out visit at the end of the study. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
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• 
Clinical site monitors will document details of their activities and findings, per the Site Monitoring Plan. 
The Site Monitoring Plan describes the monitoring details (i.e., who will conduct, at what frequency, at 
what level of detail, and distribution of monitoring reports). 
12.1.7 QUALITY ASSURANCE AND QUALITY CONTROL 
Each IRB-approved site entering data will perform internal quality management of study conduct, data 
collection, documentation, and completion. Each site will follow the MOP and any additional written site-specific 
SOPs. The operating procedures will include, but are not limited to, procedures for: 1) performing the consent 
process; 2) data collection, entry, review, and submission processes; 3) assigning roles and responsibilities of site 
personnel; and 4) training methods for study staff. Sites will provide direct access to all their facilities, source 
data/documents, and reports for the purpose of monitoring and auditing by the DCOC and inspection by local 
and regulatory authorities. When electronic health records are source data/documents, sites must provide read-
only access for the monitors and auditors and anyone else authorized to inspect or verify records. 
Following the DCOC monitoring SOPs, the monitors will verify that the site is conducting the clinical trial and 
generating, documenting (recording), and reporting data in compliance with the protocol, the Site Monitoring 
Plan, site-specific SOPs, the ICH GCP E6(R2), and applicable regulatory requirements.  
The DCOC will implement quality control procedures for the database and DCOC-maintained records in 
accordance with the Site Monitoring Plan, MOP, data safety monitoring plan (DSMP), and applicable SOPs. The 
DCOC may communicate information about any data anomalies to the site(s) for clarification/resolution. 
The DCOC will address issues uncovered during quality assurance, quality control, or monitoring activities 
through simple corrections or root-cause analysis, followed by instituting corrective and preventative action 
(CAPA), as appropriate and as described in the MOP.    
12.1.7.1 
DATA QUALITY ASSURANCE 
To assure the quality of the data collected, the protocol study team will provide training specific to entering data 
related to the endpoints of initiation and completion of COVID-19 vaccination. The site research team will re-
confirm a subsample of participating caregivers’ report of COVID-19 vaccination for their child/children.  
The DCOC will provide sites with the randomly selected caregiver IDs for re-confirmation. After the sites 
complete the re-confirmation process, the DCOC will identify discrepancies and the DCOC site manager will 
meet with the site research coordinator and/or site investigator to review any discrepancies. Together they will 
discuss and document the corrective action for each error identified. The corrective action may include updating 
discrepant data in the EDC system or additional training. The DCOC will keep the protocol study team informed 
of the kinds and types of discrepancies.  
 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
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12.1.8 DATA HANDLING AND RECORD KEEPING 
12.1.8.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
A formal data management plan will describe and document the data and workflow for the trial. The data 
management plan and associated documentation will specify all operations performed on data from origination 
to database lock, including detailed descriptions of source documentation, case report forms (CRF), instructions 
for completing forms, data handling and record keeping procedures, procedures for data monitoring, and 
reconciliation procedures and coding dictionaries to be used, if applicable. The data management plan will also 
describe the specific data collection and management responsibilities required of the sponsor, PIs, site 
investigators, site awardees, clinics, and DCOC. The data management plan contents will be consistent with 
those described in the Good Clinical Data Management Practices (GCDMP). The DCOC will provide the data 
management plan components that document operations performed on the data to the PIs for review and 
approval prior to implementation. 
Data collection is the responsibility of the trial staff at the individual sites under the supervision of the site 
investigator. The site investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. All source documents must be completed using standard good documentation 
practices (i.e., the ALCOA-C method [attributable, legible, contemporaneous, original, accurate and complete]). 
It is best practice for site coordinators to use hardcopies of any data recorded on paper case-report forms or 
trial visit worksheets/assessment forms as source document worksheets for recording data for each participant 
consented. Data recorded in EDC derived from source documents must be consistent with the data recorded on 
the source documents.  
Site personnel will enter data (including demographics and intervention-specific questionnaires) into an EDC 
system that complies with HIPAA regulations, provided by the DCOC. During this process, sites will assign each 
participant a participant identification number and include this number in the EDC and source documents. The 
EDC system includes password protection and internal quality checks, such as automatic range checks, to 
identify data that appear inconsistent, incomplete, or inaccurate. Study personnel will enter clinical data directly 
from the source documents. 
12.1.8.2 STUDY RECORDS RETENTION 
Throughout the course of the trial, all sites will retain the source documents on site in accordance with current 
site-specific medical record storage procedures. 
Sites must retain all trial documents in accordance with local and/or federal regulations, whichever is most 
stringent. Sites will not destroy any records without the written consent of the DCOC. The DCOC will inform all 
site investigators when they no longer need to retain these documents. 

Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
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12.1.9 PROTOCOL DEVIATIONS 
Protocol deviations are any instances in which study team members and site personnel (e.g., site investigator, 
site coordinator, etc.) do not follow the study procedures as written in the protocol. Protocol deviations are not 
allowed, unless the DCOC or Operational PI gives specific written permission for the deviation. Anyone who 
receives written permission for a protocol deviation must keep this with other study documentation. Sites must 
record all deviations in the trial source documents. Whenever a deviation occurs, the DCOC will conduct an 
assessment (which they do not need to write) of the severity and risk of the deviation. Depending on the results 
of the assessment, the DCOC will request/ensure that there is either a corrective action or a simple one-time 
correction, as appropriate. A corrective action institutes a process designed to keep the specific problem from 
reoccurring. Typically, assessors will determine the root cause of the problem to develop the most appropriate 
corrective action plan. 
We will provide the specific methods for handling deviations in the trial-specific MOP and/or trial-specific SOPs.  
12.1.10 PUBLICATION AND DATA SHARING POLICY 
We will conduct this trial in accordance with the following publication and data sharing policies and regulations: 
• 
NIH Public Access Policy, which ensures that the public has access to the published results of NIH-
funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from 
NIH funds to the digital archive PubMed Central upon acceptance for publication. 
• 
ECHO ISPCTN Publications and Presentations Policy, which ensures accurate, responsible, and efficient 
communication of findings from ECHO ISPCTN clinical trials. The ECHO ISPCTN Steering Committee has 
approved and ratified the ECHO ISPCTN Publications and Presentations Policy, which includes 
representatives from all site awardees, as well as representatives from the NIH and the DCOC.  
• 
NIH Data Sharing Policy and the policy on the Dissemination of NIH-Funded Clinical Trial Information 
and the Clinical Trials Registration and Results Information Submission Rule. We will register this trial 
at ClinicalTrials.gov, and we will submit trial results to ClinicalTrials.gov. In addition, we will make every 
attempt to publish results in peer-reviewed journals. Other researchers my request data from this trial 
by contacting Jeannette Lee, PhD, at the DCOC.  
12.1.11 CONFLICT OF INTEREST POLICY 
The independence of this trial from any actual or perceived influence, such as by the pharmaceutical industry, is 
critical. Therefore, we will disclose and manage any actual conflict of interest of persons who have a role in the 
design, conduct, analysis, publication, or any aspect of this trial. Furthermore, persons who have a perceived 
conflict of interest will be required to have such conflicts managed in a way that is appropriate to their 
participation in the design and conduct of this trial. The trial leadership in conjunction with the NIH ECHO office 
has established policies and procedures for all trial group members to disclose all conflicts of interest and will 
establish a mechanism for the management of all reported dualities of interest. 

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12.2 
ADDITIONAL CONSIDERATIONS 
n.a.  
 
 

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13. 
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Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
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Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
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cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
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Title: Improving pediatric COVID-19 vaccine uptake using an mHealth tool: a randomized, controlled trial 
 
PI: Jessica Snowden, MD 
  
Version #: 10 
cIRB (UAMS IRB) #: 273761 
Date: 02/13/2023 
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