Evaluating an eHealth Solution for Screening in Pediatric Care
Phase: NA
Conditions: Pain, Stress Disorders, Post-Traumatic
Sponsor: Children's Hospital of Philadelphia

 
Template version: May 28, 2014 
PROTOCOL TEMPLATE: INTERVENTION STUDY (CLINICAL TRIALS) 
  
Title: 
Evaluating an eHealth solution for screening in pediatric care 
Short Title 
Evaluating eHealth solution for screening 
Drug or Device 
Name(s): 
N/A 
FDA IND 
N/A 
Regulatory Sponsor: 
N/A 
eIRB Number 
IRB 20-017351 
Protocol Date: 
1 December 2021 (Last approved by IRB on 3 February 2022) 
Amendment 1 Date:  
Amendment 3 Date:  
Amendment 2 Date: 
Amendment 4 Date: 
Sponsor  
National Institute of Child Health and Human Development (NICHD) 
 
Study Principal Investigator (multicenter study with CHOP PI responsible) 
Nancy Kassam-Adams, PhD 
Children’s Hospital of Philadelphia 
Roberts Center for Pediatric Research - 2716 South Street, 13th floor (13-291) 
Philadelphia PA  19146  
Office 215-590-3118 
email: adamsn@email.chop.edu  
Site Principal Investigator - University of Kentucky 
Meghan L. Marsac, PhD 
800 Rose Street, MN 472 
Lexington, KY 40536 
Office: 859-323-3850  
email: meghan.marsac@uky.edu   
 

  
 
 
 
 
 
 
 
ii
TABLE OF CONTENTS 
Table of Contents ................................................................................................................... ii 
Abbreviations and Definitions of Terms ............................................................................. iv 
Abstract .................................................................................................................................. v 
Table 1: Schedule of Study Procedures ............................................................................. vii 
Figure 1: Study Diagram .................................................................................................... viii 
1 
BACKGROUND INFORMATION AND RATIONALE ....................................................................... 1 
1.1 
INTRODUCTION ..................................................................................................................................... 1 
1.2 
NAME AND DESCRIPTION OF INVESTIGATIONAL PRODUCT OR INTERVENTION ..................................... 2 
1.3 
RELEVANT LITERATURE AND DATA ..................................................................................................... 2 
1.3.1 
Background and rationale ............................................................................................................... 2 
1.3.2 
Measures addressing primary and secondary study aims ............................................................... 3 
1.4 
COMPLIANCE STATEMENT .................................................................................................................... 5 
2 
STUDY OBJECTIVES .............................................................................................................................. 5 
2.1 
PRIMARY OBJECTIVE (OR AIM) ............................................................................................................ 5 
2.2 
SECONDARY OBJECTIVES (OR AIM) ...................................................................................................... 5 
3 
INVESTIGATIONAL PLAN .................................................................................................................... 6 
3.1 
GENERAL SCHEMA OF STUDY DESIGN ................................................................................................. 6 
3.1.1 
Screening & Baseline Research Assessment ................................................................................... 6 
3.1.2 
Study Treatment Phase .................................................................................................................... 6 
3.1.3 
Follow-up ........................................................................................................................................ 7 
3.2 
ALLOCATION TO TREATMENT GROUPS AND BLINDING ........................................................................ 7 
3.3 
STUDY DURATION, ENROLLMENT AND NUMBER OF SITES ................................................................... 7 
3.3.1 
Duration of Study Participation ...................................................................................................... 7 
3.3.2 
Total Number of Study Sites/Total Number of Subjects Projected .................................................. 7 
3.4 
STUDY POPULATION ............................................................................................................................. 8 
3.4.1 
Inclusion Criteria ............................................................................................................................ 8 
3.4.2 
Exclusion Criteria ........................................................................................................................... 8 
4 
STUDY PROCEDURES ............................................................................................................................ 8 
4.1 
SCREENING & BASELINE RESEARCH ASSESSMENT ............................................................................... 8 
4.2 
STUDY TREATMENT PHASE .................................................................................................................. 9 
4.3 
FOLLOW-UP .......................................................................................................................................... 9 
4.4 
SUBJECT COMPLETION/WITHDRAWAL ............................................................................................... 10 
5 
STUDY EVALUATIONS AND MEASUREMENTS ............................................................................ 10 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS ................................................ 10 
5.1.1 
Medical Record Review ................................................................................................................. 10 
5.2 
EFFICACY EVALUATIONS ................................................................................................................... 10 
5.2.1 
Diagnostic Tests, Scales, Measures, etc. ....................................................................................... 10 
5.3 
SAFETY EVALUATION ......................................................................................................................... 11 
6 
STATISTICAL CONSIDERATIONS .................................................................................................... 11 
6.1 
PRIMARY ENDPOINT ........................................................................................................................... 11 
6.2 
SECONDARY ENDPOINTS .................................................................................................................... 12 
6.3 
STATISTICAL METHODS ...................................................................................................................... 12 
6.3.1 
Baseline Data ................................................................................................................................ 12 
6.3.2 
Efficacy Analysis ........................................................................................................................... 12 
6.4 
SAMPLE SIZE AND POWER .................................................................................................................. 13 
7 
STUDY INTERVENTION ...................................................................................................................... 14 

 
 
 
 
 
 
 
 
iii 
7.1 
DESCRIPTION ...................................................................................................................................... 14 
7.1.1 
Treatment Compliance and Adherence ......................................................................................... 15 
8 
SAFETY MANAGEMENT ..................................................................................................................... 15 
8.1 
CLINICAL ADVERSE EVENTS .............................................................................................................. 15 
8.2 
ADVERSE EVENT REPORTING ............................................................................................................. 15 
9 
STUDY ADMINISTRATION ................................................................................................................. 15 
9.1 
TREATMENT ASSIGNMENT METHODS ................................................................................................. 15 
9.1.1 
Randomization............................................................................................................................... 15 
9.1.2 
Blinding ......................................................................................................................................... 15 
9.1.3 
Unblinding .................................................................................................................................... 15 
9.2 
DATA COLLECTION AND MANAGEMENT ............................................................................................ 15 
9.3 
CONFIDENTIALITY .............................................................................................................................. 17 
9.4 
REGULATORY AND ETHICAL CONSIDERATIONS .................................................................................. 18 
9.4.1 
Data and Safety Monitoring Plan ................................................................................................. 18 
9.4.2 
Risk Assessment ............................................................................................................................. 18 
9.4.3 
Potential Benefits of Trial Participation ....................................................................................... 19 
9.4.4 
Risk-Benefit Assessment ................................................................................................................ 19 
9.5 
RECRUITMENT STRATEGY .................................................................................................................. 19 
9.6 
INFORMED CONSENT/ASSENT AND HIPAA AUTHORIZATION ............................................................ 19 
9.6.1 
Waiver of HIPAA Authorization .................................................................................................... 20 
9.7 
PAYMENT TO SUBJECTS/FAMILIES ...................................................................................................... 21 
10 
PUBLICATION ........................................................................................................................................ 21 
11 
REFERENCES ......................................................................................................................................... 22 
Appendix .................................................................................... Error! Bookmark not defined. 
 

  
 
 
 
 
 
 
 
iv
ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
 
Adverse event 
AUC 
 
Area under the curve (in ROC analyses) 
CPSS-5 
 
Child PTSD Symptom Scale for DSM-5 
eScreen 
 
Game-based online screening system under development 
at CHOP 
HRQoL 
 
Health=related quality of life 
NICHD 
 
National Institute for Child Health and Human 
Development 
NIH 
 
National Institutes of Health 
NRSI 
 
Numerical Rating Scale for Pain Intensity 
PPPM 
 
Parents Postoperative Pain Measure 
PROMIS 
 
Patient-Reported Outcomes Measurement Information 
System  
PTS 
 
Posttraumatic stress 
PTSD 
 
Posttraumatic stress disorder 
PTSS 
 
Posttraumatic stress symptoms 
ROC 
 
Receiver Operating Curve  
SCD 
 
Sickle cell disease 
STTR 
 
Small Business Technology Transfer 
 
 
 
 
 
 
 
 
 

  
 
 
 
 
 
 
 
v
ABSTRACT 
Context:   
A significant minority of ill or injured children experience pain or posttraumatic stress 
symptoms (PTSS) that interfere with recovery and may indicate a need for follow-up care 
from the health care team. Many of these phenomena are best reported via children 
themselves, yet there is currently no practical validated means to screen and monitor 
children after hospitalization or a medical event, and connect results of screening to follow-
up care.  The “eScreen” system is being developed as part of an NIH-funded Phase II STTR 
project, and will encompass a game-based system for children, parent messages and 
dashboard, and integration of eScreen findings into the electronic health record. Prior work 
by our team established concurrent validity of eScreen-delivered measures compared to 
validated research measures of pain and posttraumatic stress, in a single assessment for 
research purposes.1 The current project will further evaluate several key components of the 
system (game-based child screening, parent messages / dashboard) as these are used by 
children and parents over a 6 week period. 
Objectives:  
The primary objective of the current prospective validation study is to evaluate predictive 
validity of eScreen measures of pain and PTSS during children’s at-home use of the eScreen 
system to predict ongoing symptoms or problematic recovery at 6 weeks.  
The secondary objective, addressed via randomized assignment of participants to usual care 
plus eScreen  versus usual care, is to evaluate the impact of using the eScreen system on 
factors related to parents’ management of child symptoms and recovery. 
Study Design:  
This study is a randomized controlled trial that will examine validity of eScreen measures 
(primary aim) and assess the impact of the eScreen system on parent management 
(secondary aim). At T1, after baseline assessment (questionnaires), children will be 
randomized to the usual care plus eScreen (eScreen) or usual care alone (Usual Care) 
groups. In the eScreen group, children will use the game-based screening component and 
parents the parent information component for 6 weeks.  All participants will complete 
follow-up research assessments by phone, online, or mail at T2 (6 weeks) and T3 (12 
weeks). Following their T3 research assessment, child participants in the Usual Care group 
will be provided with the option to play the game and invited to provide feedback on the 
game if they wish. 
Setting/Participants: 
We will enroll up to 10 child-parent pairs in a pilot phase and then enroll a cohort of 300 
children (and one parent per child) recently treated for illness or injury at CHOP or 
Kentucky Children’s Hospital inpatient or outpatient services.  

  
 
 
 
 
 
 
 
vi
Inclusion criteria: a) age 8 – 17 years, b) treated or admitted for injury or illness event that 
occurred within the past month, c) child has regular access to a compatible (IOS or Android) 
tablet at home, d) parent has an internet-capable smartphone and can receive text messages 
on that phone OR has email account that can receive messages about child status, and e) the 
child and parent read or understand English well enough to consent / assent to participation 
and complete study tasks (e.g., checklists, use of screening system).  
Exclusion criteria: a) index event is an injury due to family violence. 
Study Interventions and Measures:  
The study intervention includes two key eScreen system components:  
• A child screening component: a set of brief screening measures (of pain, PTSS, 
functional recovery) for children age 8 to 17, delivered within a game played multiple 
times per week on a compatible (IOS or Android) tablet, and  
• A parent information component: weekly messages sent to parents (via text or email) 
that summarize child ratings and include a link to an online dashboard with additional 
personalized information for parents.   
Participants will be randomized to usual care plus eScreen or to usual care alone, in a 2-to-1 
ratio. 
The primary study endpoints employ validated measures of ongoing symptoms / problematic 
recovery: pain (NRSI rating), pain interference (PROMIS Pain Interference T score) and 
PTSS (CPSS-5 scores) at T2 (6 weeks post-baseline). Reflecting our primary aim of 
prediction, the primary study endpoints are not participant scores on these measures, but 
rather the results of ROC analyses; i.e. the area under the curve (AUC) for eScreen pain 
score predicting pain and pain interference and the AUC for eScreen PTSS score predicting 
PTSS.  
The secondary study endpoint relates to the potential impact of the eScreen system on parent 
management of child symptoms and recovery. We will compare eScreen and Usual Care 
groups on parent ratings at T2 of the extent to which they (a) have received the information 
they needed to take care of their child after leaving the clinic or hospital, and (b) have felt 
confident in taking care of their child (related to their illness / injury) in this 6 week period.  
 
 
 
 
           

 
vii  
 
 
 
 
 
 
 
TABLE 1: SCHEDULE OF STUDY PROCEDURES  
Study Phase 
Screening 
and 
Baseline 
Intervention 
(use of eHealth 
tools at home) 
Follow-up 
(phone, online, or mail) 
Visit Number 
T1 
 
T2 
T3 
post-T3 
(optional) 
Informed consent / assent 
X 
 
 
 
 
Review inclusion / exclusion criteria 
X 
 
 
 
 
Demographics / medical history 
X 
 
 
 
 
Complete study questionnaires 
X 
 
X 
X 
 
Randomization  
X 
 
 
 
 
eScreen group:  
Use eScreen system (child screening 
and parent information components) 
 
X 
 
 
 
Usual Care group:  
Optional use of game & feedback on 
game 
 
 
 
 
X 
 
.

 
page viii 
  
 
 
 
FIGURE 1: STUDY DIAGRAM 
 
 
 
 
.
RANDOM ASSIGNMENT 
eScreen group: 
Usual Care plus use of eScreen system child 
screening and parent information components 
T1 
Consent and Baseline Assessment 
Usual Care group 
T3 (12 weeks post-baseline) 
Follow-up Assessment 
T2 (6 weeks post-baseline) 
Follow-up Assessment 
Usual Care group: 
After T3 assessment, optional opportunity for 
child to use game only (no in-game 
assessment / no parent messages)  

 
  
 
 
 
1
1 
BACKGROUND INFORMATION AND RATIONALE 
1.1 Introduction 
Undetected and unaddressed persistent pain and post-traumatic stress symptoms are major 
modifiable factors in suboptimal outcomes after child illness or injury. No solution exists for 
monitoring child self-reported pain, traumatic stress, or functional recovery after hospital or 
clinic discharge. Our team’s NIH-funded STTR project proposes to address this critical, 
systemic problem by focusing on the gap between current approaches for identifying child 
pain and PTSS post-discharge, and the unmet needs of recently ill or injured children, their 
families, health care providers, and health systems. 
Our long-term vision encompasses an integrated screening and intervention system with 
child, parent, provider, and health system integration points. The eScreen system will 
proactively deliver regular screening questions to children, collect child and parent data, and 
connect parents with timely resources via automated follow-up messaging. The child 
screening component is embedded in an episodic game, promoting user engagement and 
measurement fidelity. Screening will be repeated at regular intervals to identify children 
with symptoms or problems, such as persistent/impairing PTSS or pain, that may warrant 
attention by parents or the health care team. Ultimately, raw, aggregate, and derived data 
collected by the system can be made available to external systems via a set of application 
program interfaces (APIs) that utilize industry-standard protocols, maximizing flexibility in 
how data may be integrated into clinical practice, analytics systems, or care management 
platforms.  
Funded via a prior Phase I and current Phase II STTR grant from NICHD, Radiant is the 
small business developing this system, with CHOP and UK as research partners.  Overall 
research aims for Phase II are to evaluate the extent to which eScreen measures delivered via 
a mobile game-based system:  
(a) serve as valid indicators of pain, posttraumatic stress symptoms (PTSS), and 
functional recovery, compared to gold standard (but resource-intensive) means of 
assessment,  
(b) can detect concerns that may warrant follow-up care, i.e. that parents, providers, and 
insurers need to identify or monitor, and  
An additional research aim is to determine whether use of the eScreen system can improve 
adherence with follow-up care and parent / health system awareness and detection of post-
discharge pain, PTSS, and delayed recovery in pediatric patients.  
In keeping with these research aims, in a prior study (IRB-16-013517) we demonstrated 
solid validity for eScreen measures presented in a game-based context compared to 
validated research measures for pain and posttraumatic stress1. The current study will 
evaluate predictive validity of eScreen measures, and evaluate the impact of using the 
eScreen system on parents’ information (i.e., meeting their information needs regarding 
child recovery and care) and confidence regarding management of child symptoms and 
recovery. Future studies will address the impact of making eScreen findings available to the 
health care team.  

 
  
 
 
 
2
1.2 Name and Description of Investigational Product or Intervention 
The study intervention includes two key components of the eScreen system:  
• A child screening component delivered in this study on a compatible (IOS or Android) 
tablet -  A set of brief screening measures for children age 8 to 17, delivered within a 
game played by the child (ideally multiple times per week over the course of at least 6 
weeks), and  
• A parent information component delivered in this study via text or email messages plus a 
dashboard that can be accessed online via any internet-connected device or computer - 
Messages sent to parents (at least weekly) that summarize child ratings and include a 
link to an online dashboard with additional personalized information for parents.   
See further details on eScreen screening measures in Section 1.3.2 and on the eScreen 
system and components in Section 7.   
1.3 Relevant Literature and Data 
1.3.1 Background and rationale  
Undetected and unaddressed persistent pain and post-traumatic stress symptoms are major 
modifiable factors in suboptimal outcomes after child illness or injury. For example, in the 
first 3 months post-injury 40 - 50% of injured children have delays in functional recovery2, 
over >50% have pain that interferes with functioning3, and up to 40% report impairment 
from posttraumatic stress symptoms (PTSS).4 Accreditation standards from The Joint 
Commission help ensure that assessment and management of pain receive attention during 
clinic visits and hospital care5, but pain is often not systematically assessed or managed once 
a child is discharged home.3,6  
No solution exists for monitoring child self-reported pain, traumatic stress, or functional 
recovery after hospital or clinic discharge. While structured approaches to detecting and 
addressing pain and PTSS among children have shown promise7,8, their widespread 
implementation in health care settings is hindered by a number of challenges. One challenge 
is timing: even when admitted, many pediatric patients are released home after a brief 
hospital stay. Systemic issues (health care incentive structures, limited information 
exchange) have also presented hurdles. Recent shifts in health care financial models, 
systems of care, and e-Health approaches present new opportunities to incorporate tools, 
such as the screening system being developed in this project, that increase the effectiveness 
and value of care and improve patient satisfaction.  
Our team’s NIH-funded STTR project proposes to address this critical, systemic problem by 
focusing on the gap between current approaches for identifying child pain and PTSS post-
discharge, and the unmet needs of recently ill or injured children, their families, health care 
providers, and health systems. We are developing an integrated screening system that takes 
advantage of advances in e-Health and developmentally-appropriate engagement strategies, 
as well as a shifting economic landscape that provides health systems with incentives for 
optimizing short- and long-term patient outcomes and for meaningful use of health 
information technology. Stakeholders interviewed in Phase I noted the paucity of reliable 
and actionable monitoring data in the post-discharge period (particularly in pediatrics), and 

 
  
 
 
 
3
the absence of (gold standard) child self-report outcomes for pediatric patients to enhance 
predictive analytics.  
Developmental considerations and child self-report  
Middle childhood into adolescence is a key period for children’s development of self-
management and social-emotional skills needed to manage physical and emotional 
symptoms, cope with challenges, and solicit support from others when needed.61 An acute 
medical event such as injury or illness event challenges children’s growing capabilities and 
represents an opportunity for parents and providers to intervene and support the child’s 
development of critical competencies for this and future challenges. In this age range, child 
self-report is the gold standard for assessing pain, PTSS, and health-related quality of life. 8-
10 A large body of research, including work by our team, has established that it can be 
difficult for parents to accurately assess their child’s acute pain and PTSS.11,12 Thus direct 
screening of school-age children is optimal but requires validated, developmentally 
appropriate methods such as those in the eScreen system.  
Using e-Health tools and engaging game mechanics for repeated screening post-discharge 
Digital screening tools and interventions are made increasingly feasible by the fact that the 
vast majority of US families have access to online e-Health tools via tablet or phone. Across 
our target age range of school-age children and adolescents, online activity is widespread 
and increasing: 26% of 8-10 year olds and 45% of 11-14 year olds have their own personal 
smartphone or tablet; 73% of 8-10 year olds go online at least weekly and 29% spend > 1 
hour per day online, and 95% of 11-14 year olds are online at least weekly and 52% spend 
>1 hour per day online.13 Children in this age range are motivated to play electronic games 
for a variety of reasons, including fun, mastery, competition, and managing emotions. Game 
mechanics (i.e., avatars. feedback, levels, digital rewards like points and badges) are linked 
to increased usage and adherence in e-Health tools.14 Our system directly engages school-
age children and adolescents in screening via an e-Health tool directly embedded in a child-
friendly game experience.  
In summary, the scientific premise of this study and the overall project is that (a) gaps in 
parent, provider, and health system ability to monitor children’s post-discharge pain, 
traumatic stress, and functional recovery impede optimal follow-up care, and (b) a novel 
game-based experience can address these gaps via practical, valid assessment of key child-
reported indicators.  
1.3.2 Measures addressing primary and secondary study aims 
Background is presented here for measures addressing primary and secondary study aims. 
More information on study measures is in Section 5 and in the Appendix. 
eScreen measures  
In this study, these eScreen measures will be delivered to the child on a compatible (IOS or 
Android) tablet. 
eScreen Pain Screener  This measure is a visual analog scale designed for delivery on a 
mobile device by adapting key elements of existing validated pain measures15 and adding 
personalization features. In our prior study, the eScreen Pain Screener was highly correlated 
(r =.86 - .92) with, and evidenced strong agreement with, two validated pain measures. The 

 
  
 
 
 
4
measure appears on screen as a visual analog ‘slider’ with a movable marker; the width and 
color intensity increased from bottom to top. The face of the child’s avatar (i.e. selected by 
the child in the eScreen system) anchors the lower and upper ends of the slider with a ‘no 
pain’ and a ‘most pain’ facial expression, respectively. On-screen instructions state “The 
bottom of this scale is no pain, and the top is the most pain you can imagine. Slide the 
marker to show how much pain you feel right now.”  The child uses their finger on the touch 
screen to slide the virtual marker. 
eScreen PTSS Screener  The Acute Stress Checklist for Children 6-item Short Form (ASC-
6) was developed as a short form of the Acute Stress Checklist for Children (ASC-Kids) 16. 
Across multiple samples, it has demonstrated concurrent validity with severity of symptoms 
as assessed via the full-length ASC-Kids checklist (correlations from .88 to .92) or a 
structured clinical interview (correlations of .61 - .62).16 In our prior study, scores on the 
ASC-6 presented within the eScreen system were strongly correlated with a validated PTSS 
measure (r=.67); a positive PTSS screen was associated with significantly higher PTSS 
severity.  
eScreen Functional Recovery Screener  Our team developed a single item screener 
“Would you say you are all the way back to normal from the injury / illness?” (Response 
options = Yes, completely; Partway or Somewhat; Not at all) to assess a child’s global 
perception of their recovery. Across multiple samples, responses on this item have shown 
significant associations with validated full-length measures of health-related quality of life, 
such as the Physical, Emotional, and Social functioning scales of the PedsQL. 
In the eScreen system, the PTSS and functional recovery screeners are delivered on a mobile 
device with the child’s avatar appearing on each screen. The child uses the touch screen to 
select a response to each item.  
Research measures 
Numerical Rating Scale for Pain Intensity (NRSI) The NRSI is a verbally-administered 
pain evaluation in which children are asked to rate their pain by choosing a number from 0 
to 10 “that best tells us how much you are hurting, where 0 = no pain or hurt and 10 = the 
most or worst pain/hurt.”  The NRSI has demonstrated  strong convergent validity with other 
measures of pain intensity in children age 7 to 18 across multiple studies,17,18 as well as 
sensitivity to change over time.17 Child and parent-proxy-report versions will be used in this 
study; the child report version will be used in analyses of the primary endpoint.  
PROMIS pediatric pain interference scale The PROMIS Pain Interference Scale is a brief 
measure that assesses interference by pain on children’s daily activities (interference on 
physical, psychological, and social functioning) during the past 7 days. The Pain 
Interference Scale has demonstrated construct validity in assessing clinically meaningful 
interference from pain and in detecting change over time.  Child and parent-proxy-report 
versions will be used in this study; the child report version will be used in analyses of the 
primary endpoint. 
Child PTSD Symptom Scale for DSM-5 (CPSS-5) The CPSS-5 includes 20 items 
assessing posttraumatic stress symptoms aligned with the DSM-5 criteria for posttraumatic 
stress disorder (PTSD), rated by the child on a 5-point Likert scale, scored as 0 to 4.19 The 
DSM-5 update of the CPSS builds on the well-validated DSM-IV version,20,21 and has 

 
  
 
 
 
5
demonstrated strong internal consistency, test-retest reliability, convergent and discriminant 
validity in initial evaluations.19 
The Parent Information and Confidence scale was developed at CHOP to assess the 
extent to which parents feel prepared for the care of their ill or injured child after hospital or 
clinic discharge. Items in the measure have been used in prior studies by our team. 22,23  
1.4 Compliance Statement 
This study will be conducted in full accordance all applicable Children’s Hospital of 
Philadelphia Research Policies and Procedures and all applicable Federal and state laws and 
regulations including 45 CFR 46. All episodes of noncompliance will be documented. 
The investigators will perform the study in accordance with this protocol, will obtain 
consent and assent, and will report unanticipated problems involving risks to subjects or 
others in accordance with The Children’s Hospital of Philadelphia IRB Policies and 
Procedures and all federal requirements. Collection, recording, and reporting of data will be 
accurate and will ensure the privacy, health, and welfare of research subjects during and 
after the study.  
2 
STUDY OBJECTIVES 
Primary study objective: Examine ability of eScreen system to identify patients with 
clinically-relevant problems (pain, pain interference, PTSS symptoms and related 
impairment) in the 6 weeks after a medical event or hospital discharge. 
Secondary study objective: Examine impact of eScreen system (vs usual care) on factors 
related to parents’ management of child symptoms and recovery in this 6 week period.   
 
2.1 Primary Objective (or Aim) 
The primary objective of the current study is to evaluate predictive validity of eScreen 
measures during children’s at-home use of the eScreen system, for prediction of ongoing 
symptoms or problematic recovery at 6 weeks: pain, pain interference, PTSS, impairment 
from PTSS.  
2.2 Secondary Objectives (or Aim) 
The secondary objectives are to examine the impact of the eScreen system (vs usual care) on 
factors related to parents’ management of child symptoms and recovery in this 6 week 
period.   
• (a) parent perceptions that they have the information they need to care for their child’s 
illness or injury, and  
• (b) parent confidence in their ability to manage their child’s care. 
 

 
  
 
 
 
6
3 
INVESTIGATIONAL PLAN 
3.1 General Schema of Study Design 
This study is a randomized controlled trial examining validity of eScreen measures (primary 
aim) and assessing the impact of the eScreen system on parent management (secondary 
aim). 
Pilot of study procedures:  Before we begin enrollment for the randomized trial, we will 
enroll up to 10 child-parent pairs at each site in a pilot phase to allow a “dry run” of study 
procedures. We will implement study procedures (other than randomization) described 
below, and conducting procedures consistent with assignment to the intervention arm 
(“usual care plus eScreen”).  We will not include pilot phase cases in any analyses of 
effectiveness.    
 
We will recruit a cohort of 300 children (and one parent per child) recently treated for illness 
or injury at CHOP or Kentucky Children’s Hospital inpatient or outpatient services.  
Participants will be randomly assigned to usual care plus eScreen (“eScreen group”) or usual 
care alone (“UC group”).  Analyses addressing the primary study aim will use data from the 
eScreen group; analyses addressing the secondary aim will compare eScreen and UC groups. 
We have powered our study to answer our primary aims within our eScreen group.  
Figure 2. Research assessments for both groups (above timeline) & eScreen system use / actions 
(below timeline)  
 
3.1.1 Screening & Baseline Research Assessment 
Research staff will examine clinic schedules and inpatient admission records daily to 
identify potentially eligible patients. Research staff will approach parents to describe the 
study, review eligibility criteria, and invite their and their child’s participation. We will 
obtain parent consent, followed by child assent, for study participation before any other 
research assessments are administered. After consent / assent is obtained, children and 
parents will complete baseline research assessments (see Table 2 in Section 5), and will then 
be randomized to the eScreen or Usual care group.  
3.1.2 Study Treatment Phase  
Over the next 6 weeks, children in the eScreen group will be asked to play the game at least 
3 times per week.  Each instance of game play includes an embedded eScreen assessment of 
current pain, PTSS and functional recovery. The system will provide templated weekly 
T1: at 
enrollment 
T2:  
6 weeks 
T3:  
12 weeks 
eScreen group:  
Child plays game (>=3x/wk);   
Parent receives weekly info on child 
screening results 
Outpatient 
or inpatient 
treatment 
for illness 
or injury 
Usual Care group: 
Optional 
opportunity to use 
system (game 

 
  
 
 
 
7
messages to parents regarding their child’s ratings of pain, PTSS, and functional recovery, 
with links to more information as appropriate.   
3.1.3 Follow-up  
Follow-up research assessments will take place at T2 (6 weeks post-T1) and T3 (12 weeks 
post-T1) via phone, online, or mailed questionnaires – see Table 2 in Section 5.  
After completion of their T3 assessment, children in the Usual Care group will be provided 
with sign-in information and offered the opportunity to play the game (without eScreen 
measures). We will include a modified TAM questionnaire to allow us to collect additional 
pilot data on their satisfaction with the game).   
Follow up research assessments for subjects at both sites will be completed by study teams 
at CHOP or UK.  
3.2 Allocation to Treatment Groups and Blinding 
We will prepare a set of  sealed files (sealed envelopes or a virtual / digital analog), with appropriate 
numbers  for the eScreen condition and for Usual Care. Each file will contain directions for either: a) 
proceeding with the eScreen system or b) proceeding with the Usual Care condition.  
We will randomize in blocks (2-to-1 ratio of eScreen to Usual Care within each block). 
Randomization files will be prepared at CHOP and released in blocks at each of the two 
study sites. As each participant is enrolled, and after completion of baseline measures,  
research staff will open the next available file and proceed with the designated activity. 
Participants, as well as research staff conducting the baseline assessment visit, cannot be 
blinded as to study condition. Research staff conducting the T2 and T3 follow-up 
assessments will be blinded to the family’s study condition. These staff will not have access 
to study tracking sheets that indicate condition, and will not participate in meetings in which 
case allocation is discussed. Questionnaires regarding acceptability of the eScreen system 
will be administered separately for those families in the eScreen condition. 
3.3 Study Duration, Enrollment and Number of Sites 
3.3.1 Duration of Study Participation 
The study duration per subject will be up to approximately 12 weeks, with (a) one brief 
screening / baseline assessment, (b) for the eScreen group only: intermittent involvement 
(using eHealth tools at home) over a 6 week period, and (c) two brief follow-up research 
assessments at approximately 6 weeks and 12 weeks post-baseline. 
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 
The study will be conducted at 2 investigative sites: CHOP and the University of Kentucky. 
Recruitment will stop when approximately 300 randomized child-parent pairs are enrolled.  
It is expected that approximately 300 randomized child-parent pairs will need to be enrolled 
to produce 127 evaluable families for completer analysis.  

 
  
 
 
 
8
3.4 Study Population 
We will enroll children (and one parent per child) at CHOP or KCH (N=300 child-parent 
pairs ; plus up to 10 child-parent pairs in a pilot phase) who meet the following criteria.    
3.4.1 Inclusion Criteria 
• Child age 8 – 17 years 
• Child treated or admitted for injury or illness event that occurred within the past 
month 
• Child has regular access to a compatible (IOS or Android) tablet at home 
• Parent has an internet-capable smartphone and can receive text messages on that 
phone, OR has email account that can receive messages about child status 
• Child and parent read or understand English well enough to consent / assent to 
participation and complete study tasks (e.g., checklists, use of screening system) 
3.4.2 Exclusion Criteria 
• Index medical event is injury due to family violence.  
Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations 
of these criteria must be reported in accordance with IRB Policies and Procedures.  
4 
STUDY PROCEDURES 
4.1 Screening & Baseline Research Assessment 
Research staff will approach parents to describe the study, review eligibility criteria, and 
invite their and their child’s participation. We will obtain parent consent, followed by child 
assent, for study participation. We will document consent/assent via RedCap or on paper. 
Consent / assent will include child and parent agreement that, if assigned to the eScreen 
group, the child will be asked to sign in and play the eScreen game at least 3 times per week 
for 6 weeks. (Children may play more often, and beyond the 6 week time frame if they 
choose.) 
At enrollment (T1), before randomization, children and parents will complete baseline 
research assessments (see Table 2 in Section 5). Following baseline assessments, study staff 
will open a file to reveal the condition to which the child is assigned. Those randomized to 
the eScreen group will then receive sign-in instructions for the mobile / online interface, 
practice signing in, and begin to play the eScreen game. (Parents will be introduced to these 
procedures so they can assist their child if needed.)  
We will make every effort to approach parents and children in person to obtain consent / 
assent and initiate study procedures.  In cases where an eligible participant / parent is missed 
at the hospital or clinic and during periods when we are unable to conduct in-person 
enrollment for public health reasons, we may obtain consent / assent (via REDCap or 
telephone) when staff are not present with the family. (See Section 9.6) After consent / 
assent are obtained, we will administer baseline (T1) study questionnaires verbally or online 
for parent and child. Following completion of T1 assessments, study staff will open a file to 

 
  
 
 
 
9
reveal the condition to which the child is assigned. Those randomized to the eScreen group 
will then receive sign-in instructions for the mobile / online interface. We will also offer to 
schedule a phone call at a convenient time for the family to answer any questions about the 
sign-in process and encourage children to practice signing in and begin to play the eScreen 
game. (Parents will be introduced to these procedures so they can assist their child if 
needed.)  
4.2 Study Treatment Phase 
Over the next 6 weeks, children in the eScreen group will be expected to play the game at 
least 3 times per week, and will able to play the game more often if they want to. Reminders 
to parents will encourage children to play at least 3 times per week.  
Each instance of game play will include an embedded eScreen assessment of current pain, 
PTSS and functional recovery (unless the child has completed this assessment within the 
past 24 hours).  
For the eScreen group, the system will provide templated weekly messages (weeks 1 to 6) to 
parents regarding child pain, PTSS, and functional recovery. Design of message timing and 
delivery mode is based on lessons from stakeholder interviews in Phase I. Message content 
and specific screening algorithms are derived from our team’s prior studies. Parent messages 
(sent via text or email per parent preference) will include information drawn from evidence-
based resources on pain and PTSS, with links to more information as appropriate.   
The research team will provide parents at CHOP and UK with a study-specific CHOP email 
and phone number which they can use to alert the team of any technical difficulties with the 
system. 
4.3 Follow-up  
For both study groups, research assessments at T2 (6 weeks post-T1) and T3 (12 weeks 
post-T1) will repeat baseline measures and also assess pain interference and impairment 
from PTSS – see Table 2 in Section 5. Additional outcomes will be gathered from parents at 
T3 and abstracted from medical records and each hospital’s Trauma Registry (for injured 
children).  
At the completion of each research assessment, all participants will be provided with a 
message about talking with their primary care provider if they have any concerns about 
physical or emotional recovery. Depending on context of measure administration, this will 
be delivered verbally by study staff and/or as a written message at the end of self-
administered questionnaires in the REDCap system. Additionally, when a T2 or T3 research 
assessment indicates that a child is currently experiencing high pain or may meet symptom 
criteria for posttraumatic stress disorder, we will inform parents and suggest that they check 
in with their child and consider contacting their child’s doctor.  
After completion of their T3 assessment, children in the Usual Care group will be provided 
with sign-in information and offered the opportunity to play the game. For this group, we 

 
  
 
 
 
10 
will not administer eScreen in-game assessments. We will ask about the child’s perceptions 
of game use – via a modified TAM questionnaire. 
Study teams at CHOP and UK will complete the follow up research assessments for CHOP 
and UK subjects.  
4.4 Subject Completion/Withdrawal 
Subjects may withdraw from the study at any time without prejudice to their care.  They 
may also be discontinued from the study at the discretion of the Investigator for lack of 
adherence to study protocols.  The Investigator may also withdraw subjects who violate the 
study plan, or to protect the subject for reasons of safety, or for administrative reasons.  It 
will be documented whether or not each subject completes the study. 
5 
STUDY EVALUATIONS AND MEASUREMENTS 
5.1 Screening and Monitoring Evaluations and Measurements 
5.1.1 Medical Record Review 
Variables that will be abstracted from the medical record: 
 Age 
 Gender 
 Race 
 Ethnicity 
 Medical diagnos(es) for this admission or ED/outpatient visit 
 For injured children, date and mechanism / circumstances of injury  
 For children with a medical event (other than injury), date of onset and 
circumstances of current complaint  
o e.g., for children with SCD, date of onset and any circumstances related to 
onset of pain crisis or other medical event that precipitated their specialty 
care or ED visit or their admission 
 
5.2 Efficacy Evaluations 
5.2.1 Diagnostic Tests, Scales, Measures, etc. 
Measures used in analyses of primary and secondary study objectives are in bold in Table 2. 
More detailed information about each of these measures is presented in Section 1.3.2.  Other 
measures are used to assess sample descriptives or covariates, or are used in exploratory 
analyses.  Timing of each assessment is also presented in Table 2.   
Table 2. Study measures by reporter, mode of delivery, and time point.  
Measure 
Construct  
Reporter  
In-
game* 
Assessments* 
T1 
T2 
T3 
Demographic & health form 
Demographics and child 
health / health utilization 
Parent** 
 
X 
 
 
eScreen pain screener: Analog 
Current pain intensity 
Child 
X 
 
 
 

 
  
 
 
 
11 
pain scale 
eScreen PTSS screener: ASC- 6 
Current traumatic stress 
symptoms 
Child 
X 
 
 
 
eScreen functional recovery 
screener: “Back to Normal”  
Current functional 
recovery 
Child 
X 
 
 
 
Numerical Rating Scale (NRSI)  
Current pain intensity 
Child 
 
X 
X 
X 
Colored Analogue Scale 
Current pain intensity 
Child 
 
X 
 
 
PROMIS Pediatric Pain 
Interference 
Impact of pain on 
functioning - past wk  
Child / 
Parent** 
 
 
X  
X 
Parent Post-op Pain Measure 
(PPPM)  
Current pain intensity 
Parent* 
 
X 
X 
X 
PROMIS Sleep Disturbance Short 
Form 
Sleep problems (covariate) 
Child / 
Parent** 
 
X 
X 
X 
Child PTSD Symptom Scale for 
DSM5 (CPSS-5) 
Traumatic stress symptoms 
& impairment from these 
symptoms  
Child 
 
X 
X 
X 
PTSD Checklist for Children – 
Parent Report (PCL-C/PR) – 
adapted for DSM5 
Traumatic stress symptoms 
& impairment from these 
symptoms  
Parent** 
 
X 
X 
X 
Pediatric Quality of Life Inventory 
(PedsQL-C & -P) Acute Version 
Functional recovery /  
Health-related quality of life 
- past wk  
Child / 
Parent** 
 
X 
X 
X 
Health and Recovery Questionnaire  
Health status & follow-up 
care *** 
Parent** 
 
 
X 
(X) 
Parent Information / Confidence 
Questionnaire 
Management of child 
health & recovery 
Parent 
 
 
X 
X 
Technology Acceptance Model 
(TAM) questionnaire (eScreen 
group only)  
Perception of eScreen system 
utility & acceptability 
Child / 
Parent 
 
 
X 
 
Modified Technology Acceptance 
Model (TAM) questionnaire (Usual 
Care group only – optional with 
game play after T3)  
Perception of game and 
acceptability 
Child 
 
 
 
optio
nal 
after 
T3 
* Timing of assessments: T1 = at enrollment in hospital / clinic; T2 =  6 wks post-T1; T3 = 12 wks post-T1;  
plus, for eScreen group only: In-game assessment at T1 and at each subsequent game session  
** Parent reporting on child symptoms / functioning 
*** Health and Recovery Questionnaire admin at T2, but if T2 is missed will admin at T3 
 
5.3 Safety Evaluation 
This is a minimal risk study. There is no known physical risk for subjects of completing 
measures of pain or stress symptoms, nor in using a prototype screening system.   
 
6 
STATISTICAL CONSIDERATIONS 
6.1 Primary Endpoint 
The primary study endpoints employ validated measures of ongoing symptoms / problematic 
recovery: pain (NRSI rating), pain interference (PROMIS Pain Interference T score) and 
PTSS presence and related impairment (CPSS-5 scores) at T2 (6 weeks post-baseline). 

 
  
 
 
 
12 
Reflecting our primary aim of prediction, the primary study endpoints are not participant 
scores on these measures, but rather the results of ROC analyses; i.e. the area under the 
curve (AUC) for eScreen pain score predicting pain and pain interference and the AUC for 
eScreen PTSS score predicting PTSS symptom presence and related impairment.  
6.2 Secondary Endpoints 
The secondary study endpoint relates to the potential impact of the eScreen system on parent 
management of child symptoms and recovery. We will compare eScreen and Usual Care 
groups on parent ratings at T2 of the extent to which they (a) have received the information 
they needed to take care of their child after leaving the clinic or hospital, and (b) have felt 
confident in taking care of their child (related to their illness / injury) in this 6 week period.  
6.3 Statistical Methods 
We will first conduct descriptive analyses of key variables, examine missing data, and 
consider whether the distribution of any key study variables warrants alternative, non-
parametric analyses. All primary study analyses use child self-report measures; we collect 
additional parent-report measures of some variables for use in later exploratory analyses.  
6.3.1 Baseline Data  
Baseline and demographic characteristics will be summarized by standard descriptive 
summaries (e.g. means and standard deviations for continuous variables such as age and 
percentages for categorical variables such as gender). 
6.3.2 Efficacy Analysis 
Primary endpoint   
Hypothesis: Results of eScreen-delivered in-game assessments will predict ongoing 
symptoms / problematic recovery at T2 (6 weeks post-baseline), i.e. in ROC analyses, good 
to excellent AUC (≥ .80) for prediction of problems as follows: eScreen pain score 
predicting pain (NRSI ≥ 6) and pain interference (PROMIS pain interference T score ≥ 65); 
eScreen PTSS score (ASC-6) predicting PTSS (significant PTSS indicated by CPSS-5 
symptom endorsement) and impairment from PTSS symptoms (impairment endorsed on 
CPSS-5).  
Analyses: In ROC analyses, we will estimate AUC as a global indicator of predictive 
efficiency of eScreen results in detecting children with clinically meaningful ongoing 
symptoms or problematic recovery. We will then calculate sensitivity and specificity for 
dichotomous indicators predicting presence of these problems using cutoff scores based on 
results of prior studies:  
- eScreen pain indicator (pain score ≥ 6) predicting pain and pain interference (NRSI / 
PROMIS scale);  
- eScreen PTSS indicator (ASC-6 ≥ 6) predicting PTSS and related impairment (CPSS-5);  
- eScreen functional recovery indicator predicting reduced HRQoL (PedsQL-C score < 70).  
After primary analyses with a priori cutoffs, we will use results of ROC analyses to examine 
potential adjustments to cutoff scores for eScreen-delivered measures to optimize prediction 

 
  
 
 
 
13 
of problems. Given the system’s aim to detect children whose ongoing symptoms or 
problematic recovery might otherwise be missed (to allow parents and providers to further 
assess and respond in a timely manner) the goal for eScreen cutoff scores is to optimize 
sensitivity while maintaining reasonable specificity. 
Secondary endpoint  
Hypothesis: At T2, compared to the Usual Care group, the eScreen group will demonstrate 
higher parent information and confidence in managing child symptoms and recovery.  
Analyses: All analyses comparing groups will be conducted first on an intent-to-treat basis. 
We will calculate Cohen’s d as the between-group difference in summed parent information 
/ confidence ratings, standardized by the pooled SD for the groups.  
Exploratory analyses:  
We have already examined concurrent validity in a prior study, but will conduct exploratory 
analyses in this new sample to determine the association between scores on brief child-
report measures delivered via the eScreen system and scores on validated measures 
administered by trained research staff at the closest available research assessment. 
After primary study analyses above, we will examine the ability of the eScreen measures to 
predict the same outcomes at a more distal point (T3:  12 weeks post-baseline).  
We will also examine whether eScreen performance varies by child sex, age, race/ethnicity, 
or socio-economic status.  
In exploratory analyses to better understand eScreen performance, we will examine a) the 
association of eScreen measures with sleep disturbance, parent-reported medication usage, 
new medical concerns, and service utilization, b) the potential impact of relevant child 
history (prior injury or illness, hospital admission, trauma exposure) on eScreen 
performance, and c) prediction of parent-reported outcomes (pain / pain interference, PTSS / 
impairment, HRQoL).  
Results of these exploratory analyses will inform future development and deployment of the 
eScreen system. 
6.4 Sample Size and Power 
Precision of estimates / power considerations:  
Sample size is driven by planned analyses to address the primary study objective. We will 
randomize up to 300 child-parent dyads, with 2/3 randomized to the eScreen condition, and 
1/3 to usual care.  
Analyses for the primary study objective utilize data only from participants assigned to the 
eScreen condition. We will estimate the area under the curve (AUC) and calculate 
sensitivity and specificity for prediction of recovery problems. The precision of these 
estimates depends on N and the proportion who demonstrate the (problem) outcome of 
interest, i.e., interference from pain or PTSS.114,115 We estimate this proportion from prior 

 
  
 
 
 
14 
studies with injured children that suggest 40-50% have delays in functional recovery,50 
≥40% have impairment from PTSS47, and >50% have pain that interferes with functioning 
post-discharge.45,46 With an analyzable sample of at least 85 children, if 50% have the 
outcome of interest, the 95% CI for an AUC of .80 will be ± .10. Our anticipated evaluable 
sample for these analyses is based on projected retention from the point of consent through 
intervention completion 9use of the eScreen system) and completion of follow up 
assessments. 
Analyses for the secondary study objective use data from participants assigned to both 
conditions in order to estimate effect sizes (between-group differences). An analyzable 
sample (for completer analyses) of 85 (in eScreen group) compared to 42 (UC group) will 
enable us to detect between-group differences in proportions as small as 23% (i.e. 50% vs 
73%), and a medium effect size (Cohen’s d of .49) for between-group differences in mean 
scores on continuous measures, both with 80% power (α ≤ .05). 
 
7 
STUDY INTERVENTION 
7.1 Description 
The study intervention includes two key components of the eScreen system: a child 
screening component and a parent information component.  
Child screening component  
This component will be delivered via a game played on an iOS or Android tablet. Each 
instance of game play includes an embedded eScreen assessment of current pain, PTSS and 
functional recovery, unless the child has completed this assessment within the past 24 hours.  
Design of the eScreen game leverages “idle game” mechanics to create a cyclical game 
experience that supports the overall goal of engaging children in game play, and delivering 
screening questionnaires directly to children repeatedly for several weeks. Over the period 
of 6 weeks, children are expected to play the game (and rate symptoms and feelings) at least 
3 times per week, and they will be able to play the game as often as they want to. Reminders 
to parents will encourage children to play at least 3 times per week. 
Parent information component 
The system will provide templated weekly messages for parents in weeks 1 to 6 regarding 
child pain, PTSS, and functional recovery. Messages will be sent to parents at least weekly, 
via text or email, with brief updates summarizing child ratings. Each message will include a 
link to an online dashboard with additional personalized information for parents, and links to 
evidence-based resources on pain or PTSS as appropriate. Parents may access the dashboard 
from any internet connected device or computer. 
The design of message timing and delivery mode is based on lessons from stakeholder 
interviews in Phase I. Message content and specific screening algorithms are derived from 
our team’s prior studies.  

 
  
 
 
 
15 
7.1.1 Treatment Compliance and Adherence  
The use of online, eHealth tools makes it possible to accurately track many aspects of child 
and parent use of each intervention component.  Electronic data / metadata collected by the 
eScreen system (child screening component and parent information component) will include 
responses to screening items (child ratings), when and whether a parent clicks a link in a text 
message, as well as a date / time stamp for each participant interaction with the system. 
 
8 
SAFETY MANAGEMENT 
8.1 Clinical Adverse Events 
Clinical adverse events (AEs) will be monitored throughout the study.  
8.2 Adverse Event Reporting 
Since the study procedures are not greater than minimal risk, SAEs are not expected. If any 
unanticipated problems related to the research involving risks to subjects or others happen 
during the course of this study (including SAEs) they will be reported to the IRB in 
accordance with CHOP IRB SOP 408: Unanticipated Problems Involving Risks to Subjects. 
AEs that are not serious but that are notable and could involve risks to subjects will be 
summarized in narrative or other format and submitted to the IRB at the time of continuing 
review.  
9 
STUDY ADMINISTRATION 
9.1 Treatment Assignment Methods 
9.1.1 Randomization 
Participants will be randomized to eScreen or Usual Care groups (2:1 ratio) after baseline 
assessment is complete. See Section 3.2 for randomization procedures. 
9.1.2 Blinding 
Given the nature of the intervention to be evaluated, it is not possible for participants or 
research staff conducting the baseline assessment visit to be blinded as to study condition. 
Research assistants conducting the T2 and T3 follow-up assessments will be blinded to the 
family’s study condition.  
9.1.3 Unblinding 
Not applicable.  
9.2 Data Collection and Management 
Data will be collected via written and electronic questionnaires completed by child and 
parent participants, or administered verbally by research staff. Electronic data (coded, not 
identifiable to Radiant) will be gathered during participants’ use of mobile device-delivered 
eScreen system tools and stored in a database hosted on the Radiant server. Existing records 

 
  
 
 
 
16 
will yield medical information about the index child’s diagnoses, clinical pain ratings, and 
treatment.  
Identifiable information linking individual subjects to their PHI (i.e., the master list) will be 
stored electronically in a password-protected file. The study dataset will not include 
identifiable information.  
For enrollment or administration of research measures, when an in-person meeting is not 
possible, or based on the family’s preference and convenience, we will offer families the 
option of a telephone or virtual meeting (e.g. at the CHOP site, meeting virtually via 
CHOP’s Webex account). 
Each site, CHOP and Kentucky, will utilize online REDCap questionnaires hosted at CHOP 
that will allow online data entry by participants or research staff.  Each site will also offer 
paper copies of each research questionnaire, in case of internet connectivity issues at the 
time of the research assessment, or if a family requests that questionnaires be mailed to 
them. Data collected via paper questionnaires will be entered by research staff into an 
electronic database, and maintained via a secure, password-protected database at each site. 
Data entry screens will contain range and logic checks to minimize data entry errors. The PI 
will monitor data accuracy and identify ways to resolve any problem areas.  
CHOP and Kentucky study staff will receive identifiable information from both sites to 
facilitate completion of follow up assessments. This information will be shared between 
sites via CHOP’s secure systems.  
De-identified data will be shared between sites via secure systems such as CHOP’s 
Sharefile.  All study data, at both CHOP and Kentucky, will be maintained for at least 6 
years post study completion at CHOP and for at least 5 years at Kentucky, per institutional 
policy.  
Security:  
Database security will be assured at the server, application, table and entry screen levels. 
Disaster recovery procedures will guard against loss of data.  
Electronic data / metadata collected by the eScreen system (child screening component and 
parent information component) will include responses to screening items (child ratings), 
whether a text or email message is successfully delivered, and when and whether a parent 
clicks a link in a text or email message; as well as automated collection of IP address and 
date / time stamp for each participant interaction with the system. These data will be 
captured in the custom software application (the prototype screening system) and stored in a 
relational database that is hosted externally at Radiant Creative, LLC (Radiant), our study 
partner, developer of the screening system prototype, and Business Associate of CHOP.  All 
such data will be coded and not identifiable to Radiant Creative LLC.  If Radiant and the 
CHOP/UK study team need to communicate about a specific case in order to troubleshoot 
technical difficulties, we will use the Case ID (i.e. if a text message fails delivery, Radiant 
will alert the study team – using the Case ID - so that the team can contact the parent to 
confirm we have correct contact information for message delivery). 

 
  
 
 
 
17 
Via Radiant, the relational database will be stored on a fully-managed, secured, HIPAA-
compliant web server. Study data on this server will be stored in a relational database that 
utilizes encrypted fields. Database read/write privileges will be strictly controlled via an 
access control layer. At the application layer, data will be protected via a role-based access 
system and robust authentication requirements. All data access via the application layer will 
be recorded in a persistent audit log. All code will be tested regularly for brute force, XSS, 
SQL injection and other vulnerabilities. Any identified vulnerabilities will be remediated 
within 24 hours. At the server layer, data will be protected by continuous backup, a robust 
firewall, and pro-active server management practices. At the host layer, data will be 
protected in physically locked cabinets and on-premises site access security protocols.  
Study data stored from this external server will be transferred to CHOP personnel via secure 
FTP website. FTP site access will require a unique username/password combination, and 
each investigator will be granted a single account. Data will be made available on the FTP 
site for a limited time (typically 24 hours or less). Security-focused FTP account 
management practices will be required (e.g., nontrivial password requirements, password 
reset every 60 days, etc.) 
9.3 Confidentiality 
All data and records generated during this study will be kept confidential in accordance with 
Institutional policies and HIPAA on subject privacy. Investigator and other site personnel 
will not use such data and records for any purpose other than conducting the study. Study 
staff at CHOP and Kentucky will receive identifiable information from the both sites in 
order to complete follow up research assessments.   
Participants’ identities will be disguised by a unique identification number which will 
appear on all interview and questionnaire materials instead of their name. The identification 
numbers will be linked with participant names only in password-protected electronic 
documents. 
No identifiable data will be used for future study without first obtaining IRB approval. The 
investigator will obtain a data use agreement between the provider (the PI) of the data and 
any recipient researchers (including others at CHOP or UKentucky) before sharing a limited 
dataset (PHI limited to dates and zip codes).  
The participant consent process will inform participants that de-identified data will be 
archived in appropriate data archives or repositories, in keeping with NIH Data Sharing 
policies.  De-identified data from this study will be added to the Prospective studies of 
Acute Child Trauma & Recovery (PACT/R) Data Archive.  
We will ask participants if they would like to be added to a list of future “testers” who may 
be invited to participate in later stages of evaluating the screening system under 
development.  Name and contact information (parent contact information for children) for 
this list of potential future testers will be kept separate from study data, and will not be 
connected to any participant’s study data. 

 
  
 
 
 
18 
9.4 Regulatory and Ethical Considerations 
9.4.1 Data and Safety Monitoring Plan 
This is a multi-site, low risk study.  Each site will maintain their own full data sets. De-
identified data will be shared between sites for the purpose of summarizing results. Dr. 
Nancy Kassam-Adams, as the PI, will be responsible for monitoring the safety of study 
participants and complying with all reporting requirements.  She will report any adverse 
events to the CHOP IRB in accordance with CHOP IRB policies.  Dr. Marsac will promptly 
report any adverse events to Dr. Kassam-Adams for reporting to CHOP IRB.  Dr. Kassam-
Adams will also be responsible data accuracy, security, and validity. 
Linda Fleisher, PhD, MPH, Associate Research Professor at Fox Chase Cancer Center with 
more than 20 years of experience in development and assessment of eHealth interventions, 
will serve as the Data Safety Monitor. She will meet every six months with the PI and Study 
Coordinator. During these meetings, the team will review participant demographic 
characteristics, expected versus actual recruitment, retention to follow-up, and any ethical, 
quality assurance or regulatory issues that have arisen. Dr. Fleisher will also review any 
concerns about participant distress associated with the study that might not qualify as an 
adverse event. She will make recommendations, as needed, regarding changes to the study 
protocol. 
9.4.2 Risk Assessment 
Risks are not greater than minimal.  
The risk of ongoing distress created by the research procedures is extremely low. 
Completing questionnaires about pain symptoms or traumatic stress reactions could be 
distressing for some children or for their parents. However it is not likely that answering 
questions about one’s symptoms or recovery after illness or injury will create additional 
distress beyond that which is already present.  Empirical data regarding research 
participants’ evaluation of similar studies of child and parent acute reactions to trauma 
indicates a very low risk of emotional distress for participants.116 Children and parents will 
be able to discontinue the study at any time if they become uncomfortable. 
Protections against risk:  
Our recruitment procedures are sensitive to child medical status and family well-being. We 
determine whether the child’s medical status warrants a delay in approaching the family for 
study recruitment by reviewing the medical chart and/or asking the child’s primary nurse if 
the child is able to complete the necessary study tasks prior to approaching the family.  
If indicated, Drs. Kassam-Adams (clinical psychologist) and Winston (pediatrician) at 
CHOP or Dr. Marsac (clinical psychologist) at U Kentucky will work with the respective 
hospital’s social work team to make appropriate referrals for further psychosocial support 
for a child or parent. Research consent forms contain standard language to inform children 
and parents of potential reporting of abuse or other safety concerns. 

 
  
 
 
 
19 
9.4.3 Potential Benefits of Trial Participation 
There may be no direct benefit to participants. However, children in the eScreen group may 
enjoy engaging with the game-like aspects of the eScreen system, and may benefit from 
rating their post-injury or illness traumatic stress or pain symptoms. There is a body of 
research that indicates that disclosing traumatic stress responses is likely to be therapeutic.82 
In addition, children who are troubled by post-injury or illness symptoms but who have not 
sought help may benefit from being identified and referred for assistance through their 
participation in this study.   
Indirect, societal benefits for the broader population of injured and ill children and their 
parents and health care providers include the opportunity to develop, and ultimately make 
broadly available, a screening system that would facilitate optimal care to promote 
children’s emotional and physical recovery after injury and illness. 
9.4.4 Risk-Benefit Assessment 
The very low risk of emotional distress for participants is balanced by the protections built 
into the study protocol, and the importance of improving screening and care in the aftermath 
of pediatric injury and illness.  
9.5 Recruitment Strategy 
Research staff will examine clinic schedules and inpatient admission records daily to 
identify potentially eligible patients, and approach parents to describe the study, review 
eligibility criteria, and invite their and their child’s participation. We will obtain parent 
consent, followed by child assent, for study participation. At enrollment / consent, we will 
collect multiple methods of contacting families (multiple phone numbers, email addresses, 
etc) and ask permission to reach parents via text if needed to remind or schedule study-
related follow-up calls.  
9.6 Informed Consent/Assent and HIPAA Authorization 
Prior to enrolling patients, study staff will review the electronic medical record to determine 
potential eligibility of the parent and child before obtaining consent; we have requested a 
Waiver of HIPAA authorization for this screening process only.   
Study staff will then approach parents and children, describe the study, provide time for 
parents and children to ask any questions and consider their decision.  Staff are trained to 
explain the consent form to the subjects thoroughly, emphasizing their freedom to choose to 
participate or not in this study as well as emphasizing the fact that the subjects' healthcare 
will not be affected by their decision. 
Study staff will enroll eligible participants, and obtain combined informed consent / assent 
and HIPAA authorization / assent before administering research interviews with children 
and parents/legal guardians.  
Families will be asked to provide electronic signatures on a tablet computer utilizing the 
REDCap interface. Consent/assent and HIPAA authorization will be obtained by research 
team members. Families will be able to read, digitally sign their name, which will be 

 
  
 
 
 
20 
logically associated with the participant, and will receive an signed copy of the Study 
Consent for their files. Families who are unable to access the necessary technology to 
provide an electronic signature will give verbal consent. In this case, study staff will sign the 
documentation of verbal consent form via REDCap and provide the families with a copy of 
the verbal consent form for their records. 
We will offer paper consent/assent forms as a back-up in case of internet connectivity issues 
at time of consent. Signed paper consent/assent forms will be scanned and the digital copy 
saved on a secure server at CHOP or UK, respectively.  Once digital copies are saved, paper 
consent forms will be destroyed in a manner consistent with institutional policy for 
confidential documents.  
In cases where a non-legal guardian (e.g., grandparent) is identified as the child’s primary 
caregiver and meets all other study eligibility criteria, we will obtain parental (legal 
guardian) consent for youth participation, in addition to verbal parental approval for the non-
legal guardian to participate in the caregiver role.  
 
We will make every effort to approach parents and children in person to describe the study 
and invite their consent / assent and participation.  In cases where an eligible participant / 
parent is missed at the hospital or clinic (e.g. study team is unable to approach them at a 
convenient time for the family), and during periods when we are unable to conduct in-person 
enrollment for public health reasons, we will contact the parent using contact information 
that is in the medical record or that we have obtained from the parent in an initial brief 
contact while at the hospital / clinic.  In that case, we will describe the study, via telephone 
or in a virtual meeting with the family, and obtain consent / assent via REDCap.  
We will prioritize obtaining consent / assent via REDCap. In cases where eligible 
participants enrolled via telephone are unable to access necessary technology we have 
requested a waiver of documentation of consent in order to obtain verbal consent / assent. 
Study staff will complete documentation of verbal consent / assent via REDCap for the 
study records.  
 
9.6.1 Waiver of HIPAA Authorization 
We have requested a waiver of HIPAA authorization only for the process of screening 
medical records to identify potentially eligible participants.  Prior to enrolling patients, study 
staff will review the electronic medical record to determine potential eligibility of the parent 
and child before obtaining written consent and HIPAA authorization.  
This waiver of authorization satisfies the following criteria: 
(A) The use or disclosure of protected health information involves no more than a 
minimal risk to the privacy of individuals. We have a plan to protect the identifiers from 
improper use and disclosure; to destroy the identifiers at the earliest opportunity 
consistent with conduct of the research; and the protected health information will not be 
reused or disclosed to any other person or entity, except as required by law, for 
authorized oversight of the research project, or for other research for which the use or 
disclosure of protected health information would be permitted by this subpart;  

 
  
 
 
 
21 
(B) The research could not practicably be conducted without the waiver or alteration, and 
(C) The research could not practicably be conducted without access to and use of the 
protected health information. We would not be able to identify potentially eligible 
patients without this waiver. 
 
9.6.2 Waiver of Documentation of Consent 
We have requested a waiver of documentation of consent to obtain verbal consent in 
cases when participants are enrolled over the phone and unable to access the necessary 
technology to consent via REDCap.  
 
This waiver of documentation of consent satisfies the following criteria:  
(A) The procedures being consented to verbally involve no procedures for which written 
consent is normally required outside of the research context. Study staff will review 
the consent form and all relevant study materials over the phone, and families will 
receive a copy of the verbal consent form for their records; 
(B) The research could not be practicably conducted without the waiver of documentation 
of consent. In cases where participants are unable to access their email during virtual 
study enrollment, we may miss out on enrolling eligible patients without this waiver. 
The waiver of documentation of consent will allow us to enroll patients with limited 
technology capabilities over the phone; 
(C) The research could not practicably be conducted without the access and use of 
protected health information.  
 
9.7 Payment to Subjects/Families 
Payment in appreciation for completion of research assessments:  We will provide child and 
parent participants with thank you gifts in the form of prepaid cards potentially totaling $100 
per family across T1, T2, and T3 assessments. We will provide child participants with an 
incentive valued at $10 (T1), $20 (T2), and $20 (T3), and parent participants with an 
incentive valued at $10 (T1), $20 (T2), and $20 (T3). 
Payment in appreciation for use of eScreen system:  For the eScreen group, in order to 
encourage full use of the system being tested, we will provide incentives to parents for their 
own use of the eScreen system and their encouragement of their child’s use of the system 
during the 6 weeks after T1. For each week in which the child completes in-game 
assessments on at least 3 days and the parent clicks through to the information portal, $5 will 
be added to this amount, for a total additional incentive valued at $0 to $30 provided to the 
parent at T2. An additional brief weekly message to parents will inform them of the status of 
this incentive as of that point.   
10 PUBLICATION 
This research will be reported in peer-reviewed presentations and publications.  
 

 
  
 
 
 
22 
11 REFERENCES 
 
1. 
Kassam-Adams N, Kohser KM, J, Winston F, Marsac M. Evaluating the 
acceptability and validity of assessing pain and posttraumatic stress symptoms in an 
adaptable eHealth system for school-age children. Clinical Practice in Pediatric 
Psychology. 2019;7(1):9-19. 
2. 
Ding R, McCarthy M, Houseknecht E, et al. The health-related quality of life of 
children with an extremity fracture: A one-year follow-up study. Journal of Pediatric 
Orthopedics. 2006;26:157=163. 
3. 
Gill M, Drendel AL, Weisman SJ. Parent satisfaction with acute pediatric pain 
treatment at home. The Clinical journal of pain. 2013;29(1):64-69. 
4. 
Kassam-Adams N, Palmieri PA, Rork K, et al. Acute stress symptoms in children: 
Results from an international data archive. Journal of the American Academy of 
Child & Adolescent Psychiatry. 2012;51(8):812-820. 
5. 
Fein JA, Zempsky WT, Cravero JP, et al. Relief of pain and anxiety in pediatric 
patients in emergency medical systems. Pediatrics. 2012;130(5):e1391-e1405. 
6. 
Zisk R, Frey M, Medoff-Cooper B, MacLaren J, Kain Z. The squeaky wheel gets the 
grease: Parental pain management of children treated for bone fractures. Pediatric 
Emergency Care. 2008;24(2):89=96. 
7. 
Kramer DN, Landolt MA. Characteristics and efficacy of early psychological 
interventions in children and adolescents after single trauma: a meta-analysis. 
European Journal of Psychotraumatology. 2011;2:24. 
8. 
McGrath PJ, Walco GA, Turk DC, et al. Core outcome domains and measures for 
pediatric acute and chronic/recurrent pain clinical trials: PedIMMPACT 
recommendations. The Journal of Pain. 2008;9(9):771-783. 
9. 
Varni JW, Limbers CA, Burwinkle TM. How young can children reliably and validly 
self-report their health-related quality of life?: an analysis of 8,591 children across 
age subgroups with the PedsQL 4.0 Generic Core Scales. Health Qual Life 
Outcomes. 2007;5:1. 
10. 
Nader K. Assessing traumatic experiences in children. In: Wilson J, Keane T, eds.  
Assessing Psychological Trauma and PTSD. New York: Guilford Press; 1997. 
11. 
Chambers C, Reid C, Craig K, McGrath P, Finley G. Agreement between child and 
parent reports of pain. Clinical Journal of Pain. 1998;14(4):336-342. 
12. 
Kassam-Adams N, Garcia-España J, Miller V, Winston F. Parent-child agreement 
regarding children’s acute stress: The role of parent acute stress reactions. Journal of 
the American Academy of Child and Adolescent Psychiatry. 2006;45 1485-1493. 
13. 
Lauricella AR, Cingel DP, Blackwell C, Wartella E, Conway A. The mobile 
generation: Youth and adolescent ownership and use of new media. Communication 
Research Reports. 2014;31(4):357-364. 
14. 
Baranowski T, Buday R, Thompson DI, Baranowski J. Playing for real: video games 
and stories for health-related behavior change. Am J Prev Med. 2008;34(1):74-82. 
15. 
McGrath P, Seifert C, Speechly K, Booth J, Stitt L, Gibson M. A new analogue scale 
for assessing children's pain: An initial validation study. Pain. 1996;64:435-443. 

 
  
 
 
 
23 
16. 
Kassam-Adams N, Marsac M. Brief practical screeners in English and Spanish for 
acute posttraumatic stress symptoms in children. Journal of Traumatic Stress. 
2016;29(6):483-490. 
17. 
Page MG, Katz J, Stinson J, Isaac L, Martin-Pichora AL, Campbell F. Validation of 
the numerical rating scale for pain intensity and unpleasantness in pediatric acute 
postoperative pain: sensitivity to change over time. Journal of Pain. 2012;13(4):359-
369. 
18. 
von Baeyer CL, Spagrud LJ, McCormick JC, Choo E, Neville K, Connelly MA. 
Three new datasets supporting use of the Numerical Rating Scale (NRS-11) for 
children's self-reports of pain intensity. Pain. 2009;143(3):223-227. 
19. 
Foa E, Asnaani A, Zang Y, Capaldi S, Yeh R. Psychometrics of the Child PTSD 
Symptom Scale for DSM-5 for trauma-exposed children and adolescents. Journal of 
Clinical Child & Adolescent Psychology. 2018;47(1):38-46. 
20. 
Foa E, Johnson K, Feeny N, Treadwell K. The Child PTSD Symptom Scale: A 
preliminary examination of its psychometric properties. Journal of Clinical Child 
Psychology. 2001;30(3):376-384. 
21. 
Meyer R, Gold J, Beas V, Young C, Kassam-Adams N. Psychometric evaluation of 
the Child PTSD Symptom Scale in Spanish and English. Child Psychiatry Hum Dev. 
2015;46(3):438-444. 
22. 
Marsac M, Hildenbrand A, Kohser K, Winston F, Li Y, Kassam-Adams N. 
Preventing posttraumatic stress following pediatric injury: A randomized controlled 
trial of a web-based psycho-educational intervention for parents. Journal of Pediatric 
Psychology. 2013. 
23. 
Marsac M, Kassam-Adams N, Hildenbrand AK, Kohser K, Winston FK. After The 
Injury: Initial evaluation of a web-based intervention for parents of injured children. 
Health Education Research. 2011;26(1).