A Pragmatic Clinical Trial of the WE BEAT Well-Being Education Program in Adolescent Congenital Heart Disease: WE BEAT CHD Study
Phase: NA
Conditions: Patient-Reported Outcome Measures (PROMs), Pragmatic Trial, Adolescent Congenital Heart Disease, Resiliency-building Intervention, Resilience, Psychological, Telemedicine-Based Education
Sponsor: Carelon Research

 
 
 
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A Pragmatic Clinical Trial of the WE BEAT  
Well-Being Education Program in  
Adolescent Congenital Heart Disease: 
WE BEAT CHD Study 
 
 
 
PROTOCOL 
 
Version Number: VERSION 1.0 
Version Date: September 1, 2025 
 
 
 
 
 
 
Funded by 
The National Heart, Lung, and Blood Institute (NHLBI) 
NIH/DHHS 
 
 
 
 
 

 
 
 
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1. GENERAL INFORMATION 
1.1 Protocol Synopsis 
Title 
A Pragmatic Clinical Trial of the WE BEAT Well-Being Education Program in Adolescent 
Congenital Heart Disease: WE BEAT CHD Study 
Study 
Objectives 
To improve access to preventative, promotive, evidence-based psychosocial care through 
a telemedicine-based resiliency-building intervention, WE BEAT, in adolescent congenital 
heart disease (CHD) and create a data repository for the study of associations between 
self-reported psychosocial health, cardiac health, and biomarkers.  
Significance 
Adolescents with moderate and severe CHD experience considerable risk of mental health 
comorbidities. Psychological health is important to cardiovascular health and related 
outcomes. Access to mental health care, however, is limited, particularly for youth from 
historically disadvantaged backgrounds and for those with subclinical emotional and 
behavioral health concerns. There have been few psychological interventions specific to 
adolescent CHD. This study will evaluate the effectiveness of a resilience and well-being-
focused telemedicine intervention in adolescents with CHD and provide one of the largest 
linkages of adolescent self-reported psychosocial data with cardiac clinical outcomes.  
Study 
Design 
This is a 2-arm, 2-staged stratified randomized, parallel, multi-center pragmatic trial in a 
sample of 390 12-17-year-olds with moderately or severely complex CHD.  
Primary Aim 
To evaluate the effectiveness of the WE BEAT telemedicine intervention compared to 
usual care on self-reported resiliency and related psychosocial outcomes.  
Secondary 
Aim(s) 
1) To determine associations between self-reported psychosocial survey data and clinical 
outcomes. 2) To establish the WE BEAT CHD biorepository to study self-reported 
psychosocial data and stress-related biomarkers. 
Accrual  
N=390; 300 participants in the intervention arm and 90 in usual care  
Study 
Duration 
Approximately 5 years (6-12 months for study start-up; 3 years for enrollment and study 
follow-up; 1 year for analysis and dissemination).  
Inclusion 
Criteria 
• 
Age 12-17 years old 
• 
CHD of moderate or severe complexity (Class II/III, 2018 AHA/ACC ACHD, Table 4) 
• 
English or Spanish language proficiency  
• 
Receives cardiology care at a PHN or PHN auxiliary site  
• 
Parent or guardian and participant willing to comply with protocol and provide 
written/electronic informed consent and assent  
Exclusion 
Criteria 
• 
CHD of mild or simple complexity (Class I, 2018 AHA/ACC ACHD, Table 4) 
• 
Prior heart transplant to treat CHD  
• 
Heart disease that is not classified as structural CHD (e.g., connective tissue disease, 
genetic cardiomyopathy, or acquired heart disease) 
• 
Cognitive or developmental conditions that limit program participation and/or ability to 
complete self-reported measures as determined by a primary cardiology clinician  
• 
Suicidality, homicidality, or psychosis in the past 12 months as per medical chart 
review, clinician report, or eligibility screening  
• 
Medically unable to participate (e.g., intubated, unable to respond verbally, active 
delirium) 

 
 
 
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1.2 Table of Contents 
 
1. GENERAL INFORMATION .......................................................................................................... 2 
1.1 
Protocol Synopsis ................................................................................................................ 2 
1.2 
Table of Contents ................................................................................................................ 3 
1.3 
List of Figures ...................................................................................................................... 5 
1.4 
Protocol Version Log ........................................................................................................... 5 
1.5 
Table of Revisions ............................................................................................................... 5 
1.6 
List of Abbreviations ............................................................................................................ 6 
2. STUDY AIMS AND HYPOTHESES .............................................................................................. 7 
2.1 
Primary Aim ......................................................................................................................... 7 
2.1.1 
Hypothesis 1 ............................................................................................................ 7 
2.1.2 
Hypothesis 1A ......................................................................................................... 7 
2.1.3 
Hypothesis 1B ......................................................................................................... 7 
2.1.4 
Hypothesis 2 ............................................................................................................ 8 
2.1.5 
Hypothesis 3 ............................................................................................................ 8 
2.2 
Secondary Aim 1 ................................................................................................................. 8 
2.2.1 
Hypothesis 1 ............................................................................................................ 8 
2.3 
Secondary Aim 2 ................................................................................................................. 9 
2.3.1 
Hypothesis 1 ............................................................................................................ 9 
3. BACKGROUND INFORMATION ................................................................................................. 9 
3.1 
Background on Condition, Disease, or Other Primary Study Focus .................................... 9 
3.2 
Prior Studies ...................................................................................................................... 11 
3.3 
Rationale for the Study ...................................................................................................... 11 
3.4 
Rationale for Study Outcomes .......................................................................................... 11 
4. STUDY / TRIAL DESIGN ............................................................................................................ 12 
4.1 
Overview ........................................................................................................................... 12 
4.2 
Procedures to Minimize/Avoid Bias ................................................................................... 13 
4.2.1 
Sample Bias .......................................................................................................... 13 
4.2.2 
Generalizability ...................................................................................................... 13 
4.2.3 
Randomization ....................................................................................................... 13 
4.2.4 
Stratification ........................................................................................................... 14 
4.3 
Study Measures ................................................................................................................ 14 
4.3.1 
Measures of Primary Outcome .............................................................................. 14 
4.3.2 
Measures of Secondary Outcome(s) ..................................................................... 14 
4.3.3 
Covariate Measures .............................................................................................. 15 
4.4 
Study Visits ........................................................................................................................ 16 
Table 1. Schedule of Visits/Measurements ....................................................................... 17 
5. SELECTION AND WITHDRAWAL OF PARTICIPANTS ........................................................... 18 
5.1 
Participant Inclusion Criteria .............................................................................................. 18 
5.2 
Participant Exclusion Criteria ............................................................................................ 18 
5.3 
Participant Withdrawal Criteria .......................................................................................... 19 
5.3.1 
Discontinuation of Study Treatment ...................................................................... 19 
5.3.2 
Participant Withdrawal from Study ........................................................................ 19 
5.4 
Participant Availability ....................................................................................................... 19 
5.5 
Recruitment / Enrollment Procedures ............................................................................... 19 
6. TREATMENTS TO BE ADMINISTERED ................................................................................... 20 
6.1 
Description of Study Treatments ....................................................................................... 20 
Table 2. WE BEAT Program Modules ............................................................................... 20 

 
 
 
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6.2 
Medications/Treatments Permitted and Not Permitted during the Study ........................... 21 
6.3 
Procedures for Monitoring Participant Adherence ............................................................. 22 
6.4 
Study Completion .............................................................................................................. 22 
7. SAFETY ASSESSMENTS AND MONITORING ......................................................................... 23 
7.1 
Recording and Reporting Adverse Events ........................................................................ 23 
7.1.1 
Definition of Adverse Events ................................................................................. 23 
7.1.2 
Classification of Adverse Events ........................................................................... 23 
7.1.3 
Identification of and Data Collection Procedures for AEs ...................................... 24 
7.1.4 
Reporting Timeframe and Procedures .................................................................. 24 
Table 3.  Reporting Timeframe of Adverse Events ........................................................... 24 
7.1.5 
Reporting Adverse Events to IRBs for NIH-Supported Trials ................................ 25 
7.1.6 
Follow-up of Participants after Adverse Events ..................................................... 25 
7.2 
Safety Monitoring .............................................................................................................. 25 
8. STATISTICS ............................................................................................................................... 26 
8.1 
Planned Statistical Analyses ............................................................................................. 26 
8.1.1 
Primary Aim, Hypothesis 1, Primary Outcome ...................................................... 26 
8.1.2 
Primary Aim, Hypothesis 1, Secondary Outcomes ................................................ 26 
8.1.3 
Primary Aim, Hypothesis 1A .................................................................................. 26 
8.1.4 
Primary Aim, Hypothesis 1B .................................................................................. 26 
8.1.5 
Primary Aim, Hypothesis 2 .................................................................................... 26 
8.1.6 
Primary Aim, Hypothesis 3 .................................................................................... 27 
8.1.7 
Secondary Aim 1 ................................................................................................... 27 
8.1.8 
Secondary Aim 2 ................................................................................................... 27 
8.2 
Sample Size and Power .................................................................................................... 27 
Table 4: Summary of Sample Size Calculations ............................................................... 27 
8.2.1 
Primary Outcome (Hypothesis 1) .......................................................................... 28 
8.2.2 
Exploratory Secondary Outcome (Hypothesis 1B, booster session) ..................... 28 
8.3 
Level of Significance ......................................................................................................... 29 
8.4 
Interim Analyses and Stopping Rules for Termination of the Study .................................. 29 
8.4.1 
Reassessment of Assumptions ............................................................................. 29 
8.4.2 
Stopping Rules ...................................................................................................... 29 
8.4.3 
Additional Considerations ...................................................................................... 30 
8.5 
Spurious Data Procedures ................................................................................................ 30 
8.6 
Deviation Reporting Procedure ......................................................................................... 30 
8.7 
Participants to be Included in Analyses ............................................................................. 31 
8.8 
Subpopulations .................................................................................................................. 31 
9. DATA MANAGEMENT ............................................................................................................... 32 
9.1 
Data Entry ......................................................................................................................... 32 
9.2 
Data Validation and Monitoring ......................................................................................... 32 
9.3 
Data Security and Integrity ................................................................................................ 32 
9.4 
Biospecimen Tracking ....................................................................................................... 33 
10. QUALITY CONTROL AND QUALITY ASSURANCE ................................................................. 33 
11. ETHICS AND HUMAN SUBJECTS CONSIDERATIONS .......................................................... 33 
11.1 Potential Risks ................................................................................................................... 33 
11.2 Confidentiality, Protection against Risks ........................................................................... 34 
11.3 Potential Benefits .............................................................................................................. 35 
11.4 Risk/Benefit Ratio and Importance of Information to Be Obtained .................................... 35 
12. STUDY LIMITATIONS ................................................................................................................ 36 
13. REFERENCES ........................................................................................................................... 37 
 
 

 
 
 
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1.3 List of Figures 
Figure 1. WE BEAT Theoretical Framework ......................................................................................... 10 
Figure 2. WE BEAT CHD Study Schematic .......................................................................................... 12 
Figure 3. WE BEAT CHD Study Flow Diagram .................................................................................... 16 
 
 
1.4 Protocol Version Log 
Version 
Number 
Version Date 
Comment(s) 
Version 0.1 
17 FEB 2025 
Initial version posted for PHN Protocol Review Committee review. 
Version 0.2 
01 MAY 2025 
Incorporated PRC feedback: clarified exploratory nature of booster 
session hypothesis, added community service hours to the participant 
compensation plan, increased dropout rate to a cumulative 30% 
(baseline to Week 18); modified intervention adherence target, and 
elaborated on interim analysis and stopping rules. Approved by PRC. 
Initial version posted for PHN Data Safety Monitoring Board review.  
Version 0.3 
30 JUN 2025 
Incorporated DSMB feedback: clarified assessment of cognitive ability 
and suicidality exclusion criteria, clarified how suicide-risk would be 
identified/addressed as part of safety plan, added study flow diagram, 
streamlined language around intervention description, sample size, 
interim analysis, and throughout protocol. Added list of figures. 
Version 1.0 
01 SEP 2025 
Minor/administrative edits; no significant changes to content. First 
version submitted to CCHMC sIRB. 
 
 
 
 
 
 
 
 
1.5 Table of Revisions 
 
(for future version change control) 
 
 
 

 
 
 
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1.6 List of Abbreviations 
Common abbreviations are listed in tabular format below.  
 
ACC 
American College of Cardiology 
ACHD 
Adult Congenital Heart Disease 
AE 
Adverse Event 
AHA 
American Heart Association 
ASQ 
Ask Suicide-Screening Questions Toolkit 
CD-RISC© 
Connor-Davidson Resilience Scale 
CHD 
Congenital Heart Disease 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCC 
Data Coordinating Center 
DMP 
Data Management Plan 
DSMB 
Data and Safety Monitoring Board 
eConsent 
Electronic Consent 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
GUID 
Global Unique Identifier 
HRQOL 
Health-Related Quality of Life 
ICF 
Informed Consent Form 
ICH 
International Conference of Harmonization 
IRB 
Institutional Review Board 
K6 
Kessler-6 
LE8™ 
Life’s Essential 8™ 
MedDRA 
Medical Dictionary for Drug Regulatory Activities 
MM 
Medical Monitor 
NHLBI 
National Heart, Lung and Blood Institute 
NIH 
National Institutes of Health 
PedsQL™ 
Pediatric Quality of Life Inventory™ 
PHN 
Pediatric Heart Network 
PI 
Principal Investigator 
PROMIS® 
Patient-Reported Outcomes Measurement Information System® 
QA 
Quality Assurance 
QC 
Quality Control 
QOL 
Quality of Life 
RRC 
Recruitment and Retention Committee 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
UC 
Usual Care 
WBC 
WE BEAT CHD Study 
WE BEAT 
Wellbeing Education Program: Breathe, Energize, Adjust, Thank 
 
 
 
 

 
 
 
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2. STUDY AIMS AND HYPOTHESES 
2.1 Primary Aim  
To evaluate the effectiveness of the WE BEAT (Wellbeing Education Program: Breathe, Energize, 
Adjust, Thank) telemedicine intervention compared to usual care on psychosocial outcomes in 
adolescents ages 12-17 years with congenital heart disease (CHD) of moderate or severe complexity 
through a 2-arm, 2-staged stratified randomized, parallel, multi-center pragmatic trial. 
 
2.1.1 Hypothesis 1 
Participants randomized to the intervention arm will experience greater improvements in self-
reported resiliency compared to participants in the usual care (UC) arm.  
 
Primary Outcome: Change in participant self-reported resiliency as measured by the Connor-
Davidson Resilience Scale© (CD-RISC©) from baseline to Week 5.0F0Fa 
 
Secondary Outcomes: Change in participant self-reported quality of life (QOL) as measured by 
the Pediatric Quality of Life Inventory™ (PedsQL™), general distress as measured by the 
Kessler-6 (K6), life satisfaction, meaning/purpose in life, and depressive/anxiety symptoms as 
measured by the National Institutes of Health (NIH) Patient-Reported Outcomes 
Measurement Information System® (PROMIS®) scales, and adolescent lifestyle behaviors as 
measured by Life’s Essential 8™ (LE8™) from baseline to Week 5.a 
 
2.1.2 Hypothesis 1A 
Participants randomized to the intervention arm will maintain gains in self-reported resiliency 
compared to participants in the UC arm.  
 
Primary Outcome: Change in participant self-reported resiliency (CD-RISC©) from baseline to 
Weeks 18 and 30, respectively.a 
 
Secondary Outcomes: Change in participant self-reported QOL (PedsQL™), general distress 
(K6), life satisfaction, meaning/purpose, depressive/anxiety symptoms (PROMIS®), and 
adolescent lifestyle behaviors (LE8™) from baseline to Week 18 and Week 30, respectively.a  
 
2.1.3 Hypothesis 1B 
Intervention arm participants randomized to the booster session at Week 18 (~3 months after 
intervention) will maintain larger gains in self-reported resiliency compared to intervention arm 
participants without the booster session.  
 
Primary Outcome: Change in participant self-reported resiliency (CD-RISC©) from baseline to 
Weeks 18 and 30, respectively.a  
 
 
 
a Parent-reported surveys of adolescent psychosocial outcomes will be optional and collected when available. 
 

 
 
 
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2.1.4 Hypothesis 2 
The WE BEAT telemedicine intervention will demonstrate feasibility and acceptability among 
participants randomized to the intervention arm as measured by program adherence and 
overall program satisfaction rating at Week 5.  
 
Primary Outcomes: Participant adherence will be defined as 70% overall session attendance (all 
participants) and 60% within-participant attendance for WE BEAT sessions (3 of 5 sessions). 
Overall program satisfaction will be defined as a mean rating of ≥7/10 on the WE BEAT 
Program participant survey.  
Secondary Outcomes: Session ratings, open-ended program feedback, and additional program 
information collected via the WE BEAT program survey.  
 
2.1.5 Hypothesis 3 
Perceived social support and family finances are expected to modify the effect of the WE BEAT 
intervention on self-reported psychosocial outcomes among intervention arm participants, 
such that those with lower levels of perceived social support at baseline will experience 
greater intervention effects, while those with lower family financial means at baseline will 
experience lesser intervention effects. 
 
Primary Outcome: Change in participant self-reported resiliency (CD-RISC©) from baseline to 
Week 5.a 
Secondary Outcome: Change in participant self-reported QOL (PedsQL™), general distress 
(K6), life satisfaction, meaning/purpose, depressive/anxiety symptoms (PROMIS®), and 
adolescent lifestyle behaviors (LE8™) from baseline to Week 5.a  
Primary Predictors: Multidimensional Scale of Perceived Social Support and family finances 
(income, household structure, marital status, makes ends meet).  
 
2.2 Secondary Aim 1   
To develop a data repository to examine associations between participant-reported psychosocial 
survey data, cardiac clinical factors gathered via medical chart extraction and registry-linkage, and 
family, social, and community factors.  
 
2.2.1 Hypothesis 1 
Participant self-reported resilience, general distress, and depressive/anxiety symptoms will be 
associated with cardiac outcomes.  
 
Primary Outcome: Composite event score (all-cause mortality or non-elective cardiovascular 
hospitalization).  
Secondary Outcomes: Emergency room visits, hospital days, heart failure (NT-proBNP), 
metabolic markers (blood glucose/lipids) and participant-reported QOL (as measured by 
PedsQL™).  
Primary Predictors: Participant self-reported resilience (CD-RISC©), general distress (K6), 
depressive/anxiety symptoms (PROMIS®), and single-item self-perceived health status 
assessment.  
Secondary Predictors: Parent-reported surveys of adolescent resilience, general distress, 
depressive/anxiety symptoms, and perceived adolescent health status.  
 
 

 
 
 
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2.3 Secondary Aim 2   
To examine the impact of the WE BEAT intervention on stress response pathways and assess the 
effect of baseline physiologic stress on individual response to the intervention through development of 
the WE BEAT biorepository. Hair, saliva, urine, and blood specimens will be collected from study 
participants. Urine and blood specimens will be optional.  
 
2.3.1 Hypothesis 1 
Participant-reported resilience, general distress, and depressive/anxiety symptoms will be 
associated with biomarkers of stress that may help quantify the physiologic impact of 
psychosocial stressors and predict and track the intervention response.  
 
Primary Predictors: Hair cortisol and cortisone levels will be assayed from hair samples collected 
at baseline, Week 5, and Week 30 to assess change over time in response to the intervention 
and usefulness in predicting participant response. 
Secondary Predictors: Since chronic stress can affect inflammation and accelerate aging, 
markers of inflammation (CRP, TNF alpha, and IL-6) and epigenetic markers of aging (from 
genome-wide epigenetic profiling) will be collected from saliva samples collected at baseline, 
Week 5, and Week 30.  
3. BACKGROUND INFORMATION 
3.1 Background on Condition, Disease, or Other Primary Study Focus 
Psychological Health in Pediatric Congenital Heart Disease (CHD). Recent national prevalence 
rates indicate that approximately 1 in 6 children and adolescents in the United States experience a 
mental health disorder, with approximately half of these youth not receiving necessary mental health 
treatment.1F1F1 A National Emergency in Youth Mental Health was declared in October 2021 by leading 
pediatric and psychiatric societies. This was prompted by a doubling in youth depressive and anxiety 
symptoms seen globally.2F2F2 Children with CHD experience even greater risk of mental health concerns. 
In a comparative cross-sectional analysis study, it was found that children with simple CHD had a 5 
times greater odds of treatment or diagnosis of anxiety or depression than children without CHD, 
while those with single ventricle CHD had 7 times greater odds compared to healthy peers. 3F3F3 Two-
thirds of pediatric patients with single ventricle CHD will experience a mental health condition, such as 
depression or anxiety, in their lifetime,4F4F4,
5F5F5 and these mental health risks continue into adulthood with 
high rates of mental health diagnoses among the growing adult CHD (ACHD) population.6F6F6  
Gaps in Mental Health Care in Pediatric CHD. Family, social, and community factors have 
contributed to a widening mental health gap between children from households with fewer resources 
when compared to those with higher financial status.7F7F7 CHD patients of minority race and those without 
private insurance have lesser odds of receiving a diagnosis of a mental health condition and/or 
receiving treatment when compared to non-Hispanic White peers.3,
8F8F8 Additionally, there remains a 
critical gap in the development, implementation and testing of psychological interventions in 
CHD.9F9F9,
10F10F10,
1F1F11 A recent review identified only four studies of psychological interventions in youth with 
CHD, all of which were limited in efficacy.12F12F12 Through an international study of over 1200 
patients/caregivers with pediatric heart disease, 30% of respondents indicated a desire for more 
access to mental health/self-care information while nearly 1 in 4 stated a need for increased access to 
psychology/therapy services, as well as support groups. 13F13F13 In a recent preliminary analysis of a 
Pediatric Heart Network (PHN) dataset, more than half of parents of children with single ventricle CHD 
endorsed having concerns about their child’s mental health (McCormick et al., unpublished data).  

 
 
 
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Psychological Health and Cardiac Outcomes. Lack of access to specialized mental health care has 
the potential to impact medical and cardiac outcomes. Associations between psychological health and 
adult cardiovascular outcomes, such as mortality and hospitalizations, have been established.14F14F14 In a 
sample of adults with CHD, a diagnosis of depression was found to be associated with inflammation 
(hsCRP), heart failure (NT-proBNP), all-cause mortality, and composite outcome of death or non-
elective cardiac hospitalization. 15F15F15 Similarly, in multi-variate models, depression was found to be a 
significant driver of perceived 
health status in adults with CHD, 
even more so than cardiac-
specific variables.16F16F16 Among a 
single-center sample of adults 
with moderate or severe CHD, 
depressive symptoms and self-
efficacy were associated with 
self-care behaviors (i.e., health 
behaviors, symptom monitoring 
and management) in multi-
variate modeling.17F17F17 While there 
has been limited study of self-
reported psychological health 
and 
cardiac 
outcomes 
in 
pediatric CHD, the broader child 
health literature underscores the importance of such investigation. Childhood adversities known to be 
prevalent in CHD populations, including negative life events (i.e., hospitalizations, surgeries, impact on 
activities of daily living, family conflict), parental mental health conditions,18F18F18,
19F19F19 and economic hardship,20F20F20 
are drivers of cardiovascular risk, morbidity, and mortality through biological, behavioral and 
psychological mechanisms (as shown in Figure 1).   
Resilience, Psychological Health, and Cardiac Health. Resiliency has been defined as the process 
by which an individual harnesses internal, external and learned resources to maintain wellness and 
wellbeing amidst a stressor.21F21F21 Resilience is conceptualized as a multi-faceted promotive and 
protective process that is derived from internal and external resources. Further, one’s resilience is 
dynamic, changing and modifiable. 2F2F22,
23F23F23,
24F24F24 Resilience is associated with important outcomes in general 
child/adolescent and pediatric chronic illness populations. In a recent systematic review of the general 
child and adolescent literature, greater resilience was found to be associated with fewer mental health 
concerns across all studies.17 Similarly, in recent sample of 332 patients with CHD (M = 17.2 ± 5.1 
years), higher self-reported resilience was associated with fewer mental health diagnoses and 
involvement in CHD peer support communities/camps.25F25F25 Moreover, resiliency has been shown to be 
associated with improved health-related quality of life in pediatric cancer patients, 26F26F26 better glycemic 
control in adolescents with diabetes,27F27F27 and decreased depressive symptoms in youth with CHD. 28F28F28 As 
shown in Figure 1, we conceptualize resiliency as a modifiable process that serves an important role 
between the stressors associated with CHD and mental health and related well-being outcomes. This 
pathway is likely to continue on to impact cardiac health and health behaviors. Interventions targeting 
resilience across other pediatric chronic illness groups and adult CHD (ACHD) have shown promise at 
increasing resilience26,
29F29F29 and decreasing health-related anxiety29 and depressive symptoms,30F30F30 with 
positive effects on resiliency sustained 3 months post-intervention.29 These intervention studies in 
pediatric cancer and ACHD also identified areas for improvement in terms of intervention design and 
delivery. For example, in the ACHD intervention trial, transportation was the biggest barrier to study 
participation. Only half of the participants attended all 8 study sessions, yet 71% attended at least 4 
sessions.30 The benefits of peer support in adjustment to pediatric chronic illness have been well-
established31F31F31 and pediatric CHD patients report a desire for more opportunities for peer-to-peer 
Figure 1. WE BEAT Theoretical Framework 

 
 
 
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connection;13 however, resilience interventions in pediatric populations have been largely delivered 
via individual, in-person sessions to-date.26,
32F32F32  
Improving Access and Increasing Resilience through the WE BEAT Well-Being Education 
Program. The WE BEAT Well-Being Education Program was developed for pediatric patients with 
heart disease.3F3F33 This program was developed by a clinical psychologist with 10+ years of mental 
health practice with youth with heart disease and serious childhood illness. WE BEAT program 
development was further informed by a NHLBI-funded (5K23HL45096) semi-structured interview 
study conducted with representative sample of youth ages 12-24 years of age with advanced heart 
disease and their caregivers.34F34F34 The evidence-based components of the 5-module WE BEAT 
intervention, which are described in detail in the design manuscript,33 are derived from cognitive 
behavioral theory, stress management and resiliency research, and behavioral intervention science 
across pediatric populations and adult heart disease. The five WE BEAT modules include: (1) Well-
being Education--Introduction, (2) Breathe--Mindfulness and Relaxation-Based Skills, (3) Energize--
Positive Psychology Skills, (4) Adjust--Cognitive Skills Training, and (5) Thanks--Gratitude Practice. 
The overall objective of the WE BEAT CHD Program is to foster positive psychological well-being and 
resilient outcomes in adolescents with CHD through a mental health promotion and prevention lens 
while providing access to safe, peer-to-peer community building. Through its group-based 
telemedicine delivery, the program aims to increase access to mental health care (i.e., provider 
availability, lack of insurance, need for diagnosis) for the representative population of young people 
we care for while emphasizing prevention-focused, early mental health intervention.  
 
3.2 Prior Studies 
WE BEAT Pilot Study in Fontan CHD. The WE BEAT telemedicine group program was recently 
piloted in a single-center sample of adolescents 13-18 years old with Fontan-palliated CHD who were 
also willing to participate in a 6-month individualized exercise training program.35F35F35 Among eligible 
patients reached, 68% expressed interest in study participation. Of those consented, 77% had been 
scheduled for a group program at time of analysis with 87% program completion. Twenty adolescents 
(mean age 16.1 ± SD 1.6 years) participated in five WE BEAT group cohorts (range: 3-6 participants 
per group). The majority (80%) attended 4 or 5 sessions in the 5-session program, and the median 
program satisfaction rating was a 9 out of 10 (10=most favorable rating). Due to the small pilot sample 
size, an effect size calculation was used. Effect size is a measure of clinical meaningfulness or 
impact. Even a small effect of an intervention on an identified outcome can have a meaningful clinical 
impact for an individual. Following WE BEAT participation, resiliency (d=0.44; medium effect size) and 
perceptions of purpose in life increased (d=0.26; small effect size), while depressive symptoms 
decreased (d=0.36; medium effect size). 
 
3.3 Rationale for the Study 
Adolescents with moderately and severely complex CHD experience considerable risk of mental 
health comorbidities. Psychological health is important to cardiovascular health and related outcomes. 
Access to mental health care, however, is limited for many young people and for those with subclinical 
emotional and behavioral health concerns. There have been few psychological interventions specific 
to adolescent CHD. This study will evaluate the effectiveness of a resilience and well-being-focused 
telemedicine intervention, WE BEAT, in adolescents with CHD and provide one of the largest linkages 
of adolescent self-reported psychosocial functioning, cardiac factors and outcomes, family, social and 
community factors, and stress, cardiac and genetic biomarkers.  
 
3.4 Rationale for Study Outcomes 
Participant self-reported resiliency is the primary study outcome. Higher resiliency is associated with 
lower levels of depression, anxiety, and stress among adolescents, as well as reduced risk 

 
 
 
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behaviors.22,23,24,
36F36F36  Resilience is modifiable and skills that promote resilience can be taught and 
fostered, even among those living in higher-risk environments. The intervention was developed to be 
a preventive and promotive evidence-based psychosocial intervention as opposed to a specific mental 
health treatment for a presenting mental health concern. Secondary outcomes, including general 
stress, depression, anxiety, self-perceived illness status, and health behaviors were selected given 
their associations with resilience and intervention domains (e.g., cognitive skills training, relaxation 
training).  
 
4. STUDY / TRIAL DESIGN 
4.1 Overview  
This study will employ a 2-arm, 2-staged stratified randomized, parallel, multi-center pragmatic trial 
design. Pragmatic trials aim to provide evidence for the adoption of an intervention in the real-world 
clinical setting.37F37F37 Given that the overall objective of this study is to demonstrate effectiveness of the 
WE BEAT intervention across diverse sites and participants to increase access to preventative and 
promotive psychological health intervention, the emphasis on real-world applicability is important. The 
PRECIS-2 (PRagmatic Explanatory Continuum Indicator Summary-2) tool was used to enhance 
pragmatism in this trial design, particularly with respect to inclusion/exclusion criteria, study arms (i.e., 
usual care as comparator), measurement selection (i.e., emphasis on brevity), and intervention 
delivery.38F38F38  
 
The study objective is to evaluate the effectiveness of the WE BEAT telemedicine intervention on 
resiliency and related psychosocial outcomes in adolescents with congenital heart disease (CHD) of 
moderate or severe complexity, defined as Class II or III in Table 4 of the 2018 American Heart 
Association (AHA)/American College of Cardiology (ACC) Guidelines for the Management of Adults 
with CHD. A sample of adolescents with CHD who meet eligibility criteria (refer to Section 5) will be 
recruited across participating PHN sites with stratified randomization to the intervention or UC arm 
(see Figure 2. WE BEAT CHD Study Schematic). Following completion of the WE BEAT program, 
intervention arm participants will be randomized to a single booster session at Week 18 vs. no booster 
session. 
The primary outcome will be participant self-reported resiliency at Week 5 (i.e. primary endpoint, 
immediately post-intervention). Follow-up assessments will occur at Weeks 18 (~3 months post-
intervention) and 30 (~6 months post-intervention) to allow for the study of intervention maintenance 
effects. Secondary aims will include the retrospective study of participant-reported psychosocial 
outcomes with a) cardiac clinical outcomes, b) family, social, and community factors, and c) stress, 
cardiac, and genetic biomarkers through the development of a WE BEAT CHD biorepository.  
 
Figure 2. WE BEAT CHD Study Schematic 

 
 
 
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4.2 Procedures to Minimize/Avoid Bias  
4.2.1 Sample Bias  
The PHN sites represent broad geographical coverage with each being national/international referral 
centers for increased diversity and generalizability within the study sample. This study will employ 
several strategies to ensure a representative participant sample. Study participation will require 
access to an electronic device with internet capabilities for participation in the virtual group program. 
Recent Pew Center national survey data show 95% of U.S. teens have access to a smartphone and 
97% report using the Internet daily. This PHN study will provide loaned internet-capable devices 
and/or prepaid Wi-Fi cards if needed. Patient/family representatives will serve on the PHN 
Recruitment and Retention Committee (RRC) to help develop best practices and support participant 
recruitment and retention efforts (see the PHN Manual of Operations for more information). In addition 
to co-design of recruitment materials and procedures with the PHN RRC, we will employ community-
based participatory research practices to study recruitment, enrollment and retention, which have 
been outlined for clinical trials within pediatric chronic and critical illness populations.39F39F39 In-person, 
electronic, and phone-based recruitment and consent procedures will be employed.38,
40F40F40  Multiple 
contacts will be made to optimize recruitment of a representative participant sample. Previous 
research has shown that nearly 10 months and 15 contacts were needed, on average, to recruit a 
representative sample in a behavioral health clinical trial.41F41F41 English and Spanish electronic consent (e-
consent) forms will be available.  
 
Parents/guardians may opt-in to secondary data collection for parent-reported assessment of child 
psychosocial functioning. However, parent participation in the study is not necessary for participant 
enrollment in the study. Eliminating the requirement of parent participation in the study increases 
opportunities to recruit a representative participant sample,41 as systematic review demonstrates 
higher participation of youth from lower resourced groups in adolescent-only focused clinical trials.42F42F42  
 
4.2.2 Generalizability 
Based on the recruitment, eligibility, and pragmatic clinical trial design strategies described throughout 
this protocol, we expect the results of the trial to be generalizable. Additionally, the study population 
includes participants with both moderately and severely complex CHD to support generalizability of 
findings and implications. Lastly, the intervention will be delivered by a team of psychologists from 
three PHN sites, supporting generalizability of intervention delivery. 
 
4.2.3 Randomization 
Eligible participants will be randomly assigned to one of two treatment arms: intervention or usual 
care. Participants will be randomized in a 3:1 ratio (3 in the intervention arm to 1 in the usual care 
arm) and in the order they are enrolled into the study. Randomization assignments will be generated 
by a web-based system at the data coordinating center (DCC) to receive the allocated treatment 
according to a computer-generated randomization plan using the DCC’s randomization program, after 
confirmation of trial eligibility. Once a participant has been assigned a treatment allocation code, the 
participant will remain in the same study arm for the duration of the study. While randomization does 
not ensure that any particular baseline characteristic, other than the stratification variable, will be 
balanced between treatment groups, it does minimize potential for study team members or 
participants to decide who would receive the WE BEAT intervention. Participants in the intervention 
arm who complete the intervention program will be further randomized in a 1:1 ratio post-intervention 
with one group receiving an additional booster session at Week 18. 
 

 
 
 
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4.2.4 Stratification 
Randomization will occur within strata defined by participant self-reported resilience using the Connor-
Davidson Resilience Scale© (CD-RISC©)43F43F43,
4F4F44 at time of study enrollment. We will stratify participants 
by high resilience (defined as approximately top 20% of CD-RISC©) and moderate-low resilience 
(defined as the lower 80% of CD-RISC©) as assessed by their enrollment resilience score. The 
results of the pilot study suggest that high resilience group could be initially defined as CD-RISC© ≥ 
34 (see Section 8.4 for additional details). The rationale for stratification is based on the results of 
previous PHN studies suggesting that participants with high baseline scores may have a different 
pattern of response to the intervention.  
 
Randomization will be also balanced within clinical site so that any site-specific characteristics will be 
approximately evenly balanced between treatment arms. We acknowledge that usual care as it 
pertains to psychosocial support and mental health is likely to vary across PHN and auxiliary sites. 
We will collect institution-level data annually throughout the course of the trial to describe and 
understand the center-level psychosocial supports available to participants during the course of their 
study participation. 
 
4.3 Study Measures  
All surveys are self-reported measures and will be administered electronically by secure link, email, or 
in-person via tablet if requested. A research coordinator can aid in completion as needed. Parent 
reports of adolescent psychosocial outcomes will be optional and collected when available. 
 
4.3.1 Measures of Primary Outcome 
Connor-Davidson Resilience Scale© (CD-RISC©).43,44 10 items; self-reported, unidimensional 5-
point Likert scale measuring resilience. Total scores range from 0-40 with higher scores indicating 
greater resilience. A modified parent-reported version will also be available. Available in Spanish. The 
CD-RISC© is one of the most widely used measures of resilience. It has been validated for use in 
children and adolescents across various countries.45F45F45,
46F46F46 The CD-RISC© been used in intervention 
studies targeting resilience in adolescents with cancer26,32 and was used as the primary outcome 
measure of the WE BEAT pilot study in Fontan CHD.35 Time to complete is 1-5 minutes.  
 
4.3.2 Measures of Secondary Outcome(s) 
NIH Patient-Reported Outcomes Measurement Information System® (PROMIS®) Scales.47F47F47,
48F48F48,
49F49F49 
24 items; self-reported, 5-point Likert scales measuring depressive symptoms (8 items); anxiety (8 
items); meaning and purpose in life (4 items); life satisfaction (4 items). Participant- and parent-
reported versions available. Available in Spanish. The NIH PROMIS® Scales have been validated for 
use in children with chronic health conditions ages 8-17 years old48 and were utilized as the 
secondary outcomes measures in the WE BEAT pilot study in Fontan CHD.35 Time to complete is 5-
10 minutes. 
 
Kessler-6 (K6).50F50F50 6 items; self-reported, 5-point Likert scale measuring general distress. Total scores 
range from 0-24 with higher scores indicating more psychological distress. The K6 is available in 14 
languages, including Spanish. The K6 is a widely used, well-validated screening measure of non-
specific, general psychological distress over the past 30 days. 51F51F51  Time to complete is 2 minutes.50  
 
PedsQL™, Generic Core52F52F52 and Cardiac Module.53F53F53 23 items and 27 items; self-reported; 5-point 
Likert scale measuring health-related quality of life (HRQOL). Scores will be transformed to a 0-100 
scale with higher scores indicating more positive HRQOL. The PedsQL™ Generic Core is widely used 
and includes four domains: Physical, Emotional, Social, and School functioning. The Spanish version 

 
 
 
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of the measure was determined to be psychometrically sound in a sample of Spanish speaking youth 
with CHD.54F54F54 The PedsQL™ Generic has been validated for use in pediatric heart disease 
populations.5F5F55,
56F56F56 The PedsQL™ Cardiac Module is administered in addition to the PedsQL™ Generic 
Core to gather cardiac-specific constructs important to QOL. Subscales include: Heart Problems and 
Treatment (e.g., symptoms, medical interventions), Treatment Barriers (e.g., difficulty accessing care, 
adherence with treatment), Perceived Physical Appearance (e.g., concerns related to scars, body 
image), Treatment Anxiety (e.g., worries about medical procedures and hospital visits), Cognitive 
Problems (e.g., difficulties in concentrating, memory issues), and Communication (e.g., ability to 
discuss condition and treatment with others). Both the Generic Core and Cardiac Module take 5-10 
minutes to complete (total of 10-20 minutes).  
 
Life’s Essential 8™ (LE8™). 8 items; self-reported scoring tool measuring lifestyle behaviors. Items 
align with the American Heart Association’s key metrics for promoting cardiovascular health and 
overall well-being.57F57F57 Items include assessment of diet, sleep, physical activity, and nicotine 
use/exposure. This survey has been recommended by the International Consortium for Health 
Outcomes Measurement as patient-centered outcomes measure for CHD.58F58F58 Time to complete is 1-5 
minutes. 
 
Multidimensional Scale of Perceived Social Support. 59F59F59 12 items; self-reported; 7-point Likert scale 
measuring perceived social support. Available in Spanish.60F60F60 Total score ranges from 1-7 with higher 
scores indicating more perceived social support. Subscales include: family subscale, friends subscale, 
and significant other subscale. The psychometric properties of this scale have been established in 
diverse samples of adolescents.61F61F61,
62F62F62 Time to complete is 5 minutes.  
 
Self-Perceived Health Status. 1 item; self-reported; linear analog scale. Subjectively perceived 
health status will be measured with a linear analogue scale ranging from the ‘‘worst imaginable health 
state’’ (score of 0) to the ‘‘best imaginable health state’’ (score of 100). This linear analog scale is part 
of the EuroQol instrument and has been used to measure self-perceived health status in adolescents 
and young adults with CHD.63F63F63 Time to complete is 1 minute. 
 
WE BEAT Survey. 10 items; self-reported. An investigator-designed survey used to gather WE BEAT 
session and overall program ratings and acceptability, as well as feedback and ideas for program 
improvement. Time to complete is 1-5 minutes.  
 
4.3.3 Covariate Measures 
Demographics and Family, Social and Community Factors. At study enrollment, the consenting 
parent/guardian will complete a PHN-designed survey to collect key participant and family 
demographic information as well as family, social, and community information known to relate to 
health outcomes. This survey was developed in partnership with the PHN Data Science Committee. 
Domains include: participant/family neighborhood (GEOID, or geographic identifiers), race/ethnicity, 
language, employment/school status, health insurance coverage, health costs/barriers, parental 
marital status and education, household structure, housing stability, family income/finances, 
spirituality, food security, cell phone access, and social media use.  
 
Mental Health History and Services. At study enrollment, the consenting parent/guardian will 
complete an investigator-designed survey of child and family mental health history and current mental 
health services. This survey includes questions regarding current child/family mental health 
diagnoses, current child/family mental health treatment (i.e., psychotherapy, pharmacologic), past 
mental health diagnoses, past mental health treatment, current/past serious risk concerns (i.e., 
suicidality), and child/family mental health needs.  
 

 
 
 
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4.4 Study Visits 
There will be 5 visits over the course of the study. eConsent and randomization will be completed at 
the enrollment visit. Surveys will be completed electronically at baseline (Week 0), Week 5, Week 18, 
and Week 30. Biospecimens will be collected at baseline, Week 5, and Week 30 either on-site at 
enrolling centers (or approved local laboratory) or by participants at home with biospecimen collection 
kits (see Figure 3. WE BEAT CHD Study Flow Diagram and Table 1. Schedule of Visits/ 
Measurements for details). 
 
Participants will be compensated for each survey timepoint completed and for each biospecimen 
provided. In addition, participants who complete the study in its entirety will receive a certificate of 
completion documenting five community service hours for their time participating in research that is 
not compensated (e.g., enrollment visit, intervention sessions, additional survey time).  
 
Parents/guardians who choose to complete optional parent-reported surveys will also be 
compensated for each survey timepoint completed.  
 
Figure 3. WE BEAT CHD Study Flow Diagram 
 

 
 
 
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Table 1. Schedule of Visits/Measurements 
Study Measure 
Reporter 
Enrollment 
Week 0¥ 
Weeks 
1°-4 
Week 5 
Week 18 
Week 30 
ENROLLMENT (ALL) 
 
 
 
 
3 MONTHS 
POST-INT 
6 MONTHS 
POST-INT 
Eligibility 
Site 
X 
 
 
 
 
 
Site Survey  
Site 
X 
 
 
 
 
 
Informed Assent 
Participant 
X 
 
 
 
 
 
Informed Consent 
Parent 
X 
 
 
 
 
 
Demographics, 
Socioeconomic Status 
Parent 
X 
 
 
 
 
 
Mental Health History  
Parent 
X 
 
 
 
 
 
Randomization 
Site 
X 
 
 
X (subset) 
 
 
BIOSPECIMENS 
 
 
 
 
 
 
 
Hair/Saliva Specimens 
Participant 
X 
 
 
X 
 
X 
Urine Specimens^ 
Participant 
X 
 
 
 
 
 
Blood Specimens^ 
Participant 
X 
 
 
X (subset) 
 
X (subset) 
INTERVENTION (INTERVENTION ARM ONLY)  
~45 MINUTES PER VIRTUAL SESSION 
 
 
WE BEAT SESSIONS  
1-5 
BOOSTER 
SESSION 
 
WE BEAT Program  
Participant 
 
 
X 
X 
 
 
WE BEAT Survey 
Participant 
 
 
 
X 
 
 
WE BEAT Booster Session  
Participant 
 
 
 
 
X (subset) 
 
SURVEYS (ALL)+ 
 
 
W0 
 
W5 
W18 
W30 
CD-RISC© 
Participant* 
X 
X* 
 
X* 
X* 
X* 
PedsQL™ Generic Core 
and Cardiac Module 
Participant* 
 
X* 
 
X* 
X* 
X* 
NIH PROMIS® Scales 
Participant* 
 
X* 
 
X* 
X* 
X* 
Kessler-6 
Participant* 
 
X* 
 
X* 
X* 
X* 
Life’s Essential 8™ 
Participant* 
 
X* 
 
X* 
X* 
X* 
Multidimensional Survey of 
Perceived Social Support 
Participant 
 
X 
 
X 
X 
X 
Self-Perceived Illness 
Severity 
Participant* 
 
X* 
 
X* 
X* 
X* 
Estimated Survey Time 
 
10 minutes 
60 
minutes 
N/A 
60 
minutes 
60 
minutes 
60 
minutes 
VISIT/SESSION/SURVEY MODALITY 
In Person/ 
Electronic 
Electronic/ 
Virtual 
Virtual 
Electronic
/ Virtual 
Electronic 
Electronic 
¥ Week 0 window opens immediately after enrollment for participants randomized to the Usual Care arm, and 10 days 
prior to Week 1 for participants randomized to the Intervention arm.  
°  For those randomized to the Intervention arm, Week 1 will start in conjunction with the first session of the WE BEAT 
program, and therefore will depend on cohort scheduling and availability. Post-intervention study timepoints will be 
based on the completion of the 5-session program.  
^ Participant urine and blood specimens are optional; on-site specimen collection preferred. See study manual for 
details. 
+ In general, surveys should be completed within 2 weeks of due date. See study manual for details. 
* Parents who consent to optional surveys will complete parent-reported versions of each survey. 
 

 
 
 
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5. SELECTION AND WITHDRAWAL OF PARTICIPANTS 
5.1 Participant Inclusion Criteria 
a) Ages 12-17 years old 
b) CHD of moderate or severe complexity (Class II/III per 2018 AHA/ACC ACHD, Table 4) 
c) English or Spanish language proficiency  
d) Receives cardiology care at a PHN or PHN auxiliary site  
e) Parent or guardian and participant willing to comply with protocol and provide written informed 
consent and assent  
 
5.2 Participant Exclusion Criteria 
a) CHD of mild or simple complexity (Class I) 
b) Prior heart transplant to treat CHD  
c) Heart disease that is not classified as structural CHD (e.g., connective tissue disease, genetic 
cardiomyopathy, or acquired heart disease) 
d) Cognitive or developmental conditions that limits ability to complete self-reported measures 
and/or participate in group intervention as determined by a parent/guardian or primary 
cardiology clinician 
e) Suicidality, homicidality, or psychosis in the past 12 months as per medical chart review, 
clinician report, or eligibility screening  
f) Medically unable to participate (i.e., intubated, unable to respond verbally, active delirium) 
 
Cognitive and Developmental Functioning. Cognitive or developmental conditions will be 
assessed by asking parents/caregivers and cardiology care team about the adolescent’s ability to 
join a group session and complete surveys independently or with minimal assistance (i.e., items 
read to them but they answer); no diagnoses or intelligence quotient levels will be utilized to 
exclude participation. It is acceptable for a participant to complete surveys with parent or caregiver 
assistance. 
 
Suicidality, Homicidality, and Psychosis. Any potential participant with documentation of 
suicidality (with intent or plan), homicidality, or auditory/visual hallucinations in medical chart or by 
cardiology clinician report will not be approached for study. At eligibility screening, study staff will 
screen for suicidality and homicidality using two modified questions from the Ask Suicide-
Screening Questionnaire (ASQ):  
1. In the past year, have you had thoughts of hurting or killing yourself or others?  
2. Have you ever tried to seriously hurt or kill yourself or others?  
If a screened participant indicates ‘yes’ to either, they will be deemed ineligible for the study, and a 
brief suicide safety assessment will be conducted by a trained clinician at the research site per 
their local institutional practices (e.g., psychologist, social worker, nurse practitioner, physician 
assistant, physician, or other mental health clinicians) to determine next steps. Training on these 
processes and safety protocols will be provided to study PIs and coordinators prior to site 
activation by the study chair and/or other clinical psychologist and will also be detailed thoroughly 
in the study manual. A resource list will be provided to all participating sites. Throughout study 
participation, any report of suicidality will be recorded as an adverse event according to standard 
safety reporting procedures (Section 7). Upon completion of the study, sites will be asked to 
report if new concerns or reports of suicidality or homicidality presented during the course of the 
study for both intervention and UC arm participants.   
 

 
 
 
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5.3 Participant Withdrawal Criteria  
5.3.1 Discontinuation of Study Treatment 
Participants may be withdrawn from the study for the following reasons: 
• 
Participant (or legal guardian) declines further study participation. 
• 
In the investigator’s, interventionist’s or primary cardiology clinician’s judgment, it is in 
the participant’s best interest. 
• 
Change in medical, cognitive, developmental or psychiatric status now meeting study 
exclusion criteria or resulting in inability to participate in intervention sessions.  
 
5.3.2 Participant Withdrawal from Study  
If the participant refuses to continue with the study visits, every attempt should be made to 
continue contact by telephone, written communication, or record review to determine if 
outcome events have occurred, unless the participant specifically refuses such follow-up. The 
reason for withdrawal will be documented for all participants withdrawn from the study.  
 
5.4 Participant Availability 
Study participants will be enrolled from the Pediatric Heart Network, including the 9 PHN core 
sites/consortia (consisting of 12 institutions). A review of surgical procedures, medical records, and 
clinic volume was performed to confirm each institution’s ability to recruit 32-33 participants during the 
enrollment period to reach the planned sample size. Additional PHN auxiliary sites will be onboarded 
as needed to bolster recruitment.  
 
Identifying Eligible Participants. Eligible participants will be identified by the site principal 
investigator (PI), research coordinator, or PI designee via review of inpatient census and weekly 
outpatient clinic schedules of clinicians who care for patients with moderately to severely complex 
CHD. A member of the research team will approach the parents of patients meeting all inclusion 
criteria with no known exclusion criteria to discuss eligibility and participation. Additionally, cardiology 
clinicians can refer patients to the study for consideration of eligibility and participation. In 
collaboration with the PHN RRC, recruitment materials (fliers, postcards) will also be created and 
distributed to facilitate recruitment and encourage patients/families to self-identify as eligible and 
interested.  
 
5.5 Recruitment / Enrollment Procedures 
Consent Procedures. Study consent and enrollment will occur in-person at the enrolling site in 
accord with other clinic visits, or virtually. eConsent and assent forms will be available in English and 
Spanish. A member of the research team will explain the trial and ensure that parents/participants 
have ample opportunity to read the consent form and any study documents, taking time to review 
details and answer questions. Parents/guardians will provide e-consent, and participants will provide 
electronic assent. Enrollment measures will be completed electronically at the baseline visit by 
participants and parent/guardian as indicated (see Table 1. Schedule of Visits/Measurements).  
 
Study Communication. Communication with enrolled participants will occur via parents/guardians for 
study coordination and survey completion using multiple methods, including phone calls, study emails, 
text messages, and HIPAA-compliant messaging in the study data capture platform. When permitted 
by parent/guardian, a participant email and/or text can also be sent in accord with those sent to 
parent/guardian. Site research coordinators will assist with reminders and follow-up to support data 
collection and completion for up to 12 months after study enrollment.  
 
 
 

 
 
 
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6. TREATMENTS TO BE ADMINISTERED 
6.1 Description of Study Treatments 
Participants will be randomized to one of two treatment arms: Usual Care or Intervention. Usual care 
(UC) will be defined as the standard psychosocial treatment or management practices that are 
typically provided to patients at their care center outside of a research study. Participants randomized 
to the intervention arm will receive the WE BEAT intervention program (described in Section 3). 
 
WE BEAT Telemedicine Group Program.33 Intervention arm participants will be placed in a WE 
BEAT group cohort based on schedule preference and availability. Group cohorts of approximately 10 
participants across enrolling sites will be developed on a rolling basis. 
 
The program will be delivered over five weekly 45-minute sessions. The five WE BEAT modules that 
will be covered include: (1) Wellbeing Education, Introduction, (2) Breathe, Mindfulness and 
Relaxation-Based Skills, (3) Energize, Positive Psychology Skills, (4) Adjust, Cognitive Skills Training, 
and (5) Thanks, Gratitude Practice (see Table 2. WE BEAT Program Modules). Each module was 
developed based on supporting resilience theory and evidence, as referenced in Table 2. An 
accompanying WE BEAT workbook will be provided to program participants.  
 
Table 2. WE BEAT Program Modules 
 
WE BEAT group sessions will be conducted via a HIPAA-compliant electronic meeting platform, such 
as Zoom, etc. Reminders and meeting links will be disseminated electronically to participants prior to 
each session.  
 
Session Format. Each WE BEAT session follows the same outline: (I) Welcome/Check-In/Review (10 
minutes), (II) Evidence (i.e., developmentally appropriate overview of science related to session; 5-10 
minutes), (III) Instruction in three skills/activities (15-20 minutes), and (IV) Goal Setting and Wrap-Up 
(5-10 minutes). Each session includes a review of topics and skills covered in the previous weekly 
session, and skill practice between sessions will be encouraged. The WE BEAT workbook follows 
along with each telemedicine-based session, providing written overview/instruction in each of the 
skills as well as goal setting and reflective prompts. Following each weekly session, participants will 
Session 
Module 
Supporting Theory and  
Evidence14,
64F64F64,
65F65F65,
6F6F66 
Skills Taught 
1 
Introduction 
Resources; Social Support / 
Peer Connection31,
67F67F67,
68F68F68 
Introduction to Program and Community 
Building  
2 
Breathe 
Assets; Relaxation, 
Mindfulness 69F69F69,
70F70F70,
71F71F71 
Diaphragmatic Breathing, Guided 
Imagery, Word Focus Meditation  
3 
Energize 
Assets; Purpose in Life, 
Positive Psychology72F72F72  
Finding Purpose, Pleasant 
Events/Passions, Movement/Exercise  
4 
Adjust 
Assets; Cognitive Skills,73F73F73,
74F74F74 
Optimism75F75F75  
Thought Challenge, Self-Talk, Radical 
Acceptance 
5 
Thank 
Assets and Resources; 
Gratitude75,
76F76F76,
7F7F77,
78F78F78  
Others Gratitude, Self-Gratitude, Heart 
Journey Gratitude  
6 
Booster 
 
Review of Modules 2-5 

 
 
 
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receive an electronic reminder to review the previously covered module and skills. This post-session 
notification will include links to videos or other resources shared during the previous session for all 
participants to reference. See Section 6.3 for information on monitoring intervention adherence and 
resources for missed sessions. 
 
Booster Session. Following completion of the primary WE BEAT intervention at Week 5, intervention 
arm participants will be randomized to a single-session booster session (occurring at Week 18) vs no 
booster session. Intervention arm participants who missed more than 2 program sessions will not be 
eligible for the booster. The booster session will be provided in a similar format to the WE BEAT 
program. A review of all modules/skills introduced in the program will be provided. Participants will be 
encouraged to discuss and reflect on what skills they have utilized and barriers they have 
encountered to putting skills into practice.  
 
Intervention Core: Delivery and Treatment Fidelity. The NIH Behavior Change Consortium (NIH BCC)79F79F79 
emphasizes the importance of maintaining intervention fidelity to ensure reliable and valid outcomes in 
behavioral health research. The NIH BCC recommendations for enhancing treatment fidelity in 
behavioral health research informed the development of intervention delivery and training.  
 
The University of Michigan will serve as the Intervention Core Lead under the direction of study chair 
and intervention developer, Melissa Cousino, PhD. The Intervention Core Lead will maintain program 
materials, develop language translations, and work with the program’s design team if additional 
materials are needed (i.e., retention postcards). In addition to Dr. Cousino, interventionists selected 
from three U.S. sites representing the West, Midwest, and Northeast will join the Intervention Core to 
deliver and facilitate the telemedicine program. Interventionists undergoing facilitator training must hold 
an independent license for the practice of psychology in their state.  
 
Initially, interventionists will complete a 1-day in-person training program led by the study chair using 
the standardized WE BEAT intervention manual which details session content and delivery procedures. 
The training will emphasize theoretical underpinnings and educational objectives of the WE BEAT 
program. Training sessions will include role-playing to enhance interventionists’ competence in 
managing group dynamics and delivering interventions via telemedicine platforms. Ongoing fidelity will 
be monitored via live observation of 20% of sessions facilitated by each interventionist using fidelity 
checklists to assess adherence to the protocol, quality of delivery, and participant engagement. 
Observations and checklists will be completed by study chair and other trained interventionists. Regular 
supervision meetings will be conducted to provide feedback to each interventionist based on session 
reviews, helping them refine their delivery techniques.  
 
WE BEAT Program Survey. To ensure participant receipt fidelity, an evaluative measure of the WE 
BEAT program will be completed at the final session (Week 5). This structured approach aims to 
maintain high fidelity across all elements of the intervention, thereby bolstering the internal validity and 
overall effectiveness of the program. Treatment fidelity findings will be reported as study findings, 
consistent with NIH BCC guidelines.   
 
6.2 Medications/Treatments Permitted and Not Permitted during the Study  
All participants in this study will receive UC as prescribed at each institution at which the study is 
being conducted. Participants will be treated with medications and other treatments at the discretion 
of their healthcare providers.  

 
 
 
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6.3 Procedures for Monitoring Participant Adherence 
The interventionists will record session attendance. Adherence to the WE BEAT telemedicine group 
program will be defined as 70% overall (all participants), which is consistent with resilience 
intervention literature,80F80F80 while maintaining 60% to delineate within-participant adherence (3 of 5 
sessions). The within-participant outcome (Section 2.1.4 Hypothesis 2) is supported by research 
demonstrating that even a single-session intervention can result in improved outcomes for 
adolescents with psychiatric concerns, 81F81F81 as well as increased growth-mindset among teens 
completing a single session promotive mental health intervention.82F82F82,
83F83F83,
84F84F84  Additionally, 60% adherence 
for within-participant analysis was determined with our pragmatic trial design in mind, particularly 
because we know adolescents are busy and this population may experience illness/hospitalizations 
impacting session attendance.  
 
Resources for Missed Sessions. While it will be encouraged, perfect adherence is not expected nor 
practical for this target population. As such, the WE BEAT intervention was designed to include 1) 
review of previous session in each session, 2) a look ahead to the next session in each session, and 
3) an accompanying workbook that includes each skill/rationale for self-directed instruction and 
practice. Participants who miss a group session will be able to review the missed module in the 
applicable workbook section at their convenience. The post-session notification will serve as a 
reminder to review the missed material and allow participants to access videos and other resources 
that were shared in the missed group session. 
  
6.4 Study Completion 
Participants will be considered to have completed the study when they have completed the Week 30 
assessment.  
 
Participants in the UC arm will be offered an opportunity to participate in an open label WE BEAT 
telemedicine group program delivered by our study intervention core. Additional compensation or 
surveys will not be administered. This will be offered to support study recruitment and is aligned with 
the protocol’s overall objective to provide increased access to psychosocial care to those with CHD. 
Participants in the intervention arm will not be offered post-study intervention.  
 
Any additional mental health services for intervention arm and UC arm participants will be directed by 
his/her primary cardiology team. Participants may be contacted in the future for follow-up and about 
future studies. 
 
 
 

 
 
 
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7. SAFETY ASSESSMENTS AND MONITORING 
7.1 Recording and Reporting Adverse Events  
A major component of safety monitoring is ascertainment and reporting of adverse events, including 
adverse reactions to study intervention and/or questionnaires. The approach to these activities for this 
study is summarized in the sections that follow. 
 
7.1.1 Definition of Adverse Events 
An adverse event (AE) is any untoward medical occurrence experienced by a study participant. An 
event can be any unfavorable and unintended sign, symptom, laboratory abnormality, or disease 
associated with study participation.  
Due to the nature of the study intervention, we do not anticipate that serious adverse events related to 
this study will occur. The minor potential risks to study participation are described in detail in Section 
11, Ethics and Human Subjects Protection. Reportable events are limited to those associated with 
risks identified in Section 11, as well as active suicidal ideation and/or intent.  
7.1.2 Classification of Adverse Events  
Monitoring AEs requires that they be classified as to seriousness, severity, expectedness, and 
causality (potential relationship to the study intervention or questionnaires), all of which drive the 
reporting process. 
 
a. Seriousness  
A serious adverse event (SAE) is one that: 
• 
Results in death, 
• 
Is life-threatening (the participant was, in the view of the Principal Investigator (PI), in 
immediate danger of death from the event as it occurred), 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization,  
• 
Results in persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions,  
• 
Is a congenital anomaly/birth defect in the offspring of a participant, or 
• 
Is an Important Medical Event that may jeopardize the participant or may require 
medical/surgical intervention to prevent one of the serious adverse event outcomes. 
 
b. Severity 
The Common Terminology Criteria for Adverse Events (CTCAE) (http://ctep.cancer.gov), which 
incorporates elements of MedDRA terminology, provides a grading system that is used to categorize 
the severity of adverse events, as follows: 
 
Grade 1 
Mild 
transient, requires no special treatment or intervention,  
does not interfere with daily activities 
Grade 2 
Moderate 
alleviated with simple treatments, may limit daily activities 
Grade 3 
Severe 
requires therapeutic intervention and interrupts daily 
activities 
Grade 4 
Life-threatening 
Or disabling 
urgent or emergent intervention needed 
Grade 5 
Death 
 
 

 
 
 
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c. Expectedness  
The purpose of reporting is to provide new, important information on serious reactions or events 
previously unobserved or undocumented. Therefore, all AEs will be evaluated as to whether their 
occurrence was unexpected, using the following definitions:  
• 
Unexpected: An unexpected AE or adverse reaction is one for which the nature or severity is 
not consistent with information in the protocol or consent form. An AE or adverse reaction also 
may be categorized as unexpected if the event has not previously been observed at the same 
specificity and/or severity.  
• 
Expected: An event is considered expected if it is known to be associated with the disease 
state. 
 
d. Causality 
Causality assessment is required to determine which events require expedited reporting. The 
following criteria will be used to determine causality: 
• 
Not Related: The event is clearly related to other factors, such as the participant’s clinical 
state, or non-study drugs or interventions. 
• 
Possibly Related: The event follows a compatible temporal sequence from the time of study 
evaluation but could have been produced by other factors such as the participant’s clinical 
state or non-study drugs or interventions. 
• 
Probably Related: The event follows a reasonable temporal sequence from the time of study 
evaluation and cannot be reasonably explained by other factors such as the participant’s 
clinical state, or non-study drugs or interventions. 
 
The seriousness, severity, expectedness, and causality of each event will be categorized and 
reported according to the reporting procedures in Section 7.1.4. 
 
7.1.3 Identification of and Data Collection Procedures for AEs 
AEs will be identified when they are reported to the clinical center or study interventionist during 
scheduled study visits/sessions. AEs will be assessed using self-report, physical examination data, 
and medical record review.  
 
7.1.4 Reporting Timeframe and Procedures 
Table 3.  Reporting Timeframe of Adverse Events 
Seriousness 
Reporting Timeframe to the DCC 
Fatal or life-threatening 
Within 24 hours of learning of the event 
Serious, but not fatal or life 
threatening 
Within 24 hours of learning of the event 
All other AEs 
Within 7 calendar days of learning of the event 
 
All SAEs are to be reported to the DCC within 24 hours of first knowledge of the event.  
• 
Fatal or life-threatening SAEs that are unexpected and considered possibly or probably related 
to study participation will be reported by the DCC to the Medical Monitor (MM), NHLBI, and the 
PHN Data and Safety Monitoring Board (DSMB), as needed, within 7 calendar days after first 
knowledge of the event, followed by a complete report within 15 calendar days.  
• 
Serious (but not fatal or life-threatening) AEs that are unexpected and considered possibly or 
probably related to study participation will be reported by the DCC to the MM, NHLBI, and 
PHN DSMB, as needed, within 15 calendar days after first knowledge of the event. 

 
 
 
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• 
All other SAEs that are unrelated to study participation will be reported semiannually to the 
DSMB and NHLBI. 
 
All other AEs not meeting the criteria for expedited reporting will be reported to the DCC within 7 
calendar days of first knowledge of the event. The DCC will report these AEs semiannually to the 
DSMB and NHLBI. 
 
7.1.5 Reporting Adverse Events to IRBs for NIH-Supported Trials 
The DCC is responsible for reporting adverse events (or facilitating site reports) to the sIRB according 
to sIRB guidelines. In addition to following sIRB reporting requirements, the site PI or designee is 
responsible for reporting all serious adverse events to the local IRB in accordance with local policies 
and procedures.  
 
7.1.6 Follow-up of Participants after Adverse Events  
For AEs with a causal relationship to study participation, follow-up by the PI is required until the event 
or its sequelae resolve or stabilize at a level acceptable to the investigator. 
 
7.2 Safety Monitoring 
The Data and Safety Monitoring Plan for this trial will follow standard PHN monitoring principles. 
Oversight of data and safety is provided by the DSMB, appointed by NHLBI. The DSMB meets at 
least twice a year to review data on AEs, patient-reported outcomes, data quality, and study 
recruitment at regular intervals, and makes recommendations about study conduct to the NHLBI.  
 
After each DSMB meeting, a summary report will be prepared within 30 days and will be distributed by 
NHLBI staff to the DCC for sIRB submission and review. Once obtained, sIRB approval of DSMB 
summaries will be disseminated to the trial investigators and coordinators, who will then forward the 
approval/summary report to their local IRB, as needed. The summary report will contain the following 
information: 
• 
A statement that a DSMB review of outcome data, adverse events, and information 
relating to study performance across all centers took place on a given date. 
• 
A statement as to whether or not the frequency of adverse events exceeded what was 
expected and indicated in the informed consent. 
• 
A statement that a review of recent literature relevant to the research took place. 
• 
The DSMB’s recommendation with respect to progress or need for modification of the 
protocol or informed consent. If the DSMB recommends changes to the protocols or 
informed consent, the rationale for such changes and any relevant data will be provided. 
• 
A statement that if safety concerns are identified, the NHLBI Program Official will 
communicate these promptly to the investigators. 
 
In addition to the DSMB, a single IRB (sIRB) with reliance from local IRBs will also be responsible for 
the safe conduct of research at each study site. Participation in the study cannot begin at a clinical 
center until the sIRB (and local IRBs via reliance agreements) have approved the protocol. Per NHLBI 
policy, the consent form, if modified by individual sites, will be reviewed again centrally to ensure that 
no changes inconsistent with the Office of Human Research Protections policy of study design have 
occurred. 
 
The DSMB and NHLBI are assisted by the MM in reviewing serious adverse events in PHN studies. 
The PHN MM is NHLBI’s designee for determining causality and expectedness of all SAEs.  

 
 
 
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8. STATISTICS 
8.1 Planned Statistical Analyses  
This section briefly describes key aspects of the planned statistical analyses. A separate, detailed 
Statistical Analysis Plan (SAP) will be completed prior to database lock and unblinding of the data. 
Refer to Section 2 for aims and their associated hypotheses and outcomes. 
 
8.1.1 Primary Aim, Hypothesis 1, Primary Outcome  
Primary Analysis of Primary Aim’s Primary Outcome 
Difference in CD-RISC© score (change score) from baseline to Week 5 (immediately post-
intervention) will be calculated and compared between intervention and control arms. Intention-to-treat 
analysis will be used as the primary analysis.  
 
The treatment arm difference in the mean change scores (i.e. change in CD-RISC© score from 
baseline to Week 5) will be assessed with an analysis of covariance (ANCOVA) with fixed factors for 
treatment arm with a continuous covariate of baseline CD-RISC© score.85F85F85 
 
Secondary Analysis of Primary Aim’s Primary Outcome   
A similar analysis will be performed for the subpopulation of participants with moderate to low 
baseline resistance scores (Section 8.8). 
 
8.1.2 Primary Aim, Hypothesis 1, Secondary Outcomes 
Secondary outcomes for the primary aim are continuous measures and will be analyzed in the 
manner described above for the primary outcome. If measures are highly skewed, then regression 
modeling will be conducted on a suitably transformed outcome, where possible, to achieve a 
distribution that is closer to normality. 
 
8.1.3 Primary Aim, Hypothesis 1A 
The primary and secondary outcomes for Hypothesis 1A are the same as those described for 
Hypothesis 1 above (CD-RISC© change score and change in participant self-reported survey 
measures), but across different time periods—from baseline to Week 18 (3 months post-intervention) 
and baseline to Week 30 (6 months post-intervention). For both timepoints, the analysis outlined in 
Section 8.1.1 will be used to compare intervention and control arms. 
 
8.1.4 Primary Aim, Hypothesis 1B 
The primary outcome for Hypothesis 1B is the CD-RISC© change score from baseline to Weeks 18 
and 30, respectively, but instead of comparing the two treatment arms, the comparison will be 
between the two intervention-arm subpopulations: those randomized to the intervention with the 
booster session vs. those randomized to the intervention without the booster session. At both 
timepoints, the analysis outlined in Section 8.1.1 will be used to compare the intervention-arm 
subpopulations. Additional sensitivity and secondary analyses will be described in the SAP. 
 
8.1.5 Primary Aim, Hypothesis 2 
Descriptive statistics will be provided to characterize adherence (primary outcome) and program 
satisfaction ratings (secondary outcome). 
 

 
 
 
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8.1.6 Primary Aim, Hypothesis 3 
The primary and secondary outcomes for Hypothesis 3 mirror those described for Hypothesis 1 (CD-
RISC© change score and change in participant self-reported survey measures). Regression modeling 
(bi-variate and multi-variate) of the change scores with family, social, and community-related 
covariates will be used to assess associations between the change scores and these predictors. 
 
8.1.7 Secondary Aim 1 
Appropriate regression modeling (bi-variate and multi-variate) of the key cardiac outcomes listed in 
Secondary Aim 1 Hypothesis 1 (Section 2.2) will be used to assess associations between the cardiac 
outcomes and key participant-reported predictors.  
 
8.1.8 Secondary Aim 2   
Regression modeling of change scores in key PRO outcomes (resilience score, etc.) will be used to 
assess associations with various biomarkers.  
 
8.2 Sample Size and Power 
The planned sample size for the study is N=390 enrolled participants (N=300 in the intervention arm 
and N=90 in the control arm). The sample size calculations (summarized in Table 4) reflect the 
intention to power two secondary outcomes in addition to the primary outcome (see Sections 8.2.1 - 
8.2.2 below).  
 
Based on prior studies, we conservatively estimated a cumulative dropout rate of 30% from baseline 
to Week 18 (post-intervention booster session). Specifically, dropout estimates will be assumed to be 
15% for primary outcomes/endpoint (Week 5) and 18% for secondary outcomes/endpoint (Week 18). 
Our estimated dropout rates were informed by our WE BEAT pilot study (13% dropout rate)35 and 
previous resilience interventions in ACHD, pediatric cancer, and pediatric diabetes, which have 
experienced dropout rates ranging 14-25%.86F86F86,
87F87F87,
8F8F88 
 
Table 4: Summary of Sample Size Calculations  
 85% power for Primary Outcome 
 80% power for Booster vs No-Booster exploratory outcome 
 Based on assuming Commutative Dropout of 30% (with 15% at the 1st stage and 18% at the 2nd stage)  
 
Treatment 
Control 
Total 
N in Treatment arm post-booster 
83 x 2=166 
 
 
N in Treatment arm post-intervention 
after inflating for 18% drop-out 
202 
 
 
 
N for Primary outcome 
202 
62 
 
N at baseline after inflating for 15% 
drop-out 
238 
73 
311 
 
Inflating for Stratification 
 
 
 
N at baseline after 20% inflation for 
stratification 
298 
91 
389 
 
Final N after rounding 
300 
90 
390 
 

 
 
 
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8.2.1 Primary Outcome (Hypothesis 1) 
Primary Analysis 
A sample size of N=311 (238 participants in the intervention arm and 73 participants in the control 
arm) will provide 85% power to detect a mean treatment group difference in change from baseline to 
Week 5 in CD-RISC© score of 8.2%; that is, an improvement of 2.3 in the intervention arm compared 
to zero change in the control arm, assuming a Type I error of 0.05 and standard deviation of 5.25. A 
difference of 2.3, equivalent to an 8.2% increase from a baseline of 27.8, represents approximately 
0.4 standard deviations and is considered clinically significant in this field.36 
 
Assumptions used in power calculations: 
• 
Primary Outcome – Change score defined as change in CD-RISC© score between baseline and 
Week 5  
• 
Population – Age between 12 and 17 (< 18) years at baseline, moderate or severe CHD 
• 
Comparison – Change score between 2 treatment groups (intervention vs. control) 
• 
Baseline mean value of CD-RISC© score:  27.8±7.2 (based on historical data for a similar 
population) 
• 
Standard deviation of the change score: 5.25 (based on historical data for a similar population) 
• 
Dropout & incomplete testing: cumulative attrition (from enrollment to Week 18/post-booster) of 
30%, including 15% attrition at the first stage (from baseline to Week 5/post-intervention; based 
on historical data for a similar population and conservatively inflated). 
• 
α = .05 
 
Secondary Analysis (Hypothesis 1 for subpopulation with moderate-low baseline CD-RISC© score) 
Under the same assumptions, an overall sample size of 389 (298 participants in the intervention arm 
and 91 participants in the control arm) will provide 85% power to detect treatment arm difference in 
change scores in a subset of 80% of participants after excluding those with the top 20% CD-RISC© 
scores at baseline. 
 
8.2.2 Exploratory Secondary Outcome (Hypothesis 1B, booster session) 
A sample size of N=202 in the intervention arm (equally divided between the booster and no-booster 
subpopulation) will provide 80% power to detect a mean treatment group difference in change from 
Week 5 to Week 18 in CD-RISC© score of 2.3 in the booster subpopulation compared to zero change 
in the no-booster subpopulation, assuming a Type I error of 0.05 and standard deviation of 5.25. A 
difference of 2.3 represents approximately 0.4 standard deviations. 
 
Assumptions used in power calculations for the exploratory booster outcome: 
• 
Since the booster session is a novel concept in this population, there is no historical data to 
inform our assumptions. Hence, we will rely on and replicate the assumptions used for the 
primary outcome, which were based on historical data 
• 
Exploratory outcome – Change score defined as change in CD-RISC© score between 
baseline and Week 18 (immediately post-booster)  
• 
Comparison – Change score between the two intervention arm subpopulations (booster vs. 
no-booster) 
• 
Dropout & incomplete testing: cumulative attrition (from baseline to Week 18/post-booster) of 
30%, including 18% attrition at the second stage (from Week 5/post-intervention to Week 
18/post-booster) 
• 
Standard deviation of the change score: 5.25 (used for the primary outcome) 
• 
α = .05. 
 
 

 
 
 
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Connection with calculations in Section 8.2.1: 
• 
To power the primary outcome comparison between intervention and control arms at 85% with 
N=202 participants in the intervention arm, an additional N=62 participants in the control arm 
would be needed. 
• 
Adjusting these numbers for a 15% attrition rate from baseline to Week 5 leads to N=311 (238 
participants in the intervention arm and 73 participants in the control arm) at baseline. 
 
8.3 Level of Significance 
The type I error probability for the trial will be 0.05. Formal hypothesis testing will be performed only 
for the primary efficacy endpoint (Section 8.1.1). Thus, no adjustment for multiple comparisons will be 
necessary. No adjustments will be made for the multiple hypothesis tests among the secondary 
endpoints, but conclusions will be interpreted with caution due to the multiple tests proposed. 
The report will note the number of comparisons made, and the possibility that when many outcomes 
are analyzed, it is not unexpected that one or more might have a statistically significant treatment 
difference just by chance. 
 
8.4 Interim Analyses and Stopping Rules for Termination of the Study  
The study will be monitored by the PHN DSMB as described in Section 7. In addition to routine DSMB 
reviews, the following assessments and interim analysis will be performed at designated timepoints. 
 
8.4.1 Reassessment of Assumptions 
High Resilience Group Cut-off Value Recalculation 
After baseline CD-RISC© is obtained for approximately 30% of the target sample size (N=~117 
participants), the cut-off value for the high resilience group (defined as the top 20% of CD-RISC© 
scores) will be reevaluated. The updated cut-off value will be used for stratification (Section 4.2.4) for 
the remainder of the trial. 
 
Lumped Variance Recalculation 
After Week 5 CD-RISC© (primary outcome data) is obtained for approximately 30% of the target 
sample size (N=~117 participants), the variance of the primary outcome will be estimated, using a 
blinded method with lumped variance. If this estimated variance is higher than the one used for the 
sample size calculations (Section 8.2), then the sample size will be recalculated and may be 
increased correspondingly. Otherwise, the sample size will not change (i.e. a potential decrease of the 
sample size is not planned) and the trial will proceed as planned. This approach is based on blinded 
re-estimation of nuisance parameters and does not lead to inflation of type I error.89F89F89 This is consistent 
with FDA guidance for industry in adaptive design of clinical trials. 90F90F90 
  
Dropout Rate Reassessment 
After Week 18 CD-RISC© is obtained for approximately 30% of the target sample size (N=~117 
participants), aggregate dropout rates will be reassessed. The sample size will be recalculated based 
on the observed dropout rates and may be adjusted accordingly after consultations with the DSMB.  
 
8.4.2 Stopping Rules 
An early evaluation of the treatment effect will be implemented for the interim analysis when 
approximately 50% of the target sample size (N=~195, unless sample size will be increased based on 
the lumped variance recalculation) have CD-RISC© score values at the Week 5 timepoint.  
 
A non-binding recommendation of early stopping for efficacy, or conversion to a one-arm study, will be 
suggested to the DSMB if the estimate of the treatment effect obtained at the interim analysis is 

 
 
 
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positive and the corresponding one-sided p-value is lower than the reference value of alpha=0.0015. 
This reference value corresponds to the value of the O’Brien-Fleming spending function at the 
information fraction of 0.5.89  
 
Interim analysis for futility will be performed via a conditional power analysis (with a 10% margin). 
Formal stopping boundaries are not proposed for other endpoints.  
 
Based on the results of the primary analysis (immediately post-intervention), the DSMB may 
recommend stopping further follow-up (e.g. in case of a weak or absent efficacy signal). 
 
8.4.3 Additional Considerations 
DSMB Role 
The DSMB may recommend stopping the study for other reasons, taking into account the efficacy and 
safety data from this trial and other studies, or concerns about study conduct. Early stopping rules are 
only guidelines; the DSMB may take a more global view of the trial during data monitoring.  
 
Other Factors 
Premature termination of this study may occur due to a regulatory authority decision, the impact of 
results released from other studies, failure to enroll, withdrawal of sIRB approval, or investigational 
intervention safety problems. In addition, NHLBI retains the right to discontinue the study prior to the 
inclusion of the intended number of participants but intends to exercise these rights only for valid 
scientific or administrative reasons.  
 
8.5 Spurious Data Procedures  
Consistency checks and range checks will be built into the data management system. This will allow 
many errors to be identified and corrected at the time of data entry. Queries regarding any problems 
with data will be sent to site coordinators regularly throughout the course of the study. Sites will also 
be monitored during the study. Therefore, spurious data are expected to be rare. Any data which are 
judged to be definitely incorrect, and which cannot be resolved, will be set to missing.  
 
The study report will indicate the number of participants who have missing data on each study 
endpoint. For covariate-adjusted analyses, the number of participants who have missing data on the 
covariates will be reported. Imputation of missing data is not planned for this study. 
 
Throughout the study, the rate, timing, and reasons for participant withdrawal will be monitored by site 
and treatment arm. Any site with a pattern of differential withdrawal by treatment arm will be queried. 
If necessary, retraining will take place or the site may be barred from enrolling additional participants 
to the study. 
 
8.6 Deviation Reporting Procedure 
Any modifications or deviations from the statistical plan described in this protocol will be documented 
in a revised SAP document.  
 
 
 

 
 
 
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8.7 Participants to be Included in Analyses  
All randomized participants will be included in the analysis. Unless otherwise specified, all analyses 
will be intention-to-treat, i.e., participants will be analyzed in the group to which they were randomized. 
 
Additionally, randomized participants will be compared with those who were eligible but not consented 
using available key baseline characteristics. 
 
8.8 Subpopulations 
The effect of the proposed intervention, if any, may vary according to participant subpopulation. 
Though formal testing is not planned, treatment effect (intervention vs. control) will be examined in the 
prespecified subpopulations in secondary analyses. Subpopulations are defined based on 
characteristics known at the time of randomization and have two strata. These strata are defined 
prospectively as: 
• 
Age at enrollment (12-14 vs. 15-17) 
• 
Lesion complexity (moderate, severe) 
• 
Baseline resilience (high vs. moderate/low) 
• 
Baseline depression (per PROMIS, y/n) 
• 
Baseline anxiety (per PROMIS, y/n) 
• 
Baseline mental health condition (y/n, per reported diagnosis) 
• 
Baseline mental health treatment (y/n, per reported diagnosis) 
 
A 95% confidence interval of the difference in treatment group means for the primary outcome will be 
provided within each subpopulation. 
 
Additionally, treatment group differences for the primary efficacy endpoint will be analyzed using the 
approach described in Section 8.1.1 in the subpopulation of participants with moderate/low baseline 
resilience score (approximately 80% of enrolled participants). Of note, due to stratification (Section 
4.2.4), participants were randomized into this subpopulation, and the study was designed to provide 
85% of power in this subpopulation. 
 
 
 

 
 
 
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9. DATA MANAGEMENT    
An Electronic Data Capture (EDC) system will be used for the study that is designed to support 
reliable and secure data entry for clinical research purposes. The system also provides seamless 
integration of eCRFs and paper-based CRFs within a single protocol if desired; implementation of 
protocol amendments; and SAS and XML study data exports. 
 
One EDC system that may be utilized for this study is a customizable, complete end-to-end solution 
for collecting data from participants via their smartphones or any device connected to the internet via 
the MyDataHelps app (available on iOS, Android, and web browser). Participants join the study 
database via the app, which enables them to consent and enroll into the study, fill out study surveys, 
receive engagement notifications and reminders, dispense biospecimen collection kits, and track 
obtained biospecimens sent to the biorepository. There is also an optional feature to share data from 
various sensors and wearable technologies (e.g., fitness trackers, continuous glucose monitors, blood 
pressure cuffs, etc.).  
 
9.1 Data Entry 
Data will be entered directly by participants and study staff via a fully validated and Title 21 of the 
Code of Federal Regulations (CFR) Part 11-compliant, secure web application.  
 
9.2 Data Validation and Monitoring 
Integrated into the data entry system are real time validations, including both inter- and intra-
instrument data checks. Inconsistent or questionable values are flagged during entry, and an edit 
report is automatically generated to the data entry client. These edit reports provide the information 
necessary to investigate any data entry errors or resolved questions regarding out-of-range or 
questionable values.  
 
9.3 Data Security and Integrity 
Data is securely stored in the HIPAA compliant, Meaningful Use Certified EDC HIEBus platform, and 
is then exported in an easy-to-use format. The MyDataHelps platform complies with the security and 
privacy controls defined by NIST 800-53 Rev. 5 at the FISMA Moderate and Privacy baseline. They 
regularly undergo external formal assessments by a FedRAMP-accredited Third Party Assessment 
Organization (3PAO). The platform has been granted an Authorization to Operate (ATO) by the 
National Institutes of Health (NIH) and is FDA Part 11 Compliant. 
 
All data changes are written to an audit trail. The audit trail identifies the data item by table, column 
and key field. The entry includes the user, date and time, as well as the old value and new value. Both 
participant-related data as well as trial configuration data are written to the audit trail. Data are saved 
at regular intervals during data entry to prevent loss of information in the event of a disruption of the 
Internet connection. In the unlikely event of a major disruption, a backup connection allows full access 
to the data management system.  
 
Several levels of security are employed to ensure privacy and integrity of the study data, including the 
following: Study access requires use of assigned usernames and passwords. Individual roles and 
access levels are assigned by the study data manager. Passwords are changed regularly. Web-based 
entry uses secure socket layer data encryption. Data will not be stored on laptop computers. 
 

 
 
 
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9.4 Biospecimen Tracking 
Specimen tracking will begin from the time that the biospecimen is obtained for shipment via at-home 
collection kits or the time of receipt at the site, during shipment to and handling at the PHN 
Biorepository, and through shipment to other core laboratories, as applicable. Each specimen will be 
labeled with a bar-coded label identified by a unique specimen number that is different from the 
participant’s unique study ID number. The master list linking the barcode numbers to the participant 
study ID numbers will be maintained under password protection in the data management system at 
the DCC. This blinding code system will maintain the confidentiality of the specimens yet allowing 
linkage of the specimens with clinical study data for analyses. 
 
10. QUALITY CONTROL AND QUALITY ASSURANCE  
The DCC has primary responsibility for QC/QA activities of the phenotypic data. The DCC also 
requires that the sites complete certain QC activities, most of which are monitored by the DCC and 
study chair. The key QC/QA activities are: 
• 
Development of a study manual; 
• 
Carefully constructed data collection forms/CRFs accompanied by manuals of instruction; 
• 
Sign-off procedures for applicable CRFs; 
• 
Central protocol training and certification of all site data collection staff with the use of 
standardized checklists; 
• 
Data management training and certification of site personnel completing data entry 
      and/or data management; 
• 
Verification of participant eligibility;  
• 
Fidelity checks on intervention sites; 
• 
On-going monitoring of all protocols/data collection activities; and, 
• 
Completion of reliability and/or pilot studies for key measurements as appropriate. 
11. ETHICS AND HUMAN SUBJECTS CONSIDERATIONS 
11.1 Potential Risks 
The overall risks of participation in this study are no more than minimal. Potential risks include: 
a) breach of confidentiality due to telemedicine group participation and/or collection of personally 
identifying information,  
b) discomfort/distress when answering survey questions or during group intervention, and  
c) minor discomfort associated with blood draws.  
 
Confidentiality (due to group participation) 
While the sharing of personal contact information will not be encouraged through the telemedicine 
group program, it is possible that participants will voluntarily share such information in an effort to 
maintain relationships and peer support. These peer connections are no more than minimally likely to 
pose additional risks and are similar to risks experienced through school and community settings but 
must be acknowledged for the purposes of this study.  
 
Psychological Discomfort/Distress 
In the previous WE BEAT pilot study experience, no safety/risk concerns presented among 
intervention participants during group sessions requiring follow-up. However, it is possible that 
participation in this study could cause psychological distress or lead to identification of mental health 
concern requiring a higher level of care, or identification of child protective services concern resulting 
in mandated reporting. Although these may cause stress or strain on participants, these possible 

 
 
 
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events would occur within the context of supporting participants (i.e., not causing additional harms). In 
summary, the potential risks of this study are minimal. The alternative to participating in the protocol is 
simply non-participation. 
 
We estimate low risk of emotional discomfort and/or distress completing study measures/surveys. 
There is no evidence across the broad scientific literature to suggest that assessing depressive 
symptoms or mental health concerns prompts risks related to mood/behavior, however, we will still 
engage in actions to protect against such distress. Specifically, participants (and participating parents) 
will be reminded that they do not have to answer any survey questions that they prefer not to answer 
or those that may cause distressing feelings.  
 
Biospecimen Collection 
Minor temporary discomfort may be associated with the removal of blood by venipuncture. There is a 
risk of bruising, and a very small amount of bleeding associated with blood drawing. There is also a 
very small risk of infection at the site. Whenever possible, blood samples will be gathered when the 
participant is scheduled for routine blood testing or procedures. There are no known risks to collecting 
saliva, hair, or urine. 
 
11.2 Confidentiality, Protection against Risks 
Investigators will take all reasonable measures to protect the confidentiality of participants and their 
families, including the following: 
 
Use of Study ID numbers 
Each participant is assigned a study identification number (SID). All interview and clinical research 
data are stripped of identifiers and labeled with the study number. Any enrollment logs with participant 
identifiers will be maintained at each site in a secured, locked location available only to site study 
staff. Samples for the biorepository will be labeled with sample ID numbers and not the SID. The 
informed consent form states that study data will be made available to the Data Coordinating Center 
(DCC) and NIH/NHLBI to ensure study safety and quality control. The participant’s name and any 
other identifying information will not appear in any presentation or publication resulting from this study.  
 
Global Unique Identifiers (where applicable)  
A unique identification number, called a Global Unique Identifier or GUID, will be assigned to each 
study participant, if applicable. A GUID is a universal ID that allows researchers to share data specific 
to a study participant without exposing personally identifiable information (PII) and at the same time 
be able to match participants across labs, databases or research studies. Personal information does 
not leave the research site, only a unique set of encrypted codes that are then decrypted to determine 
if the participant already exists within the data repository. The GUID is then sent to the enrolling site. 
This tokenization process is similar to the one used by the National Database for Autism Research. 
The GUID would allow data from this study to be combined with data from other research studies or 
databases in an effort to improve outcomes in children and young adults with heart disease. 
 
Intervention-associated Discomfort/Distress 
During WE BEAT group sessions, interventionists will iterate that participant comfort is a priority of 
intervention delivery, and they may participate (on screen, off screen, muted, chat text) in a manner 
that feels most comfortable. WE BEAT interventionists will all be licensed psychologists, and as such, 
will have considerable expertise in the mitigation of emotional discomfort and/or distress. 
Interventionists will undergo training specific to responding to risks and concerns that may present in 
the group telemedicine sessions.  
 

 
 
 
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If a participant expresses discomfort, distress, or a need for additional mental health support during or 
after group sessions, the interventionist will complete an assessment and conduct safety planning as 
needed. Safety planning may include: 
- 
contacting a parent/guardian to disclose safety/risk concerns if imminent risk is identified,  
- 
contacting psychosocial clinician at participant’s PHN site for additional follow-up to occur 
locally, and/or  
- 
providing general information on how to identify and obtain additional local mental health 
referrals, including provision of the national mental health crisis line (988).  
 
Information from clinical studies or medical records may be placed into a central data repository in the 
future, such as the National Center for Biotechnology Information (NCBI) repository. Data and 
samples will be de-identified before submission to this or any other central repository. 
 
11.3 Potential Benefits 
Treatment and Study Findings 
In the WE BEAT pilot trial, participants experienced positive psychological wellbeing effects from the 
intervention. Similar benefits may be experienced by those in the intervention arm, as well as those in 
the usual care arm who opt to participate in an open-label WE BEAT program following their study 
completion. Participation in the study may lead to increased knowledge about the benefits of 
psychological health for those with CHD and subsequent increased openness to future resources or 
support. 
 
Biospecimens 
Currently, there is no known direct benefit from the participation of the participant and family in the 
biorepository. However, we hope that DNA and serum donation will help investigators to learn more 
about the relationship between genetic factors or biomarkers and longer-term cardiac and 
neurodevelopmental outcomes. This information may help physicians provide better answers to 
families’ questions regarding causes, risk, and recurrence risks. It may also provide clues to future 
interventions and/or treatments. 
 
Indirect Benefit 
There might be an indirect benefit from the awareness that study results may help to improve the care 
of children with similar problems in the future. Families may derive a sense of altruism, 
accomplishment, and contribution to furthering understanding of the problem through their 
participation.  
 
11.4 Risk/Benefit Ratio and Importance of Information to Be Obtained 
The risk/benefit ratio is favorable for this study and adverse events are not anticipated. The baseline 
risk is minimal because the intervention is a well-being and resiliency-building virtual program. In 
addition, although an individual participant may not benefit from participation, the results of this study 
will make important contributions to the improvement of knowledge about CHD, the management of 
complex CHD in adolescents, and ultimately in the improvement of treatment and prognosis for 
affected families.  
 
 
 

 
 
 
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12.  STUDY LIMITATIONS 
Study limitations include:  
 
1. Generalizability. Lack of intervention availability in languages other than English or Spanish 
limits generalizability of intervention and study results to other patient populations.  
2. Recruitment, Retention and Program Management. Intervention studies present unique 
study management challenges. It is likely that participants will have variable availability. 
Finding consistent meeting times across 5 weeks for a group of participants will be challenging 
and may limit recruitment, participation and retention. We will attempt to mitigate this limitation 
by offering intervention groups across diverse days and times with interventionists across time 
zones.  
3. Standardization. Maintaining consistency in intervention delivery can be difficult in virtual 
settings. Variations in interventionists’ styles or technical issues can affect the uniformity of the 
intervention. We will attempt to mitigate this limitation by keeping to a small core team of 
interventionists, ensuring robust interventionist training with use of a manualized intervention 
manual and fidelity monitoring planning, and continued access to interventionist 
training/development as needed.  
4. Engagement and Interaction. Virtual settings may limit opportunities for natural interactions 
and non-verbal communication, which are important aspects of group dynamics and 
psychoeducation. Some participants may be comfortable with telemedicine-based, group 
sessions. The pilot study experience suggests many young people are comfortable with using 
the chat features. We will reiterate to participants that their comfort is our priority, and they 
may participate in a manner that feels most comfortable to them.  
5. Statistical Power. The study may be underpowered for subpopulation analyses and some 
secondary endpoints. 
 
 

 
 
 
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13. REFERENCES 
 
1 Whitney DG, Peterson MD. US national and state-level prevalence of mental health disorders and 
disparities of mental health care use in children. JAMA pediatrics. 2019;173(4):389-391. 
2 Racine N, McArthur BA, Cooke JE, Eirich R, Zhu J, Madigan S. Global prevalence of depressive and 
anxiety symptoms in children and adolescents during COVID-19: a meta-analysis. JAMA 
pediatrics. 2021;175(11):1142-1150. 
3 Gonzalez VJ, Kimbro RT, Cutitta KE, et al. Mental health disorders in children with congenital heart 
disease. Pediatrics. 2021;147(2). 
4 DeMaso DR, Calderon J, Taylor GA, et al. Psychiatric disorders in adolescents with single ventricle 
congenital heart disease. Pediatrics. 2017;139(3). 
 
5 McCormick AD, Wilde MM, Charpie CE, et al. Psychological functioning in paediatric patients with 
single ventricle heart disease: a systematic review. Cardiology in the Young. 2022;32(2):173-184. 
6 Kovacs AH, Saidi AS, Kuhl EA, et al. Depression and anxiety in adult congenital heart disease: 
Predictors and prevalence. International Journal of Cardiology. 2009;137(2):158-164. 
7 Elgar FJ, Pförtner T-K, Moor I, De Clercq B, Stevens GW, Currie C. Socioeconomic inequalities in 
adolescent health 2002–2010: a time-series analysis of 34 countries participating in the Health 
Behaviour in School-aged Children study. The Lancet. 2015;385(9982):2088-2095. 
8 Gonzalez VJ, Kimbro RT, Shabosky JC, et al. Racial Disparities in Mental Health Disorders in Youth 
with Chronic Medical Conditions. The Journal of Pediatrics. 2023:113411. 
9 Kovacs AH, Brouillette J, Ibeziako P, et al. Psychological outcomes and interventions for individuals 
with congenital heart disease: a scientific statement from the American Heart Association. 
Circulation: Cardiovascular Quality and Outcomes. 2022;15(8):e000110. 
10 Cassidy AR, Butler SC, Briend J, et al. Neurodevelopmental and psychosocial interventions for 
individuals with CHD: a research agenda and recommendations from the Cardiac 
Neurodevelopmental Outcome Collaborative. Cardiology in the Young. 2021:1-12. 
11 Opotowsky AR, Allen KY, Bucholz EM, et al. Pediatric and Congenital Cardiovascular Disease 
Research Challenges and Opportunities: JACC Review Topic of the Week. Journal of the 
American College of Cardiology. 2022;80(23):2239-2250. 
12 Psychological interventions for people affected by childhood-onset heart disease: A systematic 
review [press release]. US: American Psychological Association. 2019.  
13 Cousino MK, Pasquali SK, Romano JC, et al. Impact of the COVID-19 pandemic on CHD care and 
emotional wellbeing. Cardiology in the Young. 2021;31(5):822-828. 
14 Levine GN, Cohen BE, Commodore-Mensah Y, et al. Psychological health, well-being, and the 
mind-heart-body connection: a scientific statement from the American Heart Association. 
Circulation. 2021;143(10):e763-e783. Carazo MR, Kolodziej MS, DeWitt ES, et al. Prevalence and 
Prognostic Association of a Clinical Diagnosis of Depression in Adult Congenital Heart Disease: 
Results of the Boston Adult Congenital Heart Disease Biobank. Journal of the American Heart 
Association. 2020;9(9):e014820. 
15 Carazo MR, Kolodziej MS, DeWitt ES, et al. Prevalence and Prognostic Association of a Clinical 
Diagnosis of Depression in Adult Congenital Heart Disease: Results of the Boston Adult 
Congenital Heart Disease Biobank. Journal of the American Heart Association. 
2020;9(9):e014820. 
 

 
 
 
Pediatric Heart Network 
WBC Protocol Version 1.0 | Version Date: 2025.09 
Page 38 of 42 
 
16 Ko JM, Tecson KM, Al Rashida V, et al. Clinical and psychological drivers of perceived health 
status in adults with congenital heart disease. The American Journal of Cardiology. 
2018;121(3):377-381. 
17 McCabe N, Dunbar SB, Butler J, Higgins M, Book W, Reilly C. Antecedents of self-care in adults 
with congenital heart defects. International journal of cardiology. 2015;201:610-615. 
18 Woolf‐King SE, Anger A, Arnold EA, Weiss SJ, Teitel D. Mental health among parents of children 
with critical congenital heart defects: a systematic review. Journal of the American Heart 
Association. 2017;6(2):e004862. 
19 Sood E, Lisanti AJ, Woolf-King SE, et al. Parent mental health and family functioning following 
diagnosis of CHD: A research agenda and recommendations from the Cardiac 
Neurodevelopmental Outcome Collaborative. Cardiology in the Young. 2021;31(6):900-914. 
20 Ludomirsky AB, Bucholz EM, Newburger JW. Association of Financial Hardship Because of Medical 
Bills With Adverse Outcomes Among Families of Children With Congenital Heart Disease. JAMA 
Cardiol. 2021;6(6):713-717. 
21 Rosenberg AR, Yi-Frazier JP. Commentary: Resilience Defined: An Alternative Perspective. 
Journal of Pediatric Psychology. 2016;41(5):506-509. 
22 Kichler JC, Kaugars AS. Topical Review: Applying Positive Development Principles to Group 
Interventions for the Promotion of Family Resilience in Pediatric Psychology. Journal of Pediatric 
Psychology. 2015;40(9):978-980. 
23 Masten AS. 113C6Resilience in Developmental Systems: Principles, Pathways, and Protective 
Processes in Research and Practice. In: Ungar M, ed. Multisystemic Resilience: Adaptation and 
Transformation in Contexts of Change: Oxford University Press; 2021:0. 
24 Ungar M, Theron L. Resilience and mental health: How multisystemic processes contribute to 
positive outcomes. The Lancet Psychiatry. 2020;7(5):441-448. 
25 Glenn T, Cousino MK, Wernovsky G, Schuchardt EL. Resilient Hearts: Measuring Resiliency in 
Young People With Congenital Heart Disease. Journal of the American Heart Association. 
2023:e029847. 
26 Rosenberg AR, Bradford MC, McCauley E, et al. Promoting resilience in adolescents and young 
adults with cancer: Results from the PRISM randomized controlled trial. Cancer. 
2018;124(19):3909-3917. 
27 Yi-Frazier JP, Yaptangco M, Semana S, et al. The association of personal resilience with stress, 
coping, and diabetes outcomes in adolescents with type 1 diabetes: Variable-and person-focused 
approaches. Journal of Health Psychology. 2015;20(9):1196-1206. 
28 Moon JR, Huh J, Kang I-S, Park SW, June T-G, Lee HJ. Relationship between depression and 
resilience in adolescents with congenital heart disease. Am Heart Assoc; 2006. 
29 Luberto CM, Wang A, Li R, Pagliaro J, Park ER, Bhatt A. Videoconference-delivered Mind-Body 
Resiliency Training in Adults with congenital heart disease: A pilot feasibility trial. International 
Journal of Cardiology Congenital Heart Disease. 2022;7:100324. 
30 Kovacs AH, Grace SL, Kentner AC, Nolan RP, Silversides CK, Irvine MJ. Feasibility and outcomes 
in a pilot randomized controlled trial of a psychosocial intervention for adults with congenital heart 
disease. Canadian Journal of Cardiology. 2018;34(6):766-773. 
 

 
 
 
Pediatric Heart Network 
WBC Protocol Version 1.0 | Version Date: 2025.09 
Page 39 of 42 
 
31 Olsson CA, Boyce MF, Toumbourou JW, Sawyer SM. The role of peer support in facilitating 
psychosocial adjustment to chronic illness in adolescence. Clinical Child Psychology and 
Psychiatry. 2005;10(1):78-87. 
32 Rosenberg AR, Yi-Frazier JP, Eaton L, et al. Promoting Resilience in Stress Management: A Pilot 
Study of a Novel Resilience-Promoting Intervention for Adolescents and Young Adults With 
Serious Illness. Journal of Pediatric Psychology. 2015;40(9):992-999. 
33 Cousino MK, Dusing CR, Rea KE, et al. Developing the WE BEAT Well-Being Education 
Programme to foster resilience and build connection in paediatric heart disease. Cardiology in the 
Young. 2024:1-7. 
34 Glenn T, Smith C, Miller VA, et al. From worries to resilience: a qualitative study of the psychosocial 
experiences of diverse adolescents and young adults with heart failure and their caregivers. 
Cardiology in the Young. 2024:1-8. 
35 Cousino MK, Rea KE, Dusing CR, Glenn T, Armstrong B, Yu S, Lowery R, Les AS, Goldberg CS, 
Hansen JE, Schumacher KR. A pilot study of the WE BEAT Well-Being Education Programme to 
build resilience in adolescents with heart disease. Cardiology in the Young. 2024:1-8. 
36 Mesman E, Vreeker A, Hillegers M. Resilience and mental health in children and adolescents: an 
update of the recent literature and future directions. Current Opinion in Psychiatry 34(6):p 586-
592, November 2021. | DOI: 10.1097/YCO.0000000000000741. 
37 Ford I, Norrie J. Pragmatic trials. New England Journal of Medicine. 2016;375(5):454-463. 
38 Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-2 tool: 
designing trials that are fit for purpose. BMI. 2015;350. 
39 Williford DN, McTate EA, Hood AM, et al. Psychologists as leaders in equitable science: 
Applications of antiracism and community participatory strategies in a pediatric behavioral 
medicine clinical trial. American Psychologist. 2023;78(2):107. 
40 Kilbourne AM, Switzer G, Hyman K, Crowley-Matoka M, Fine MJ. Advancing Health Disparities 
Research Within the Health Care System: A Conceptual Framework. American Journal of Public 
Health. 2006;96(12):2113-2121. 
41 Ellis DA, Rhind J, Carcone AI, et al. Optimizing recruitment of black adolescents into behavioral 
research: A multi-center study. Journal of pediatric psychology. 2021;46(6):611-620. 
42 Cui Z, Seburg EM, Sherwood NE, Faith MS, Ward DS. Recruitment and retention in obesity 
prevention and treatment trials targeting minority or low-income children: a review of the clinical 
trials registration database. Trials. 2015;16:1-15. 
43 Campbell‐Sills L, Stein MB. Psychometric analysis and refinement of the connor–davidson 
resilience scale (CD‐RISC): Validation of a 10‐item measure of resilience. Journal of Traumatic 
Stress: Official Publication of The International Society for Traumatic Stress Studies. 
2007;20(6):1019-1028. 
44 Connor KM, Davidson JR. Development of a new resilience scale: The Connor‐Davidson resilience 
scale (CD‐RISC). Depression and anxiety. 2003;18(2):76-82. 
45 Yu X-n, Lau JT, Mak WW, Zhang J, Lui WW. Factor structure and psychometric properties of the 
Connor-Davidson Resilience Scale among Chinese adolescents. Comprehensive Psychiatry. 
2011;52(2):218-224. 
 

 
 
 
Pediatric Heart Network 
WBC Protocol Version 1.0 | Version Date: 2025.09 
Page 40 of 42 
 
46 Levey EJ, Rondon MB, Sanchez S, Williams MA, Gelaye B. Psychometric properties of the Spanish 
version of the 10-item Connor Davidson Resilience Scale© (CD-RISC©) among adolescent 
mothers in Peru. Journal of Child & Adolescent Trauma. 2021;14:29-40. 
47 Irwin DE, Stucky BD, Thissen D, et al. Sampling plan and patient characteristics of the PROMIS® 
pediatrics large-scale survey. Quality of Life Research. 2010;19:585-594. 
48 DeWalt DA, Gross HE, Gipson DS, et al. PROMIS® pediatric self-report scales distinguish 
subgroups of children within and across six common pediatric chronic health conditions. Quality of 
Life Research. 2015;24:2195-2208. 
49 Forrest CB, Bevans KB, Tucker C, et al. Commentary: the patient-reported outcome measurement 
information system (PROMIS®) for children and youth: application to pediatric psychology. 
Journal of Pediatric Psychology. 2012;37(6):614-621. 
50 Kessler RC, Andrews G, Colpe LJ, et al. Short screening scales to monitor population prevalences 
and trends in non-specific psychological distress. Psychological Medicine. 2002;32(6):959-976. 
51 Mewton L, Kessler RC, Slade T, et al. The psychometric properties of the Kessler Psychological 
Distress Scale (K6) in a general population sample of adolescents. Psychological assessment. 
2016;28(10):1232. 
52 Varni JW, Seid M, Kurtin PS. PedsQL™ 4.0: Reliability and validity of the Pediatric Quality of Life 
Inventory™ Version 4.0 Generic Core Scales in healthy and patient populations. Medical care. 
2001:800-812. 
53 Uzark K, Jones K, Burwinkle TM, Varni JW. The Pediatric Quality of Life Inventory™ in children with 
heart disease. Progress in pediatric cardiology. 2003;18(2):141-149. 
54 González-Gil T, Mendoza-Soto A, Alonso-Lloret F, Castro-Murga R, Pose-Becerra C, Martín-
Arribas MC. The Spanish version of the health-related quality of life questionnaire for children and 
adolescents with heart disease (PedsQL™). Revista Española de Cardiologia (English Edition). 
2012;65(3):249-257. 
55 Mellion K, Uzark K, Cassedy A, et al. Health-related quality of life outcomes in children and 
adolescents with congenital heart disease. Journal of Pediatrics. 2014;164(4):781-788. e781. 
56 Marino BS, Uzark K, Ittenbach R, Drotar D. Evaluation of quality of life in children with heart 
disease. Progress in Pediatric Cardiology. 2010;29(2):131-138. 
57 Lloyd-Jones DM, Allen NB, Anderson CA, Black T, Brewer LC, Foraker RE, Grandner MA, 
Lavretsky H, Perak AM, Sharma G, Rosamond W. Life’s essential 8: updating and enhancing the 
American Heart Association’s construct of cardiovascular health: a presidential advisory from the 
American Heart Association. Circulation. 2022 Aug 2;146(5):e18-43 
58 Hummel K, Whittaker S, Sillett N, Basken A, Berghammer M, Chalela T, Chauhan J, Garcia LA, 
Hasan B, Jenkins K, Ladak LA. Development of an international standard set of clinical and 
patient-reported outcomes for children and adults with congenital heart disease: a report from the 
International Consortium for Health Outcomes Measurement Congenital Heart Disease Working 
Group. European Heart Journal-Quality of Care and Clinical Outcomes. 2021 Oct 1;7(4):354-65. 
59 Zimet GD, Dahlem NW, Zimet SG, Farley GK. The Multidimensional Scale of Perceived Social 
Support. Journal of Personality Assessment 1988;52:30-41. 
60 Multidimensional-Scale-of-Perceived-Social-Support-Spanish.pdf 
 

 
 
 
Pediatric Heart Network 
WBC Protocol Version 1.0 | Version Date: 2025.09 
Page 41 of 42 
 
61 Bruwer B, Emsley R, Kidd M, Lochner C, Seedat S. Psychometric properties of the 
Multidimensional Scale of Perceived Social Support in youth. Compr Psychiatry. 2008 Mar-
Apr;49(2):195-201. doi: 10.1016/j.comppsych.2007.09.002. Epub 2007 Dec 21. PMID: 18243894. 
62 Canty-Mitchell J, Zimet GD. Psychometric properties of the Multidimensional Scale of Perceived 
Social Support in urban adolescents. Am J Community Psychol. 2000 Jun;28(3):391-400. doi: 
10.1023/A:1005109522457. PMID: 10945123. 
63 Moons P, Van Deyk K, De Geest S, Gewillig M, Budts W. Is the severity of congenital heart disease 
associated with the quality of life and perceived health of adult patients? Heart. 2005;91(9):1193-
1198. 
64 Fergus S, Zimmerman MA. Adolescent resilience: A framework for understanding healthy 
development in the face of risk. Annu Rev Public Health. 2005;26:399-419. 
65 Steiner JM, Blakeney EA-R, Baden AC, et al. Definitions of resilience and resilience resource use 
as described by adults with congenital heart disease. International Journal of Cardiology 
Congenital Heart Disease. 2023;12:100447. 
66 Joyce S, Shand F, Tighe J, Laurent SJ, Bryant RA, Harvey SB. Road to resilience: a systematic 
review and meta-analysis of resilience training programmes and interventions. BMJ open. 
2018;8(6):e017858. 
67 Rosenberg AR, Wolfe J, Bradford MC, et al. Resilience and psychosocial outcomes in parents of 
children with cancer. Pediatric blood & cancer. 2014;61(3):552-557. 
68 Lewis P, Klineberg E, Towns S, Moore K, Steinbeck K. The effects of introducing peer support to 
young people with a chronic illness. Journal of Child and Family Studies. 2016;25:2541-2553. 
69 Levine GN, Lange RA, Bairey‐Merz CN, et al. Meditation and cardiovascular risk reduction: a 
scientific statement from the American Heart Association. Journal of the American Heart 
Association. 2017;6(10):e002218. 
70 Meiklejohn J, Phillips C, Freedman ML, et al. Integrating mindfulness training into K-12 education: 
Fostering the resilience of teachers and students. Mindfulness. 2012;3:291-307. 
71 Pidgeon AM, Keye M. Relationship between resilience, mindfulness, and pyschological well-being 
in University students. International Journal of Liberal Arts and Social Science. 2014;2(5):27-32. 
72 Cohen R, Bavishi C, Rozanski A. Purpose in life and its relationship to all-cause mortality and 
cardiovascular events: A meta-analysis. Psychosomatic medicine. 2016;78(2):122-133. 
73 Law E, Fisher E, Eccleston C, Palermo TM. Psychological interventions for parents of children and 
adolescents with chronic illness. Cochrane Database of Systematic Reviews. 2019(3). 
74 Mak WW, Ng IS, Wong CC. Resilience: enhancing well-being through the positive cognitive triad. 
Journal of counseling psychology. 2011;58(4):610. 
75 Huffman JC, Beale EE, Celano CM, et al. Effects of optimism and gratitude on physical activity, 
biomarkers, and readmissions after an acute coronary syndrome: the gratitude research in acute 
coronary events study. Circulation: Cardiovascular Quality and Outcomes. 2016;9(1):55-63. 
76 Cousin L, Redwine L, Bricker C, Kip K, Buck H. Effect of gratitude on cardiovascular health 
outcomes: a state-of-the-science review. The Journal of Positive Psychology. 2021;16(3):348-355. 
77 Legler SR, Beale EE, Celano CM, Beach SR, Healy BC, Huffman JC. State gratitude for one’s life 
and health after an acute coronary syndrome: Prospective associations with physical activity, 
medical adherence and re-hospitalizations. The journal of positive psychology. 2019;14(3):283-
291. 
 

 
 
 
Pediatric Heart Network 
WBC Protocol Version 1.0 | Version Date: 2025.09 
Page 42 of 42 
 
78 Vieselmeyer J, Holguin J, Mezulis A. The role of resilience and gratitude in posttraumatic stress and 
growth following a campus shooting. Psychological Trauma: Theory, Research, Practice, and 
Policy. 2017;9(1):62. 
79 Bellg AJ, Borrelli B, Resnick B, Hecht J, Minicucci DS, Ory M, Ogedegbe G, Orwig D, Ernst D, 
Czajkowski S. Enhancing treatment fidelity in health behavior change studies: best practices and 
recommendations from the NIH Behavior Change Consortium. Health psychology. 2004 
Sep;23(5):443. 
80 Steiner, J.M., Marshall, A.R., Kovacs, A.H., Engelberg, R.A., Brumback, L., Stout, K.K., 
Longenecker, C.T., Joyce, P. and Rosenberg, A.R., 2024. Rationale and design of a randomized 
controlled clinical trial of a resilience-building intervention in adults with congenital heart 
disease. Contemporary Clinical Trials, 145, p.107638. 
81 Schleider JL, Weisz JR. Little Treatments, Promising Effects? Meta-Analysis of Single-Session 
Interventions for Youth Psychiatric Problems. J Am Acad Child Adolesc Psychiatry. 2017 
Feb;56(2):107-115. doi: 10.1016/j.jaac.2016.11.007. Epub 2016 Nov 25. PMID: 28117056. 
82 Schleider JL, Weisz JR. Reducing risk for anxiety and depression in adolescents: Effects of a 
single-session intervention teaching that personality can change. Behav Res Ther. 2016 
Dec;87:170-181. doi: 10.1016/j.brat.2016.09.011. Epub 2016 Sep 26. PMID: 27697671; PMCID: 
PMC5127737.  
83 Schleider JL, Weisz JR. A single-session growth mindset intervention for adolescent anxiety and 
depression: 9-month outcomes of a randomized trial. J Child Psychol Psychiatry. 2018 
Feb;59(2):160-170. doi: 10.1111/jcpp.12811. Epub 2017 Sep 18. PMID: 28921523.  
84 Schleider JL, Burnette JL, Widman L, Hoyt C, Prinstein MJ. Randomized Trial of a Single-Session 
Growth Mind-Set Intervention for Rural Adolescents' Internalizing and Externalizing Problems. J 
Clin Child Adolesc Psychol. 2020 Sep-Oct;49(5):660-672. doi: 10.1080/15374416.2019.1622123. 
Epub 2019 Jun 20. PMID: 31219698; PMCID: PMC6923626. 
85 Senn S., Julious S. Measurement in clinical trils: a neglected issue for statisticians. Statistics in 
Medicine. 2009, 28:3189-3209. 
86 Kovacs AH, Grace SL, Kentner AC, Nolan RP, Silversides CK, Irvine MJ. Feasibility and Outcomes 
in a Pilot Randomized Controlled Trial of a Psychosocial Intervention for Adults With Congenital 
Heart Disease. Can J Cardiol. 2018 Jun;34(6):766-773. doi: 10.1016/j.cjca.2018.02.023. Epub 
2018 Mar 2. PMID: 29801741. 
87 Rosenberg, A.R., Bradford, M.C., McCauley, E., Curtis, J.R., Wolfe, J., Baker, K.S. and Yi-Frazier, 
J.P. (2018), Promoting resilience in adolescents and young adults with cancer: Results from the 
PRISM randomized controlled trial. Cancer, 124: 3909-3917. https://doi.org/10.1002/cncr.31666 
88 O'Donnell MB, Scott SR, Ellisor BM, Cao VT, Zhou C, Bradford MC, Pihoker C, DeSalvo DJ, Malik 
FS, Hilliard ME, Rosenberg AR, Yi-Frazier JP. Protocol for the Promoting Resilience in Stress 
Management (PRISM) intervention: A multi-site randomized controlled trial for adolescents with 
type 1 diabetes. Contemp Clin Trials. 2023 Jan;124:107017. doi: 10.1016/j.cct.2022.107017. Epub 
2022 Nov 21. PMID: 36410689; PMCID: PMC9839528. 
89 Proshan M, Lan G, WIttes J. Statistical monitoring of clinical trials. Springer. 2007. 
90 Adaptive Design Clinical Trials for Drugs and Biologics, Guidance for Industry.