Urological and Renal Disease Engaging Adolescents in Adherence Collaborative Trial
Phase: NA
Conditions: Spina Bifida, Kidney Transplant
Sponsor: Children's Hospital of Philadelphia

 
 
Official title of study 
Urological and Renal Disease Engaging Adolescents in 
Adherence Collaborative Trial 
NCT Number 
NCT03045276 
Document Date 
May 14, 2020 
 

 
 
 
 
 
 
1
Title: 
U-REAACT study (Urological and Renal disease Engaging 
Adolescents in Adherence Collaborative Trial) 
Short Title: 
U-REAACT study  
Regulatory Sponsor: 
National Institutes of Health 
eIRB Number: 
16-013000 
Protocol Date: 
 Version 18, May 14, 2020 
 
 
 
 
Sponsor: National Institutes of Health 
National Institute of Diabetes and Digestive and Kidney Disorders 
 
 
Principal Investigator: Sandra Amaral, MD, MHS 
The Children’s Hospital of Philadelphia 
Colket Translational Research Building  
3501 Civic Center Boulevard, Suite 9300, Philadelphia, PA, 19104 
Phone 267-590-2449 
Email: amarals@chop.edu 
 

  
Protocol No. 16-013000 
 
 
 
 
 
 
ii
TABLE OF CONTENTS 
Abbreviations and Definitions of Terms ............................................................................. iv 
Table 1: Schedule of Study Procedures – Arm 1 and Arm 2 ............................................. v 
1 
BACKGROUND INFORMATION AND RATIONALE ....................................................................... 1 
1.1 
INTRODUCTION ..................................................................................................................................... 1 
1.2 
NAME AND DESCRIPTION OF INVESTIGATIONAL PRODUCT OR INTERVENTION ..................................... 1 
1.3 
FINDINGS FROM CLINICAL STUDIES ..................................................................................................... 1 
1.4 
RELEVANT LITERATURE AND DATA ..................................................................................................... 2 
1.5 
COMPLIANCE STATEMENT .................................................................................................................... 5 
2 
STUDY OBJECTIVES .............................................................................................................................. 5 
2.1 
PRIMARY OBJECTIVE ............................................................................................................................ 5 
2.2 
SECONDARY OBJECTIVE ....................................................................................................................... 6 
2.3 
   TERTIARY OBJECTIVE…………………………………………………………………………...…….6 
3 
INVESTIGATIONAL PLAN .................................................................................................................... 6 
3.1 
GENERAL SCHEMA OF STUDY DESIGN ................................................................................................. 6 
3.1.1 
Screening Phase .............................................................................................................................. 6 
3.1.2 
Run-in and Intervention Phase ........................................................................................................ 7 
3.1.3 
Follow-up Phase ............................................................................................................................. 9 
       3.1.4     Study Staff Involvement…………………………………………………………………..…………...……. 9 
3.2 
ALLOCATION TO TREATMENT GROUPS AND BLINDING ........................................................................ 9 
3.3 
STUDY DURATION, ENROLLMENT AND NUMBER OF SITES ................................................................. 10 
3.3.1 
Duration of Study Participation .................................................................................................... 10 
3.3.2 
Total Number of Study Sites/Total Number of Subjects Projected ................................................ 10 
3.4 
STUDY POPULATION ........................................................................................................................... 10 
3.4.1 
Inclusion Criteria .......................................................................................................................... 10 
3.4.2 
Exclusion Criteria ......................................................................................................................... 10 
4 
STUDY PROCEDURES .......................................................................................................................... 11 
4.1 
SCREENING VISIT ............................................................................................................................... 11 
        4.1.1    Run-in Period…..……………………………………………………………………………….. 11 
4.2 
STUDY TREATMENT FOR ARM 1 GROUP ............................................................................................. 11 
4.2.1 
Intervention Phase ........................................................................................................................ 11 
4.2.2 
Follow-up Phase ........................................................................................................................... 11 
4.3 
STUDY TREATMENT FOR ARM 2 GROUP ............................................................................................. 12 
4.3.1 
Intervention Phase ........................................................................................................................ 12 
4.3.2 
Follow-up Phase ........................................................................................................................... 12 
4.4 
STUDY STAFF CHECK- INS .................................................................................................................. 12 
4.5 
SUBJECT COMPLETION/WITHDRAWAL ............................................................................................... 12 
5 
STUDY EVALUATIONS AND MEASUREMENTS ............................................................................ 13 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS ................................................ 13 
5.1.1 
Medical Record Review ................................................................................................................. 13 
5.2 
EFFICACY EVALUATIONS ................................................................................................................... 13 
5.2.1 
Diagnostic Tests, Scales, Measures, etc. ....................................................................................... 13 
       5.2.2     Survey Descriptions………………………………………………………………………………14 
6 
STATISTICAL CONSIDERATIONS .................................................................................................... 16 
6.1 
PRIMARY ENDPOINT ........................................................................................................................... 16 

 
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6.2 
SECONDARY ENDPOINTS .................................................................................................................... 16 
    6.3        TERTIARY ENDPOINTS …………………………………...…………………………………………..17 
6.4 
STATISTICAL METHODS ...................................................................................................................... 17 
6.5 
SAMPLE SIZE AND POWER .................................................................................................................. 18 
7 
SAFETY MANAGEMENT ..................................................................................................................... 18 
7.1 
CLINICAL ADVERSE EVENTS .............................................................................................................. 18 
7.2 
ADVERSE EVENT REPORTING ............................................................................................................. 18 
7.3 
INCIDENTAL FINDINGS ....................................................................................................................... 19 
8 
STUDY ADMINISTRATION ................................................................................................................. 20 
8.1 
TREATMENT ASSIGNMENT METHODS ................................................................................................. 20 
8.1.1 
Randomization............................................................................................................................... 20 
8.1.2 
Blinding ......................................................................................................................................... 20 
8.2 
DATA COLLECTION AND MANAGEMENT ............................................................................................ 20 
8.3 
CONFIDENTIALITY .............................................................................................................................. 24 
8.4 
REGULATORY AND ETHICAL CONSIDERATIONS .................................................................................. 24 
8.4.1 
Data and Safety Monitoring Plan ................................................................................................. 24 
8.4.2 
Risk Assessment ............................................................................................................................. 25 
8.4.3 
Potential Benefits of Trial Participation ....................................................................................... 25 
8.4.4 
Risk-Benefit Assessment ................................................................................................................ 25 
8.5 
RECRUITMENT STRATEGY .................................................................................................................. 25 
8.6 
INFORMED CONSENT/ASSENT AND HIPAA AUTHORIZATION ............................................................ 25 
8.7 
PAYMENT TO SUBJECTS/FAMILIES ...................................................................................................... 26 
9 
INTENTION FOR PUBLICATION…………………………………………………………………... 27 
10    REFERENCES ......................................................................................................................................... 27 
 

  
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ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
 
 
(S)AE 
 
(Serious) Adverse event 
AMBS 
 
Adolescent Medication Barrier Scale 
ATR 
 
Allocation of Treatment Responsibility 
ATR-C 
 
Allocation of Treatment Responsibility – Caregiver 
AYA 
DSMB 
GEE 
GFR 
KT 
SB 
PI 
SES 
NIDDK 
WTH 
 
Adolescent and young adult 
Data safety monitoring board 
Generalized estimating equations 
Glomerular filtration rate 
Kidney transplant 
Spina bifida 
Principal investigator 
Socioeconomic status 
National Institute of Diabetes and Digestive and Kidney Diseases 
Way to Health 
BET 
 
Behavioral Economics Theory 
BRIEF 
 
Behavior Rating Inventory of Executive Function 
CIC 
 
Clean Intermittent Catheterization 
CKD 
 
Chronic Kidney Disease 
ESRD 
 
End-stage Renal Disease 
KOSB 
UDS 
CV 
QLS 
DCC 
UPenn 
PMACS 
SQL 
 
Knowledge of Spina Bifida 
Urodynamic Studies 
Coefficient of Variation  
Quasi-Least Squares 
Data Coordinating Center 
University of Pennsylvania  
The Penn Medicine Academic Computing Services 
Structured Query Language 
NA 
 
Non-adherence  
PMBS 
 
Parent Medication Barrier Scale 
SOSBMR 
 
Sharing of Spina Bifida Management Responsibilities 
UTI 
 
Urinary Tract Infection 
WHO 
CHOP 
mhealth 
Participant/Subject 
 
World Health Organization 
The Children's Hospital of Philadelphia 
Mobile Health 
Refers to the child age 12-24 with KT or SB, NOT the parent/legal 
guardian 

 
page v 
Protocol No. 16-013000 
 
 
 
 
 
 
TABLE1: SCHEDULE OF STUDY PROCEDURES – ARM 1 AND ARM 2 
Phase 
Run-in 
Intervention 
Follow-up 
Duration 
2 weeks 
6 months 
2 months 
2 months 
2 months 
Both Arms 
$10 for withdrawals who complete an OPTIONAL Exit Survey within 5 days. 
Complete of 
baseline 
surveys and 
$20 lump 
sum for 
adherence 
reporting. 
$20 if 
baseline 
surveys are 
completed 
within 5 days 
and $10 if 
baseline 
surveys are 
completed in 
6 – 10 days 
Access to 
Way to 
Health portal 
with 
educational 
modules and 
personal 
dashboard to 
see adherence 
progress. 
Complete 
surveys after 
six months 
post.  
$20 if post 
intervention 
surveys are 
completed 
within 5 days 
and $10 if 
post 
intervention 
surveys are 
completed in 
6 – 10 days. 
No further access to Way to Health portal.  
$2/week for adherence reporting. 
Complete surveys six months post. 
$20 if post follow-up surveys are completed 
within 5 days and $10 if post follow-up 
surveys are completed in 6 – 10 days. 
Arm 1 
(not 
randomized 
yet) 
$2/week for 
adherence 
reporting. 
Arm 2 
(not 
randomized 
yet) 
Adherence 
progress sent 
to phone by 
text with 
personalized 
feedback on 
performance. 
$10/week if 
Adherence progress sent to phone by text 
with weekly personalized feedback on 
performance. 
$10 every 2 
weeks if 
adherence 
goal met over 
$10 every 4 
weeks if 
adherence 
goal met over 
No further 
“extra” 
incentive.  

 
page vi 
Protocol No. 16-013000 
 
 
 
 
 
 
adherence 
goal met.  
2 week 
average. 
4 week 
average. 

 
 
Protocol No. 16-013000 
 
  
 
 
 
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1 
BACKGROUND INFORMATION AND RATIONALE 
1.1 Introduction 
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has funded 
a cooperative agreement including six leading pediatric renal transplant and spina bifida (SB) 
care centers in the United States, the Children’s Hospital of Philadelphia (CHOP), Boston 
Children’s Hospital, Children’s Healthcare of Atlanta, Seattle Children’s Hospital, Lurie’s 
Children of Chicago, and Children’s Mercy Kansas City. 
The overarching goal of this five-year, phase II, randomized clinical trial is to improve poor 
long-term health outcomes in both adolescents and young adults (AYA) with either a kidney 
transplant (KT) or spina bifida (SB), respectively. More specifically, this study will focus on 
decreasing premature allograft loss in subjects with kidney transplant (KT) due to medication 
nonadherence and kidney damage in subjects with SB due to urinary non-continence. To 
achieve these goals, this study will implement a real-time feedback system, Way to Health 
(WTH), that will provide education and support, increase awareness and incentivize positive 
health behavior, in addition to standard of care. Further, this study will investigate the 
mechanisms of behavior change by examining the role of financial incentives, positive 
feedback and the relationship between the two. The study will compare two cohorts of KT 
and SB subjects, which will undergo varied levels of financial incentives and positive 
feedback. Data from KT and SB subjects will be analyzed separately. This innovative mobile 
health (mhealth) strategy will improve our current measures of adherence and increase our 
understanding of factors that influence adherence for two AYA populations, KT and SB 
subjects, respectively. Our study will contribute novel insight to inform the design of future 
interventions targeting persistence of behavior change and can be used in other centers and 
for other chronic disease groups. 
1.2 Name and Description of Investigational Product or Intervention 
The study intervention will use the WTH web-based platform to support AYA with KT or SB 
as they navigate their daily treatment burdens. This will be achieved via bi-directional text 
messaging, including the sending of reminders and positive feedback by WTH and the 
messaging of pictures of medication or catheter in hand at time of treatment by the participant. 
This intervention will assess sustainability of this novel bi-directional messaging system and 
the impact of providing education and support, increasing awareness and incentivizing 
positive health behavior in real-time.  
 
1.3 Findings from Clinical Studies  
Kidney Transplant: AYA with KT have lower five year allograft survival than any other age 
group besides patients over 65 years of age, and once diagnosed with rejection, they do not 
respond as well to treatment, with fewer complete rejection reversals and greater residual graft 
dysfunction.2-4 High rates of non-adherence (NA) play a key role in high rates of rejection, 
premature allograft dysfunction and graft failure.5-8 AYA KT recipients who experience graft 
failure are twice as likely to be NA (OR 2.07, 95% CI 1.12-4.06).9 Recent evidence also 
demonstrates a significant association between NA and development of de novo donor-
specific antibody.10 AYA who develop donor-specific antibody wait substantially longer for 

 
 
Protocol No. 16-013000 
 
  
 
 
 
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re-transplantation.11 Thus, nonadherent AYA with KT are primed to spend less of their 
lifetime with a functioning graft and more time on dialysis, leading to tremendous loss in 
quality of life and increased co-morbidities and astounding economic burden.12 After the first 
year post-transplant, Medicare costs for patients with a functioning graft are $30,000 annually, 
less than half the annual costs of dialysis care.2 Persistent NA leads to over $21,000 in 
increased adjusted medical costs over 3 years per patient, with AYA less than 24 years of age 
having the highest rates of persistent NA.9 
 
Spina Bifida: SB is one of the most common and disabling birth defects, occurring in 3.1 of 
every 10,000 live births.13 Despite dramatic advances in our understanding and treatment of 
SB, the lower urinary tract outcomes for patients with SB continue to show urodynamic 
patterns consistent with neurogenic bladders.14 Bladder dysfunction, if not treated, leads to 
kidney damage and failure. Clean Intermittent Catheterization (CIC) remains a critical 
component of medical treatment to achieve urinary continence and optimize bladder 
function.15 Recognizing that the risk for kidney damage can often be significantly reduced or 
eliminated with close monitoring and medical treatment, the CDC has established a protocol 
to standardize bladder and kidney assessments starting from infancy.16 Yet, even with better 
assessments, patient continence cannot be achieved without rigorous adherence to treatment 
regimens. Health professionals and patients with SB both rate adherence to catheterization as 
highly problematic.17,18 When patients do not succeed in achieving urinary continence with 
medical management, surgical reconstruction, with bladder augmentation or creation of a 
catheterizable stoma, may be needed. However, these procedures incur significant secondary 
complications, including increased risks of urinary tract infection (UTI), urolithiasis, 
metabolic abnormalities, cancer and bowel perforation.19  
 
Patients with SB experience rates of inpatient admissions with UTI that are over 50 times 
higher than the general population.20,21 It is estimated that if the number of UTI 
hospitalizations among SB patients were reduced by half, $4.4 million would be saved per 
1000 patients.20 Among SB patients who progress to end-stage renal disease (ESRD), ESRD 
is usually caused by urological complications and is reached at a substantially younger age 
compared to patients without SB (41 vs. 62 years, p<0.001). ESRD increases the already high 
complexity of SB care, and consequently, AYA with SB face tremendous difficulties in 
accessing care, contributing to reduced access to transplantation.22 Thus, similar to AYA KT 
recipients, AYA with SB are primed to spend more of their lifetime on dialysis, leading to 
tremendous loss in quality of life, increased co-morbidities and increased costs. In addition, 
the incontinent AYA is more likely to remain socially isolated and disengaged.23 These 
significant burdens of cost and quality of life emphasize the crucial need to support AYA with 
KT and SB in their ability to comply with treatment regimens.   
 
1.4 Relevant Literature and Data 
NA in chronic conditions is a particularly challenging problem to solve primarily because: 1) 
adherence is a complex behavior that requires long-term engagement and 2) adherence is 
difficult to measure.  
 

 
 
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NA is often considered a patient-driven problem and, as a consequence, many interventions 
focus solely on the patient. However, The World Health Organization (WHO) has emphasized 
that this perception fails to acknowledge that many external factors influence people’s 
behavior and their capacity to adhere to prescribed treatments.24 The WHO Multi-
Dimensional Adherence Model identifies five interrelated categories of risk factors for NA: 
social and economic, condition-related, treatment-related, patient-related and healthcare 
system factors.  
 
These five elements provide an excellent framework for conceptualizing barriers and 
facilitators to treatment adherence in AYA with KT and SB. In addition to the economic 
burdens of chronic illness, social factors, such as family conflict and lack of cohesion, are 
associated with NA. Children with SB and KT tend to lag behind typically developing youth 
in general independence, and their parents are more likely to be overprotective.17 This 
dynamic often contributes to family conflict as adolescents with SB emerge into adults.17,25 
There are also important condition-related factors that result from the effects of underlying 
chronic illness. Neither chronic kidney disease (CKD) nor SB is an isolated condition. The 
co-morbidities associated with these diseases increase adherence burden, by augmenting the 
number of treatments, labs and doctors’ visits. Neurocognitive dysfunction is also common 
among AYA with SB and KT, which results in increased learning challenges.26,27 AYA with 
KT and SB experience many treatment-related factors as well. Immunosuppressives and 
catheterization have many unfavorable side effects. Treatment complexity, particularly in 
terms of numbers of medications or frequency of treatments, impairs adherence.28,29 Patient-
related factors include low self-esteem, low self-efficacy and social adjustment difficulties. 
Patients who are more self-motivated and perceive greater control over their health tend to be 
more adherent.28 AYA with chronic conditions do not want to appear different from their peers 
and often struggle accepting their healthcare needs because they do not feel “normal”.30-32 
Further, AYA who have overprotective parents may not receive the practice and 
encouragement needed to gain confidence and skills to become autonomous in their care.17 
Lastly, the healthcare system poses barriers to treatment adherence. Factors linked to NA 
include limited time providers spend with patients, lack of information about health and 
treatments, and little focused discussion of adherence barriers.33  
 
Historically, interventions to address NA have been limited to enhanced monitoring with 
increased lab screening and clinic visits to provide supplemental education and counseling.34-
36 This approach has been met with limited success, largely because clinic-based interventions 
increase patient and caregiver burden, for families who are already overwhelmed with tasks 
at hand. Moreover, education alone is not sufficient to promote long-term patient engagement 
in health-promoting behavior37; most patients know what they need to do to stay healthy but 
they face everyday challenges in doing so.24  
 
Another great challenge in designing adherence interventions is that there is no “gold 
standard”. No single measure of adherence shows high sensitivity and specificity.38 Current 
methods of adherence measurement are fraught with feasibility challenges. Shemesh and Fine 
suggest the ideal measure of adherence should: a) be easily integrated into practice, b) pose 
minimal additional burden to patients c) be simple d) correlate with adverse clinical outcomes 
and e) identify nonadherence in real time.39 To date, no adherence interventions have 

 
 
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4
successfully achieved these goals for KT recipients. Adherence research in SB is even more 
limited. Some insight has been gleaned regarding adherence barriers for AYA with SB and 
there is evidence that cathing adherence declines over time. However, few adherence 
interventions have been tested in AYA with SB, and among those, a caregiver questionnaire 
has been the primary assessment used.1,17 Thus, for AYA with SB, there remains very little 
understanding of day-to-day treatment adherence patterns and challenges.40 
 
Mobile Technology: Well-Suited to Address Current Gaps in Adherence Interventions 
for AYA 
 
Mobile technology presents a novel opportunity to transform AYA participation in their own 
healthcare, creating a space for AYA with KT or SB to practice autonomy in healthcare self-
managements skills and receive feedback on performance. Mhealth interventions that use 
mobile technology, such as apps or texting, have shown early promise in acceptability and 
feasibility as an adherence tool for AYA across a wide range of chronic conditions.18,41,42 
Using texting as a mode of intervention is low-cost, highly available and uniquely allows 
ecological momentary assessments, i.e. assessments and interventions are provided when 
patients need support the most - at the time behavior is performed. Text messaging 
interventions pose minimal burden, are simple and can identify nonadherence in real-time. 
 
Innovation in Theoretical Framework  
 
Behavioral economics theory (BET) starts with empirical observations that humans often 
behave in predictably irrational ways. BET endorses theory-driven interventions that make it 
easy for subjects to do what is in their best interests and harder to do what is not. BET targets 
the human tendency toward present bias, counteracting long-term negative outcomes which 
are often heavily discounted.37 Incentive motivation is another key construct. Behavioral 
economics also targets regret aversion, the desire to avoid regret or loss. In BET intervention 
models, subjects are often told what they could have gained if they had performed the positive 
health behavior. This approach promotes motivation to avoid loss of a reward in the future. 
BET models have been rigorously tested and shown to be effective across a wide range of 
adult chronic disease conditions43-45, but BET has not been widely applied in AYA.  
 
Bandura’s social cognitive theory, an important theoretical framework for behavioral 
economics, suggests that behavior can be changed through new learning experiences, 
guidance in the adjustment of perceptions, and support for the development of capacities.57 
Bandura identified increased self-efficacy as a common mechanism to promote behavior 
change. Methods for increasing self-efficacy include: 1) helping subjects gain mastery of 
behavior, 2) showing subjects that others like them can do it (social modeling), 3) improving 
physical and emotional states by reducing stress and fear and 4) persuading through 
encouragement.46 BET relies heavily on effective feedback loops that incorporate these 
methods.  
 
Our study will pair financial incentives with positive text messages. Although the use of 
financial incentives is common in children in everyday parenting, i.e. allowances, there has 

 
 
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5
been limited use in research. In two pediatric studies, giving children small incentives to 
increase healthy food consumption more than doubled fruit and vegetable intake, and effects 
were sustained for two months.47,48 Another study recently showed that giving young adults 
with food allergies $10 a week for carrying epinephrine auto-injectors was more effective in 
increasing carriage than text reminders alone.49  Our study will be the first to test the effects 
of paired text messages with small incentives to promote adherence among AYA with KT or 
SB. 
 
Innovation in Methods 
 
Bi-directional texting has shown good acceptability in other AYA populations.41,49,50 In a 
small study of AYA with HIV, increased adherence reported by interactive text messaging 
showed a trend toward positive improvements in biomarkers.41 Co-investigator, Lisa 
Schwartz, has applied interactive text messaging in THRIVE 2.0, a randomized clinical trial 
to improve healthcare self-management skills in AYA cancer survivors, with very low refusal 
rates (<20%) and 90% study retention.51  
 
1.5 Compliance Statement 
This study will be conducted in full accordance with all applicable Research Policies and 
Procedures and all applicable federal and state laws and regulations including 45 CFR 46. All 
episodes of noncompliance will be documented. 
The investigators will perform the study in accordance with this protocol, will obtain consent 
and assent, and will report unanticipated problems involving risks to subjects or others in 
accordance with IRB Policies and Procedures and all federal requirements. Collection, 
recording, and reporting of data will be accurate and will ensure the privacy, health, and 
welfare of research subjects during and after the study.  
2 
STUDY OBJECTIVES 
The purpose of this study is to determine the effectiveness of behavioral feedback plus 
economic incentives to promote treatment adherence among a large diverse population of 
AYA with KT or SB.  
2.1 Primary Objective 
The primary objective is to compare the efficacy of two 6-month mhealth-based interventions 
to promote treatment adherence among AYA with KT or SB. In Arm 1, subjects will receive 
text reminders and a nominal weekly payment for participation. Arm 2 is an enhanced, tailored 
intervention with individualized feedback on adherence behavior and financial incentives for 
meeting adherence goals. The primary outcome is change in proportion of time adherent 
between run-in and 6-month intervention. Adherence data will be collected in real-time when 
subjects take pictures of their medicines (or catheter) in hand. Secondary outcomes are 
coefficient of variation (CV) in immunosuppressive drug levels for KT recipients and change 
in bladder wall compliance for SB subjects. Hypothesis 1: Adherence will be higher during 
the 6-month intervention in Arm 2 vs. Arm 1.  

 
 
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6
 
2.2 Secondary Objective 
The secondary objective is to evaluate differences in sustainability of adherence in a 6-month 
post-intervention period in which financial incentives are tapered then stopped in Arm 2. We 
will compare the change in adherence from the intervention’s end to 6 months post-
intervention. Hypothesis 2: Arm 2 (vs. Arm 1) will demonstrate greater sustained adherence 
as incentives are slowly removed due to ongoing tailored feedback. 
 
2.3 Tertiary Objective  
The tertiary objective is to identify psychosocial correlates of adherence changes in AYA with 
KT and SB. Using validated surveys, we will examine perceived barriers, self-efficacy and 
healthcare responsibility before and after the 6-month intervention and follow-up periods. 
Hypothesis 3: Positive change in adherence behavior is associated with positive changes in 
self-efficacy, reduced perceived barriers and increased healthcare responsibility. 
 
2.4 Quaternary Objective  
The quaternary objective is to evaluate differences in comorbidities and demographic data of 
lost to follow up participants to that of those who complete the study intervention. This will 
contribute to understanding generalizability.  
 
3 
INVESTIGATIONAL PLAN 
3.1 General Schema of Study Design 
3.1.1 Screening Phase 
Potential subjects in the Nephrology, Urology and Spina Bifida outpatient clinics will be 
screened using the protocol inclusion and exclusion criteria. Those who meet the criteria will 
be approached by a member of the study team at their regularly scheduled clinic visit or by 
phone and asked if they would like to hear about the study. If the subject expresses interest, 
he or she will have an orientation to the WTH platform facilitated by the research coordinator. 
The research coordinator will help subjects open an account, sign an informed consent, and 
complete a baseline questionnaire at study entry during a clinic visit. At this enrollment visit, 
coordinators will explain the bi-directional texting and smartphone adherence reporting to 
participants and show them how to perform the reporting. Participant phones will be checked 
to ensure texting and camera capabilities. If a participant does not have a smartphone, a study 
phone will be provided. Coordinators will also give each participant a Greenfire Clin Card, 
explaining to the participant how the card works. A member of the Data Coordinating Center 
(DCC) research staff will activate each card remotely. If participants are pressed for time, they 
may complete the baseline questionnaires via the WTH platform and will be requested to do 
so within five days of study entry. Participants who complete their surveys within this time 
frame will receive $20. Participants who complete their surveys within 6 – 10 days will receive 
$10. They will be sent a text reminder to complete their questionnaires if they have not done 
so within five days. Coordinators will tell participants that they can earn either a water bottle 

 
 
Protocol No. 16-013000 
 
  
 
 
 
7
or a phone wallet at baseline for the completion of surveys within this time. They will be given 
this prize in clinic if they are able to complete all baseline surveys during the clinic visit. If 
not, they will be mailed their prize.    
Additionally, the research coordinator will help a parent/legal guardian set up his/her WTH 
portal. The parent/legal guardian will sign an informed consent and also complete a baseline 
questionnaire. Through this portal, parents/legal guardians will have access to educational 
information, a copy of the consent form and the ability to answer questionnaires when 
prompted. The IRB has waived consent and HIPAA authorization for the child’s absent 
parent/legal guardian in the case that both parents/legal guardians are not present at time of 
enrollment. The waivers will occur for the purpose of collecting demographic information 
about the absent parent/legal guardian, such as income and education level. If both 
parents/legal guardians are present then both will be consented. 
 
An iPad will be provided to each site by the DCC for ease of facilitating this phase in clinic. 
 
After the informed consent process, a medical history and medical record review will take 
place.  
 
3.1.2 Run-In and Intervention Phase  
During the first two weeks (run-in period) after questionnaire completion, all participants will 
be asked to take a photo of their medicines or catheter in hand at the time of treatment without 
prompts from Way to Health. The photo will be automatically transmitted to WTH and time 
stamped to record treatment adherence. Coordinators will emphasize that these data will be 
used to collect baseline information on the routine adherence behavior of AYA with KT and 
SB, and these data will not be reported to healthcare providers. Participants will receive $20 
(to be administered via Greenfire Clin Card), given as a lump sum at the end of the 2-week 
period. Participants can track payments in the WTH portal.  
 
After the run-in period, coordinators will call participants to explain the randomization 
process. Participants will be told that WTH will randomly assign them to one of two groups 
and will notify them of their status by text. Participants will either be assigned to 1) access 
personal weekly adherence reports by logging into the WTH website or 2) receive weekly 
adherence reports automatically to their smartphone with direct feedback on their 
performance. Participants will also be told that they will receive ongoing weekly 
compensation for adherence reporting, but that the compensation structure will change and 
vary by group during the intervention so that we can learn more about the role of financial 
incentives for AYA.  
 
Study Arms: At 2 weeks, a computerized randomization scheme will be generated by WTH 
to assign participants to one of two arms, stratified by disease group (KT or SB), and age 
category (12-17 vs. 18-24). User written code in Stata 14.0 will utilize a block randomization 
scheme that, within each disease/age group stratum stratification, first randomly orders blocks 
of size 2 and 4 and then randomly orders subjects within blocks. Due to the nature of the study, 
blinding of participants and research staff is not possible. However, the relying site PI’s will 

 
 
Protocol No. 16-013000 
 
  
 
 
 
8
be blinded. WTH will send a text to each participant explaining the compensation scheme. 
Participants will be asked to reply yes to confirm receipt and willingness to participate. 
Additionally, coordinators will call participants at the time to explain the intervention and 
answer any questions. Subjects will be randomized as follows:  
 
Arm 1: Participants will begin to receive daily text messages as reminders and continue to 
report real-time treatment adherence with photos. They will receive $2/week to encourage 
real-time adherence reporting. Pay is not contingent on meeting a target adherence score, but 
only on submitting at least one photo per week. In addition to the payments, participants will 
be able to log in to WTH to see their personal dashboard with a visual display of their weekly 
adherence performance. They will also be able to access educational resources related to their 
primary disease. Educational materials for KT recipients will include web links to participant 
resources specific for AYA, including resources publicly available through the American 
Society of Transplantation, National Kidney Foundation and the United Network for Organ 
Sharing and educational videos created by CHOP’s care team.52-54 The major transplant 
themes that will be covered include: medication management, infection precautions, energy 
and physical activity, mental health and social adjustment, nutrition, sexuality and risk 
behavior education, and vocational resources. Similarly, educational materials for the SB 
subjects will be drawn from web-based AYA-specific resources, including web links to the 
Centers for Disease Control Living with Spina Bifida Program and the National Spina Bifida 
Association.55,56 The major SB themes that will be covered include: bladder and bowel 
management, infection precautions, skin health, physical health, mental health and social 
adjustment, nutrition, sexuality and risk behavior, safety and vocational resources. All of the 
educational materials that will be used have been vetted by healthcare professionals, but every 
resource will be reviewed and adapted by the investigative team to ensure relevance, currency, 
accuracy and readability. Every month, participants will receive a text encouraging them to 
visit the WTH educational modules and to check their earnings. WTH is able to track usage 
of the modules by individual. Parents/legal guardians will have access to these same 
educational materials via their own WTH portals. Additionally, to mitigate the minimal risk 
of this study, parents/legal guardians will be notified if their child is excessively non-adherent.  
 
Arm 2: Participants randomized to Arm 2 will also begin to receive daily text messages as 
reminders and report real-time treatment adherence with photos, and will have web access to 
the educational modules through the WTH portal. Similarly, every month, participants will 
receive a text encouraging them to visit the WTH educational modules and to check their 
earnings. In contrast to Arm 1, they will receive their weekly performance results by text to 
their phone with tailored feedback, e.g. “Congratulations. You performed your cathing every 
time you needed to this week. Cathing regularly helps you prevent infections and keeps your 
kidneys healthy. Keep up the strong work!” or “You took your medicines on time 3 out of 4 
times this week. Taking medicines can be hard. Check out the WTH link on tips for improving 
your timing (with URL inserted). Hang in there!” In Arm 2, participants will not receive 
$2/week for adherence reporting during this 6-month intervention phase. Instead, they will 
receive a larger incentive of $10/week if they perform their desired treatment behavior at least 
85% of the time. Incentive notification will be texted to participants: “Congratulations. You 
earned $10 for your hard work being consistent with cathing/taking your medicine. Way to 
take care of yourself!” or “You just missed earning $10 this week. You were really close. If 

 
 
Protocol No. 16-013000 
 
  
 
 
 
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you remember just two more times next week, your hard work will pay off with $10 in your 
pocket and better health.” 
 
Text messages will be gain-framed, i.e. will focus on what the participant has accomplished 
vs. what he/she has not. The text message bank for U-REAACT will be adapted from Dr. Lisa 
Schwartz’ prior texting intervention with AYA cancer survivors (THRIVE: Texting Health 
Resources to Inform, Motivate and Engage) which has an established repository of over 120 
positively-framed motivational health messages.51  
 
Similarly to Arm 1, parents/legal guardians will have access to the same educational materials 
via their own WTH portals. Additionally, to mitigate the minimal risk of this study, 
parents/legal guardians will be notified if their child is excessively non-adherent. 
 
At the end of the intervention phase, participants and parents/legal guardians, again, will 
complete the baseline questionnaires. Participants who complete their surveys within 5 days 
will receive $20. Participants who complete their surveys within 6 – 10 days will receive $10. 
 
3.1.3 Follow-up Phase 
Six months after randomization, participants will receive a message that the main study 
intervention is ending but that we will continue to track their adherence reporting to 
understand the benefits of the study. At this time, all participants and parents/legal guardians 
will repeat the baseline questionnaires. Arm 1 will continue to receive reminders and report 
their daily adherence with mobile phone camera photography and earn $2/week for reporting, 
but they will no longer have access to their WTH portal, i.e. no visualization of dashboard or 
educational modules. Arm 2 will be told that incentives will be tapered. They will no longer 
be able to access the WTH portal. Arm 2 participants will get $2/week for reporting during 
this follow-up period and will continue to receive weekly adherence feedback texted to them. 
They will be eligible to receive an additional $10 for meeting their adherence target of ≥ 85% 
over a lengthened time interval. Specifically, they will receive feedback and $10 every 2 
weeks x 4 (if goal is met over average of preceding 2 weeks), then $10 every month x 2 (if 
average monthly goal is met) then no incentive (beyond the $2/week for reporting) for the last 
two months. At the end of the follow-up phase, participants and parents/legal guardians, again, 
will complete the baseline questionnaires.  Participants who complete their surveys within 5 
days will receive $20. Participants who complete their surveys within 6 – 10 days will receive 
$10. 
 
Parents/legal guardians will no longer have access to their WTH portal during this phase, but 
will still receive messages if their child is excessively non-adherent. 
 
3.1.4 Study Staff Involvement 
Beyond enrolling and helping set up WTH portals, coordinators and/or study staff will phone 
participants at the time of randomization, at the end of six months and end of follow-up period 
to answer any questions. Coordinators and/or study staff will also contact participants if they 
fail to report adherence for more than 3 days in a row to assess barriers, such as technical 

 
 
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issues, etc. The DCC research staff will pay participants monthly by uploading earnings to 
their Clin Cards. Research staff will confirm the participant has possession of his/her Clin 
Card prior to loading the card with the money earned 
 
3.2 Allocation to Treatment Groups and Blinding 
Subjects will be randomized to Arm 1 or Arm 2 via a computerized randomization scheme 
generated by WTH to assign participants to one of two arms, stratified by disease group (KT 
or SB), and age category (12-17 vs. 18-24). User written code in Stata 14.0 will utilize a block 
randomization scheme that, within each disease/age group stratum stratification, first 
randomly orders blocks of size 2 and 4 and then randomly orders subjects within blocks. Lead 
investigators at each site will be blinded to which Arm their participants are in. The research 
staff must know which participants are in which Arm in order to appropriately manage each 
participant.  
3.3 Study Duration, Enrollment and Number of Sites 
3.3.1 Duration of Study Participation 
The study duration per subject will be 12.5 months, with a 2-week run-in, 6-month 
intervention and 6-month follow-up. 
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 
The study will be conducted at CHOP, Boston Children’s Hospital, Children’s Healthcare of 
Atlanta, Seattle Children’s Hospital, Lurie’s Children of Chicago, and Children’s Mercy. 
CHOP will act as the DCC.  
We will recruit 3 cohorts. Cohort one and two are the KT and SB subjects, respectively. Cohort 
three is the parent/legal guardian(s) of those enrolled in cohort one and two. Recruitment will 
stop when 200 total subjects are recruited in both cohort one (KT) and cohort two (SB), 
respectively. It is expected that approximately 400 subjects will be enrolled between the two 
cohorts to produce 180 evaluable KT and 180 evaluable SB subjects. Approximately 50 KT 
and 50 SB participants will be recruited at each of the four centers. Recruitment for cohort 3 
will stop when 800 parent/legal guardian(s) are recruited. Recruitment of the parent 
population will be dependent upon the recruitment of cohorts one and two. Up-to 200 
parents/legal guardians may be recruited at each of the four centers.  
3.4 Study Population 
Subjects 12 to 24 years of age and their legal parent/guardian(s) will be recruited from the 
Nephrology, Urology and Spina Bifida clinics at CHOP, Boston Children’s Hospital, 
Children’s Healthcare of Atlanta, Seattle Children’s Hospital, Lurie’s Children of Chicago, 
and Children’s Mercy.   
3.4.1 Inclusion Criteria 
1) Males or females age 12-24 years.   
2) KT subjects must be greater than 3 months post-transplant.  
3) SB subjects must be able to perform CIC as part of their treatment.  

 
 
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4) Able to speak and read in English. 
5) Willing and able to provide informed assent or consent. 
6) Parental/guardian permission (informed consent) if appropriate. 
3.4.2 Exclusion Criteria 
1) Unwilling to participate. 
2) Unable to speak or read in English. 
3) Unable to provide informed assent or consent.  
4) Severe cognitive impairment, as reported by treating team in recruiting clinic.  
5) On dialysis 
6) Acquired post-transplant lymphoproliferative disease less than one year prior to 
enrollment 
7) Less than 3 months post-transplant. 
8) Unable to perform CIC.  
9) Prescribed Immunosuppressive medications once per day. 
10) Provider recommendations of CIC once per day  
 
Parents/legal guardians meet the inclusion criteria if their child is eligible for the study. 
Parents/legal guardians will be excluded if they meet one or more of items #1-4 of the above 
exclusion criteria. Subjects that do not meet all of the enrollment criteria may not be enrolled. 
If a subject’s parent is unwilling to participate, the subject may still enroll in the study. In this 
case, clinical information about the parent, such as household income and education level, 
will not be collected. Any violations of these criteria must be reported in accordance with IRB 
Policies and Procedures.  
4 
STUDY PROCEDURES  
4.1 Screening Visit 
Using the WTH web-based research portal, a research coordinator will help subjects and their 
parents/legal guardians open an account, electronically sign an informed consent and complete 
a baseline questionnaire. The baseline questionnaire will include the surveys listed in section 
5.2.1 Diagnostic Tests, Scales, Measures, etc. as well as a general demographics 
questionnaire. The coordinator will explain the WTH portal, and set-up text reminders with 
the participant’s input.  
4.1.1 Run-In Period 
During this two-week period, all participants will send a photo of their medicine or catheter 
in hand at time of treatment to the WTH phone number provided at enrollment. Participants 
will receive $20 (to be administered via Greenfire Clin Card), regardless of their adherence 
score, given in a lump sum at the end of the run-in period.  

 
 
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4.2 Study Treatment for Arm 1  
4.2.1 Intervention Phase 
Participants will receive daily text messages as reminders and continue to report real-time 
treatment adherence with photos. They will receive $2/week to encourage real-time adherence 
reporting. Pay is not contingent on meeting a target adherence score, but only on submitting 
at least one photo at time of treatment per week. In addition, participants will be able to log in 
to WTH to see their personal dashboard with a visual display of their weekly adherence 
performance and educational materials relevant to their disease group. Parents/legal guardians 
will have access to these same educational materials via their own WTH portals. Additionally, 
to mitigate the minimal risk of this study, parents/legal guardians will be notified if their child 
is excessively non-adherent. This portion of the study will last for 6 months. At the end of this 
phase, participants and parents/legal guardians will be asked to answer the baseline 
questionnaires again. Participants who complete their surveys within 5 days will receive $20. 
Participants who complete their surveys within 6 – 10 days will receive $10. 
 
4.2.2 Follow-Up Phase 
After 6 months, participants will receive a message that the main study intervention is ending. 
At this time, participants and parents/legal guardians, if applicable, will be prompted to 
complete the baseline questionnaires again. Arm 1 will continue to receive reminders and 
report their daily adherence with mobile phone camera photography and earn $2/week for 
reporting. Parents/legal guardians will continue to be notified if their child is excessively non-
adherent. Parents/legal guardians and participants will no longer have access to their WTH 
portal during this period. This portion of the study will last for 6 months. At study completion, 
participants and parents/legal guardians will be asked one final time to answer the baseline 
questionnaires. Participants who complete their surveys within 5 days will receive $20. 
Participants who complete their surveys within 6 – 10 days will receive $10. 
4.3 Study Treatment for Arm 2 
4.3.1 Intervention Phase 
Participants randomized to Arm 2 will also begin to receive daily text messages as reminders 
and report real-time treatment adherence with photos, and will have web access to the 
educational modules through the WTH portal. In contrast to Arm 1, they will receive their 
weekly performance results by text to their phone with tailored feedback. In Arm 2, 
participants will receive $10 per week for adherence reporting during this 6-month 
intervention phase if they perform their desired treatment behavior at least 85% of the time. 
Incentive notification will be texted to participants based on their adherence behavior. 
Parents/legal guardians will have access to these same educational materials via their own 
WTH portals. Additionally, to mitigate the minimal risk of this study, parents/legal guardians 
will be notified if their child is excessively non-adherent. This portion of the study will last 
for 6 months. At the end of this phase, participants and parents/legal guardians will be asked 
to answer the baseline questionnaires again. Participants who complete their surveys within 5 
days will receive $20. Participants who complete their surveys within 6 – 10 days will receive 
$10. 

 
 
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4.3.2 Follow-Up Phase 
After 6 months, participants will receive a message that the main study intervention is ending. 
At this time, participants and parents/legal guardians will be prompted to complete the 
baseline questionnaires again. Arm 2 will be told that incentives will be tapered. Parents/legal 
guardians and participants will no longer be able to access the WTH Portal. Arm 2 participants 
will get $2 per week for reporting during this follow-up period and will continue to receive 
weekly adherence feedback texted to them. Parents/legal guardians will continue to be notified 
if their child is excessively non-adherent. They will be eligible to receive an additional $10 
for meeting their adherence target of > 85% over a 2 week period x 4 (as opposed to one week 
during the intervention period). The incentive will then become $10 every month for two 
months (if the average monthly goal is met), and finally no incentive beyond the $2 per week 
for reporting. This portion of the study will last for 6 months. At study completion, participants 
and parents/legal guardians will be asked one final time to answer the baseline questionnaires. 
Participants who complete their surveys within 5 days will receive $20. Participants who 
complete their surveys within 6 – 10 days will receive $10. 
4.4 Study Staff Check-Ins 
Study staff will phone participants at the time of randomization, at the end of six months and 
end of follow-up period to answer any questions. Study staff will also contact participants if 
they fail to report adherence for more than 3 days in a row to assess barriers, such as technical 
issues, etc. 
4.5 Subject Completion/Withdrawal 
Study subjects may withdraw from the study at any time for any reason without prejudice to 
their care. If a participant who has been randomized chooses to withdraw, a study member 
will send them a link to the Exit Survey. If the participant completes the Exit Survey within 
five days of receiving the link, the participant will be paid $10 as a thank you for their time.  
5 
 STUDY EVALUATIONS AND MEASUREMENTS 
5.1 Screening and Monitoring Evaluations and Measurements 
5.1.1 Medical Record Review 
• Date of birth 
• Weight and height 
• Demographic data including age, race, gender, education level, insurance status, 
household income, possession of a 504/IEP plan, languages spoken at home, living 
arrangement and accessibility to care  
• Medical history, including reason for transplant, time since transplant, etiology of 
renal or hepatic disease, age at initial diagnosis, history and length of preceding 
dialysis, baseline GFR, transplant complications, and delayed graft function  
• Chart review in EPIC will be updated every 6 months from study entry for each 

 
 
Protocol No. 16-013000 
 
  
 
 
 
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subject. For kidney transplant recipients, chart review will include immunosuppressive 
drug levels, hospitalization events, rejection episodes, graft failure events, biopsies 
and serum creatinine, number of medications, number of pills and other clinically 
relevant data. For spina bifida subjects, chart review will include level of lesion, type 
of spina bifida, number of shunt surgeries, ambulation method, other co-morbidities, 
baseline bladder capacity and compliance, route of catheterization, history of urinary 
tract infection, number of medications, frequency of catheterization and other 
clinically relevant data.   
• No biopsies or any other medical procedures beyond standard of care will be done 
solely for this study. Study staff will review clinical biopsy results when chart reviews 
are completed. 
5.2 Efficacy Evaluations 
5.2.1 Diagnostic Tests, Scales, Measures, etc. 
All surveys will be administered and entered directly by and into the WTH portal. The KT 
and SB subjects will complete the same baseline executive function measure, perceived 
adherence barriers, and self-efficacy scale. Since few other forms have been validated in both 
disease groups, KT and SB participants will complete different forms measuring healthcare 
responsibility & disease knowledge. The forms parents/legal guardians will complete are 
indicated below. Surveys will be completed at enrollment, end of intervention and study 
completion.  
Both KT and SB subjects will complete: 
• Behavior Rating Inventory of Executive Function – Adult (BRIEF-A) for participants 
over 18 & parents will complete BRIEF2-Parent (BRIEF-P) if the subject is <18 years 
of age 
• Adolescent Medication Barrier Scale (AMBS) & parents will complete Parent 
Medication Barrier Scale (PMBS)  
• Self-Efficacy for Managing Chronic Disease 6-Item Scale  
• Way to Health Exit Survey – to be completed at withdrawal or study completion  
Only KT subjects will complete: 
• Allocation of Treatment Responsibility (ATR) & parents will complete the Allocation 
of Treatment Responsibility – Caregiver (ATR-C)  
• Heart Transplant Knowledge questionnaire (adapted for KT) 
Only SB subjects will complete: 
• Sharing of Spina Bifida Management Responsibilities - Child (SOSBMR-C) parents 

 
 
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15
will complete the Sharing of Spina Bifida Management Responsibilities – Parent 
(SOSBMR-P)  
• Knowledge of Spina Bifida (KOSB) 
• SB Barriers and Cathing Barriers Measure 
Item Measured 
Forms for KT Group 
Forms for SB Group 
Executive Function 
BRIEF-Adult; BRIEF2-Parent BRIEF-Adult; BRIEF2-Parent 
Perceived Adherence 
Barriers 
AMBS/PMBS 
SB Barriers and Cathing 
Barriers Measure 
Self-Efficacy 
Self-Efficacy For Managing 
Chronic Disease 6-item Scale 
Self-Efficacy For Managing 
Chronic Disease 6-item Scale 
Treatment 
Responsibility 
ATR; ATR-Caregiver 
SOSBMR-Child; SOSBMR-
Parent 
Knowledge of Condition 
Assessment 
Heart Transplant Knowledge 
Questionnaire (adapted for 
KT) 
KOSB 
Efficacy of Way to 
Health Portal 
Way to Health Exit Survey; 
Way to Health Exit Survey - 
Parent 
Way to Health Exit Survey; 
Way to Health Exit Survey - 
Parent 
 
5.2.2 Survey Descriptions 
• Adolescent/Parent Medication Barriers Scale (AMBS and PMBS) is a 17-item scale 
that examines perceived barriers to medication adherence, in 3 categories: Disease 
Frustration/Adolescent Issues, Ingestion Issues, and Regimen Adaptation/Cognitive 
Issues. AYA answer questions on a Likert scale, from “strongly disagree” to “strongly 
agree,” with higher scores representing a greater amount of perceived barriers to 
treatment. For KT subjects < 18 years of age, parents will complete a parallel parent-
specific survey (PMBS). The PMBS measures the same 3 factors, plus a Parent 
Reminder item. Results of these surveys will be recorded in the WTH study database. 
• Allocation of Treatment Responsibility (ATR and ATR-Caregiver): all participants 
will complete the ATR; their parents will complete the ATR-Caregiver. The ATR 
questionnaire helps to identify who is responsible for the medication taking routine 
and how those responsibilities are divided between the subject and their parent/ 
caregiver(s). The ATR is a 3 part questionnaire: Part 1: General Information on 
treatment responsibility, Part 2: Report of adolescent subject’s treatment 

 
 
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responsibility, Part 3: Report of parent/ caregiver’s treatment responsibility. The ATR-
Caregiver has the same 3 parts.  
• Behavior Rating Inventory of Executive Function (BRIEF) is a validated measure 
designed to assess executive function in daily life. The BRIEF2-P (Parent version) is 
a 63-item validated measure that documents the parent’s perception of their child’s 
problem-solving and behavioral functioning. This form will be administered to parents 
of participants under18 years of age. The BRIEF-A (Adult version) is a 75-item 
validated, self-report measure for participants 18 or older. Both study forms take 
approximately 10-15 minutes to complete and measure different aspects of executive 
function, such as inhibition, self-monitoring, organization, planning, and emotional 
control. The BRIEF is scored against population normative data and reported as an 
overall summary score with subscales and two broad indexes (behavioral regulation 
and metacognition). Both versions of the BRIEF have high reliability, validity and 
clinical utility across diverse disease populations and age groups. 
• Heart Transplant Knowledge Questionnaire (adapted for KT) is a 20-question survey 
used to assess the participants understanding of their medication, transplant and 
healthcare plan. The survey resembles a quiz, with each multiple choice and true/false 
question having only one correct answer.   
• Knowledge of Spina Bifida (KOSB) is an 18-item survey assessed as a summary 
score.57 Higher scores indicate greater knowledge. 
• Self-Efficacy for Managing Chronic Disease 6-Item Scale is a Likert-scale survey that 
measures the following six domains of self-efficacy: (1) fatigue, (2) physical 
discomfort, (3) emotional distress, (4) symptoms or health problems, (5) health-related 
self-management tasks and (6) taking medicines.58 Each item is answered on a 10-
point Likert scale, with higher scores representing greater healthcare self-efficacy. 
• Sharing of Spina Bifida Management Responsibilities – Child and – Parent 
(SOSBMR-C and -P) measure perceived responsibility for health-related tasks, asking 
who took responsibility, child, parent or equal, for 34 health-related tasks pertaining 
to SB.  
• Spina Bifida Barriers and Cathing Barriers Measures are two barriers measures 
combined into one survey for ease of administration. The first, SB Barriers, was used 
in a prior study by Dr. Alexandra Psihogios, a member of the DCC study staff. This 
measure was adapted from a validated diabetes barriers scale and asks subjects about 
their perceived barriers to proper care. The Cathing Barriers Measure is not formally 
validated but showed content validity in a recent study.59 The survey asks subjects to 
indicate the items that make cathing difficult and then to rank the top three items out 
of those indicated. To our knowledge, there are no validated measures that address 
perceived barriers to cathing for the SB population. 
• Way to Health Exit Survey measures the efficacy of the Way to Health portal as a tool 
for the research and engagement of AYA with a kidney transplant of spina bifida in 

 
 
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their health care management. This measure was developed by the study research 
team; it asks about the participants’ attitude towards the portal, the study and asks 
about the effectiveness of the portal.  
6 
STATISTICAL CONSIDERATIONS   
6.1 Primary Endpoint 
The primary endpoint for this pilot clinical trial is to compare the efficacy of two 6-month 
mhealth-based interventions to promote treatment adherence among AYA with KT or SB. 
The independent variable in the analyses for Aim 1 is exposure to feedback + incentive 
(intervention, Arm 2). The dependent variable, or primary outcome measure, is: change in 
the proportion of weeks with adherence behavior ≥ 85% expected between baseline (run-in 
period) and intervention period. Weekly adherence proportions will be calculated by 
observing the number of non-missed/late treatment episodes over the total number of episodes 
in that week.  
 
The outcome will then be the proportion of weeks with treatment adherence ≥ 85%. 
Participants who do not submit the correct number of pictures within the prescribed window 
of their expected time due for treatment will be counted as nonadherent for that episode of 
med taking/cathing. Over the study period, changes in weekly timing adherence will be 
assessed as a repeated measure over time. In secondary analysis, we will examine variability 
in inter-dose intervals (based on time-stamping of photos) to account for doses that are taken 
beyond the time window. 
 
6.2 Secondary Endpoints 
The secondary endpoint for SB subjects is change in bladder wall compliance as assessed by 
urodynamic studies (UDS) at study entry and study end. 
We expect that SB subjects who perform CIC as prescribed will experience either no change 
or improvement in bladder compliance compared with those who do not improve their CIC 
adherence behavior. We expect nonadherence with CIC to result in either no change or 
worsening from baseline.  
For KT subjects, the secondary endpoint is change in CV of immunosuppressive drug levels 
(tacrolimus or sirolimus) between the baseline (run-in) and intervention period. CV of 
immunosuppressive drug levels will be compared with the real-time adherence measures of 
mobile phone camera reporting.  
Other important outcomes examined in exploratory analysis include rejection, de novo donor 
specific antibody accumulation, graft loss and death.  
6.3 Tertiary Endpoints 
The tertiary endpoint is to identify psychosocial correlates of adherence changes in AYA with 
KT and SB. We hypothesize that improved treatment adherence from baseline to intervention 

 
 
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end will be mediated by increases in self-efficacy and healthcare responsibility and declines 
in perceived barriers, but will not be related to knowledge gained. We also hypothesize that 
we will observe greater changes in self-efficacy in Arm 2 vs. Arm 1 because of the specifically 
targeted text messages that emphasize people’s progress and ability to perform difficult 
behavior. For this Aim, all participants will complete the baseline survey measures of self-
efficacy, healthcare responsibility, perceived barriers and knowledge again at the end of the 
6-month intervention via WTH. The independent variables in the analyses for Aim 3 are: 1) 
change in self-efficacy score 2) change in healthcare responsibility score 3) change in 
perceived barriers and 4) change in knowledge score from baseline to end of intervention. The 
dependent variable, or primary outcome measure, is: change in the proportion of weeks with 
adherence behavior performance ≥ 85% prescribed/expected between baseline (run-in 
period) and intervention period. A secondary analysis will examine usage of the educational 
modules viewed in the WTH portal. Usage will be tracked as yes/no and time spent. We 
hypothesize that increased usage will associate with increased knowledge but will have no 
effect on increased treatment adherence. Prior research supports the hypothesis that increased 
knowledge is not sufficient to promote positive health behavior. 
6.4 Quaternary Endpoints 
The quaternary objective is to evaluate differences in comorbidities and demographic data of 
lost to follow up participants to that of those who are complete the study intervention. We 
hypothesize participants with comorbid or more severe conditions may be less likely to 
complete or participate in the study. 
6.5 Statistical Methods 
Clinical and demographic variables will be compared with chi-square or two-sample t-tests 
for parametric and Fisher’s exact or Wilcoxon rank-sum tests for non-parametric data. 
Treatment groups will be compared with similar analyses to confirm equity in randomization. 
We will compare change over time in % adherence between arms by fitting quasi-least squares 
(QLS) and generalized estimating equation (GEE) longitudinal models. The QLS/GEE 
models include a regression model for the primary outcome variable, in addition to a separate 
model for the correlation amongst the repeated measures on each subject. The AR (1) 
correlation structure is plausible because it forces a decline between measures with increasing 
separation in time; however, we will assess the sensitivity of results to choice of structure. In 
addition, the models will include treatment group and a time by treatment group interaction. 
If the interaction term differs significantly from zero, this will indicate that the change over 
time differs significantly between treatment groups. All analyses will follow the intention-to-
treat principle. We will analyze the results for each disease group (SB, KT) separately, 
although the overall analytical models are the same. 
Analysis for Aim 1 and Aim 2 will utilize GEE/QLS models to compare the change over time 
in the outcome between arms. 
 
For Aim 3, Pearson’s or Spearman’s Correlations will be calculated to observe the association 
between outcome and each independent variable. 
The statistical analysis will follow the intention-to-treat principle. 

 
 
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6.6 Sample Size and Power 
The disease groups (KT or SB) will be analyzed separately in the primary analysis. We assume 
180 KT and 180 SB recipients will complete the study, allowing for 10% drop-outs. With 90 
participants per arm per disease group, setting alpha at 0.05, we will have >90% power to 
detect a medium effect size of 0.5 in timing change in proportion of timing adherence, using 
a two group t-test (based on TAKE-IT). Based on preliminary data from TAKE IT and 
published studies, it is reasonable to expect an average of 8% improvement in timing 
adherence when a behavioral economics model with financial incentives is applied.53,57,104 An 
effect size of 0.50 would be observed if the difference in average improvement was 8% 
between groups, while the standard deviation of post minus pre improvement was 16. With 
90 subjects per arm, the detectable effect size is also 0.50 for Aim 2. For Aim 3, a 0.050 two-
sided Fisher's z test of the null hypothesis that the Pearson correlation coefficient is 0 will 
have 82% power to detect a correlation of 0.300 when the sample size is 90.  
 
7 
SAFETY MANAGEMENT 
7.1 Clinical Adverse Events 
Clinical adverse events (AEs) will be monitored throughout the study. 
7.2 Adverse Event Reporting 
Since the study procedures are not greater than minimal risk, SAEs are not expected. If any 
unanticipated problems related to the research involving risks to subjects or others happen 
during the course of this study (including SAEs) these will be reported to the IRB in 
accordance with CHOP IRB SOP 408: Unanticipated Problems Involving Risks to Subjects. 
AEs that are not serious but that are notable and could involve risks to subjects will be 
summarized in narrative or other format and submitted to the IRB at the time of continuing 
review. The Data Safety Management Board (DSMB) will review all adverse events.  
This study supports and encourages bi-directional messaging. Because of this capability, study 
participants may reveal sensitive and serious thoughts or feelings, such as the desire to kill 
oneself, the occurrence of a serious medical incident requiring immediate medical attention 
Table 3. Anticipated Participant Enrollment 
 
 
 
 
 
Year 1 
Year2 
Year 3 
Year 4 * 
Expected Participant Recruitment (Cohort 1 
and 2) 
100 
100 
100 
100 
Expected Parent Recruitment (Cohort 3) 
200 
200 
200 
200 
Anticipated drop-outs (10%) 
30 
30 
30 
30 
Anticipated cumulative n by end of study year 270 
540 
810 
1080 

 
 
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and other possibilities. While we expect events like this to be rare, we have implemented the 
following protocol to ensure these events are handled efficiently and effectively.  
1. Study personnel will review participant-derived messages daily. 
2. If a participant reaches out without the portal prompting him/her, an incident report is 
generated and sent to the site’s research coordinator and the team project managers 
(DCC personnel).  
3. Relying site coordinators are responsible for monitoring and addressing their site’s 
incident reports and messages between normal working hours (0800-1700) Mondays 
through Fridays. The DCC is responsible for monitoring and addressing any incident 
reports and messages at all other times outside of the window mentioned. 
4. If the content of the message (whether sent when prompted, reviewed in step 1, or sent 
when not prompted) indicates a serious adverse event, the coordinator who discovered 
the message will first contact the DCC PI, Dr. Sandra Amaral. 
5. Dr. Amaral will decide how to proceed. Options include, but are not limited to, 
contacting the local treatment team, the team psychologist or an emergency response 
team.   
6. If the coordinator cannot reach Dr. Amaral, the coordinator will contact the DCC 
psychologist, Dr. Lisa Schwartz.   
A list of emergency contacts, including national hotlines for suicide prevention, child abuse 
support and more, is available to all study team members, and is attached to the eIRB 
application in section 12. Study personnel are instructed to have a low-threshold for contacting 
emergency response teams.   
7.3 Incidental Findings 
In rare cases, during the course of study procedures a participant may be found to demonstrate 
clinically significant incidental findings, such as signs of depression or domestic abuse. 
Members of the study team may consult with the psychologist or appropriate clinician to 
determine whether such a finding has enough health importance to the research participant to 
mandate or permit disclosure. At the study team’s discretion, a qualified investigator or 
facilitator will inform the participant and/or the participant’s family of the incidental finding 
at the next study visit. If the incidental finding is discovered at the last visit, every effort will 
be made to contact the participant by phone. The participant and/or the participant’s family 
will be referred to an appropriate clinician or resource for follow-up when deemed necessary 
by the study team. 
8 
 STUDY ADMINISTRATION 
8.1 Treatment Assignment Methods 
8.1.1 Randomization  
Subjects will be randomized to either Arm 1 or Arm 2, stratified by disease group (KT or SB) 
and age category (12-17 vs. 18-24) via user written code in Stata 14.0. The code will utilize a 
block randomization scheme that, within each disease/age group stratum stratification, first 
randomly orders blocks of size 2 and 4 then randomly orders subjects within blocks. 

 
 
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8.1.2 Blinding 
Due to the nature of the study, it is not possible to blind subjects to their treatment assignment 
once they are assigned. Lead investigators at each site will be blinded to which Arm their 
participants are in. The research staff must know which participants are in which Arm in order 
to appropriately manage each participant.  
8.2 Data Collection and Management 
Each study subject will be assigned a study ID at the time of enrollment, which will serve as 
the means of protecting personal health information during data transfers and storage.   
EPIC medical record will be entered into REDCap and study questionnaire data will be 
entered into the WTH platform. Coded electronic adherence data (i.e. picture messages) will 
be downloaded from the web-based mobile messaging service, Twilio, directly to the WTH 
Platform via secure data transfer. An additional data transfer will be used to extract a coded 
analytic data set to the CHOP server for analysis.  
Way to Health Platform: 
All personal information that the participant is asked to provide will be collected via WTH. 
WTH collects subjects’ names, dates of birth, addresses, email addresses, and phone numbers. 
They also request the name and phone number of an alternate contact. To assure that 
participant confidentiality is preserved, individual identifiers are stored in a single password 
protected system that is accessible only to study research, analysis and IT staff. An 
investigator or statistician who logs in will be able to access only coded data. The WTH 
administrative group and research coordinators responsible for contacting participants for 
follow-up study visits or responding to questions about the study are able to view participant 
names and contact information.   
The WTH web development team and Project Director currently have administrative access 
to PHI. All of these personnel will have completed Human Subjects Protection and HIPAA 
privacy training. The system automatically generates logs of all data queries which can be 
reviewed by research staff to ensure that no unauthorized persons have gained access to 
identifiable information. This system is hosted on site at The University of Pennsylvania 
(UPenn) and is protected by a secure firewall and several layers of operational security. Once 
a participant has been entered into this system, they are given a unique study identification 
number (ID). Any datasets and computer files that leave the firewall are stripped of all 
identifiers and individuals are referred to by their study ID. The study ID is also used on all 
analytical files. 
The Penn Medicine Academic Computing Services (PMACS) is the hub for the hardware and 
database infrastructure that supports the project and the WTH web portal is built on this 
infrastructure. The data collected for WTH based studies is stored in My Structured Query 
Language databases on a PMACS-operated blade server environment devoted specifically to 
WTH. The data center is housed in Information Systems and Computing at 3401 Walnut 
Street. All data are stored in a single relational database, allowing researchers to correct 
mistakes. Every Structured Query Language (SQL) transaction, including accessing and 
changing data, is logged for auditing purposes. Data are entered into the database through 

 
 
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several different mechanisms. Participants enter their own personal information and respond 
to surveys through a PHP-based web interface. Researchers have a separate interface that 
allows them to manually enter data if needed. Data from biometric/monitoring devices are 
uploaded automatically, this includes data from mobile phones such as picture or text 
messaging. Datasets are blinded of all personally identifiable information when exported for 
analysis. The web application automatically removes all identifiers when a researcher requests 
an analytic dataset. The only people with access to identifiable participant information are 
pre-specified Research Coordinators responsible for contacting participants for follow-up. 
Personal information and research data will be stored in separate SQL tables and will be linked 
by a computer-generated ID number. Additionally, any information that leaves this system to 
communicate with third party data sources (biometrics devices, survey software, etc.) is 
stripped of any identifiers and transmitted in encrypted format. The same unique study ID is 
used to link these outside data to the participants. 
The WTH Research Data Center staff is responsible for preventing unauthorized access to the 
trial participant tracking system database. The secure servers are located in a specially 
designed, highly secured facility at UPenn with dedicated uninterrupted power supply and 
strictly limited access. The study will utilize a client-server deployed Data Management 
System rather than a 'Store and Forward' database configuration, obviating research site 
database security concerns. Confidential participant information will be entered into the 
database. Thereafter, confidential information will be made available to authorized users only 
as specifically needed. No one can gain access to an individual SQL database table unless 
explicitly granted a user ID, password, and specific access. Even those with user names and 
passwords cannot gain access to the tables that contain the identifying participant information. 
No results will be reported in a personally identifiable manner. All tracking system data will 
be password-protected with several levels of protection. The first will allow access to the 
operating system of the computer. The second will allow access to the basic menus of the 
integrated system; within certain menu options, such as database browsing, a third password 
will be required. WTH’s team’s prior research employing similar precautions has 
demonstrated that these techniques are very successful in assuring the protection of subjects. 
The same procedure used for the analysis of automated data sources to ensure protection of 
participant information will be used for the survey data, in that subject identifiers will be used 
only for linkage purposes or to contact subjects. The study identification number, and not 
other identifying information, will be used on all data collection instruments.  
Each investigator and staff member involved in the proposed study will sign and adhere to a 
Standard Operating Procedure for managing participant data through the WTH platform and 
has participated in required IRB/HIPAA compliance training. We will also continue to make 
use of password protection programs for all computerized records. In no instances will 
identifying information be publicly disclosed. Prior to conducting any analyses, all identifiers 
(e.g., names, medical record numbers, birth dates, etc.) will be removed. Results from this part 
of the investigation will be reported in aggregate. 
1) Questionnaire Data: 

 
 
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This study will use the online survey tool Qualtrics to collect answers to survey questions 
from participants. The DCC research staff will build the surveys in Qualtrics and connect them 
to the WTH platform. Then participants will enter survey answers directly on their personal, 
password-protected WTH dashboard. Study staff members will review the survey content to 
ensure that no questions in any of the surveys ask for participant identifiers. To ensure no 
participant identifiable data is stored by Qualtrics, randomly generated 64 bit identifiers are 
used to link responses in Qualtrics to study events in the system. No PHI will ever be stored 
by this application in Qualtrics. 
2) Electronic Adherence Data: 
Following enrollment and completion of the participant’s WTH profile, a research coordinator 
will help connect the participant’s mobile device to the study’s Twilio account. Twilio is a 
third party provider that supplies a unique mobile number with bidirectional, automatable 
SMS and picture messaging capabilities. If the participants do not have a phone with picture-
taking capabilities, researchers will provide one. Data from Twilio will be uploaded 
automatically to the WTH platform. Once uploaded to WTH, the cellular transmission will 
have no participant-identifying information and after it is received in the platform, the content 
will be deleted from the Twilio servers. No IP addresses are collected during this information 
transfer. The coded daily adherence data will then be available to the study team on the secure, 
password-protected WTH platform.  
The WTH portal applies security and privacy requirements generated by the HIPAA Security 
Rule and subsequently the HITECH requirements.  Currently, the data is encrypted at rest and 
in motion in accordance with these laws and is certified by FDA.   
3) EPIC Medical Record Data: 
Study staff will extract relevant data (see section 5.1.1 Medical Record Review) from EPIC 
into REDCap via individual chart review. Individual subject data will be labeled with the 
subject’s study ID upon population of REDCap for subsequent storage and data analysis. 
Medical Record Review data will be managed and stored using the research-focused 
electronic web-based data capture system REDCap.  
• Data listed in section 5.1.1 will be entered directly into REDCap. For exact data, 
please see the attached Medical Record Review survey (section 12.02 of our 
application) 
• Research staff from relying sites will be on-boarded as external collaborators under 
the umbrella of Data Access Groups. These coordinators will only have access to 
their site’s participant data. Research staff from the DCC will have access to all 
sites’ data.  
• Research staff at all sites will be required to obtain a Medical Authorization form to 
release/obtain patient information from the local institution to obtain medical record 
data of participant’s transitioning to another institution for medical care during the 
study period. Method of receiving medical records data for participant’s that consent 
to release of information will be determined by the institution’s policy for sharing 
data.  

 
 
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• The following de-identification options will be used, when necessary, when 
exporting data for analysis: removing known identifier fields, hashing of record 
names, removing invalidated Text fields, Notes fields, or date fields and date 
shifting. 
Data backup is performed nightly via a dedicated backup system.  The backup environment 
is maintained by a dedicated staff using dedicated resources.  Access to the backup 
environment is restricted to Research Information Systems staff. 
Some medical record data will be stored in WTH as well. This data includes the 
participant’s date of birth, address, email address and phone number.  
Data Transfer Description 
1.) Twilio to Way to Health platform: every day, deidentifed study adherence data will be 
downloaded from Twilio to the WTH platform. WTH code automates this transfer of data. 
Once data are received in the platform, the content will be deleted from the Twilio servers. 
2.) Way to Health to Site Server: Coded data from the study visits, including initial survey, 
follow-up surveys, and adherence data will be converted to a CSV file and uploaded onto the 
CHOP server to a dedicated research folder on the study PI’s virtual desktop (shared drive). 
No PHI will be involved in this transfer, only the subject’s study ID.   
All transferred and created files will be stored in a password-protected folder available only 
to study staff in the lead investigator’s CHOP virtual desktop. All identifiers will be deleted 
following publication of the study results. 
Study Recruitment Tracking File: 
This password-protected Microsoft Excel file, saved on the PI’s virtual desktop (shared drive) 
will include participant-identifying information necessary for registration, enrollment, and 
follow-up. Following enrollment, this document will be used to maintain a log of enrolled 
subjects. For families who are not enrolled, subject-identifying information will be destroyed. 
A non-identifiable list of subjects that were not enrolled will be retained for the purpose of 
calculating response rate.  
Consent Forms: 
Electronic copies of the consent forms will be stored in a password-protected folder on the 
PI’s virtual desktop (shared drive). Participants will have access to the consent form 
throughout the study, via their WTH dashboard. If a participant turns 18 during the study, they 
will be re-consented by signing an electronic form through the WTH platform.  
Anonymization: 
Data will be extracted from the secure WTH platform for the purpose of data analysis. Any 
datasets and computer files that leave the WTH firewall will be stripped of all identifiers and 
individuals will be referred to by their study ID. The study ID will also be used on all analytical 
files. 

 
 
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8.3 Confidentiality  
Access to the systems used for this project, including the WTH database, will be limited to 
staff who meet all relevant training requirements and are assigned to (or support) this project. 
Security procedures will follow the CHOP Information System Security Plan and in 
accordance with the National Institute of Standards and Technology Special Publication 
guidelines. All staff will have completed the Human Subjects Protection Training.  
Electronic adherence monitoring data associated with the mobile application will be 
maintained by WTH, Inc. WTH has designed their database to comply with HIPAA 
regulations. Survey responses will also be stored on the WTH platform. The site is HIPAA 
compliant. The data are maintained on secure servers that are password-protected. Please see 
Section 8.2 for measures taken to assure confidentiality.  
All results will be kept confidential and separate from the medical record. WTH will assign a 
study identification number to each subject, and all data will be coded under this number. The 
master list of subject names and identification numbers will be stored in a password protected 
excel file on a password protected computer. Only the study PI and study staff will have access 
to this excel file and password. Only the PI and assistant(s) directly involved in the research 
project will have access to the survey data.  
No identifiable data will be used for future study without first obtaining IRB approval. The 
master list, linking PHI to study ID numbers, will be destroyed six years after data analysis is 
complete, in compliance with CHOP’s data retention plan policy (A-3-9). Way to Health 
permissions will be adjusted so no PHI will be viewable by study staff.. 
8.4 Regulatory and Ethical Considerations 
8.4.1 Data and Safety Monitoring Plan 
A DSMB will be convened as needed, at least once annually, to ensure participant safety and 
study integrity. This board will consist of 4 faculty members, Drs. Nadia Downshen, Laura 
Mee, Jodie Smith and biostatistician Hauquin Zhoa, who are not directly involved in this 
research study. Specifically, at least one member will be a psychologist (Dr. Laura Mee). The 
DSMB will routinely assess issues of data quality, study fidelity and conduct, and adverse 
events. In the unlikely event of an adverse outcome associated with the study protocol, it will 
be immediately reported by investigators to the DSMB, the institutional IRBs and to the NIH, 
as appropriate. Any SAEs will be reported immediately to the principal investigator and the 
DSMB. At which time, a conference call will be set up for DSMB members to assess the event 
and make recommendations of action. The DSMB will also review interim and final data 
results to ensure no unanticipated harm (in terms of adherence behavior) occurred in either 
the intervention or comparison group. The DSMB will be apprised of study progress by email 
at a minimum of every 6 months. 
8.4.2 Risk Assessment  
There are no greater than minimal risks to subjects of this study. This is a randomized phase 
II clinical trial that will use participant clinical data obtained as part of routine medical care. 
Subjects in this study will not receive any additional medical procedures, such as biopsies or 

 
 
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lab work, beyond standard of care. Clinical data will be captured from the medical record 
database. This database is password protected and privilege for access is limited.  
Subjects may decline to answer any question on any survey for any reason.  
8.4.3 Potential Benefits of Trial Participation 
Nonadherence, in both KT and SB populations, has grave consequences, including graft loss 
and dialysis for KT patients and kidney damage and failure for SB patients. Participants may 
benefit directly from this study by experiencing improved adherence and increased self-
efficacy. Information gained from this study will help to identify whether this type of 
intervention is feasible and potentially effective. Thus, subjects enrolled in this study may 
provide indirect benefit to others by helping to set a path toward establishing evidence-based, 
effective interventions that impact longitudinal adolescent nonadherence and allograft/spina 
bifida outcomes.  
8.4.4 Risk-Benefit Assessment 
In relation to the potential benefit of this study, the risks of this study are small. Coordinators 
will closely supervise participants’ adherence and parents/legal guardians will also be notified 
if adherence behavior becomes erratic to minimize the risk further. 
8.5 Recruitment Strategy 
Eligible subjects will be identified by screening the medical records of patients in the 
outpatient Nephrology, Urology and Spina Bifida clinics of the four participating sites. A 
member of the research team will ask the clinician’s permission to approach eligible 
subjects in person or by telephone and offer information about the study. Where 
appropriate, subjects may be consented by phone by the study coordinator and be 
prompted to sign the electronic consent. Brochures with information about the study 
including inclusion criteria, study procedures and the contact information for study 
personnel will be available in clinic. Furthermore, the study staff may show an eligible 
patient the Welcome to U-REAACT video in clinic. Each site may use this video to post 
on media sources such as Nephrology and Urology departmental electronic newsletters, 
on their department website, or on their department social media page to teach patients 
about the study. When posting this link, the following description will be provided: U-
REAACT uses text reminders, positive messaging and rewards to help keep teens with 
kidney transplants and spina bifida healthy. Contact [insert contact information here] to 
ask if you may be eligible for this research study! 
 
8.6 Informed Consent/Assent and HIPAA Authorization 
Those who choose to enroll in this study will be required to read a thorough description of the 
study objectives and methods. A member of the study staff will present the study consent form 
(electronically or hard copy) to each participant and parent/legal guardian and address any 
questions or concerns at the time of consent. Subjects less than 18 years of age will be required 
to provide verbal and written/electronic assent and also to obtain written/electronic parental 
consent. Subjects over 18 years of age will be required to provide written consent for 

 
 
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themselves. Subjects who consented or received parental consent may participate without their 
parent/legal guardians enrolling in the study. Parents/legal guardians of all subjects will be 
required to provide written consent for themselves to participate in this study. The IRB has 
waived consent and HIPAA authorization for the child’s absent parent/legal guardian in the 
case that both parents/legal guardians are not present at time of enrollment. The waivers will 
occur for the purpose of collecting demographic information about the absent parent/legal 
guardian, such as income and education level. If both parents/legal guardians are present then 
both will be consented. Parents/legal guardians of eligible subjects may not participate if their 
child chose not to enroll in this study. It will be clearly stated, both verbally and within the 
text of the written/electronic consent, that participation in the study is voluntary and the 
decision to participate or decline participation will have no bearing on the medical care of the 
subject. Prospective subjects may take a paper consent form home to consider their interest in 
the study. No study procedures will take place prior to receiving a signed consent form. If the 
participant turns 18 years of age during the study, the subject will be prompted to re-consent 
by the Way to Health portal on or immediately after his/her 18th birthday and a new consent 
will be available to the participant via a direct URL and via his/her personal portal dashboard. 
The study team will be notified via text or email to call the participant to discuss the consenting 
process again and answer any questions. 
8.7 Payment to Subjects/Families 
Participants with a kidney transplant or the spina bifida diagnosis will be administered a 
Greenfire ClinCard at the time of enrollment. All compensation to the participant will be done 
electronically and participants will be able to access their funds once their card is activated by 
the DCC. All payments and prizes will be given to the adolescent or young adult. Parents will 
not be compensated. In the paragraphs below, the term participant refers to the AYA. 
Participants will receive a lump sum of $20 at the end of the 2-week run-in interval if they 
have sent at least one photo during this time. After the run-in period, all participants will be 
paid monthly dependent on their participation. Participants will receive a monthly text 
message, sent via WTH or the Greenphire website, prompting them to check their money 
earned on the WTH portal.  
Participants randomized to Arm 1 will receive $2/week throughout the entirety of the 6-month 
intervention period and the 6-month follow-up period to encourage real-time adherence 
reporting. Pay is not contingent on meeting a target adherence score, but only on submitting 
at least one photo at time of treatment per week. 
Participants randomized to Arm 2 will receive a larger incentive of $10/week if they perform 
their desired treatment behavior at least 85% of the time. During the follow-up period, Arm 2 
participants will get $2 per week for reporting. They will be eligible to receive an additional 
$10 for meeting their adherence target of > 85% over a 2 week period (as opposed to one week 
during the intervention period). The incentive will then become $10 every month (if the 
average monthly goal is met), and finally no incentive beyond the $2 per week for reporting. 
Participants in both arms who complete surveys at baseline, post intervention and post follow-
up within 5 days of administration will receive $20 (per survey set). Participants who complete 
surveys within 6 – 10 days of administration will receive $10 (per survey set). Participants 

 
 
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with partially complete surveys, will not be eligible to receive survey compensation for the 
data collection time point.  The DCC study staff will monitor taking behaviors and reports 
generated by the WTH platform to discern the amount of money owed to the participants 
every month. The amount owed will then be uploaded to each participant’s ClinCard. To 
ensure participants are still in possession of study payment cards, study staff will contact 
participants at time of payment before allocating funds to the cards.  
Furthermore, after subjects are consented and enrolled, they may earn small tokens of 
appreciation during the study to thank them for their continued participation. These tokens 
will be valued at ≤ $10 per item and may include such items as cell phone/smart phone covers, 
ear buds or water bottles. Subjects only be informed about the potential to receive such tokens 
for the completion of baseline surveys. They will not be informed about the potential to 
receive such tokens for the completion of future surveys nor will any tokens be provided prior 
to the consent process so as to not coerce subjects in any way. Subjects can earn these tokens 
by accumulating prize points. Prize points are administered when participants complete their 
intervention and follow-up surveys in a timely manner. 20 points/survey are earned for 
completing a survey on the day it is administered. Prize points decrease by 5 points/survey 
per day uncompleted until the potential to earn points is zero. Participants can earn up to 220 
points. These points are redeemable for the aforementioned tokens, with 100 points 
approximately equivalent to a $10 item. 
If a participant chooses to withdraw from the study, they will receive a text through the Way 
to Health portal thanking them for their participation and asking them for their feedback with 
a link to the exit survey. They may earn a $10 payment to their ClinCard if they choose to 
complete this survey within five days, as to mimic the compensation they would have received 
for completing this survey at the end of the study. All participants will have the option to 
complete this survey; participants who complete the study may earn prize points for the exit 
survey, along with their other follow-up surveys.  
9 
INTENTION FOR PUBLICATION 
The research staff intends to submit a minimum of two manuscripts for publication in peer-
reviewed journals. Additionally, throughout the duration of the study, research staff will 
submit abstracts and posters to present at conferences hosted by organizations such as the 
American Society of Nephrology, the Eastern Society of Pediatric Research, the American 
Transplant Conference and more. 
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