Positive Airway Pressure for the Treatment of the Obstructive Sleep Apnea Syndrome in Children With Down Syndrome (Stage 1)
Phase: NA
Conditions: Down Syndrome, Obstructive Sleep Apnea
Sponsor: Children's Hospital of Philadelphia

 
Observational Template: May 28, 2014 
 
Title: 
Investigating the experience of living with Down syndrome and 
obstructive sleep apnea syndrome 
Short Title 
DS and OSAS 
Sponsor: 
Children’s Hospital of Philadelphia 
eIRB Number 
 
Protocol Date: 
August 2, 2019 
Amendment 1 Date: September 23, 2019 
Amendment 4 Date:  
Amendment 2 Date:  February 20, 2020 
Amendment 5 Date: 
Amendment 3 Date: 
Amendment 6 Date: 
 
Ignacio E. Tapia, MD, MS 
3501 Civic Center Boulevard, CTRB office 11403 
Philadelphia, PA 19104 
Phone 267-426-1238 
email: tapia@email.chop.edu 
 

 
  
 
 
ii
TABLE OF CONTENTS 
Table of Contents ................................................................................................................... ii 
Abbreviations and Definitions of Terms............................................................................. iv 
Abstract .................................................................................................................................. v 
Table 1: Schedule of Study Procedures ............................................................................... 1 
1 
BACKGROUND INFORMATION AND RATIONALE ....................................................................... 2 
1.1 
INTRODUCTION ..................................................................................................................................... 2 
1.2 
RELEVANT LITERATURE AND DATA ..................................................................................................... 2 
1.3 
COMPLIANCE STATEMENT .................................................................................................................... 4 
2 
STUDY OBJECTIVES .............................................................................................................................. 4 
2.1 
PRIMARY OBJECTIVE (OR AIM) ............................................................................................................ 4 
3 
INVESTIGATIONAL PLAN .................................................................................................................... 4 
3.1 
GENERAL SCHEMA OF STUDY DESIGN ................................................................................................. 4 
3.2 
STUDY DURATION, ENROLLMENT AND NUMBER OF SITES ................................................................... 4 
3.3 
TOTAL NUMBER OF STUDY SITES/TOTAL NUMBER OF SUBJECTS PROJECTED ...................................... 4 
3.3.1 
Duration of Study Participation ...................................................................................................... 4 
3.3.2 
Total Number of Study Sites/Total Number of Subjects Projected .................................................. 4 
3.4 
STUDY POPULATION ............................................................................................................................. 5 
3.4.1 
Inclusion Criteria ............................................................................................................................ 5 
3.4.2 
Exclusion Criteria ........................................................................................................................... 5 
4 
STUDY PROCEDURES ............................................................................................................................ 5 
4.1 
SCREENING VISIT ................................................................................................................................. 5 
4.2 
INTERVIEW ................................................................................... ERROR! BOOKMARK NOT DEFINED. 
4.2.1 
Visit 1 .............................................................................................................................................. 6 
4.3 
UNSCHEDULED VISITS .......................................................................................................................... 6 
4.4 
SUBJECT COMPLETION/WITHDRAWAL ................................................................................................. 6 
4.4.1 
Early Termination Study Visit ......................................................................................................... 6 
5 
STUDY EVALUATIONS AND MEASUREMENTS .............................................................................. 6 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS .................................................. 6 
5.1.1 
Medical Record Review ................................................................................................................... 6 
5.2 
INTERVIEW ........................................................................................................................................... 7 
5.3 
SAFETY EVALUATION ........................................................................................................................... 7 
6 
STATISTICAL CONSIDERATIONS ...................................................................................................... 7 
6.1 
PRIMARY ENDPOINT ............................................................................................................................. 7 
6.2 
CONTROL OF BIAS AND CONFOUNDING ................................................................................................ 7 
6.3 
STATISTICAL METHODS........................................................................................................................ 7 
6.3.1 
Baseline Data .................................................................................................................................. 7 
6.3.2 
Analysis of Interviews...................................................................................................................... 7 
6.4 
SAMPLE SIZE AND POWER .................................................................................................................... 8 
7 
SAFETY MANAGEMENT ....................................................................................................................... 8 
7.1 
CLINICAL ADVERSE EVENTS ................................................................................................................ 8 
7.2 
ADVERSE EVENT REPORTING ............................................................................................................... 8 
8 
STUDY ADMINISTRATION ................................................................................................................... 8 
8.1 
DATA COLLECTION AND MANAGEMENT .............................................................................................. 8 
8.2 
CONFIDENTIALITY ................................................................................................................................ 9 
8.3 
REGULATORY AND ETHICAL CONSIDERATIONS.................................................................................... 9 

 
 
 
 
iii
8.3.1 
Data and Safety Monitoring Plan ................................................................................................... 9 
8.3.2 
Risk Assessment ............................................................................................................................... 9 
8.3.3 
Potential Benefits of Study Participation ...................................................................................... 10 
8.3.4 
Risk-Benefit Assessment ................................................................................................................ 10 
8.4 
RECRUITMENT STRATEGY .................................................................................................................. 10 
8.5 
INFORMED CONSENT AND HIPAA AUTHORIZATION .......................................................................... 10 
8.6 
PAYMENT TO SUBJECTS/FAMILIES ..................................................................................................... 10 
8.6.1 
Payments to participants for time and inconvenience (i.e. compensation) ................................... 10 
9 
PUBLICATION ........................................................................................................................................ 10 
10 
REFERENCES ......................................................................................................................................... 11 
 
 

 
  
 
 
iv
ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
 
 
 
 
 
AE 
 
Adverse event 
AT 
DS 
 
Adenotonsillectomy 
Down syndrome 
OSAS 
 
Obstructive sleep apnea syndrome 
PAP 
 
Positive airway pressure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
  
 
 
v
ABSTRACT 
Context:  (Background) 
• OSAS is very common in children with DS 
• OSAS in children with DS does not resolve after adenotonsillectomy  
• Many children with DS and OSAS require treatment with PAP   
Objectives: (primary and important secondary objectives) 
• Identify the perceptions, beliefs, and family-relevant outcomes regarding the 
treatment of OSAS with PAP in children with DS  
Study Design:  
• Cross-sectional study 
Setting/Participants: 
• The study will be performed at CHOP and Cincinnati Children’s Hospital Medical 
Center (CCHMC)outpatient setting 
• Caregivers of children with DS and OSAS aged 6-17.5 years treated with PAP 
Study Interventions and Measures:  
• Open-ended semi-structured interviews

 
  1
TABLE 1: SCHEDULE OF STUDY PROCEDURES  
Study Phase 
Screening & 
Interview 
Informed Consent 
X 
Review Inclusion/Exclusion Criteria 
X 
Semi-structured open-ended interview 
X 
 
 
 

 
  2
1 
BACKGROUND INFORMATION AND RATIONALE 
1.1 Introduction 
Down syndrome (DS) is a common disorder, occurring in 1 per 800 births,1-3 which 
translates to approximately 5,400 children with DS born in the USA annually. 4 Hallmarks 
of the syndrome include intellectual disability, hypotonia and craniofacial anomalies, and 
congenital cardiac defects occur in 50% of individuals.5 Common comorbidities include 
hypothyroidism, obesity, and the obstructive sleep apnea syndrome (OSAS). Untreated 
OSAS is associated with significant morbidity such as growth failure,6 systemic,7-9 and 
pulmonary hypertension,10,11 endothelial dysfunction,12,13 and cognitive and behavioral 
deficits.14-19 Median life expectancy in individuals with DS has increased from 25 years in 
1983 to 58 years20,21 in the present day. While this represents a significant advance in health, 
individuals with DS still have early mortality compared to the general population.  It is 
therefore incumbent upon health care practitioners to diagnose and treat comorbidities, such 
as OSAS, in order to optimize health and cognitive/behavioral function, increase survival, 
and maximize health-related quality of life. Individuals with DS are predisposed to OSAS 
due to craniofacial features (midface hypoplasia, glossoptosis), hypotonia, comorbid obesity, 
and hypothyroidism.22 Studies have shown a prevalence of OSAS in children with DS 
between 45 and 55%.23-25 These rates are markedly higher than that of typically developing 
children24,25 in whom the prevalence of OSAS is about 2%.26  
Adenotonsillectomy (AT) is considered first-line treatment for childhood OSAS.27 However, 
available data indicate that polysomnography (PSG) improves in only a portion of children 
with DS after AT.28 In fact, many children with DS are referred for positive airway pressure 
(PAP) therapy initiation due to persistent OSAS after AT, and PAP appears to be an 
important feature of the experience of living with DS.29 PAP has been shown to be highly 
effective at resolving polysomnographic manifestations of OSAS in children and 
adolescents, including those with DS and other disabilities.30,31  However, PAP as a 
treatment for OSAS has not been well-studied in children with DS. Furthermore, 
patient/family reported outcomes are an important knowledge gap long overdue in this 
population. 
1.2 Relevant Literature and Data 
DS Prevalence and morbidity: Down syndrome (DS) is a common disorder, occurring in1 
per 800 births,1-3 which translates to approximately 5,400 children with DS born in the USA 
annually.4 Hallmarks of the syndrome include intellectual disability, hypotonia and 
craniofacial anomalies. Congenital cardiac defects occur in 50% of individuals.5 Common 
comorbidities include hypothyroidism, obesity, and obstructive sleep apnea syndrome 
(OSAS).  DS is also associated with premature death and early-onset Alzheimer’s disease.32  
Median life expectancy has increased from 25 years in 1983 to 58 years 20,21 in the present 
day. While this represents a significant advance in health, individuals with DS still have 
early mortality compared to the general population.  
DS and OSAS: Individuals with DS are predisposed to OSAS due to craniofacial features 
(midface hypoplasia, glossoptosis, hypotonia), comorbid obesity, and hypothyroidism.22 
Studies have shown a prevalence of OSAS in children with DS between 45 and 55%.23-25 

 
  3
These rates are markedly higher than that of typically developing children 24,25 in whom the 
prevalence of OSAS is about 2%.26 Untreated OSAS is associated with significant morbidity 
such as growth failure,6 systemic7-9 and pulmonary hypertension,10,11 endothelial 
dysfunction,12,13 and cognitive and behavioral deficits.14-19 It is therefore incumbent upon 
health care practitioners to diagnose and treat comorbidities, such as OSAS, in order to 
optimize health and cognitive function, increase survival, and maximize health-related 
quality of life in youth with DS and OSAS.  
Treatment of OSAS in Children with DS: Given the high prevalence of OSAS, the 
American Academy of Pediatrics published a clinical report focused on the care of children 
with DS in 2011.5 In this guideline, they advised families to assess for OSAS as soon as 6 
months of age and emphasized the poor correlation between parental history and sleep study 
results. Therefore, they recommended that all children with DS undergo a sleep study by 4 
years of age, and that pediatricians discuss the impact of obesity as a risk factor for OSAS. 
Adenotonsillectomy (AT) is considered first-line treatment for childhood OSAS.27 However, 
available data indicate that polysomnography (PSG) improves in only a portion of children 
with DS after AT.28 In fact, many children with DS are referred for positive airway pressure 
(PAP) therapy initiation due to persistent OSAS after AT.29 PAP has been shown to be 
highly effective at resolving polysomnographic manifestations of OSAS in children and 
adolescents, including those with DS and other disabilities.30,31  Importantly, studies indicate 
that PAP also reduces symptoms of OSAS and improves school performance, behavior, 
mood, daytime sleepiness and quality of life (QOL) in typically developing children and 
adolescents.30,33  Another important consideration is that PSG results may not predict 
patient-reported outcomes and other physiological responses, indicating a need for studies 
that inform the medical community not only about healthcare provider-relevant outcomes 
but also about family-relevant outcomes related to the experience of living with DS and 
OSAS. In addition, RCTs that examine a range of relevant qualitative, clinical and 
physiological outcomes are lacking. These studies, such as the current proposal, could 
inform families and the medical community about variation in responses and provide the 
framework for developing a “precision medicine” approach for future single- or multiple-
staged approaches, matching the best intervention to the individual child defined by 
appropriate family-relevant, clinical, physiological and/or genetic factors.  
PAP adherence in children with DS: There is a dearth of literature regarding PAP 
adherence in children, and even less in children with DS.34-36  Generally, PAP is inherently 
difficult for individuals to use regularly.  In addition to the daily burden of putting the 
equipment on each night and discomfort of wearing a mask with pressurized air being 
administered while sleeping, common side-effects include nasal symptoms (e.g., nasal 
dryness, rhinorrhea, congestion and epistaxis), eye irritation, skin pressure sores or 
dermatitis, and aerophagia. Some patients suffer from feeling closed-in by the mask (e.g., 
claustrophia).  Not surprisingly, PAP efficacy is limited by poor adherence.37 Most studies 
in the pediatric age range have encompassed a wide age spectrum and heterogeneous 
populations,29,37-39 and have reported improved adherence over time.29,39 Importantly, the 
few studies, all retrospective, including children with DS under the larger umbrella of 
children with developmental disabilities (DD), have shown better adherence in children with 
DD compared to typically developing children.29,39 Hawkins et al reported that DD was a 
positive predictor factor for PAP adherence (OR = 2 .55, 95%CI = 1.27–5.13; p = 0.007),29 
and our group has showed that at 3 months after PAP initiation, adherence was 86.7% [33.9-

 
  4
97.9%] of nights in children with developmental disabilities and 62.9% [30.8-87.8%] in 
typically developing children (p=0.01).39  
 
1.3 Compliance Statement 
This study will be conducted in full accordance all applicable Children’s Hospital of 
Philadelphia Research Policies and Procedures and all applicable Federal and state laws and 
regulations including 45 CFR 46.  All episodes of noncompliance will be documented. 
The investigators at CHOP and CCHMC will perform the study in accordance with this 
protocol. CHOP investigators will obtain verbal consent, CCHMC will obtain written 
consent, and will report unanticipated problems involving risks to subjects or others in 
accordance with Children’s Hospital of Philadelphia IRB Policies and Procedures and all 
federal requirements. Collection, recording, and reporting of data will be accurate and will 
ensure the privacy, health, and welfare of research subjects during and after the study. 
2 
STUDY OBJECTIVES 
The purpose of this multi-center study is to further characterize the experience of living with 
DS and OSAS. 
2.1 Primary Objective (or Aim) 
• The primary objective of this study is to identify the perceptions, beliefs, and family-
relevant outcomes regarding the treatment of OSAS with PAP in children with DS. 
3 
INVESTIGATIONAL PLAN 
3.1 General Schema of Study Design 
Cross-sectional study 
3.2 Study Duration, Enrollment and Number of Sites 
This is a multi-center outpatient study  to be performed at 2 clinical sites: Children’s 
Hospital of Philadelphia and Cincinnati Children’s Hospital. Forty Caregivers of children 
with DS and OSAS treated with PAP and their children will be enrolled. The study 
comprises one 30-minute open-ended semi-structured interview per caregiver. The duration 
of the interview is approximate. It will last up to 30 minutes as some families may want to 
include more details. 
3.3 Total Number of Study Sites/Total Number of Subjects Projected 
3.3.1 Duration of Study Participation 
The study duration per subject will be 1 day. 
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 
The study will be conducted at two investigative sites in the United States. 

 
  5
Recruitment will stop when approximately 40 subjects are interviewed. It is expected that 
approximately 40 subjects will be enrolled to produce 30 evaluable subjects.  
3.4 Study Population 
Adult caregivers of children with DS and OSAS and their children will be the participants of 
this study. The inclusion/exclusion criteria below include required characteristics of the 
children to consider their caregiver eligible for participation. 
3.4.1 Inclusion Criteria-Patients 
1) Children with DS and OSAS treated with PAP for at least 6 months 
2) Children aged between 6 and 17.5 years  
3) English proficiency  
 
3.4.2 Exclusion Criteria-Patients 
4) In foster care 
5) Diagnosed with major illness, such as leukemia or severe cyanotic 
congenital heart disease listed for cardiac transplant as these severe 
diseases may add confounders 
 
3.4.3 Inclusion Criteria-Caregivers 
6) Parent or legal guardian of an eligible patient subject  
7) English proficiency 
8) Must live with the patient subject at least 4 nights of the week 
3.4.4 Exclusion Criteria- Caregivers 
9) Foster parent 
Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations 
of these criteria must be reported in accordance with IRB Policies and Procedures.  
4 
STUDY PROCEDURES 
4.1 Screening and Interview  
 

 
  6
• Informed Consent  
• Medical record review 
• One semi-structured 30 minute open-ended interview per participant will be 
conducted over the phone. The interview will be audio-recorded 
 
4.1.1 Visit 1 
• Open-ended semi-structured interviews will be conducted over the phone and audio 
recorded. 
4.2 Unscheduled Visits 
Due to the nature of this study, unscheduled visits are not expected 
4.3 Subject Completion/Withdrawal 
Subjects may withdraw from the study at any time without prejudice to their care.  They 
may also be discontinued from the study at the discretion of the Investigator if they fail to 
keep the phone interview appointment repeatedly. The Investigator or the Sponsor (if 
applicable) may also withdraw subjects who violate the study plan, or to protect the subject 
for reasons of safety or for administrative reasons.  It will be documented whether or not 
each subject completes the clinical study. If the Investigator becomes aware of any serious, 
related adverse events after the subject completes or withdraws from the study, they will be 
recorded in the source documents and on the CRF. 
4.3.1 Early Termination Study Visit 
Subjects who withdraw from the study will not have the interview as this is the only study 
procedure. 
 
5 
STUDY EVALUATIONS AND MEASUREMENTS 
5.1 Screening and Monitoring Evaluations and Measurements 
5.1.1 Medical Record Review 
• Date of birth of child 
• Race, ethnicity, maternal education of child and parent 
• Zip code of the family 
• Sleep study results of child 
• PAP information of child: date of initiation of treatment, titration study, adherence 

 
  7
• Child comorbidities 
 
5.2 Interview 
Semi-structured interviews will explore such key constructs as knowledge/belief about 
OSAS and PAP therapy, routines and resources that promote or limit PAP use, barriers, self-
efficacy, and communication and attitudes about PAP. The interviews will be performed 
with the parent and that they will be audio-recorded. 
 
5.3 Safety Evaluation 
Data safety will be strictly monitored during the study. Because of the nature of the study, 
no other safety issues are anticipated. 
 
6 
STATISTICAL CONSIDERATIONS 
6.1 Primary Endpoint 
The primary endpoint will be completing the interviews. 
6.2 Control of Bias and Confounding 
For this mixed methods research, all caregivers meeting criteria will be contacted. The first 
forty confirming participation and providing consent will be included in the study.  
6.3 Statistical Methods 
6.3.1 Baseline Data  
Baseline and demographic characteristics will be summarized by standard descriptive 
summaries (e.g. means and standard deviations for continuous variables such as age and 
percentages for categorical variables such as gender). 
6.3.2 Analysis of Interviews 
Data Analysis: Interviews will be transcribed by Datagain, a professional transcription 
company. Audio files are loaded onto a secure site. In the process of transcription, all 
identifying information will be removed. Password protected transcripts are returned to the 
Mixed Methods Research Lab where they are loaded into a password protected NVivo file 
on a secure server in the Department of Family Medicine and Community Health. Datagain 
has a business use agreement with the University of Pennsylvania. Once transcripts are 
verified for accuracy, the audio file will be destroyed. The study team will create a codebook 
by conducting a line by line reading of the first five transcripts. The investigators will 
identify key ideas in the transcripts and will use these key ideas to form codes. Each code 
will be operationalized and decision rules for their application will be included in the 
definition. Once the codebook is stabilized, the team will double code the first five 
transcripts and will use the interrater reliability function in NVivo to ascertain agreement. 

 
  8
Once 95% agreement has been achieved, the team will code the remaining transcripts, 
checking interrater reliability every fifth transcript. 
Coded data will be summarized, examined for patterns and used to identify factors 
associated with adherence and non-adherence as well as implementation. 
6.4 Sample Size and Power 
In qualitative research, sample size is dictated by the principle of saturation. Saturation is 
when no new themes arise among each of the key subgroups in the sample. Several factors 
dictate an estimation of when saturation might be achieved. Key among these is the degree 
of homogeneity within the sample. Since the families we will recruit are all dealing with a 
similar set of issues and similar clinical contexts, we anticipate that saturation will be likely 
with up to 15 families per site.40 We will conduct our analysis concurrent with data 
collection, using the constant comparative method. In this approach, we iteratively move 
between codes and texts, constantly looking for examples of existing ideas and being alert to 
new ones. This process enables us to learn when no new ideas emerge within the group as a 
whole and within each site. Although in our experience we typically achieve saturation with 
approximately 15 interviews per group, we have allowed for up to 20 interviews per site so 
that we can assure that saturation has been achieved. 
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.  
8 
STUDY ADMINISTRATION 
8.1 Data Collection and Management 
 
1. Confidentiality.  Password protected transcripts will be saved into a password 
protected NVivo file on a secure server at CHOP. Access to data will be limited to 
study team members. Demographic and PAP data will be entered and saved in a 
CHOP-based REDCap system. All identifiers will be saved in the system. 
2. Security.  Same as above. 
 

 
  9
3. Anonymization, de-identification or destruction.  All PHI identifiers and HIPAA 
related documents (consents, HIPAA authorization forms) will be deleted 6 years 
after study completion, in accordance with Policy A-3-9.  
 
4. All data from the semi-structured interviews will be audio recorded. Recordings will 
be promptly removed from portable recording devices and saved to a secure, 
password-protected CHOP-based computer, identified by study ID.  
 
 
8.2 Confidentiality 
No identifiable data will be used for a future study without first obtaining IRB approval or 
determination of exemption. The investigator will obtain a data use agreement between 
provider (the PI) and any recipient researchers (including others at CHOP) before sharing a 
limited dataset (dates and zip codes).  
8.3 Regulatory and Ethical Considerations 
8.3.1 Data and Safety Monitoring Plan 
• Principal Investigator: It is the responsibility of the Principal Investigator to oversee 
the overall safety of the study. This will include careful assessment and appropriate 
reporting of adverse events. Since the study procedures are not greater than minimal 
risk, SAEs are not expected. The PIs responsibility will be to assure that appropriate 
study data are communicated to the participant’s family and physicians and that 
appropriate referrals or interventions are initiated. 
• Institutional Review Board: CHOP will be the central IRB of this study. It is the 
responsibility of the Principal Investigator at each clinical site to provide their IRB 
with all pertinent material, including a copy of the informed consent.  Approval from 
the reviewing IRB of the informed consent form must be obtained prior to screening 
or enrolling any participants.  The clinical site’s Principal Investigator also maintains 
the responsibility of coordinating with the central IRB in initiating protocol re-
approval, notification of protocol and/or consent form changes, adverse events, and 
termination of the study according to the appropriate IRB requirements. Risk 
Assessment 
Interviews and record reviews. As with any study that involves collecting data, it is 
possible that someone who is not involved with the study may get access to participants’ 
confidential information. Every precaution will be taken to secure participants' personal 
information to ensure confidentiality. At the time of participation, each participant will be 
assigned a study identification number. This number will be used on data collection forms 
and in the study database instead of names and other private information. A separate list that 
links each participant's name to the study identification number will be maintained for future 
reference and communication. 

 
  10 
8.3.2 Potential Benefits of Study Participation 
Direct benefits: There are no direct benefit to the subjects.  
Indirect benefits: Findings derived of this study will help increasing the understanding of the 
experience of living with DS and OSAS, and provide useful information for a future 
intervention trial of adherence to PAP in this population. 
8.3.3 Risk-Benefit Assessment 
The risks of this study are not greater than minimal risk.  
8.4 Recruitment Strategy 
CHOP participants will be recruited from the Sleep Center and the Down syndrome clinic, 
which are within the division of the investigators of the current proposal. Caregivers 
meeting eligibility criteria will receive a letter and a follow-up phone call from the 
investigators inviting them to participate in a one-time phone interview.  
Cincinnati study participants will be identified for preliminary eligibility by study physicians 
and through the CCHMC DS clinic. 
8.5 Informed Consent and HIPAA Authorization 
A member of the study team at CHOP will be responsible for obtaining verbal informed 
consent from each participant. Informed consent will be obtained before this research study. 
Prospective participants will be given unlimited time to decide their participation. They will 
be asked to explain back to the investigators the nature of the study, study procedures and 
the risks and benefits of participation to assure their understanding. 
A member of the study team at Cincinnati will obtain written consent for study procedures. 
All aspects of the study will be explained in detail to each family by a team member.  All 
questions will be answered and participants and families will be given time to consider their 
decision.  They will be informed of the nature of this research, its potential benefits and 
possible risks.  They will be informed that they are free to refuse participation or to 
withdraw from the study and that this will not affect any future medical care.  
 
8.6 Payment to Subjects/Families 
8.6.1 Payments to participants for time and inconvenience (i.e. compensation) 
• Participants at CHOP will receive a $50.00 gift card for their participation. 
• Participants at Cincinnati will receive a $50.00 reloadable debit card (ClinCard).  
9 
PUBLICATION 
It is anticipated that the completed study will be submitted for publication to a peer-
reviewed medical journal. 

 
  11 
 
10 REFERENCES 
 
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de Graaf G, Buckley F, Skotko BG. Estimates of the live births, natural losses, and 
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