Home or Away From Home: Comparing Patient and Caregiver Reported Quality of Life (QoL) and Other Patient-centered Outcomes for Inpatient Versus Outpatient Management of Neutropenia in Children With AML
Conditions: Pediatric Acute Myeloid Leukemia
Sponsor: Children's Hospital of Philadelphia

 
Observational Template: February 16, 2011 
Title: 
Home or Away From Home: Comparing patient and caregiver 
reported quality of life and other patient-centered outcomes 
for inpatient versus outpatient management of neutropenia in 
children with AML or MDS receiving standard intensive AML 
frontline chemotherapy 
Short Title: 
Aim 3: AML/MDS Neutropenia Quality of Life 
 
NCT Number: 
NCT02777021 
Protocol Date: 
July 1, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
ii
Title: 
Home or Away From Home: Comparing patient and caregiver 
reported quality of life and other patient-centered outcomes 
for inpatient versus outpatient management of neutropenia in 
children with AML or MDS receiving standard intensive AML 
frontline chemotherapy 
Short Title: 
Aim 3: AML/MDS Neutropenia Quality of Life 
Sponsor: 
Children’s Hospital of Philadelphia (CHOP) 
eIRB Number: 
15-012103 
Protocol Date: 
July 1, 2019 
Amendment 1 Date: May 13, 2016 
Amendment 13 Date: Withdrawn 
Amendment 2 Date: May 26, 2016 
Amendment 14 Date: August 4, 2017 
Amendment 3 Date: September 8, 2016 
 
Amendment 4 Date: October 31, 2016 
Amendment 15 Date:  September 26, 2017 
 
Amendment 16 Date:  December 11, 2017   
Amendment 5 Date: Withdrawn 
Amendment 17 Date:  January 16, 2018 
Amendment 6 Date: November 21, 2016 
Amendment 18 Date:  February 7, 2018   
Amendment 7 Date: February 3, 2017                Amendment 19 Date:  March 5, 2018 
Amendment 8 Date: February 27, 2017              Amendment 20 Date:  April 18, 2018           
Amendment 9 Date: Withdrawn                          Amendment 21 Date: May 25, 2018                   
Amendment 10 Date: April 18, 2017                  Amendment 22 Date: August 8, 2018 
Amendment 11 Date: June 2, 2017                     Amendment 23 Date: October 18, 2018 
Amendment 12 Date: July 13, 2017 
                    
 
Richard Aplenc, MD, PhD 
The Children’s Hospital of Philadelphia 
3501 Civic Center Blvd 
Philadelphia, PA, 19104 
Phone: 267-426-7252 
Email: aplenc@chop.edu 
 

 
  
 
 
 
 
 
iii
TABLE OF CONTENTS 
Table of Contents .................................................................................................................. iii 
Abbreviations and Definitions of Terms.............................................................................. v 
Abstract ................................................................................................................................. vi 
Table 1: Schedule of Study Procedures ............................................................................. vii 
Figure 1: Study Diagram .................................................................................................... viii 
1 
BACKGROUND INFORMATION AND RATIONALE ....................................................................... 1 
1.1 
INTRODUCTION ..................................................................................................................................... 1 
1.2 
RELEVANT LITERATURE AND DATA ..................................................................................................... 2 
1.3 
COMPLIANCE STATEMENT .................................................................................................................... 3 
2 
STUDY OBJECTIVES .............................................................................................................................. 3 
2.1 
OBJECTIVES .......................................................................................................................................... 3 
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 ............................................................................................................................. 4 
3.4.1 
Inclusion Criteria ............................................................................................................................ 5 
3.4.2 
Exclusion Criteria ........................................................................................................................... 5 
4 
STUDY PROCEDURES ............................................................................................................................ 5 
4.1 
PARTICIPANT IDENTIFICATION ............................................................................................................. 5 
4.2 
SCREENING VISIT ................................................................................................................................. 5 
4.3 
VISIT 1 ................................................................................................................................................. 5 
4.4 
VISIT 2 ................................................................................................................................................. 6 
4.5 
SUBJECT COMPLETION/WITHDRAWAL ................................................................................................. 7 
4.5.1 
Early Termination Study Visit ......................................................................................................... 7 
5 
STUDY EVALUATIONS AND MEASUREMENTS .............................................................................. 7 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS .................................................. 7 
5.1.1 
Screening ......................................................................................................................................... 7 
5.1.2 
Medical Record Abstraction ............................................................................................................ 7 
5.1.3 
Evaluations and Measures .............................................................................................................. 8 
6 
STATISTICAL CONSIDERATIONS .................................................................................................... 10 
6.1 
PRIMARY ENDPOINT ........................................................................................................................... 10 
6.2 
CONTROL OF BIAS AND CONFOUNDING .............................................................................................. 11 
6.3 
STATISTICAL METHODS...................................................................................................................... 11 
6.3.1 
Analysis of Primary Outcomes of Interest ..................................................................................... 11 
       6.3.2  Analysis of Secondary Outcomes of Interest 
 
 
 
 
 
 12 
6.4 
SAMPLE SIZE AND POWER .................................................................................................................. 12 
7 
SAFETY MANAGEMENT ..................................................................................................................... 12 
7.1 
CLINICAL ADVERSE EVENTS .............................................................................................................. 12 
7.2 
ADVERSE EVENT REPORTING ............................................................................................................. 12 
8 
STUDY ADMINISTRATION ................................................................................................................. 13 

 
  
 
 
 
 
 
iv
8.1 
DATA COLLECTION AND MANAGEMENT ............................................................................................ 13 
8.1.1 
Data sources.................................................................................................................................. 13 
8.2 
CONFIDENTIALITY .............................................................................................................................. 13 
8.3 
REGULATORY AND ETHICAL CONSIDERATIONS.................................................................................. 14 
8.3.1 
Data and Safety Monitoring Plan ................................................................................................. 14 
8.3.2 
Risk Assessment ............................................................................................................................. 14 
8.3.3 
Potential Benefits of Study Participation ...................................................................................... 15 
8.3.4 
Risk-Benefit Assessment ................................................................................................................ 15 
8.4 
RECRUITMENT STRATEGY .................................................................................................................. 15 
8.5 
INFORMED CONSENT/ASSENT AND HIPAA AUTHORIZATION ............................................................ 15 
8.6 
FINANCIAL INFORMATION ......................................................................................................... 16 
8.6.1 
Payments to subject for time, effort and inconvenience (i.e. compensation) ................................. 16 
       8.6.2    Who is funding this research study?................................................................................................16 
9 
PUBLICATION ........................................................................................................................................ 16 
10 
REFERENCES ......................................................................................................................................... 16 
 
 

 
  
 
 
 
 
 
v
ABBREVIATIONS AND DEFINITIONS OF TERMS 
ABBREVIATIONS 
 
 
ALSF 
AML 
ANC 
CHOP 
 
Alex’s Lemonade Stand Foundation 
Acute Myeloid Leukemia 
Absolute Neutrophil Count 
The Children’s Hospital of Philadelphia 
CI 
COG 
FAC 
HRQOL 
ICU 
MDS 
PAC 
PCO  
PCORI 
 
Confidence Intervals 
Children’s Oncology Group 
Family Advisory Council 
Health-related quality of life 
Intensive Care Unit 
Myelodysplastic syndrome 
Patient Advocacy Committee 
Patient-Centered Outcomes 
Patient-Centered Outcome Research Institute 
PedsQL™ 
REDCap™ 
SD 
 
 
 
Pediatric Quality of Life measurement modules 
Research Electronic Data Capture 
Standard Deviation  
 
 
 
 
DEFINITIONS 
 
 
 
Bacteremia 
Positive blood culture for a bacterial pathogen unless the bacterium is 
an organism considered a common commensal organism by the 
National Healthcare Safety Network 
Early Discharge 
Discharge to outpatient management during neutropenia within 3 days 
 
 
 
after chemotherapy completion in a given course 
Neutropenia   
Absolute Neutrophil Count <200/L  
Caregiver 
A parent or adult that is the legal guardian of the pediatric study 
participant 

 
  
 
 
 
 
 
vi
ABSTRACT 
Context: (Background)  
Treatment for pediatric acute myeloid leukemia (AML) or myelodysplastic syndrome 
(MDS) involves intensive chemotherapy regimens that result in periods of profound 
neutropenia leaving patients susceptible to severe infectious complications. Infectious 
complications are the leading cause of treatment related mortality among AML and MDS 
patients, but there are little clinical data to inform whether management of neutropenia post 
AML chemotherapy should occur in an outpatient or inpatient setting. Further, no studies 
have been conducted that assess the impact of neutropenia management strategy on the 
quality of life of pediatric patients with AML/MDS and their caregivers.  
Objectives:  
The primary objective of this study is to compare patient and caregiver quality of life and 
other patient-centered outcomes (PCO) for inpatient versus outpatient management of 
neutropenia in children with AML or MDS receiving standard intensive AML frontline 
chemotherapy.  
Study Design:  
This is a prospective observational cohort study.  
Setting/Participants: 
Participants will be patients less than 19 years of age at their initial AML or MDS diagnosis 
(and their caregivers) receiving or having received frontline AML chemotherapy from 
fifteen participating pediatric hospitals across the United States (US). Due to the nature of 
the survey collected data, only dyads who are English/Spanish literate will be eligible.  We 
expect to identify 139 patient-caregiver dyads, of which we anticipate that approximately 
118 will consent to participate over the study period to compare patient- and caregiver- 
identified outcomes of neutropenia management in the outpatient and inpatient settings. 
Study Interventions and Measures:  
There is no study intervention.  Main outcomes include scores on health-related quality of 
life surveys, as well as additional patient- and caregiver- identified outcomes. 

 
  
 
 
 
 
 
vii
TABLE 1: SCHEDULE OF STUDY PROCEDURES  
 
 
Study Phase 
Screening 
Study Visits 
Visit Number 
 
1 
2 
Informed Consent/Assent 
X 
 
 
Review inclusion/exclusion 
criteria 
X 
 
 
Baseline PedsQL™  
 
X 
 
Demographic survey 
 
X 
 
Demographic survey II 
 
X 
 
Follow-up PedsQL™ 
 
 
X 
PCO survey 
 
 
X 
Financial toxicity survey 
 
X 
X 

 
  
 
 
 
 
 
viii
 FIGURE 1: STUDY DIAGRAM 
 
 
 
 
 
 
1 
Chemotherapy 
Administration
aincludes core, cancer and fatigue modules 
 
 
Inpatient Management Group 
Outpatient Management Group 
 
Neutropenic Period
 
 
 
 
 
 
 
 
 
 
Course
End 
Chemo 
START
Chemo 
END
Enroll ment 
Administer 
Baseline PedsQL a
, Demographics survey I and 
II ,and Financial toxicity survey 
Follow - up Window
Administer 
Follow - up PedsQL a 
Administer Follow-up 
PedsQL™, PCO survey, 
and Financial toxicity 
survey  

 
  
 
  
 
 
 
1
1 
BACKGROUND INFORMATION AND RATIONALE  
1.1 Introduction 
Acute myeloid leukemia (AML) is the second most common pediatric hematologic 
malignancy with approximately 600 new cases per year among patients under 20 years of 
age.  Although AML accounts for only about 20% of leukemias in children, it is responsible 
for more than half of pediatric leukemia deaths (1). The prognosis of children with AML has 
improved greatly over the past 30 years (2, 3, 4), attributable largely to the intensification 
and standardization of chemotherapy regimens.  
All pediatric patients with newly diagnosed AML receive multiple consecutive courses of 
intensive myelosuppressive chemotherapy aimed to attain complete remission (induction) 
and to prevent relapse (intensification) (5). Each regimen is followed by a period of 
prolonged severe neutropenia during which patients are at high risk for infection and 
hemorrhage.  Previous reports have found that 57-80% of febrile neutropenia episodes 
among pediatric AML patients are compromised by at least one microbiologically 
documented infection (6, 7) with bacteremia constituting the most prevalent infection (8). 
These infectious complications remain a major cause of therapy-associated morbidity and 
mortality in children with AML (9, 10). 
Recently published pediatric neutropenia guidelines make no specific recommendations 
regarding discharge from hospital after chemotherapy for AML because “there are no 
validated schemas for defining those patients at high-risk of developing complications of 
fever and neutropenia” (11). As a result, clinicians are left to decide whether to keep a child 
in the hospital until the neutropenia resolves (on average 35 days) or discharge a child to 
outpatient management within a few days of chemotherapy completion with instructions to 
return if symptoms of infection develop. Physicians that elect to observe patients with 
neutropenia in the hospital do so under the assumption that hospital observation will reduce 
the risk of serious infection and thereby reduce delays in starting the next course of 
chemotherapy.  Furthermore, this approach assumes that the potential reduction in infection 
outweighs the potential negative consequences of a prolonged inpatient stay—namely 
reduced quality of life, increased exposure to multi-resistant nosocomial infections, and 
increased healthcare cost. There is documented variation in practice across Children’s 
Oncology Group (COG) institutions on inpatient versus outpatient management of 
neutropenia with approximately 60% of COG institutions reporting a policy to always keep 
patients hospitalized during severely neutropenic periods and the remaining 40% of 
hospitals reporting a policy of home management some or all of the time (12, 13).  This 
variation in practice highlights the need for additional data on clinician-centered and patient-
centered outcomes to appropriately guide the management of neutropenia in pediatric AML 
patients.   
Myelodysplastic syndromes (MDSs) are a rare heterogenous group of hemopoietic clonal 
disorders characterized by ineffective hemopoiesis and frequent evolution to leukemia. 
Children with clinical and morphological features of MDS but with the cytogenetic features 
typical of AML are often treated with same intensive frontline chemotherapy used to treat 
AML. (38) Thus, questions regarding clinician-centered and patient-centered outcomes in 

 
  
 
  
 
 
 
2
relation to outpatient versus inpatient management of neutropenia would apply equally to 
such patients. 
 
1.2 Relevant Literature and Data  
The limited literature on the clinical consequences of outpatient versus inpatient 
management of neutropenia in AML is focused on the experience of adult patients. Adult 
patients discharged early to outpatient supportive care consistently had shorter cumulative 
lengths of stay than inpatients (14-21). Additionally, early discharge of adult AML patients 
receiving chemotherapy has been associated with fewer and shorter febrile episodes (18, 
22), a better response to first line antibiotics, and shorter duration of intravenous antibiotic 
administration (16, 18, 21, 22). While these adult studies provide some reassurance that 
outpatient management may be safe and feasible they are limited as most included data from 
only a single institution, had very small sample sizes, or lacked an appropriate inpatient 
reference population. Furthermore, it is not appropriate to extrapolate these adult findings to 
pediatric patients as the risk profile for children may be much different.  
The published literature with respect to outpatient management of neutropenia in pediatric 
AML is limited to a single study of only 13 patients from one hospital, which found similar 
rates of relapse and mortality for outpatient versus inpatient management of neutropenia 
(23).  In our own preliminary analyses based on administrative resource utilization data from 
43 free-standing children’s hospitals in the US, we found that patients who were discharged 
early to outpatient management following AML induction and intensification chemotherapy 
courses incurred fewer cumulative days of hospitalization, but were frequently readmitted 
and had higher rates of antibiotic, vasopressor, and supplemental oxygen utilization than 
patients who remained inpatient during the entirety of their neutropenia. In the absence of 
clinical data and laboratory confirmation, it is unclear whether these observed increases in 
resource utilization are an accurate proxy for a greater incidence of infection or more severe 
infection in the early discharge patients. 
Decisions regarding supportive care strategies are intended not only to improve clinical 
outcomes but also to impact patient quality of life outcomes, such as minimizing the 
psychological, social and spiritual challenges related to therapy (24).  Thus, it is imperative 
to determine the impact of a chosen neutropenia management strategy on the child’s quality 
of life and interactions with his or her broader social environment, including impact on the 
family.  There is a dearth of literature on child and caregiver (parent/guardian) perspectives 
on outpatient versus inpatient management of neutropenia (25, 26) or the impact of 
neutropenia management strategy on quality of life (27) in pediatric cancer patients. The one 
qualitative study on parent preferences for neutropenia management in pediatric cancer 
found that most respondents preferred hospital-based treatment once a patient had developed 
a fever during neutropenia (25). Factors that influenced parent preference for febrile 
neutropenia management included convenience and disruptiveness to family life, concerns 
about the child’s physical health (including infection), and concerns about the child’s 
emotional wellbeing. While this study was a good first step in identifying PCO for febrile 
neutropenia management in pediatric cancer it has some notable limitations: it was 
conducted at one center in Canada, it only included parent perspectives on febrile 

 
  
 
  
 
 
 
3
neutropenia management and not management of neutropenia prior to fever onset, children 
were not interviewed, and it involved the elicitation of parent preferences via hypothetical 
scenarios versus more in-depth study of the actual experience of neutropenia management in 
the hospital or the home.  
There are no studies evaluating clinician-centered and patient-centered outcomes in relation 
to outpatient versus inpatient management of neutropenia among MDS patients treated with 
standard intensive AML frontline chemotherapy. However, these patients suffer the same 
severe prolonged neutropenia as similarly treated AML patients and as such, assessments of 
patient quality of life and other family-centered outcomes for outpatient versus inpatient 
management of neutropenia would be equally informative to decisions on their supportive 
care strategies. 
In order to appropriately inform the decision for outpatient versus inpatient management of 
neutropenia associated with pediatric AML chemotherapy, a comprehensive study that 
considers pertinent clinical, patient and caregiver centered outcomes is necessary. Given that 
infectious complications are the leading cause of treatment-related mortality among AML 
patients (28)  and among MDS patients (39, 40), identifying such a neutropenia management 
strategy that leads to the best clinician and patient/caregiver identified outcomes will have a 
substantial impact on care of these patients.  
1.3 Compliance Statement 
This study will be conducted in full accordance with all applicable Children’s Hospital of 
Philadelphia Research Policies and Procedures and all applicable Federal and state laws and 
regulations including 45 CFR 46. All episodes of noncompliance will be documented. 
The investigators will perform the study in accordance with this protocol, will obtain 
consent and assent, and will report unanticipated problems involving risks to subjects or 
others in accordance with The Children’s Hospital of Philadelphia IRB Policies and 
Procedures and all federal requirements. Collection, recording, and reporting of data will be 
accurate and will ensure the privacy, health, and welfare of research subjects during and 
after the study. 
 
2 
STUDY OBJECTIVES 
The purpose of this study is to establish important comparative effectiveness data on patient-
directed outcomes for outpatient versus inpatient management of AML neutropenia or MDS 
in individuals receiving standard AML frontline chemotherapy.  
 
2.1 Objectives 
The primary objective of this study is to compare patient and caregiver reported quality of 
life and other PCO (established through previous qualitative interviews conducted by a 
medical sociologist at CHOP) for inpatient versus outpatient management of neutropenia in 
children with AML or MDS receiving standard intensive AML frontline chemotherapy. 

 
  
 
  
 
 
 
4
 
3 
INVESTIGATIONAL PLAN 
3.1 General Schema of Study Design 
This prospective observational cohort study will evaluate patient- and caregiver-directed 
outcomes of inpatient versus outpatient management of neutropenia following chemotherapy 
in children with AML or MDS.   
3.2 Study Duration, Enrollment and Number of Sites 
This study plans to include patients and their caregivers who are undergoing frontline 
chemotherapy starting June 1, 2016 or after.   
3.3 Total Number of Study Sites/Total Number of Subjects Projected 
3.3.1 Duration of Study Participation 
Eligible patients will be approached for consent at any time from initial AML or MDS 
diagnosis through the last day of chemotherapy in the frontline treatment course under 
study. The maximum duration of enrollment is from the initiation of their current 
chemotherapy course until the last day of their subsequent chemotherapy course. This 
duration is estimated to be approximately 30-40 days.  
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 
Surveys will be administered at the following fifteen US investigative sites: Children’s 
Hospital of Philadelphia (Philadelphia, PA), Children’s Healthcare of Atlanta (Atlanta, GA), 
C.S. Mott Children’s Hospital (Ann Arbor, MI), Ann & Robert H Lurie Children’s Hospital 
of Chicago (Chicago, IL), Arkansas Children’s Hospital (Little Rock, AR), Children’s 
Medical Center of Dallas (Dallas, TX), Texas Children’s Hospital (Houston, TX), Primary 
Children’s Medical Center (Salt Lake City, UT), Children’s Hospital of Michigan (Detroit, 
MI), Lucile Packard Children’s Hospital Stanford (Palo Alto, CA), St. Jude Children’s 
Research Hospital (Memphis, TN), Seattle Children’s Hospital (Seattle, WA), Children’s 
Hospital Colorado (Denver), Nemours/A.I. duPont Hospital for Children, and DFCI/Boston 
Children’s Hospital (Boston, MA). These sites were chosen based on geographic location, 
their substantial AML/MDS patient volume, and the variation in primary strategy of 
neutropenia management.  
We expect approximately 278 subjects across all sites to be enrolled and approximately 236 
subjects to be evaluable (118 patients and 118 caregivers).    
3.4 Study Population 
The study population will include all AML and MDS patients who are receiving a planned 
frontline chemotherapy course at any of the fifteen pediatric institutions across the US 
starting June 1, 2016. Patients discharged within 3 days after chemotherapy completion will 
be categorized as ‘early discharge’ to outpatient management during neutropenia. Patients 
remaining in the hospital more than 3 days after chemotherapy completion will be 
categorized as inpatient management.  

 
  
 
  
 
 
 
5
Caregivers of these patients will also be included.  
3.4.1 Enrollment Criteria 
3.4.1.1 Inclusion Criteria 
1) Participants will be enrolled as patient-caregiver dyads.  The patient must be:  
 Less than 19 years of age at initial AML/MDS diagnosis. 
 Receiving standard intensive AML frontline chemotherapy starting June 1, 2016 
or after. 
 Able to read English or Spanish, if 8 years of age or older 
2) Participants will be enrolled as patient-caregiver dyads.  The caregiver must be:  
 Able to read English or Spanish. 
 The legal guardian of a patient receiving standard intensive AML frontline 
chemotherapy starting June 1, 2016 or after . 
3) Parental/caregiver informed consent and, if appropriate, child assent. 
3.4.1.2 Exclusion Criteria 
 Patients being treated for relapsed AML  
 Patients with Acute Promyelocytic Leukemia (APML) 
 Patients undergoing stem cell transplant (SCT) 
 Patients receiving reduced intensity frontline chemotherapy 
Any violations of these criteria will be reported in accordance with IRB Policies and 
Procedures.  
 
4 
STUDY PROCEDURES 
4.1 Participant Identification 
Local study investigators (pediatric oncologists and study coordinators) at each of the fifteen 
participating pediatric institutions will communicate on a weekly basis with their inpatient 
leukemia service to identify AML or MDS patients potentially eligible for study enrollment. 
Once identified, study personnel will review each patient for study eligibility criteria. 
4.2 Screening Visit 
 The eligibility criteria for participation will be confirmed prior to approaching for consent. 
Eligible patients interested in the study will be approached for consent at any time from 
AML/MDS diagnosis through last day of chemotherapy in the treatment course under study. 
In some cases, the patient’s caregivers may not be present in the hospital to provide consent. 
In these cases, study personnel will obtain verbal consent from the caregivers and child 
assent (if appropriate).  

 
  
 
  
 
 
 
6
4.3 Visit 1 
Visit 1 will occur prior to the last day of chemotherapy administration in the course. This 
visit will include: 
 3 baseline health-related quality of life (HRQOL) PedsQL™ survey modules (core, 
cancer, and fatigue) 
 2 Brief demographic surveys to capture covariates unavailable in the medical record  
 1 Financial toxicity survey  
Surveys will be administered via paper or a smart device and will last a total of 15-30 
minutes per respondent. In the case that the child is 5 years of age or older, the child self-
report and parent proxy-report scales will be separately administered to the child and 
caregiver, respectively.  If the child is between 5 and 8 years of age, Study Personnel will 
read the survey questions to the patient. There is an illustrated response aid for these young 
patients. These age-specific PedsQL instruments have been previously validated. The child 
will indicate their answer as ‘Not at all’, ‘Sometimes’, or ‘A lot’ by pointing to a smiling, 
middle, or frowning face, respectively. If the child is under 5 years of age, only the parent-
proxy version will be administered.  Caregivers will also be asked to complete the 
demographic covariate surveys and the financial toxicity survey during Visit 1. The brief 
demographic surveys capture covariates unavailable in the medical record, such ‘patient 
race/ethnicity’,‘patient/parent education level’, and ‘parent marital status’. The financial 
toxicity survey assesses the financial situation of the caregiver/family. 
4.4 Visit 2  
Visit 2 will occur within the period after absolute neutrophil count recovery and ideally prior 
to the start of the subsequent course of chemotherapy, but no later than the last day of 
chemotherapy in that next treatment course. For the small number of patients who will begin 
the next course of chemotherapy before count recovery, Visit 2 will occur within the period 
from one day prior to the start of chemotherapy in that next treatment course and no later 
than the last day of chemotherapy in that course. This visit will include: 
 3 follow-up health-related quality of life (HRQOL) PedsQL™ surveys (core, cancer, 
and fatigue)  
 1 PCO survey 
 1 Financial toxicity survey 
 
All surveys will be administered via paper or a smart device and will last a total of 15-30 
minutes per respondent. In the case that the child is 5 years of age or older, the PedsQL child 
self-report and parent proxy-report scales will be administered to the child and caregiver, 
respectively. If the child is between 5 and 8 years of age, Study Personnel will read the 
survey questions to the patient. There is an illustrated response aid for these young patients. 
These age-specific PedsQL instruments have been previously validated. The child will 
indicate their answer as ‘Not at all’, ‘Sometimes’, or ‘A lot’ by pointing to a smiling, 
middle, or frowning face, respectively. If the child is under 5 years of age, only the parent-
proxy version will be administered. Caregivers will also be asked to complete the PCO 

 
  
 
  
 
 
 
7
survey at follow-up. The PCO survey assesses dimensions such as parental stress and 
anxiety, patient’s sleep behaviors, impact on siblings, and hospital discharge teaching 
practices. In addition, caregivers will be asked to complete the financial toxicity survey 
again at follow-up. The caregiver completing the follow-up assessments must be the same 
caregiver who completed the baseline assessments. We will provide a $50 gift card to each 
child-parent dyad upon completion of the PCO survey, financial toxicity survey, and follow-
up quality of life surveys. If the child and caregiver do not complete both visits, they will 
only be compensated a portion of the $50 for the visits they do complete. 
4.5 Subject Completion/Withdrawal 
Subjects may withdraw from the study at any time without prejudice to their care.  They 
may also be discontinued from the study at the discretion of the Investigator for lack of 
adherence to the study plan. 
4.5.1 Early Termination Study Visit 
Child-caregiver dyads who withdraw from the study during or prior to completion of the 
follow-up surveys will only be compensated a portion of the $50 for the visits they do 
complete. 
5 
STUDY EVALUATIONS AND MEASUREMENTS 
5.1 Screening and Monitoring Evaluations and Measurements 
5.1.1 Screening 
The following information will be utilized by local study investigators prior to participant 
approach:  
 Date of birth 
 Specific leukemia diagnosis and date 
 Planned treatment regimens 
 Ability to read English or Spanish for all caregivers and for patients 8 years of age or 
older  
 
Some information will be retained for screened patients who do not enroll to document 
the reasons for exclusion. Specifically, we will be retaining age, leukemia diagnosis and 
date, treatment course, and whether the patient received reduced intensity chemotherapy. 
 
5.1.2 Medical Record Abstraction 
Medical record abstraction will be performed as per the related Protocol 15-012074 Aim 1: 
Managing neutropenia in pediatric AML protocol. The table below includes a complete list 
of the data elements to be abstracted. St. Jude Children’s Research Hospital is not 
participating in Aim 1 and therefore will follow the abstraction process outlined in the Aim 
3 Protocol Addendum. The abstracted data elements will be linked to the quality of life and 
PCO data described in the current protocol.  
Variable 

 
  
 
  
 
 
 
8
Date of birth 
Sex 
Patient race/ethnicity 
Date of AML (or MDS) diagnosis 
Age at AML (or MDS) diagnosis 
Vital status 
Date of death or date of last known follow-up 
Location of death (in hospital or at home) 
AML subtype 
AML risk classification and cytogenetics 
Hospital admission start/stop dates 
Chemotherapy course number 
Chemotherapy regimen and start/stop dates 
Course start/stop dates 
On COG protocol or similar clinical trial? 
Documentation of deviation from planned chemotherapy course 
Presence/type of central line 
MRD post courses and dates of MRD obtained 
Post course remission status 
Daily max. fever; how was temperature taken 
Infections during chemotherapy courses 
ICU care during chemotherapy courses 
ANC measurements post chemotherapy 
Dates of ANC measurements  
Dates and results of microbiological cultures/PCRs onset during post chemotherapy course 
follow-up 
Mucositis severity by course 
Systemic antimicrobial prophylaxis at each course 
Height, weight, and body surface area at end of chemotherapy course 
Nutritional status/supplemental support requirements on day of chemotherapy completion 
Ability to practice oral hygiene 
Insurance status at course start (private, self-pay, public, other) 
English spoken? 
Home address 
Availability of working telephone 
Automobile/taxi voucher requirements 
Caregiver’s relation to patient 
Caregiver’s marital status 
If caregiver is married, relation between caregiver’s spouse and patient 
Date of relapse 
Site of relapse 
Date of transplant 
Type of transplant 
 
 

 
  
 
  
 
 
 
9
5.1.3 Evaluations and Measures 
Three evaluation tools will be utilized over the two study visits: 2 demographic covariate 
surveys, PedsQL™ scales, and a PCO Survey.  
 Demographic covariate survey  
The following patient-level information will be obtained via survey to capture 
covariates unavailable or less readily available in the medical record:  
o Patient race/ethnicity  
o Parental employment status 
o Household income 
o Parental and patient education level 
o Number of adults living in the primary residence  
o Number of other children living in the primary residence  
   
 Demographic covariate survey II 
The following patient-level information will be obtained via survey to capture  
covariates unavailable or less readily available in the medical record: 
o Parent/legal guardian who signed informed consent 
o Relation to patient (i.e. mother, father, other) 
o Parent/legal guardian marital status 
 
 PedsQL™ 
HRQOL will be assessed using the following validated PedsQL™ scales: 
o The 23-item multidimensional 4.0 Generic Core Scales: 
 Physical functioning (8 items) 
 Emotional functioning (5 items) 
 Social functioning (5 items) 
 School functioning (5 items) 
o The 18-item multidimensional Fatigue Scale: 
 General fatigue (6 items) 
 Sleep/rest fatigue (6 items) 
 Cognitive fatigue (6 items) 
o The 27-item multidimensional 3.0 Cancer Module: 
 Pain/hurt (2 items) 
 Nausea (5 items) 
 Procedural anxiety (3 items) 
 Treatment anxiety (3 items) 
 Worry (3 items) 
 Cognitive problems (5 items) 
 Perceived physical appearance (3 items) 
 Communication (3 items) 
 
 Financial toxicity survey 
o 11-item survey that assesses the financial situation of the caregiver/family. 
Items inquire about: 
 Having enough money to cover cost of child’s treatment 

 
  
 
  
 
 
 
10
 Out-of-pocket expenses exceeding their expectations 
 Worrying about future financial problems 
 Feeling like have no choice about amount spent on care 
 Feeling frustrated that cannot work or contribute as much as usual 
 Satisfaction with current financial situation 
 Ability to meet monthly expenses 
 Feeling financially stressed 
 Concern about keeping job and income 
 Overall control of financial situation 
 
The format, instructions, response scale and scoring methods for the three PedsQL scales are 
identical. Each is available in parallel child self-report and parent proxy-report formats. 
Child self-report versions include ages 5-7 years, 8-12 years and 13-18 years. Parent proxy 
report versions include ages 1-2 years, 2-4 years, 5-7 years, 8-12 years and 13-18 years.  In 
this study we will administer the Child Self-Report versions of the scales for children 5 
years of age and older in addition to the Parent Proxy-Report versions. 
 
A 5-point Likert response scale is used across child self-report for ages 8-18 and parent 
proxy-report (anchored by 0 = never a problem to 4 = almost always a problem).  Responses 
to each question are used to assemble a score.  
 
Each of these scales demonstrates internal reliability acceptable for group comparisons 
(PedsQL™ Generic Core Total Scale Score [Cronbach’s α = 0.88 child, 0.93 parent report]; 
Multidimensional Fatigue Total Scale Score [α = 0.89 child, 0.92 parent report]; most 
Cancer Module Scales [average α = 0.72 child, 0.87 parent report]) (29). These scales have 
also been shown to be sensitive to change over time in children with cancer (30).  
 
 PCO Survey 
o Pediatric Inventory for Parents-Difficulty scales (PIP-D)-(42 items) 
o Parental stress and anxiety (9 items) 
o Sleep Disturbance Scale for Children (SDSC): Disorders of Initiating and 
Maintaining Sleep domain (DIMS) (7 items) 
o Impact on Siblings (7 items) 
o Hospital Discharge Teaching Practices (4 items)  
 
The PCO survey will be completed by the parent during study Visit 2.  The PCO includes 
established measures of parental stress (PIP-D) and sleep disturbance in children (SDSC 
DIMS) as well as survey questions designed to measure the incidence and sources of 
parental financial stress; sources of parenting, emotional, domestic and financial support; the 
incidence and nature of sibling behavioral change, and the receipt of training prior to 
discharge from the hospital.  
 
The PIP-D assesses stress-related difficulty with events faced by parents of children with 
serious illness across four domains: communication (e.g., with child, partner, or health care 
team), emotional functioning (e.g., impact of illness on sleeping and mood), child’s medical 
care (e.g., carrying out medical regimen), and role functioning (e.g., impact of illness on 

 
  
 
  
 
 
 
11
parent’s ability to work and care for other children). All items are rated on a five-point 
Likert scale from 1 (not at all difficult) to 5 (extremely difficult) (31). 
 
The SDSC DIMS assesses sleep indices such as latency and duration, night awakenings, and 
reluctance to go to bed.   All items are measured on a five-point Likert scale, in which 1= 
never, 2= occasionally, 3= sometimes, 4= often, and 5= always. The SDSC is reported to 
have high internal consistency among both healthy (α=0.79) and sleep disordered 
participants (α=0.71), as well as high test–retest reliability (r=0.71) (32).  
 
 Financial toxicity survey 
The financial toxicity survey will be completed by the parent at both baseline and follow-up 
(Visit 1 and Visit 2). The survey includes 11 statements about the financial situation of the 
caregiver/family in relation to the child’s treatment adapted from existing literature (37). A 
5-point Likert response scale is used for the parent to indicate the degree to which they agree 
with each statement (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a bit; 4 = Very 
much).   
 
6 
STATISTICAL CONSIDERATIONS 
6.1 Primary Endpoint 
The primary outcome of interest will include the following endpoint: 
 Scores of HRQOL obtained from the PedsQL™ scales 
The secondary outcomes of interest will include the following: 
 Scores of difficulty with events faced by parents of children with serious illness from 
the PIP-D 
 Scores for patient sleep behavior from the SDSC DIMS 
 Incidence and sources of parental financial distress following patient’s AML/MDS 
diagnosis 
 Incidence of sibling behavior change following patient’s AML/MDS diagnosis 
 Financial toxicity scores obtained from the financial toxicity survey   
  
6.2 Control of Bias and Confounding 
This is an observational cohort study, so subjects are not assigned by a process of 
randomization and are therefore subject to bias. However, analyses of our data will control 
for potential confounding by various patient- and hospital- level factors.  Additionally there 
is a possibility of exposure misclassification given that patients who are discharged more 
than 3 days after chemotherapy completion but well before neutropenia recovery will still be 
included in the inpatient management group.  To account for this imperfect specificity, 
sensitivity analyses will be performed utilizing a less strict threshold for discharge 
classification (e.g., 5 or 10 days post-chemotherapy).  

 
  
 
  
 
 
 
12
6.3 Statistical Methods 
6.3.1 Analysis of Primary Outcomes of Interest 
Propensity score analyses will be used to adjust for potential confounding by baseline 
covariates.  First, bivariate analyses will be performed to evaluate relationships between 
each baseline covariate and neutropenia management strategy as well as each outcome of 
interest. Next, propensity scores will be derived from the predicted probabilities estimated 
from logistic regression models of the use of outpatient versus inpatient management during 
neutropenia conditional on all baseline factors determined to be true confounders (i.e., those 
associated with both exposure and outcome) and those determined to be potential 
confounders (i.e., those associated only with the outcome interests).  Patients will then be 
stratified into five groups using quintiles of the estimated propensity score. The distributions 
of exposure within the quintiles will be examined for sufficient sample sizes and balance. 
Within each stratum, the patients managed as outpatient and those managed as inpatient will 
ideally have similar values of the propensity score and likewise the distribution of measured 
baseline covariates will be comparable between them. 
PedsQL™ items will be reverse scored and linearly transformed to a scale of 0 to 100 such 
that higher scores will be reflective of better HRQOL. The PedsQL™ total score will be 
calculated as the sum of the item-specific scores divided by the number of answered items 
(33, 34).  
We will utilize linear mixed effect models to test the association between neutropenia 
management strategy and the PedsQL™ total score. Specifically, the two repeated measures 
of the PedsQL™ total score will be the outcome and regressed on time, group (outpatient 
versus inpatient) and interaction between time and group will be the fixed effects, and a 
subject level random effect will be included to account for the potential correlations between 
the repeated measures. Such mixed models are more powerful than ANCOVA or analysis of 
change scores, and they benefit from the added power arising from any correlation of 
repeated measures over time. A significant group by time interaction will suggest that the 
change of PedsQL™ is different between the two groups. Adjustment for differences in 
covariates across neutropenia management groups will be accomplished through the 
propensity score outlined above, and by controlling for confounding of any remaining 
unbalanced potential confounders. Secondary analyses will be performed for the cancer and 
fatigue modules as well as for the physical and psychosocial subscales of the PedsQL™. 
6.3.2 Analysis of Secondary Outcomes of Interest 
Responses to each of the items on the PIP-D were summed to obtain a total score reflecting 
the amount of difficulty experienced when handling events faced by parents of children with 
serious illness. Higher scores indicate greater difficulty and increased pediatric parenting 
stress (31).  
Responses to each of the items on the SDSC DIMS subscale are summed to get a total 
domain score that is mapped to a corresponding T-score using the SDSC scoring sheet.  
Higher T-scores are reflective of greater clinical severity of symptoms and a T-score greater 
than 70 is considered pathological (32). For the PCO, we will utilize appropriate standard 
statistical methods to evaluate the relationships with neutropenia management strategy 

 
  
 
  
 
 
 
13
(outpatient versus inpatient). For binary outcomes, log-binomial regression with robust error 
estimates will be employed to obtain risk ratios (95% CI). For continuous outcomes, 
generalized linear models will be used incorporating the appropriate distribution based on a 
graphical assessment of the outcome data. All models will be adjusted for baseline 
propensity scores by quintiles. Log-binomial regression with robust error estimates will also 
be employed to obtain risk ratios (95% CI) comparing the incidence of any financial toxicity 
(versus none), separately for each item on the financial toxicity survey as well as overall 
across all survey items. For the total score obtained from the financial toxicity survey, we 
will utilize methods comparable to those described for the PedsQL™ total score in section 
6.3.1 above. 
 
6.4 Sample Size and Power 
We expect to prospectively identify approximately 139 patients and assuming 90% of 
identified patients will be discharge eligible and 85% will consent, the anticipated study 
population will be 118patients and their caregivers. Approximately 40% will be managed as 
outpatients, so we expect 47 outpatients and 71 inpatients. The power calculation was 
conducted under the framework of a multivariate general linear hypothesis for general linear 
models, using the Wilks Lambda test with a significance level of 0.05 (35, 36). Assuming a 
standard deviation (SD) of 20 for the PedsQL™ total score, if there is no correlation we will 
have 80% power to detect a large effect size of 0.75 that is a 15.0 point difference in the 
mean change scores between the two groups. If the correlation is as high as 0.8 we will have 
80% power to detect a small effect size of 0.34, that is a 6.8 point difference in the mean 
change scores between the two groups. 
  
7 
SAFETY MANAGEMENT 
7.1 Clinical Adverse Events 
Clinical adverse events (AEs) will be monitored throughout the study, though no adverse 
events are expected to result from the work proposed in this protocol.  
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 occur 
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.  

 
  
 
  
 
 
 
14
8 
STUDY ADMINISTRATION 
8.1 Data Collection and Management 
These data will consist of patient and caregiver responses to the demographic surveys, 
HRQOL PedsQL™ scales, PCO survey, and financial toxicity survey. These scales will be 
administered via paper or by using the LSTcare application via a tablet computer or other 
smart device. The PedsQL™ scales are described above in Section 5.1.3. Survey responses 
collected through the LSTCare™ are maintained in a Software as a Service (SaaS) model.  
LSTCare™ is fully compliant with all HIPAA regulations.  Additionally, LST has 
contracted with FireHost Secure Cloud Hosting based in Dallas, Texas, to host and manage 
all computer systems and networks.  FireHost is a leader in HIPAA compliant Secure Cloud 
Hosting and delivers hosting solutions to eCommerce, SaaS, Healthcare IT and Security 
Companies around the world. Data are encrypted between the device and the back end 
services and the data are available via LST secured web application and via written queries 
and downloadable spreadsheets.  The PCO survey and financial toxicity survey are 
described in Section 5.1.3, and will be administered on paper or by using REDCap™ via a 
public survey link. When screening patients to determine their eligibility, medical record 
data will be abstracted and entered electronically directly into a REDCap™ database, a 
secure, web-based application designed exclusively to support data capture for research 
studies.  The REDCap™ database is designed so that local investigators cannot see data 
entered by other sites. We will utilize REDCap™ automated export processes to seamlessly 
download the chart abstraction data for review and analysis. All statistical output and 
generated data files, tables, and figures will be stored in password protected files on a secure 
server, which is automatically backed up each night. A unique study identification number 
will be assigned to participants so that no study file contains identifiable information.  A 
master list linking the study identification number to the individual participant will be stored 
in a password protected file on a secure drive.  Identifiers will be destroyed after publication. 
If surveys will be completed on paper, CHOP research personnel will enter all data captured 
via paper forms into the corresponding electronic study databases. Data entry will be quality 
checked by a second study team member. Electronic scans of the completed paper 
assessments will be saved on a secure server for up to one year following study completion 
and all paper forms will be immediately destroyed once scanned and entered into the study 
database. 
8.1.1 Data sources  
Local investigators will query their site’s AML/MDS registry, and if necessary patients’ 
electronic medical records, for demographic information, clinical information, and hospital 
admission/discharge dates.  The complete list of variables is detailed in Section 5.1.1 and 
5.1.2. Patient and caregiver perspectives on neutropenia management strategy and their 
reports of health related quality of life will be obtained via PedsQL™ modules described in 
Section 5.1.3. Additional outcomes including parental stress and anxiety, patient’s sleep 
behaviors, impact on siblings, and hospital discharge teaching practices will also be 
measured via the PCO survey also described in Section 5.1.3. Financial toxicity will be 
assessed via the survey described in Section 5.1.3. 

 
  
 
  
 
 
 
15
8.2 Confidentiality 
All data and records generated during this study will be kept confidential in accordance with 
Institutional policies and HIPAA on subject privacy.  The Investigator and other site 
personnel will not use such data and records for any purpose other than conducting the 
study.  No identifiable data will be used for future study without first obtaining IRB 
approval. CHOP will receive data from each participating site, but before sharing a limited 
dataset with other researchers (including those at CHOP) the investigator will obtain a data 
use agreement between the PI and any recipient researchers.  Safeguards to protect 
confidentiality were described above in Section 8.1 and are also detailed below in Section 
8.3.2. 
8.3 Regulatory and Ethical Considerations 
8.3.1 Data and Safety Monitoring Plan 
Given the types of data and the observational study design, specifically the absence of an 
imposed intervention, we do not anticipate needing to utilize a data safety and monitoring 
plan.  However, in the unlikely event of a participant necessitating psychological treatment 
due to adverse effects of study participation, a member of the research team will make 
appropriate referrals within CHOP or the external healthcare facility. The investigators are 
experienced in talking with parents who are under the stress of a child’s illness and with 
children in medical settings. 
8.3.2 Risk Assessment 
This is a minimal risk study.  There are no new patient interventions or treatments associated 
with the work outlined in this proposal. As such, there are no expected additional health 
risks that a patient would incur as a result of participation in this study. The medical care of 
subjects will not be affected in any way by their participation in this study. Similarly, the 
medical care of those who choose not to participate in this study will also be unchanged.  
There may be a small risk of discomfort or anxiety for the patients and/or caregivers while 
engaging in the surveys. To protect against discomfort of the child or caregiver during the 
survey administration we will take multiple steps. First, we will administer the surveys at a 
time and location of the respondent’s choosing. Second, we will let our respondents know 
that they can discontinue the survey at any time, for any reason, without penalty to them.  
Another possible risk is the loss of confidentiality.  We will institute strict procedures to 
maintain confidentiality. All data and personally identifiable information will be stored 
electronically on a secure server in password protected files. None of the survey responses 
on paper or electronic forms will contain patient identifiers. We will record all identifier 
information on a separate form. A unique study identification number will link the baseline 
health-related quality of life (HRQOL) PedsQL™, demographic surveys, and financial 
toxicity survey to the follow-up HRQOL PedsQL™, PCO survey, and the financial toxicity 
survey. A master list linking study identification to the individual will be stored in a 
password protected file on a secure drive. Any paperwork will be kept in study binders in 
locked file cabinets in offices with locked doors. All electronic files will be stored on 
password protected computers in locked offices. Entry to the offices is controlled at a main 

 
  
 
  
 
 
 
16
entrance by identification card readers. Research materials will be accessible only to 
members of the investigative team. Access by members of the research team to any patient 
identifiers will be limited to the minimum necessary to carry out the proposed research. Any 
publications or presentations resulting from this work will not identify participants by name, 
but will only present aggregate data. Our prior research employing similar precautions has 
demonstrated that these techniques are very successful in assuring the protection of subjects.  
8.3.3 Potential Benefits of Study Participation 
The patients involved in the study might not benefit directly, except if a survey response 
improves the patient’s understanding of his or her course and promotes additional contact 
with his or her clinicians. Results from the study may be applied in the future to AML/MDS 
patients in making decisions about the best way to manage neutropenia. Improved 
understanding of the outcomes as well as caregiver/patient perspective of outpatient versus 
inpatient management of neutropenia will be of great importance to AML/MDS patients and 
the providers who care for them.  
8.3.4 Risk-Benefit Assessment 
As minimal risk research, the risks to the subjects are reasonable with respect to the 
knowledge that may result from the research.   
8.4 Recruitment Strategy 
Local study investigators (pediatric oncologists and study coordinators) at each of the fifteen 
participating pediatric institutions will communicate on a weekly basis with their inpatient 
leukemia service to identify AML and MDS patients potentially eligible for study 
enrollment. Once identified, study personnel will review each patient for study eligibility 
criteria. The eligibility criteria for participation will be confirmed prior to approaching for 
consent. Eligible patients interested in the study will be approached for consent at any time 
from AML/MDS diagnosis through last day of chemotherapy in the treatment course under 
study.  
8.5 Informed Consent/Assent and HIPAA Authorization  
If interested in participation, parents will be given a thorough explanation of the study 
including the purpose, procedures, risks and benefits of participation, confidentiality, 
procedures for withdrawal, reimbursement, and contact information for study personnel. 
Families will be informed that their medical care at CHOP or any another healthcare facility 
will not be affected if they choose not to participate in the proposed research.  After 
reviewing eligibility we will obtain informed consent and HIPAA authorization from 
parents, and if age eligible, we will seek child assent. The assent process with children will 
include a developmentally appropriate explanation of the purpose of the research, what 
research participation entails, and procedures for withdrawal from the study. Children will 
be informed that their participation is voluntary and that they can withdraw from the study at 
any time.  Informed consent/assent and HIPAA Authorization will take place in a quiet, 
private space to ensure confidentiality and the family will be provided ample time to make 
an informed and thoughtful decision. Combined informed consent-HIPAA authorization 
documents will be used.   

 
  
 
  
 
 
 
17
8.5.1 A Waiver of Documentation of Consent and Alteration of HIPAA 
Authorization (to obtain verbal authorization) 
In some cases, the patient’s caregivers may not be present in the hospital to provide consent. 
In such cases, study personnel will obtain verbal consent from the caregivers and written 
assent for the child (if age appropriate). Verbal consent will be obtained on the telephone. 
The study personnel obtaining verbal consent will be in a quiet, private space to ensure 
confidentiality and the family will be provided ample time to make an informed and 
thoughtful decision. Combined verbal consent-HIPAA Authorization documents will be 
used. A copy of the verbal consent form will be provided to the caregiver via mail or email. 
After verbal consent is obtained from the caregiver, the study personnel will obtain written 
assent from the child, if age appropriate. The process for obtaining written assent is 
described in section 8.5. 
8.6 Financial Information 
8.6.1 Payments to subject for time, effort and inconvenience (i.e. compensation) 
Following completion of both the baseline surveys (PedsQL™, demographic surveys, and 
financial toxicity survey) and follow-up surveys (PedsQL™ modules,PCO survey, and 
financial toxicity survey), child-parent dyads will be compensated with a $50.00 gift card. If 
the child and caregiver do not complete both visits, they will only be compensated a portion 
of the $50 for the visits they do complete.   
 
8.6.2 Who is funding this research study? 
The Patient Center Outcomes Research Institute provided funding for this study until 
February 28, 2019. Effective March 1, 2019, CHOP is funding the study. 
 
9 
PUBLICATION 
The results of this study will be prepared and submitted to peer-reviewed journals.  The 
compiled de-identified data from this study will be maintained by CHOP investigators.  
Thus all submitted manuscripts will be directed by these CHOP investigators.  Any data 
presented will be presented in summary form and there will be no potential for patient 
identification through a publication. 
Additionally, to optimize the dissemination of our study results to patient and caregivers we 
will work with two organizations: Alex’s Lemonade Stand Foundation (ALSF) and the COG 
Patient Advocacy Committee (PAC). Throughout the 2.5 year study we will hold several 
Board meetings with both ALSF and the COG PAC to share our research findings and elicit 
their feedback on the best way to communicate, disseminate and translate our research 
findings into a format that will be useful (and available) to patients and their caregivers 
when they are faced with a decision about what kind of neutropenia management strategy is 
best for them.   
Because children with AML/MDS and their caregivers are participants in the study we will 
also share our study results with them. At the conclusion of their participation we will ask if 

 
  
 
  
 
 
 
18
they are interested in receiving information about what we find in our study. If they say yes, 
we will send them a newsletter summarizing the results of our study via mail, created in 
collaboration with our patient stakeholder partners. 
 
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