Self-Management for Youth and Families Living With Sickle Cell Disease - SMYLS
Phase: NA
Conditions: Sickle Cell Disease
Sponsor: Medical University of South Carolina

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PROTOCOL TITLE: 
 
Self-Management for Families and Youth Living with Sickle Cell Disease - SMYLS 
 
PRINICIPAL INVESTIGATOR: 
 
Shannon Phillips, PhD, RN 
 
 

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1.0 
Objectives / Specific Aims 
Specific Aims:  Few family-centered self-management interventions exist to assist children with 
sickle cell disease (SCD) and their families, which deprive this population of skills that may improve 
symptom management and quality of life. SCD is an inherited complex chronic condition (CCC) that 
leads to adverse health outcomes such as pain and organ damage affecting approximately 100,000 
people in the US. In addition to living with pain and negative health outcomes, children and adults 
with SCD also face disparities in access to care. Infants and young children with more complicated 
CCCs, such as SCD, and those who have fewer resources are at greater risk for adverse outcomes 
such as increased hospital and emergency department (ED) utilization and physical and psychosocial 
morbidity. Children with SCD and their families, particularly those who are underserved, would benefit 
from interventions designed to bolster self-management skills and enhance preventive management 
of the disease to reduce negative complications. Importantly, caregivers of young children with SCD 
are often new to the disease process and have unique needs and challenges.  
     Interventions designed to address the unique needs of and barriers encountered by this population 
could improve effective management of the disease in the home setting. In addition, technology-
based resources such as mobile health applications for symptom tracking, may allow intervention 
delivery to typically difficult-to-reach populations, thereby reducing access barriers to care, including 
lack of transportation and obtaining childcare. Further, incorporating theory-based family-centered 
self-management strategies is crucial to support families in developing sustainable, improved self-
management behaviors (e.g. monitoring symptoms, and attending clinic appointments) which will 
ultimately improve symptom management (e.g. pain, fatigue) and quality of life, and decrease costly 
emergency department (ED) visits and hospitalizations.  
     The interprofessional team of investigators for this study includes a mentee (Phillips) with a clinical 
background as a pediatric acute care nurse and research experience with exploring barriers in access 
to care among children with CCC. Mentors include an R01 funded nurse scientist who is an expert in 
intervention development and the conduct of clinical trials (Kelechi: primary mentor), an R01 funded 
clinical psychologist with extensive expertise in technology, user-based design, and intervention 
adaptation (Ruggiero: co-mentor), a pediatric hematologist/oncologist specializing in clinical care and 
research with populations with SCD (Kanter: co-mentor), and a biostatistician with extensive research 
experience (Mueller: co-mentor). This complementary interdisciplinary team has the knowledge, 
skills, and access to the population to successfully conduct this study, but will also provide the 
mentee with mentorship and training experiences in theory-based, technology-enhanced intervention 
research among a population of children with a CCC and their caregivers.  
     
The purpose of this second phase of this study is to conduct feasibility testing of an innovative, 
technology-based intervention to improve self-management behavior, quality of life, and symptom 
management (SMYLS) in a sample of children with SCD and their families. Three components are 
included in the intervention: previously tested educational materials for adults with SCD and their 
families, a publicly available mHealth application for tracking pain in SCD, and a model of patient-
provider communication delivered via mHealth that has been tested with older children with SCD. The 
goal of the proposed research is to use the theory-based Pediatric Self-Management Model to tailor 
and pilot test the effect of an integrated intervention on psychosocial and physical symptom 
management and quality of life for children with SCD ages 8-17 years and their caregivers.  
 
During this second phase of this study, we seek to achieve the following aims: 
 
Primary aim of the study is to: Assess feasibility of implementation processes including reach, 
enrollment, fidelity, adoption, acceptability, and satisfaction using the RE-AIM framework with process 
measures, surveys, and key informant interviews. 
Secondary Aim: Investigate the presence of signals of efficacy on measures of self-management, 
and physical and psychological symptoms and quality of life. 

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2.0 
Background 
Importance of the problem. The significance of this project lies in the fact that it is the first step 
(adaptation and feasibility testing) in a research continuum that will lead to validation of a technology-
based intervention for improving self-management, symptom management, health care utilization and 
ultimately quality of life among populations of children with complex chronic conditions (CCC) and 
their caregivers.  
     Sickle cell disease (SCD) is a highly complex and challenging chronic disorder that negatively 
influences quality of life in children and families of those with the disorder.1 SCD is a hereditary CCC 
that almost exclusively affects African Americans. Nationwide, an estimated 72,000 to 98,000 
individuals have SCD; >90% of these are African American.2 Symptoms of SCD often occur within the 
first year of life and require lifelong preventive management. SCD is a hemoglobinopathy 
characterized by an altering in the shape of red blood cells in response to hypoxia, stress, or 
acidosis.3,4 These abnormally shaped cells occlude small vessels and cause inflammation, pain, 
infarction, and ultimately, organ damage.3,4 The physiological sequelae of SCD lead to high health 
care needs and utilization, and often, to comorbidities and early death.5,6 Many children with CCC, 
particularly SCD, and their families have high health care needs that are frequently unmet or 
inadequately met. SCD is one of several CCCs affecting children that could benefit from improved 
self and family management care, such as epilepsy, cerebral palsy, and chronic respiratory 
disease.7,8  
SCD as a CCC based in health disparity. Because children with SCD and their families have high 
health care and “other” needs that endure throughout their lifetime, preventive actions are necessary 
in early childhood to avoid or mitigate adverse effects of the disease process. For optimal 
management and minimal adverse effects, persons with SCD and/or caregivers must coordinate 
appointments with various providers, continuously monitor symptoms, and obtain preventive home 
therapies. Often, challenges are pronounced early in the disease process as caregivers learn about 
the disease and treatments. Typically, a multidisciplinary team is established and caregivers learn to 
coordinate and maintain care. However, SCD primarily affects an underserved population (i.e., 
African Americans) who disproportionately face barriers such as transportation, obtaining childcare, 
and taking time from work. In fact, low-income children with SCD have significantly higher 
hospitalizations and ED visits than other children in general.9 
Methods to enhance self-care of SCD by affected individual and the family are needed. Self-
care interventions to prevent adverse effects of the disease process have not been well implemented 
for children with SCD. Fortunately, assistance with providing reliable sources of disease and 
treatment related information, decision-making, and communication with the care team via technology 
improve family-centered self-management behaviors in older children (ages 10-17 years) with SCD.10 
Assisting families caring for an infant or young child with SCD via a similar technology-based model 
may lead to improved self-management and quality of life outcomes. Providing resources via this 
mechanism may reduce burden and maximize outreach to this difficult to reach, underserved, high 
needs population. Traditional barriers to care such as transportation, childcare, and work conflicts can 
be overcome. Long-term management of SCD and prevention of adverse outcomes also requires 
support for self-management skill development. Through technological resources and collaborative 
relationships with providers, caregivers can receive support to develop self-management skills.  
Technology-based self-management has the potential to address barriers. Use of a technology-
based intervention that has been tailored to meet child/adolescent/caregiver-reported needs is 
expected to increase engagement and reach of self-management strategies. Our technology-based 
intervention (a self-management program for youth living with sickle cell disease - SMYLS) consists 
of three components: previously tested electronic educational materials on the SCD process and 
management; a publicly available, web-based, mHealth application for SCD pain monitoring and 
tracking; and a previously-tested model of patient-provider communication delivered via mHealth 
communication with a provider with expertise in SCD. Innovative delivery of coaching and support 

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provided by the provider through messaging is also expected to increase self-management behaviors 
and lead to improved health outcomes. By delivering messages, information can be personalized to 
aid in learning about pain, symptom management, and preventive care.  
 
Theoretical Framework. The Pediatric Self-Management Framework7 guides the present study and 
provides an ideal underpinning to our proposed methods because it outlines multilevel influences that 
affect self-management and family-centered self-management behaviors through multiple processes, 
and guides prediction of the outcomes associated with influences, behaviors, and processes.  
According to this framework, self-management influences, processes, and behaviors exist on the 
individual, family, community, and health care system domains. Because this study will focus on 
children ages 8- 17 years and their caregivers, and on the caregiver-provider relationship, we will 
target the family and health care system domains. Specific influences, processes, and behaviors 
addressed in this study are outlined in Table 1. 
 
Table 1: Intervention Self-Management Influences, Processes, and Behaviors 
This is Phase II of the overall study. During Phase I, we refined the development 
and design of the intervention, by conducting user focus groups and pilot 
testing the app among a target population of users. Now, in Phase II, we aim to 
deploy the intervention in a real-world settin3.0 
Intervention to be studied 
     The intervention is a multicomponent (3-part) technology-based package. 
The intervention targets influences and processes informed by the Pediatric 
Self-Management framework (Table 1). Component 1 (education) consists of 
continuous access to directed educational resources on the SCD process, 
treatment, home management strategies, symptom prevention and 
management strategies. These materials are easily accessible via a mobile 
device given to caregivers and children (8-17 years) and will include patient-
centered PDF files and links to websites developed and tested by 
authoritative sources. An example includes the patient education materials 
provided by NIH NHLBI such as the Sickle Cell Disease Infographic: 
Monitoring Pain (Figure 1). To address potential literacy barriers, an 
Self-management 
Influences 
Self-management Processes 
Self-management 
Behaviors 
• Family disease and 
treatment knowledge 
• Parental monitoring 
and supervision 
• Parental involvement 
• Patient (parental)-
provider 
communication 
• Determining child’s health care 
needs 
• Communication with medical 
team 
• Seeking disease and treatment 
related information 
• Determining child’s health care 
needs 
• Allocation of treatment 
responsibility 
• Learning about patient’s disease 
and treatments 
• Provision of support for treatment 
regimens 
• Modification of communication 
styles 
• Shared decision making 
• Giving medication and 
treatments such as home 
physical and respiratory 
therapy 
• Attending clinic 
appointments 
• Monitoring and tracking 
symptoms 
• Introducing and 
supporting lifestyle 
modifications 
• Providing recommended 
therapies 
Figure 1: Example of 
Educational Material 

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application that reads PDF files aloud (e.g. @Voice Aloud Reader) is downloaded onto devices. 
Component 2 (symptom monitoring and tracking) consists of a mobile-device based publicly available 
application for tracking and monitoring pain in SCD that also permits upload of symptom logs and text 
alerts to a health care provider (Voice Crisis Alert). Component 3 (caregiver-provider communication) 
is based on Jacob et al. (2013)’s intervention with an mHealth intervention for older children with 
SCD. This component consists of a technology-based connection with a provider who will: respond to 
alerts delivered via the mHealth application, monitor pain symptoms delivered via the mHealth 
application, and respond to messages. A provider at the MUSC Pediatric Sickle Cell Clinic will 
collaborate with caregivers to coach caregivers on the care of the child and provide support to the 
caregiver.10 Caregivers will receive a daily message using a semi-structured protocol to “check in” 
with participants and promote engagement. All components are integrated into the web-based app. A 
secure portal is in place for messaging that encrypts all messages and protects confidentiality. 
 
Children (8-17) with SCD and their caregivers will complete self-report and proxy assessments as 
described in Table 1 below; data will be recorded in REDCap by the PI or project coordinator 
 
Major tasks and domains 
Measures/instruments/ 
questions and Cronbach’s alpha ( ) 
Data sources and time points 
Demographics/clinical 
characteristics 
Age, child age, health history, race/ethnicity, 
medications, health care utilization, rural/urban 
residence, insurance, caregiver demographics, 
family characteristics 
Caregiver interview; baseline 
Reach:  
Sample  
Recruitment 
Monitoring of sample representativeness; types of 
recruitment activities; rates of recruitment; % eligible, 
consented, provided with informational session 
Recruitment tracking forms; 
quality checks by PI; weekly 
meetings with mentor, clinic staff, 
and research team 
Efficacy: 
Child (by proxy): 
Pain 
Fatigue  
Quality of life 
Caregiver: 
Fatigue 
Emotional distress: anxiety 
Emotional distress: 
depressive symptoms 
Measures of self-
management behaviors: 
Monitoring and tracking 
symptoms 
Attending clinic 
appointments 
Administering home 
medications and 
treatments 
PROMIS Parent Proxy: Pain Interference*21,22(age 5 
and older)  
Self-efficacy SEMCD-6 
PedsQL with Sickle Cell Disease Module (proxy = 
0.97)23 
(age 2 and older) 
PedsQL Multidimensional Fatigue Scale in Sickle 
Cell Disease (proxy = 0.95)24 
(age 2 and older),  
PROMIS Fatigue SF, Depression SF (>0.9)25 
PROMIS Emotional Distress: Anxiety (0.97)26 
PROMIS Emotional Distress: Depressive symptoms 
SF (0.97)27 
 
Daily pain severity rating; daily pain type rating 
 
# days recorded symptoms; # days and types of 
recorded treatments; # scheduled clinic 
appointments attended; # days daily mediation 
administered; # days PRN medications administered 
Review and content analysis of 
transcriptions of text messages; 
review and content analysis of 
recorded teleconferences; 
tracking forms; fidelity checklist; 
transmissions from web-based 
application to nurse; post-
intervention interviews; weekly 
meeting with mentor, clinic staff, 
and research team; baseline, 
mid-intervention, post-
intervention, 3-months post-
intervention 
Adoption: 
Adherence 
 
 
 
Acceptability  
 
 
Education 
 
 
# days symptoms recorded; # times educational 
component accessed; length of time in minutes 
educational component accessed; # text messages 
and videoconferences with nurse 
Caregiver satisfaction; # problems reported; types of 
problems reported 
# times accessed educational materials; length of 
time in minutes educational materials accessed 
# days recorded symptoms; # contacts (text or 
videoconferencing) with nurse pertaining to 
symptoms 
Tracking forms; content analysis 
from text messages and 
videoconferences with nurse, 
data transmitted from web-based 
application; fidelity checklist; 
weekly meetings with mentor and 
research team; caregiver 
interview at end of study 

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Symptom monitoring and 
tracking 
 
Patient-provider 
communication 
# and type (screening, referring, coaching, 
supporting) of contacts (text or videoconferencing) 
with nurse  
Collaborate for Parents 
Implementation: 
Technology 
 
Consistency of intervention 
# problems encountered with mobile device, # 
problems reported to research staff; types of 
problems reported 
instructional session conducted as planned; fidelity to 
protocol maintained 
MAPS 
Tracking forms; weekly meeting 
with mentor and research team; 
caregiver interview at end of 
study 
Maintenance: 
Projection of future 
adoption 
# caregivers who would continue intervention; 
caregiver perception of the intervention; feasibility of 
nurse role 
Caregiver interview at end of 
study; weekly meetings with 
mentor, clinic staff, and team 
 
 
4.0 
Study Endpoints  
Study end points include: Successful study completions, Consent withdrawals, PI terminations, 
Lost contact with the patient, and unexpected adverse events. 
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 
• Eligible caregiver/child dyads will be identified through the staff at the MUSC 
Pediatric Sickle Cell Clinic. After receiving permission to approach, PI or PC will 
screen the potential participants against the inclusion and exclusion criteria. 
Screening will be documented in REDCap.   
Inclusion Criteria  
• 
Children ages 8 - 17 years and parent or primary caregiver 18 years of age or 
older 
• 
Child with sickle cell disease, as reported by clinician at the MUSC Pediatric 
Sickle Cell Clinic 
Exclusion Criteria 
• 
Parent/caregiver or child with cognitive disability or delay that precludes ability 
to participate  
• 
Lack of Wi-Fi access 
 
Inclusion of Women and Minorities 
Both women and minorities will be included in the proposed study. Women are more often than 
men reported to be the primary caregiver of children with chronic conditions and approximately 
66% of caregivers of adults with chronic illness are women. Therefore, it is anticipated that 
more women will be recruited as participants than men. In addition, SCD occurs almost 
exclusively in African Americans; therefore, it is anticipated that all or nearly all of the caregiver 
participants will be African American.  
 
Inclusion of Children 
Children without cognitive delay ages between the ages of 8-17 years will be included as part 
of the child/caregiver dyad. 
 
6.0 
Number of Subjects 

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N=60 – 30 caregivers of 30 children (8-17 years) with SCD will be recruited.  
7.0 
Setting 
• 
The intervention will be used by the participants in their community environments. 
Study visits will occur at MUSC Sickle Cell Unit and via telephone to the 
participant’s home.  
8.0 
Recruitment Methods 
• 
Parents/caregivers who participated in Phase I of the study and agreed to be re-
contacted for future research will be contacted and invited to participate.  
• 
For other potential participants, the MUSC Pediatric Sickle Cell Clinic staff will be 
given the inclusion/exclusion criteria and will be asked to identify eligible 
participants in the clinic. When potentially eligible participants attend an 
appointment at the clinic, the clinician/staff will approach the parent/caregiver, 
briefly introduce the study through an IRB approved study letter, and if interested 
ask if the researchers can speak with the parent/caregiver to offer additional 
information. For parents/caregivers who agree, the PI or PC will provide an 
overview of the study either by phone or face-to-face in the clinic and conduct 
eligibility screening. Eligible and interested parents/caregivers will proceed to the 
informed consent interview.  
• 
Additionally, for the purposes of this study and in direct alignment with the mission 
of the CON P20 Symptom Self-Management Center, we will employ the use of 
MUSC Bioinformatics Center (BMIC) core services to identify and recruit patients 
across the MUSC Enterprise that meet the study inclusion/exclusion criteria and 
that have granted authorized research contact permission in MyChart through the 
electronic ‘opt in’ EPIC designation. Once these potentially eligible patients are 
identified, we will then contact them by telephone using a script to determine if they 
are interested in study participation 
• 
Flyers will be posted in the waiting room and patient rooms at the MUSC Sickle 
Cell Clinic. The flyers will include the PI’s contact information; interested 
parents/caregivers who call the PI will be screened for eligibility.  
9.0 
Consent Process 
Since research will be conducted with caregiver/child dyads, consent will be obtained from the 
parent/caregiver and written assent from the child participant (12-17 years). In this study, we will 
employ the use of two informed consenting strategies (In-person meeting and electronically through 
REDCap e-Consent) so as to increase the reach of the study and to promote the generalizability of 
findings.  
 
In-Person informed consent will occur in the comfort and safety of a private clinic room at the MUSC 
Sickle Cell Unit prior to any screening procedures being conducted and/or data collection. Potential 
participants will be given the informed consent document to read and review in advance, and/or may 
have it read to them by the researchers if they prefer. After reviewing the Consent document, both 
caregiver and child will be given the opportunity to ask any questions about the study that they may 
have, and will be requested to demonstrate what is expected from them should they enroll in the 
study through a questioning of their understanding of study procedures and risks. Prior to consenting, 
all questions will be resolved to the caregiver and child's satisfaction. If a participant does not appear 
to understand the information contained within the Consent document, the study coordinator will 
review the consent document again with the participant. If after this second review, the subject does 
not demonstrate an understanding, they will not be enrolled in the study. Only participants, with no 

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diagnosed or observed cognitive impairment, will be consented and enrolled into the study.  
 
Electronic or e-Consenting will be performed on eligible families that want to participate in the study 
but are unwilling for whatever reason and/or unable to come to MUSC for a face-to-face informed 
consent meeting. Families identified through the study recruitment processes that fall into this 
category will already have spoken with the researchers by telephone, have been introduced to the 
study and its demands, as well as had their initial questions answered. After speaking with the 
researchers, families that are further interested in study participation will be asked to provide an email 
address at which they will receive a REDCap survey link containing a scanned image of the currently 
approved Informed Consent document (developed from the MUSC REDCap e-consent template). 
Families will be able to take as much time as they like to read the consent document together in the 
comfort and privacy of their own home or at a place and time of their choosing. They will be provided 
with the telephone and email contact details in the survey instruction header for the researchers, 
should they have any questions before providing their consent by adding their respective signatures 
to the form and submitting it. Prior to providing their physical e-consent, the researchers will 
coordinate with these families; so as to be on the telephone and be available to further answer any 
questions that they may have during the e-consent process. Should a participant have any questions 
or concerns about the study, the researchers will address these issues to the best of their abilities 
and knowledge. Upon submitting the e-consent, a REDCap trigger will immediately notify the 
researchers, who will then provide their countersignature to the document.  
 
The consent form will meet the requirements of the Code of Federal Regulations and the MUSC 
Institutional Review Board. The consent form will include the following: 
1. The purpose, nature, and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. The name and a contact of the investigator(s) responsible for the protocol. 
4. The right of the participant to accept or refuse study interactions and to withdraw from participation 
at any time. 
 
The HIPPA authorization process will be conducted sequentially with the family in the same manner 
by the researchers. Participants will be able to download a copy of their executed informed e-
consent/HIPAA authorization forms directly to their own computer, or have copies emailed to them. 
They will also be given the option to have a copy of their executed e-forms mailed to them should 
they elect to do so. A copy of the executed e-consent/HIPAA authorization forms will also be stored in 
the participant's electronic case record for monitoring and audit purposes. 
 
If a child participant should reach an age of majority while enrolled in the study, they will be asked to 
provide written consent.  
 
10.0 Study Design / Methods 
The mHealth SCD management intervention will be delivered via an app on both the caregiver and 
child mobile devices over a 12-week period. This multi-component, web-based app consists of 1.) 
continuous access to directed educational resources on the SCD process, treatment, home 
management strategies, symptom prevention and management strategies; 2.) a series of pages in 
the app that allow for tracking and monitoring symptoms; and 3.) child/caregiver – provider 
communication. The educational component is based on patient-centered materials that have been 
developed and tested by authoritative sources. In the app, educational materials are organized by 
user age (for individuals with SCD) or role for parents/caregivers. Citations are provided and links to 
the sources are included. The symptom tracking and monitoring component consists of a 
customizable avatar on which the user can record the location, severity, and characteristics of pain. 
Users can record other concurrent or associated symptoms (such as fatigue) and can view a graph 

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with the pain history. This portion of the app also includes a health history page on which users can 
document important clinical information, such as sickle cell type, last sickle cell crisis hospitalization, 
medications, and allergies. The child/caregiver – provider communication component consists of the 
ability for the child/caregiver to send a secure message to providers within the app to communicate 
pain and other symptoms. Providers will have the capability to securely send a reply within the app. In 
addition, children/caregivers can choose to receive a daily “support” message that will be 
automatically sent from a list of possible messages. All communication is encrypted and sent securely 
within the app via a portal. Two to three providers at the MUSC Sickle Cell Clinic will participate as 
the designated providers in the study.  
 
To determine feasibility, we will apply the RE-AIM framework to assess the Reach, Efficacy, 
Adoption, Implementation, and Maintenance of the intervention with 30 children/caregiver dyads.18 
The domains are further explicated in Table 1. The intervention will be loaded onto the child’s and 
caregiver’s tablet or smartphone (Apple or Android); participants without a device will be provided one 
for the duration of the study. The PI or PC will deliver detailed verbal instructions to the participants 
on the use of the device and the intervention. Participants will also receive written instructions and a 
contact number for technical assistance if needed. Baseline measures (Table 1) will be collected 
during the same meeting. Participants will retain the devices and will participate in the intervention 
over a 12 week-period. At the end of the 12-week period, the PI will conduct a post-intervention 
meeting with each individual caregiver and child participant during which post-intervention data 
collected. Caregivers will also be asked to return the mobile device  at the end of the study. The PI 
will meet with the study provider weekly during the intervention. 
 
Retention: To improve retention, IRB-approved personnel will contact enrolled participants at 3-
week intervals between data collection points. The timeline for these points of contact are at the 
following weeks post baseline data collection: weeks 3, 9, 15, 18, and 21. The purpose is to maintain 
contact with enrolled participants, not data collection. Correspondence will be logged in REDCap. 
Contact will take place via text message, using the number(s) provided to study personnel upon 
enrollment. Examples of messages are provided in an uploaded attachment.  
 
 
Post-intervention interviews. All 30 caregivers and their children will be asked if they would like to 
participate in the 3-month post-intervention key informant interviews with the PI to obtain more in-
depth data on accessibility, usability, and adherence to intervention. However, only a subset of 15 
dyads will be chosen to participate. Selection will be by computer at random. Both caregiver and child 
will have to agree to participate in the interview to be eligible for selection. Dyads have a 50-50 
chance of being randomly selected. Semi-structured interviews will be conducted using a qualitative 
descriptive approach,17 will last approximately 45-60 minutes, and will be conducted according to an 
interview guide with open-ended questions and prompts. These interviews will be recorded for later 
nVivo qualitative data analysis. Reimbursement for dyads will be a $50 gift card provided at each of 
the 4 data collection points, with dyads in key informant interviews receiving an additional $40 gift 
card. All payments will be given to the caregiver. Selected caregivers will be given the option of 
having the interview conducted in-person in a private room at MUSC or by telephone in the comfort 
and safety of their own home. 
 
Measures. Children (8-17 years) and Caregivers will complete age-appropriate self-report 
assessments at baseline, mid-intervention (6 weeks), post-intervention (12 weeks), and 3 months 
post-intervention as previously described. Self-report and proxy assessments will be collected during 
meetings between the PI or PC and the participant. Depending on participants’ preference and 
availability visit 2, 3 and 4 surveys will be completed either by phone or electronically via REDCap 
survey or by paper and pencil. All data will be recorded in REDCap by the PC.  

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11.0 Specimen Collection and Banking 
Not applicable 
 
12.0 Data Management  
Sample size considerations 
The purpose of this study is to establish feasibility of implementing the integrated intervention obtain 
estimates of variability for the primary outcome measures and obtain preliminary indicators of 
effectiveness of the intervention rather than to confirm or refute hypotheses. Therefore, sample size 
considerations focus on precision of estimates. For this feasibility study, we project that we will be 
able to recruit 30 child/caregiver dyads. With such a sample we will be able to estimate outcome 
proportions for feasibility measures including recruitment and drop-out with precision ±0.11 to ±0.16 
for values of the true proportion ranging from 0.10 to 0.30 (or correspondingly, from 0.70 to 0.90). 
Assuming a drop-out rate of up to 30%, 95% confidence limits can be estimated for impact measures, 
such as change from pre-to-post in quality of life for child and caregiver with a precision ranging from 
±0.43 to ±1.35 corresponding to estimated standard deviations for change in quality of life scores 
ranging from 0.5 to 5.0 SD units. 
 
Demographic and clinical variables obtained at baseline will be described via measures of central 
tendency (mean, median), variability and frequency distributions as appropriate. Additionally, 
demographic and clinical characteristics for those who adhered to the study protocol (study 
completers) versus those who did not adhere (non-adherers and drop-outs) will be compared to 
better describe the population for this study. For continuous quality of life measures for the child and 
caregiver the difference between pre and post intervention measurements will be estimated via 95% 
confidence intervals. To assess preliminary intervention effects, we will conduct repeated measures 
ANCOVA with symptom (pain) severity and type obtained daily as dependent variable in individual 
models adjusting for “dose” defined as number of times education module was accessed and total 
time spent in education modules. 
 
Post-intervention qualitative analyses (Aim 2): Data collected from post-intervention key informant 
interviews will be analyzed using directed content analysis19 and nVivo qualitative data analysis 
software version 11.20 Consistent with the directed content analysis approach, initial coding 
categories are identified according to the guiding theoretical model, and for this study, will reflect the 
RE-AIM domains.  
 
13.0 Provisions to Monitor the Data and Ensure the Safety of Subjects 
There is a well-developed and NIH/NINR prepared SRG approved DSMP that involves the use of a 
Safety Monitoring Committee (SMC) that shall meet semi-annually post initial study enrollment. The 
Committee is comprised of key individuals that include: an independent medical safety monitor (ISM), 
a biostatistician (BS), and the Program Manager (PM). 
 
The following members of the study’s DSMC will perform data safety monitoring of the study: 
• Dr. Cristina Lopez, Independent Safety Monitor (ISM) - primary responsibility 
• Mr. Mohan Madisetti, MS, Project Manager (PM) 
• Ms. Mary Dooley, Biostatistician (BS) - supervised by Dr. Martina Mueller. 
 
Independent Safety Monitor (ISM), Dr. Lopez who is Assistant Professor at Medical University of 
South Carolina, has a PhD and a background as a clinical psychologist with expertise in adolescent 
behavioral research, and will act as the study’s Independent Safety Monitor (ISM). Dr. Lopez has no 
real or apparent conflict of interest that would affect her performance in this role on the study.  
 

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Project Manager, (PM). Mr. Madisetti, MS, has over 20 years of research experience in study 
management, quality assurance and the protection of human subjects. Mr. Madisetti is CTRC, CITI 
/GCP and NIH trained in Human Subject Protections, and has completed MUSC’s Certificate of 
Competence in Research Ethics (CREP) and member of the Institute of Human Values Ethics 
Committee. Mr. Madisetti has also been a member of over 5 federally and FDA sponsored research 
full DSMBs. 
 
Biostatistician (BS) Ms. Dooley is a biostatistician and faculty at the College of Nursing at the Medical 
University of South Carolina. Ms. Dooley has experience collaborating with investigators in clinical 
trials as well as in community based participatory research. Ms. Dooley will be supervised by Dr. 
Martina Mueller from the College of Nursing. 
 
From the initial screening of subject by inclusion and exclusion criteria to the informed consent 
process to the provision of participant study instruction to staff training in Good Clinical Practices 
(GCP) and regulations pertaining to the Conduct of Human Subject Research to routine contact with 
participants to internal quality control audits and protocol fidelity monitoring to the real-time review of 
AE’s by the SMC to the oversight of the IRB - procedures for monitoring study safety are consistently 
afforded throughout the study. Specific study procedures include: 
• Participants will be screened for inclusion and exclusion per the protocol  
• Participants will be fully informed as to all know risks and the possibility of risk from study 
participation in the informed consent process. These risks are minimal. 
• Participants will be instructed to notify the researchers of any/all suspected or experienced adverse 
events whether they believe them to be related or not to the intervention. 
• The PI or PC will track all reported participant AEs through to resolution.  
• All investigators and researchers will maintain active CITI and GCP training. 
• The PI or PC will maintain weekly contact with all participants to elicit information about AE’s and to 
monitor participant study progress, compliance and safety. 
• The PI or PC will review participants study logs for fidelity compliance with the intervention. 
• The PI or PM will conduct quarterly internal quality control audit of all participant records to ensure 
compliance with MUSC IRB regulations; the PI and PC will work together to correct any errors. 
• The BS shall generate semi-annual AE reports for the PI, SMC and IRB to review. 
• The ISM will have access to real-time study data and will be able to provide immediate 
recommendations to the PI and PD. 
• Investigator performance and compliance will be provided for through MUSC IRB and ORI study 
oversight. 
 
Protecting Confidentiality of Participant Data 
Participant Screening and Enrollment. All data from participants screened for the study will be 
entered into an electronic study database. Designated research staff will collect, gather, and enter 
required data (written informed consent, HIPAA Authorization, and demographics) onto study data 
forms. Screened patients who do not meet study eligibility will have specific screening data entered 
into the study database. The collected data will be helpful in examining the patient population and 
feasibility of enrollment criteria and will include reason for exclusion. All dates will be shifted and other 
Personal Health Information (PHI) will be removed from the study database upon study completion. 
All data obtained from this study will be used for research purposes only and will comply with Federal 
HIPAA regulations.  Master Screening and Enrollment Logs will be maintained by the PI or PD and 
will be used by the PI or PD to prepare reports on accrual and attrition for the ISM and SMC. 
 

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Case Report Forms. All proposed study specific case report forms (source documents) for data 
collection will be designed by the PI and, when possible, transferred by the PI or PC into electronic 
Case Report Forms (eCRFs) for use in the study’s REDCap database. These study specific eCRFs 
source documents (study logs for correspondence, compensation and other forms such as pre-
eligibility screens) will be coded by the participant’s unique study ID# for all data collected including 
study instruments will be maintained in the participant research record. Completed instruments that 
require signature on a paper CRF will be scanned and uploaded into the study database to all for 
remote electronic safety monitoring as well as maintained on file in accordance with MUSC policies 
and applicable Federal Regulations for the Conduct of Human Participant Research.  
 
Binders. The PI or PC will prepare and maintain a participant-specific binder for each participant 
containing all non-eCRFs records. A regulatory file will also be maintained to include the IRB-
approved Protocol, original Informed Consent documents, HIPAA forms and other study-related 
regulatory documents. All paper research records and CRFs will be maintained in a locked file 
cabinet, stored in a room for research files that is accessible only via a password protected entry 
system that features security cameras, within the College of Nursing. Access to the research records, 
study database and PHI’s will be restricted to study personnel as approved by the PI and MUSC IRB. 
As with all studies conducted at MUSC, this study is also eligible for a random audit by MUSC Office 
of Compliance. 
 
Data Processing. This study will use Research Electronic Data Capture (REDCap) for data 
capture and management. REDCap is a software toolset and workflow methodology for the 
electronic collection and management of research and clinical trials data. REDCap provides 
secure, web-based, flexible applications, including real-time validation rules with automated data 
type and range checks at the time of data entry. Exports are made available for several statistical 
packages including SPSS, SAS, SATA, R and Microsoft Excel. The study-specific REDCap 
electronic database will be designed and developed by the PI or PD in concert with the BS.  The 
provision of REDCap is made available through the South Carolina Clinical & Translational Research 
(SCTR) Institute at MUSC with NIH Grant awards UL1RR029882 and UL1TR000062.  
 
Data Security. Ensuring data security, compliance with 45 CFR 46 and maintaining the integrity of 
PHI is a top priority. MUSC has Standard Operating Procedures (SOP) to ensure a high level of data 
security while coordinating electronic and paper data management activities for clinical research 
trials. The REDCap study database will be hosted in the Biomedical Informatics secure data center at 
MUSC, a secure environment for data systems and servers on campus, and includes firewall, 
redundancy, failover capability, backups and extensive security checks. The secure data center has 
strict access control; only authorized core personnel may access the facility un-escorted. Only 
authorized users are allowed to connect to the network, and the security of the network is actively 
monitored.  Power and environmental controls have several layers of backups, from interruptible 
power supplies to alternate and redundant feeds to the local utility company. The REDCap system 
administrator contributes to the maintenance of institutional disaster recovery and business continuity 
plans.  Load balancers and a highly fault tolerant SAN infrastructure contribute to high availability.  
 
The REDCap system itself has several additional layers of protection including password protection. 
Access to the data and its security is managed institutionally by sponsored login IDs through a 
Shibboleth login with an MUSC issued NetID and features a user account management filter that 
controls who can access the data and to what degree. All personnel must pass an employment 
background check before being issued an ID. Password complexity, history and expiration standards 
are implemented at the institutional level. Access to individual REDCap projects and their data is 
managed by the owner of the project. All transactions are securely delivered to the application using 
Secure Sockets Layer (SSL – SHA-1 with RSA Encryption; 2048-bits). It is then transmitted internally 

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(behind the firewall) to the database server. All transactions are logged at the server layer (httpd 
logging), application layers (REDCap logs activity to a database table), and the database layer, using 
both query and binary logging. This feature provides audit trails for all changes, queries, data exports 
and reports. MUSC Information security policies are available at: https://mainweb-
v.musc.edu/security/policy/  
 
Data Entry. Only MUSC IRB approved study personnel that are authorized to have access to the 
REDCap study database will be granted password access. Study personnel using computers that are 
connected to the Internet will directly enter data into the remotely housed database. As such, no 
electronic study data will be stored on hard drives and/or any portable electronic devices. Additionally, 
all personnel with access to the database will have current University of Miami CITI and GCP training 
in the Conduct of Human Subject Protections, and HIPAA and Information Security trainings that are 
completed annually. Each participant will be assigned a unique study identifier, all PHIs will be 
masked, and data exports will be limited to the PI or the BS for generating reports and the conduct of 
statistical data analysis. 
 
Data Monitoring. Ongoing quality control procedures will be implemented for data collection, 
storage and processing. The PI or PD will conduct monitoring of the study database and generate a 
report for review at team meetings. Standing agenda items for these meetings will include participant 
recruitment and retention, AE’s, protocol deviations, data integrity and overall study conduct. The PI 
and PD will work to resolve and validate discrepant data. Discrepancies that warrant clarification will 
be sent to appropriate parties for review and resolution. All data entry and changes made in the 
study database by authorized study personnel will be automatically logged by REDCap, and provide 
a transparent visible audit trail for reviewers. 
 
14.0 Withdrawal of Subjects 
The PI may withdraw a participant from the study at any time if they decide it is in their best interest, if 
they do not follow the investigator’s instructions, or if they fail to keep study visits. This may also 
occur if there is a protocol violation or early closure of the study. 
 
15.0 Risks to Subjects  
 
Based on Phase I of the study, we do not anticipate any significant risks related to the completion of 
the surveys and key informant interviews in this study. However, as with any research study there is a 
risk of disclosure of information that can lead to a loss of confidentiality. As well as having a 
comprehensive DSMP that details data safety, handling, monitoring, storage and security procedures, 
we will further minimize the potential for loss of confidentiality through the physical separation of 
participant names from their research record.  
 
Additionally, it is possible that a participant might experience some emotional distress while 
responding to the survey questions or participating in key informant interviews. If this were to occur, 
the participant would be referred to a psychologist or psychiatrist for counseling. Reactions will be 
monitored by the PI (who will be conducting the interviews) and signs of significant distress will be 
followed-up to identify any serious psychological problems. In the rare and unexpected event of 
serious or life threatening level of distress, a psychologist or psychiatrist will be contacted as well as 
the participant’s primary care provider of record. 
 
16.0 Potential Benefits to Subjects or Others 
If a participant agrees to take part in this study, there will be no direct medical benefit to them. We 
hope the information learned from this study will aid patients and clinicians in the future. The data 
collected from this study will not directly affect the treatment being given to the patients. The risks 
associated with the proposed study are minimal and include psychological and physical strains that 

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might be encountered in everyday life. The benefits of the study outweigh the risks. 
 
 
 
 
 

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Literature Cited 
 
 
Choi, S., Podrabsky, T., McKinney, N., Schalet, B., Cook, K. F., & Cella, D. (n.d.). PROsetta Stone 
analysis report Retrieved from  
DeWalt, D. A., Gross, H. E., Gipson, D. S., Selewski, D. T., DeWitt, E. M., Dampier, C. D., . . . Varni, 
J. W. (2015). PROMIS pediatric self-report scales distinguish subgroups of children within and 
across six common pediatric chronic health conditions. Quality of Life Research, 24, 2195-
2208. doi:10.1007/s11136-015-0953-3 
Glasgow, R. E., Vogt, T. M., & Boles, S. M. (1999). Evaluating the public health impact of health 
promotion interventions: the RE-AIM framework. American Journal of Public Health, 89(9), 
1322-1327.  
Hassell, K. L. (2010). Population estimates of sickle cell disease in the U.S. American Journal of 
Preventive Medicine, 38(4, Supplement), S512-S521. 
doi:http://dx.doi.org/10.1016/j.amepre.2009.12.022 
Hsieh, H., & Shannon, S. E. (2005). Three approaches to qualitative content analysis. Qualitative 
Health Research, 15(9), 1277-1288. doi:10.1177/1049732305276687 
Jacob, E., Pavlish, C., Duran, J., Stinson, J., Lewis, M. A., & Zeltzer, L. (2013). Facilitating pediatric 
patient-provider communications using wireless echnology in children and adolescents with 
sickle cell disease. Journal of Pediatric Health Care, 27(4), 284-292. 
doi:10.1016/j.pedhc.2012.02.004 
Lai, J.-S., Cella, D., Choi, S., Junghaenel, D. U., Christodoulou, C., Gershon, R., & Stone, A. (2011). 
How Item Banks and Their Application Can Influence Measurement Practice in Rehabilitation 
Medicine: A PROMIS Fatigue Item Bank Example. Archives of Physical Medicine and 
Rehabilitation, 92(10, Supplement), S20-S27. doi:http://dx.doi.org/10.1016/j.apmr.2010.08.033 
Modi, A. C., Pai, A. L., Hommel, K. A., Hood, K. K., Cortina, S., Hilliard, M. E., . . . Drotar, D. (2012). 
Pediatric self-management: A framework for research, practice, and policy. Pediatrics, 129, 
e473-e485. doi:10.1542/peds.2011-1635 
National Heart  Lung and Blood Institute. (2015, June 20, 2015). What is Sickle Cell Disease?   
Retrieved from http://www.nhlbi.nih.gov/health/health-topics/topics/sca/ 
Palermo, T. M., Schwartz, L., Drotar, D., & McGowan, K. (2002). Parental report of health-related 
quality of life in children with sickle cell disease. Journal of Behavioral Medicine, 25(3), 269-
283.  
Panepinto, J. A., Torres, S., Bendo, C. B., McCavit, T. L., Dinu, B., Sherman-Bien, S., . . . Varni, J. W. 
(2013). PedsQL Sickle Cell Disease Module: Feasibility, reliability, and validity. Pediatric Blood 
& Cancer, 60, 1338-1344. doi:10.1002/pbc.24491 
Pilkonis, P. A., Choi, S., Salsman, J., Butt, Z., Moore, T. L., Lawrence, S. M., . . . Cella, D. (2013). 
Assesment of self-reported negative affect in the NIH Toolbox. Psychiatry Research, 206(1), 
88-97. doi:10.1016/j.psychres.2012.09.034 
Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., & Klug, P. P. 
(1994). Mortality in sickle cell disease -- Life expectancy and risk factors for early death. New 
England Journal of Medicine, 330(23), 1639-1644. doi:doi:10.1056/NEJM199406093302303 
Powars, D. R., Chan, L. S., Hiti, A., Ramicone, E., & Johnson, C. (2005). Outcome of sickle cell 
anemia: A 4-decade observational study of 1056 patients. Medicine, 84(6), 363-376. 
doi:10.1097/01.md.0000189089.45003.52 
QSR International Pty Ltd. (2012). NVivo qualitative data analysis software (Version 10).  
Raphael, J. L., Dietrich, C. L., Whitmire, D., Mahoney, D. J., Mueller, B. U., & Giardino, A. P. (2009). 
Healthcare utilization and expenditures for low income children with sickle cell disease. 
Pediatric Blood & Cancer, 52(263-7). doi:10.1002/pbc.21781 

Version 4.0 
 
       Revised 09/25/18 
Reddin, C. D. R. C., Cerrentano, E., & Tanabe, P. (2011). Sickle Cell Disease Management in the 
Emergency Department: What Every Emergency Nurse Should Know. Journal of Emergency 
Nursing, 37(4), 341-345. doi:http://dx.doi.org/10.1016/j.jen.2010.04.014 
Sandelowski, M. (2000). Whatever happened to qualitative description? Res Nurs Health, 23, 334-
340.  
van den Tweel, X. W., Hatzmann, J., Ensink, E., van der Lee, J., Peters, M., Fijnvandraat, K., & 
Grootenhuis, M. (2008). Quality of life of female caregivers of children with sickle cell disease: 
a survey. Haematologica, 93(4), 588-593. doi:10.3324/haematol.11610 
Varni, J. W., Magnus, B., Stucky, B. D., Liu, Y., Quinn, H., Thissen, D., . . . DeWalt, D. A. (2014). 
Psychomatric properties of the PROMIS pediatric scales: Precision, stability, and comparison 
of different scoring and administration options. Quality of Life Research, 23, 1233-1243. 
doi:10.1007/s11136-013-0544-0 
 

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Page 1 of 17 
 
 
PROTOCOL TITLE: 
 
A Family-Centered Self-Management Program for Young Children with Sickle Cell 
Disease: Phase II 
 
PRINCIPAL INVESTIGATOR: 
 
Shannon Phillips, PhD, RN 
 
 

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Page 2 of 17 
 
  
1.0 
Objectives / Specific Aims 
Specific Aims: Few family-centered self-management interventions exist to assist children 
with sickle cell disease (SCD) and their families, which deprive this population of skills that may 
improve symptom management and quality of life. SCD is an inherited complex chronic 
condition (CCC) that leads to adverse health outcomes such as pain and organ damage affecting 
approximately 100,000 people in the US. In addition to living with pain and negative health 
outcomes, children and adults with SCD also face disparities in access to care. Infants and young 
children with more complicated CCCs, such as SCD, and those who have fewer resources are at 
greater risk for adverse outcomes such as increased hospital and emergency department (ED) 
utilization and physical and psychosocial morbidity. Children with SCD and their families, 
particularly those who are underserved, would benefit from interventions designed to bolster 
self-management skills and enhance preventive management of the disease to reduce negative 
complications. Importantly, caregivers of young children with SCD are often new to the disease 
process and have unique needs and challenges.  
      
Interventions designed to address the unique needs of and barriers encountered by this 
population could improve effective management of the disease in the home setting. In addition, 
technology-based resources such as mobile health applications for symptom tracking, may allow 
intervention delivery to typically difficult-to-reach populations, thereby reducing access barriers 
to care, including lack of transportation and obtaining childcare. Further, incorporating theory-
based family-centered self-management strategies is crucial to support families in developing 
sustainable, improved self-management behaviors (e.g. monitoring symptoms, and attending 
clinic appointments) which will ultimately improve symptom management (e.g. pain, fatigue) 
and quality of life, and decrease costly emergency department (ED) visits and hospitalizations.  
 
The interprofessional team of investigators for this study includes a mentee (Phillips) 
with a clinical background as a pediatric acute care nurse and research experience with 
exploring barriers in access to care among children with CCC. Mentors include an R01 funded 
nurse scientist who is an expert in intervention development and the conduct of clinical trials 
(Kelechi: primary mentor), an R01 funded clinical psychologist with extensive expertise in 
technology, user-based design, and intervention adaptation (Ruggiero: co-mentor), a pediatric 
hematologist/oncologist specializing in clinical care and research with populations with SCD 
(Kanter: co-mentor), and a biostatistician with extensive research experience (Mueller: co-
mentor). This complementary interdisciplinary team has the knowledge, skills, and access to the 
population to successfully conduct this study, but will also provide the mentee with mentorship 
and training experiences in theory-based, technology-enhanced intervention research among a 
population of children with a CCC and their caregivers.  
 
There are three main components within the study intervention: previously tested 
educational materials for adults with SCD and their families, a publicly available mHealth 
application for tracking pain in SCD, and a model of patient-provider communication delivered 
via mHealth that has been tested with older children with SCD. The goal of the proposed 
research is to use the theory-based Pediatric Self-Management Model to tailor and pilot test the 
effect of an integrated intervention on psychosocial and physical symptom management and 
quality of life for children with SCD ages 0-7 years and their caregivers.  
 
During Phase I of this study, we refined the development and design of the intervention 
under study, by conducting user focus groups and pilot testing the app with provider feedback 
among a target population of end-users. Now, in Phase II, we aim to deploy the intervention in a 
real-world setting. The purpose of this second phase of this study is to conduct feasibility testing 
of an innovative, technology-based intervention to improve self-management behavior, quality 
of life, and symptom management in a sample of children with SCD and their families.  
 

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Page 3 of 17 
 
 
During this second phase of this study, we seek to achieve the following aims: 
 
Primary Aim: Assess feasibility of implementation processes including reach, enrollment, 
fidelity, adoption, acceptability, and satisfaction using the RE-AIM framework with process 
measures, surveys, and key informant interviews. 
 
Secondary Aim: Investigate the presence of signals of efficacy on measures of self-
management, and physical and psychological symptoms and quality of life. 
 
2.0 Background 
Importance of the problem. The significance of this project lies in the fact that it is the first 
step (adaptation and feasibility testing) in a research continuum that will lead to validation of a 
technology-based intervention for improving self-management, symptom management, health 
care utilization and ultimately quality of life among populations of children with complex 
chronic conditions (CCC) and their caregivers. As such, this project is directly in line with the 
stated core mission of the NIH’s National Institute of Nursing Research.  
     Sickle cell disease (SCD) is a highly complex and challenging chronic disorder that negatively 
influences quality of life in children and families of those with the disorder.1 SCD is a hereditary 
CCC that almost exclusively affects African Americans. Nationwide, an estimated 72,000 to 
98,000 individuals have SCD; >90% of these are African American.2 Symptoms of SCD often 
occur within the first year of life and require lifelong preventive management. SCD is a 
hemoglobinopathy characterized by an altering in the shape of red blood cells in response to 
hypoxia, stress, or acidosis.3,4 These abnormally shaped cells occlude small vessels and cause 
inflammation, pain, infarction, and ultimately, organ damage.3,4 The physiological sequelae of 
SCD lead to high health care needs and utilization, and often, to comorbidities and early 
death.5,6 Many children with CCC, particularly SCD, and their families have high health care 
needs that are frequently unmet or inadequately met. SCD is one of several CCCs affecting 
children that could benefit from improved self and family management care, such as epilepsy, 
cerebral palsy, and chronic respiratory disease.7,8  
SCD as a CCC based in health disparity. Because children with SCD and their families have 
high health care and “other” needs that endure throughout their lifetime, preventive actions are 
necessary in early childhood to avoid or mitigate adverse effects of the disease process. For 
optimal management and minimal adverse effects, persons with SCD and/or caregivers must 
coordinate appointments with various providers, continuously monitor symptoms, and obtain 
preventive home therapies. Often, challenges are pronounced early in the disease process as 
caregivers learn about the disease and treatments. Typically, a multidisciplinary team is 
established and caregivers learn to coordinate and maintain care. However, SCD primarily 
affects an underserved population (i.e., African Americans) who disproportionately face barriers 
such as transportation, obtaining childcare, and taking time from work. In fact, low-income 
children with SCD have significantly higher hospitalizations and ED visits than other children in 
general.9 
Methods to enhance self-care of SCD by affected individual and the family are 
needed. Self-care interventions to prevent adverse effects of the disease process have not been 
well implemented for children with SCD. Fortunately, assistance with providing reliable sources 
of disease and treatment related information, decision-making, and communication with the 
care team via technology improve family-centered self-management behaviors in older children 
(ages 10-17 years) with SCD.10 Assisting families caring for an infant or young child with SCD via 
a similar technology-based model may lead to improved self-management and quality of life 
outcomes. Providing resources via this mechanism may reduce burden and maximize outreach 

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Page 4 of 17 
 
to this difficult to reach, underserved, high needs population. Traditional barriers to care such as 
transportation, childcare, and work conflicts can be overcome. Long-term management of SCD 
and prevention of adverse outcomes also requires support for self-management skill 
development. Through technological resources and collaborative relationships with providers, 
caregivers can receive support to develop self-management skills.  
Theoretical Framework. The Pediatric Self-Management Framework7 guides the present 
study and provides an ideal underpinning to our proposed methods because it outlines 
multilevel influences that affect self-management and family-centered self-management 
behaviors through multiple processes, and guides prediction of the outcomes associated with 
influences, behaviors, and processes.  According to this framework, self-management influences, 
processes, and behaviors exist on the individual, family, community, and health care system 
domains. Because this study will focus on children ages birth-7 years and their caregivers, and 
on the caregiver-provider relationship, we will target the family and health care system domains. 
Specific influences, processes, and behaviors addressed in this study are outlined in Table 1. 
 
Table 1: Intervention Self-Management Influences, Processes, and Behaviors 
 
 
3.0 
Intervention to be studied 
     
The intervention is a multicomponent (3-part) technology-
based package. The intervention targets influences and processes 
informed by the Pediatric Self-Management framework (Table 1). 
Component 1 (education) consists of continuous access to directed 
educational resources on the SCD process, treatment, home 
management strategies, symptom prevention and management 
strategies. These materials are easily accessible via a mobile device 
given to caregivers and will include patient-centered PDF files and 
links to websites developed and tested by authoritative sources. An 
example includes the patient education materials provided by NIH 
NHLBI such as the Sickle Cell Disease Infographic: Monitoring 
Pain (Figure 1). To address potential literacy barriers, an 
Self-management 
Influences 
Self-management Processes 
Self-management 
Behaviors 
• Family disease and 
treatment knowledge 
• Parental monitoring 
and supervision 
• Parental involvement 
• Patient (parental)-
provider 
communication 
• Determining child’s health care 
needs 
• Communication with medical 
team 
• Seeking disease and treatment 
related information 
• Determining child’s health care 
needs 
• Allocation of treatment 
responsibility 
• Learning about patient’s disease 
and treatments 
• Provision of support for 
treatment regimens 
• Modification of communication 
styles 
• Shared decision making 
• Giving medication and 
treatments such as 
home physical and 
respiratory therapy 
• Attending clinic 
appointments 
• Monitoring and 
tracking symptoms 
• Introducing and 
supporting lifestyle 
modifications 
• Providing 
recommended 
therapies 
Figure 1: Example of Educational 
Material 

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Page 5 of 17 
 
application that reads PDF files aloud (e.g. @Voice Aloud Reader) is downloaded onto caregiver 
devices. Component 2 (symptom monitoring and tracking) consists of a mobile-device based 
publicly available application for tracking and monitoring pain in SCD that also permits upload 
of symptom logs and text alerts to a health care provider (Voice Crisis Alert). Component 3 
(caregiver-provider communication) is based on Jacob et al. (2013)’s intervention with an 
mHealth intervention for older children with SCD. This component consists of a technology-
based connection with a provider who will: respond to alerts delivered via the mHealth 
application, monitor pain symptoms delivered via the mHealth application, and respond to 
messages. A provider at the MUSC Pediatric Sickle Cell Clinic will collaborate with caregivers to 
coach caregivers on the care of the child and provide support to the caregiver.10 Caregivers will 
receive a daily message using a semi-structured protocol to “check in” with participants and 
promote engagement. All components are integrated into the web-based app. A secure portal is 
in place for messaging that encrypts all messages and protects confidentiality.  
 
 
During Phase I of this study, using an iterative design process and guided caregiver, child 
and clinician feedback, we developed and refined the intervention by conducting user focus 
groups and pilot testing the app among a target population of end-users. Specific tasks 
accomplished during this Phase I, included developing and incorporating age specific language 
into the app, refining the user graphical user interface, developing and integrating the provider 
communication component to include clinically relevant disease specific symptoms, and build-
out of the clinician’s patient portal – where individual patient’s data can be accessed for 
summary viewing. Now, in Phase II, we aim to deploy the intervention in a real-world setting.  
 
 
Children (5-7) with SCD and their caregivers will complete self-report and proxy 
assessments as described in Table below; data will be recorded in REDCap by the PI or project 
coordinator 
 
Major tasks and 
domains 
Measures/instruments/ 
questions and Cronbach’s alpha ( ) 
Data sources and time 
points 
Demographics/clinical 
characteristics 
Age, child age, health history, 
race/ethnicity, medications, health care 
utilization, rural/urban residence, 
insurance, caregiver demographics, 
family characteristics 
Caregiver interview; 
baseline 
Reach:  
Sample  
Recruitment 
Monitoring of sample 
representativeness; types of recruitment 
activities; rates of recruitment; % 
eligible, consented, provided with 
informational session 
Recruitment tracking 
forms; quality checks by 
PI; weekly meetings with 
mentor, clinic staff, and 
research team 
Efficacy: 
Child (by proxy): 
Pain 
Fatigue  
Quality of life 
Caregiver: 
Fatigue 
Emotional distress: 
anxiety 
Emotional distress: 
depressive symptoms 
PROMIS Parent Proxy: Pain 
Interference*21,22 
(age 5 and older) 
PedsQL with Sickle Cell Disease Module 
(proxy = 0.97)23 
(age 2 and older) 
PedsQL Multidimensional Fatigue Scale 
in Sickle Cell Disease (proxy = 0.95)24 
(age 2 and older) 
PROMIS Fatigue SF (>0.9)25 
Review and content 
analysis of transcriptions 
of text messages; review 
and content analysis of 
recorded teleconferences; 
tracking forms; fidelity 
checklist; transmissions 
from web-based 
application to nurse; 
post-intervention 
interviews; weekly 

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Page 6 of 17 
 
Measures of self-
management 
behaviors: 
Monitoring and 
tracking symptoms 
Attending clinic 
appointments 
Administering home 
medications and 
treatments 
PROMIS Emotional Distress: Anxiety 
(0.97)26 
PROMIS Emotional Distress: Depressive 
symptoms SF (0.97)27 
 
Daily pain severity rating; daily pain type 
rating 
 
# days recorded symptoms; # days and 
types of recorded treatments; # 
scheduled clinic appointments attended; 
# days daily mediation administered; # 
days PRN medications administered 
meeting with mentor, 
clinic staff, and research 
team; baseline, mid-
intervention, post-
intervention, 3-months 
post-intervention 
Adoption: 
Adherence 
 
 
 
Acceptability  
 
 
Education 
 
 
Symptom monitoring 
and tracking 
 
Patient-provider 
communication 
# days symptoms recorded; # times 
educational component accessed; length 
of time in minutes educational 
component accessed; # text messages 
and videoconferences with nurse 
Caregiver satisfaction; # problems 
reported; types of problems reported 
# times accessed educational materials; 
length of time in minutes educational 
materials accessed 
# days recorded symptoms; # contacts 
(text or videoconferencing) with nurse 
pertaining to symptoms 
# and type (screening, referring, 
coaching, supporting) of contacts (text or 
videoconferencing) with nurse  
Collaborate for Parents 
Tracking forms; content 
analysis from text 
messages and 
videoconferences with 
nurse, data transmitted 
from web-based 
application; fidelity 
checklist; weekly 
meetings with mentor 
and research team; 
caregiver interview at end 
of study 
Implementation: 
Technology 
 
Consistency of 
intervention 
# problems encountered with mobile 
device, # problems reported to research 
staff; types of problems reported 
instructional session conducted as 
planned; fidelity to protocol maintained 
MAPS 
Tracking forms; weekly 
meeting with mentor and 
research team; caregiver 
interview at end of study 
Maintenance: 
Projection of future 
adoption 
# caregivers who would continue 
intervention; caregiver perception of the 
intervention; feasibility of nurse role 
Caregiver interview at 
end of study; weekly 
meetings with mentor, 
clinic staff, and team 
 
4.0 Study Endpoints  
Study end points include: Successful study completions, Consent withdrawals, PI 
terminations, Lost contact with the patient, and unexpected adverse events.  
 
5.0 Inclusion and Exclusion Criteria/ Study Population 
• Eligible caregiver/child dyads will be identified through the staff at the MUSC 
Pediatric Sickle Cell Clinic. After receiving permission to approach, PI or PC will 

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screen the potential participants against the inclusion and exclusion criteria. 
Screening will be documented in REDCap.   
Inclusion Criteria  
• 
Children ages 0 – 7 years and parent or primary caregiver 18 years of age 
or older 
• 
Child with sickle cell disease, as reported by clinician at the MUSC 
Pediatric Sickle Cell Clinic 
Exclusion Criteria 
• 
Parent/caregiver with cognitive disability or delay that precludes ability 
to participate  
• 
Lack of access to Wi-Fi 
Inclusion of Women and Minorities 
Both women and minorities will be included in the proposed study. Women are more 
often than men reported to be the primary caregiver of children with chronic conditions 
and approximately 66% of caregivers of adults with chronic illness are women. Therefore, 
it is anticipated that more women will be recruited as participants than men. In addition, 
SCD occurs almost exclusively in African Americans; therefore, it is anticipated that all or 
nearly all of the caregiver participants will be African American.  
 
Inclusion of Children 
Children ages 0-7 years will be included as part of the child/caregiver dyad. Proxy data 
will be collected on children younger than 5 years, and older children (ages 5-7 years) 
without developmental delay will be invited to complete surveys and participate in key 
informant interviews with the caregiver.  
 
6.0 Number of Subjects 
• N=60 – 30 caregivers of 30 children (0-7 years) with SCD will be recruited.  
 
7.0 Setting 
• 
The intervention will be used by the participants in their community 
environments. Study visits will occur at MUSC Sickle Cell Unit and via 
telephone to the participant’s home.  
 
8.0 Recruitment Methods 
• 
Parents/caregivers who participated in Phase I of the study and agreed to be 
re-contacted for future research will be contacted and invited to participate.  
• 
For other potential participants, the MUSC Pediatric Sickle Cell Clinic staff 
will be given the inclusion/exclusion criteria and will be asked to identify 
eligible participants in the clinic. When potentially eligible participants attend 
an appointment at the clinic, the clinician/staff will approach the 
parent/caregiver, briefly introduce the study through an IRB approved study 
letter, and if interested ask if the researchers can speak with the 
parent/caregiver to offer additional information. For parents/caregivers who 

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agree, the PI or PC will provide an overview of the study either by phone or 
face-to-face in the clinic and conduct eligibility screening. Eligible and 
interested parents/caregivers will proceed to the informed consent interview.  
• 
Additionally, for the purposes of this study and in direct alignment with the 
mission of the CON P20 Symptom Self-Management Center, we will employ 
the use of MUSC Bioinformatics Center (BMIC) core services to identify and 
recruit patients across the MUSC Enterprise that meet the study 
inclusion/exclusion criteria and that have granted authorized research contact 
permission in MyChart through the electronic ‘opt in’ EPIC designation. Once 
these potentially eligible patients are identified, we will then contact them by 
telephone using a script to determine if they are interested in study 
participation 
• 
Flyers will be posted in the waiting room and patient rooms at the MUSC 
Sickle Cell Clinic. The flyers will include the PI’s contact information; 
interested parents/caregivers who call the PI will be screened for eligibility.  
9.0 Consent Process 
Since research will be conducted with caregiver/child dyads and no research will be conducted 
without the caregiver present, consent will be obtained from the parent/caregiver for both 
him/herself and the child participant (0-7 years). In this study, we will employ the use of two 
informed consenting strategies (In-person meeting and electronically through REDCap e-
Consent) so as to increase the reach of the study and to promote the generalizability of findings.  
 
In-person informed consent will occur in the comfort and safety of a private clinic room at the 
MUSC Sickle Cell Unit prior to any screening procedures being conducted and/or data 
collection. Potential participants will be given the informed consent document to read and 
review in advance, and/or may have it read to them by the researchers if they prefer. After 
reviewing the Consent document, both caregiver and child will be given the opportunity to ask 
any questions about the study that they may have, and will be requested to demonstrate what is 
expected from them should they enroll in the study through a questioning of their 
understanding of study procedures and risks. Prior to consenting, all questions will be resolved 
to the caregiver and child's satisfaction. If a participant does not appear to understand the 
information contained within the Consent document, the study coordinator will review the 
consent document again with the participant. If after this second review, the subject does not 
demonstrate an understanding, they will not be enrolled in the study. Only participants, with no 
diagnosed or observed cognitive impairment, will be consented and enrolled into the study.  
 
Electronic or e-Consenting will be performed on eligible families that want to participate in the 
study but are unwilling for whatever reason and/or unable to come to MUSC for a face-to-face 
informed consent meeting. Families identified through the study recruitment processes that fall 
into this category will already have spoken with the researchers by telephone, have been 
introduced to the study and its demands, as well as had their initial questions answered. After 
speaking with the researchers, families that are further interested in study participation will be 
asked to provide an email address at which they will receive a REDCap survey link containing a 
scanned image of the currently approved Informed Consent document (developed from the 
MUSC REDCap e-consent template). Families will be able to take as much time as they like to 
read the consent document together in the comfort and privacy of their own home or at a place 
and time of their choosing. They will be provided with the telephone and email contact details in 
the survey instruction header for the researchers, should they have any questions before 

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providing their consent by adding their respective signatures to the form and submitting it. Prior 
to providing their physical e-consent, the researchers will coordinate with these families; so as to 
be on the telephone and be available to further answer any questions that they may have during 
the e-consent process. Should a participant have any questions or concerns about the study, the 
researchers will address these issues to the best of their abilities and knowledge. Upon 
submitting the e-consent, a REDCap trigger will immediately notify the researchers, who will 
then provide their countersignature to the document.  
 
The consent form will meet the requirements of the Code of Federal Regulations and the MUSC 
Institutional Review Board; and, include the following elements: 
1. The purpose, nature, and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. The name and a contact of the investigator(s) responsible for the protocol. 
4. The right of the participant to accept or refuse study interactions and to withdraw from 
participation at any time. 
 
The HIPPA authorization process will be conducted sequentially with the family in the same 
manner by the researchers. Participants will be able to download a copy of their executed 
informed e-consent/HIPAA authorization forms directly to their own computer, or have copies 
emailed to them. They will also be given the option to have a copy of their executed e-forms 
mailed to them should they elect to do so. A copy of the executed e-consent/HIPAA 
authorization forms will also be stored in the participant's electronic case record for monitoring 
and audit purposes. 
 
10.0 Study Design / Methods 
The mHealth SCD management intervention will be delivered via an app on the caregiver’s 
mobile device over a 12-week period. This multi-component, web-based app consists of 1.) 
continuous access to directed educational resources on the SCD process, treatment, home 
management strategies, symptom prevention and management strategies; 2.) a series of pages in 
the app that allow for tracking and monitoring symptoms; and 3.) child/caregiver – provider 
communication. The educational component is based on patient-centered materials that have 
been developed and tested by authoritative sources. In the app, educational materials are 
organized by user age (for individuals with SCD) or role for parents/caregivers. Citations are 
provided and links to the sources are included. The symptom tracking and monitoring 
component consists of a customizable avatar on which the user can record the location, severity, 
and characteristics of pain. Users can record other concurrent or associated symptoms (such as 
fatigue) and can view a graph with the pain history. This portion of the app also includes a 
health history page on which users can document important clinical information, such as sickle 
cell type, last sickle cell crisis hospitalization, medications, and allergies. The child/caregiver – 
provider communication component consists of the ability for the child/caregiver to send a 
secure message to providers within the app to communicate pain and other symptoms. 
Providers will have the capability to securely send a reply within the app. In addition, 
children/caregivers can choose to receive a daily “support” message that will be automatically 
sent from a list of possible messages. All communication is encrypted and sent securely within 
the app via a portal. Two to three providers at the MUSC Sickle Cell Clinic will participate as the 
designated providers in the study.  
 
To determine feasibility, we will apply the RE-AIM framework to assess the Reach, Efficacy, 
Adoption, Implementation, and Maintenance of the intervention with 30 children/caregiver 
dyads.18 The domains are further explicated in Table 2. The intervention will be loaded onto the 

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caregivers’ tablet or smartphone (Apple or Android); participants without a device will be 
provided one for the duration of the study. The PI or PC will deliver detailed verbal instructions 
to caregivers on the use of the device and the intervention. Caregivers will also receive written 
instructions and a contact number for technical assistance if needed. Baseline measures (Table 
2) will be collected during the same meeting. Caregivers will retain the devices and will 
participate in the intervention over a 12 week-period. At the end of the 12-week period, the PI 
will conduct a post-intervention meeting with each individual caregiver participant during which 
data will be collected. Caregivers will also be asked to return the mobile device at the end of the 
study. The PI will meet with the study provider weekly during the intervention. 
 
Retention: To improve retention, IRB-approved personnel will contact enrolled participants at 
3-week intervals between data collection points. The timeline for these points of contact are at 
the following weeks post baseline data collection: weeks 3, 9, 15, 18, and 21. The purpose is to 
maintain contact with enrolled participants, not data collection. Correspondence will be logged 
in REDCap. Contact will take place via text message, using the number(s) provided to study 
personnel upon enrollment. Examples of messages are provided in an uploaded attachment. 
 
 
Post-intervention interviews. At the end of the 12-week study, all 30 caregivers will be 
asked if they would like to participate in a 3-month post-intervention key informant interviews 
with the PI to obtain more in-depth data on accessibility, usability, and adherence to 
intervention; however, only 15 will be chosen to participate. This subset will be selected 
randomly by computer. Dyads have a 50-50 chance of being randomly selected if all dyads 
express interest. Semi-structured interviews will be conducted using a qualitative descriptive 
approach,17 will last approximately 45-60 minutes, and will be conducted according to an 
interview guide with open-ended questions and prompts. These interviews will be audio 
recorded for later nVivo qualitative data analysis. Selected caregivers will be given the option of 
having the interview conducted in-person in a private room at MUSC or by telephone in the 
comfort and safety of their own home. 
 
Reimbursement for dyads will be a $50 gift card provided at each of the 4 data collection points, 
with dyads in key informant interviews receiving an additional $40 gift card. All payments will 
be given to the caregiver. 
 
Measures. Older children (5-7 years) and their caregivers will complete age-appropriate self-
report and proxy assessments at baseline, mid-intervention (6 weeks), post-intervention (12 
weeks), and 3 months post-intervention as previously described. Self-report and proxy 
assessments will be collected during meetings between the PI or PC and the participant. 
Depending on participants’ preference and availability visit 2, 3 and 4 surveys will be completed 
either by phone or electronically via REDCap survey or by paper and pencil. All data will be 
recorded in REDCap by the PC.  
 
11.0 Specimen Collection and Banking 
Not applicable 
 
12.0 Data Management  
Sample size considerations 
The purpose of this study is to establish feasibility of implementing the integrated intervention 
obtain estimates of variability for the primary outcome measures and obtain preliminary 
indicators of effectiveness of the intervention rather than to confirm or refute hypotheses. 

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Therefore, sample size considerations focus on precision of estimates. For this feasibility study, 
we project that we will be able to recruit 30 child/caregiver dyads. With such a sample we will be 
able to estimate outcome proportions for feasibility measures including recruitment and drop-
out with precision ±0.11 to ±0.16 for values of the true proportion ranging from 0.10 to 0.30 (or 
correspondingly, from 0.70 to 0.90). Assuming a drop-out rate of up to 30%, 95% confidence 
limits can be estimated for impact measures, such as change from pre-to-post in quality of life 
for child and caregiver with a precision ranging from ±0.43 to ±1.35 corresponding to estimated 
standard deviations for change in quality of life scores ranging from 0.5 to 5.0 SD units. 
 
Demographic and clinical variables obtained at baseline will be described via measures of 
central tendency (mean, median), variability and frequency distributions as appropriate. 
Additionally, demographic and clinical characteristics for those who adhered to the study 
protocol (study completers) versus those who did not adhere (non-adherers and drop-outs) will 
be compared to better describe the population for this study. For continuous quality of life 
measures for the child and caregiver the difference between pre and post intervention 
measurements will be estimated via 95% confidence intervals. To assess preliminary 
intervention effects, we will conduct repeated measures ANCOVA with symptom (pain) severity 
and type obtained daily as dependent variable in individual models adjusting for “dose” defined 
as number of times education module was accessed and total time spent in education modules. 
 
Post-intervention qualitative analyses (Aim 2): Data collected from post-intervention key 
informant interviews will be analyzed using directed content analysis19 and nVivo qualitative 
data analysis software version 11.20 Consistent with the directed content analysis approach, 
initial coding categories are identified according to the guiding theoretical model, and for this 
study, will reflect the RE-AIM domains.  
 
Data sharing with the NINR/NIH: As a condition of this National Institutes of Nursing 
Research (NINR) award, de-identified patient data will be shared by the researchers with the 
NINR and stored electronically on an NIH password protected secure server 
(https://cdrns.nih.gov/). The purpose of sharing this information is to build a NINR repository 
of data using Common Data Elements (CDE) for future research purposes among the general 
scientific community and for public health benefit. Patients will be allocated a random identifier 
through the NIH supported GUID Tool. The GUID Tool (https://cdrns.nih.gov/node/39) is a 
customized software application that generates a Global Unique Identifier for each study 
participant. The GUID is a subject ID that allows researchers to share data specific to a study 
participant without exposing personally identifiable information (PII). The GUID is made up of 
random alpha-numeric characters and is NOT generated from PII/PHI. As such, it has been 
approved by the NIH Office of General Counsel.  GUID Generation complies with HIPPA 
regulations for the protection of PII/PHI. Patients are made aware of this data sharing 
agreement with the NINR/NIH in the study’s Informed Consent document. 
 
13.0 Provisions to Monitor the Data and Ensure the Safety of Subjects 
There is a well-developed and NIH/NINR prepared SRG approved DSMP that involves the use 
of a Safety Monitoring Committee (SMC) that shall meet semi-annually post initial study 
enrollment. The Committee is comprised of key individuals that include: an independent 
medical safety monitor (ISM), a biostatistician (BS), and the Program Manager (PM). 
 
The following members of the study’s DSMC will perform data safety monitoring of the study: 
• Dr. Cristina Lopez, Independent Safety Monitor (ISM) - primary responsibility 
• Mr. Mohan Madisetti, MS, Project Manager (PM) 

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• Ms. Mary Dooley, Biostatistician (BS) - supervised by Dr. Martina Mueller. 
 
Independent Safety Monitor (ISM), Dr. Lopez who is Assistant Professor at Medical University 
of South Carolina, has a PhD and a background as a clinical psychologist with expertise in 
adolescent behavioral research, and will act as the study’s Independent Safety Monitor (ISM). 
Dr. Lopez has no real or apparent conflict of interest that would affect her performance in this 
role on the study.  
 
Project Manager, (PM). Mr. Madisetti, MS, has over 20 years of research experience in study 
management, quality assurance and the protection of human subjects. Mr. Madisetti is CTRC, 
CITI /GCP and NIH trained in Human Subject Protections, and has completed MUSC’s 
Certificate of Competence in Research Ethics (CREP) and member of the Institute of Human 
Values Ethics Committee. Mr. Madisetti has also been a member of over 5 federally and FDA 
sponsored research full DSMBs. 
 
Biostatistician (BS) Ms. Dooley is a biostatistician and faculty at the College of Nursing at the 
Medical University of South Carolina. Ms. Dooley has experience collaborating with 
investigators in clinical trials as well as in community based participatory research. Ms. Dooley 
will be supervised by Dr. Martina Mueller from the College of Nursing. 
 
From the initial screening of subject by inclusion and exclusion criteria to the informed consent 
process to the provision of participant study instruction to staff training in Good Clinical 
Practices (GCP) and regulations pertaining to the Conduct of Human Subject Research to 
routine contact with participants to internal quality control audits and protocol fidelity 
monitoring to the real-time review of AE’s by the SMC to the oversight of the IRB - procedures 
for monitoring study safety are consistently afforded throughout the study. Specific study 
procedures include: 
• Participants will be screened for inclusion and exclusion per the protocol  
• Participants will be fully informed as to all know risks and the possibility of risk from study 
participation in the informed consent process. These risks are minimal. 
• Participants will be instructed to notify the researchers of any/all suspected or experienced 
adverse events whether they believe them to be related or not to the intervention. 
• The PI or PC will track all reported participant AEs through to resolution.  
• All investigators and researchers will maintain active CITI and GCP training. 
• The PI or PC will maintain weekly contact with all participants to elicit information about AE’s 
and to monitor participant study progress, compliance and safety. 
• The PI or PC will review participants study logs for fidelity compliance with the intervention. 
• The PI or PM will conduct quarterly internal quality control audit of all participant records to 
ensure compliance with MUSC IRB regulations; the PI and PC will work together to correct any 
errors. 
• The BS shall generate semi-annual AE reports for the PI, SMC and IRB to review. 
• The ISM will have access to real-time study data and will be able to provide immediate 
recommendations to the PI and PD. 
• Investigator performance and compliance will be provided for through MUSC IRB and ORI 
study oversight. 
 
Protecting Confidentiality of Participant Data 

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Participant Screening and Enrollment. All data from participants screened for the study 
will be entered into an electronic study database. Designated research staff will collect, gather, 
and enter required data (written informed consent, HIPAA Authorization, and demographics) 
onto study data forms. Screened patients who do not meet study eligibility will have specific 
screening data entered into the study database. The collected data will be helpful in examining 
the patient population and feasibility of enrollment criteria and will include reason for exclusion. 
All dates will be shifted and other Personal Health Information (PHI) will be removed from the 
study database upon study completion. All data obtained from this study will be used for 
research purposes only and will comply with Federal HIPAA regulations.  Master Screening and 
Enrollment Logs will be maintained by the PI or PD and will be used by the PI or PD to prepare 
reports on accrual and attrition for the ISM and SMC. 
 
Case Report Forms. All proposed study specific case report forms (source documents) for 
data collection will be designed by the PI and, when possible, transferred by the PI or PC into 
electronic Case Report Forms (eCRFs) for use in the study’s REDCap database. These study 
specific eCRFs source documents (study logs for correspondence, compensation and other forms 
such as pre-eligibility screens) will be coded by the participant’s unique study ID# for all data 
collected including study instruments will be maintained in the participant research record. 
Completed instruments that require signature on a paper CRF will be scanned and uploaded into 
the study database to all for remote electronic safety monitoring as well as maintained on file in 
accordance with MUSC policies and applicable Federal Regulations for the Conduct of Human 
Participant Research.  
 
Binders. The PI or PC will prepare and maintain a participant-specific binder for each 
participant containing all non-eCRFs records. A regulatory file will also be maintained to include 
the IRB-approved Protocol, original Informed Consent documents, HIPAA forms and other 
study-related regulatory documents. All paper research records and CRFs will be maintained in 
a locked file cabinet, stored in a room for research files that is accessible only via a password 
protected entry system that features security cameras, within the College of Nursing. Access to 
the research records, study database and PHI’s will be restricted to study personnel as approved 
by the PI and MUSC IRB. As with all studies conducted at MUSC, this study is also eligible for a 
random audit by MUSC Office of Compliance. 
 
Data Processing. This study will use Research Electronic Data Capture (REDCap) for data 
capture and management. REDCap is a software toolset and workflow methodology for the 
electronic collection and management of research and clinical trials data. REDCap provides 
secure, web-based, flexible applications, including real-time validation rules with automated 
data type and range checks at the time of data entry. Exports are made available for several 
statistical packages including SPSS, SAS, SATA, R and Microsoft Excel. The study-specific 
REDCap electronic database will be designed and developed by the PI or PD in concert with the 
BS.  The provision of REDCap is made available through the South Carolina Clinical & 
Translational Research (SCTR) Institute at MUSC with NIH Grant awards UL1RR029882 and 
UL1TR000062.  
 
Data Security. Ensuring data security, compliance with 45 CFR 46 and maintaining the 
integrity of PHI is a top priority. MUSC has Standard Operating Procedures (SOP) to ensure a 
high level of data security while coordinating electronic and paper data management activities 
for clinical research trials. The REDCap study database will be hosted in the Biomedical 
Informatics secure data center at MUSC, a secure environment for data systems and servers on 
campus, and includes firewall, redundancy, failover capability, backups and extensive security 

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checks. The secure data center has strict access control; only authorized core personnel may 
access the facility un-escorted. Only authorized users are allowed to connect to the network, and 
the security of the network is actively monitored.  Power and environmental controls have 
several layers of backups, from interruptible power supplies to alternate and redundant feeds to 
the local utility company. The REDCap system administrator contributes to the maintenance of 
institutional disaster recovery and business continuity plans.  Load balancers and a highly fault 
tolerant SAN infrastructure contribute to high availability.  
 
The REDCap system itself has several additional layers of protection including password 
protection. Access to the data and its security is managed institutionally by sponsored login IDs 
through a Shibboleth login with an MUSC issued NetID and features a user account 
management filter that controls who can access the data and to what degree. All personnel must 
pass an employment background check before being issued an ID. Password complexity, history 
and expiration standards are implemented at the institutional level. Access to individual 
REDCap projects and their data is managed by the owner of the project. All transactions are 
securely delivered to the application using Secure Sockets Layer (SSL – SHA-1 with RSA 
Encryption; 2048-bits). It is then transmitted internally (behind the firewall) to the database 
server. All transactions are logged at the server layer (httpd logging), application layers 
(REDCap logs activity to a database table), and the database layer, using both query and binary 
logging. This feature provides audit trails for all changes, queries, data exports and reports. 
MUSC Information security policies are available at: https://mainweb-
v.musc.edu/security/policy/  
 
Data Entry. Only MUSC IRB approved study personnel that are authorized to have access to 
the REDCap study database will be granted password access. Study personnel using computers 
that are connected to the Internet will directly enter data into the remotely housed database. As 
such, no electronic study data will be stored on hard drives and/or any portable electronic 
devices. Additionally, all personnel with access to the database will have current University of 
Miami CITI and GCP training in the Conduct of Human Subject Protections, and HIPAA and 
Information Security trainings that are completed annually. Each participant will be assigned a 
unique study identifier, all PHIs will be masked, and data exports will be limited to the PI or the 
BS for generating reports and the conduct of statistical data analysis. 
 
Data Monitoring. Ongoing quality control procedures will be implemented for data collection, 
storage and processing. The PI or PD will conduct monitoring of the study database and 
generate a report for review at team meetings. Standing agenda items for these meetings will 
include participant recruitment and retention, AE’s, protocol deviations, data integrity and 
overall study conduct. The PI and PD will work to resolve and validate discrepant data. 
Discrepancies that warrant clarification will be sent to appropriate parties for review and 
resolution. All data entry and changes made in the study database by authorized study personnel 
will be automatically logged by REDCap, and provide a transparent visible audit trail for 
reviewers. 
 
 
 
 
14.0 Withdrawal of Subjects 
The PI may withdraw a participant from the study at any time if they decide it is in their best 
interest, if they do not follow the investigator’s instructions, or if they fail to keep study visits. 
This may also occur if there is a protocol violation or early closure of the study. 

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15.0 Risks to Subjects 
 
 
Based on Phase I of the study, we do not anticipate any significant risks related to the 
completion of the surveys and key informant interviews in this study. However, as with any 
research study there is a risk of disclosure of information that can lead to a loss of 
confidentiality. As well as having a comprehensive DSMP that details data safety, handling, 
monitoring, storage and security procedures, we will further minimize the potential for loss of 
confidentiality through the physical separation of participant names from their research record.  
 
Additionally, it is possible that a participant might experience some emotional distress while 
responding to the survey questions or participating in key informant interviews. If this were to 
occur, the participant would be referred to a psychologist or psychiatrist for counseling. 
Reactions will be monitored by the PI (who will be conducting the interviews) and signs of 
significant distress will be followed-up to identify any serious psychological problems. In the 
rare and unexpected event of serious or life threatening level of distress, a psychologist or 
psychiatrist will be contacted as well as the participant’s primary care provider of record. 
 
16.0 Potential Benefits to Subjects or Others 
If a participant agrees to take part in this study, there will be no direct medical benefit to them. 
We hope the information learned from this study will aid patients and clinicians in the future. 
The data collected from this study will not directly affect the treatment being given to the 
patients. The risks associated with the proposed study are minimal and include psychological 
and physical strains that might be encountered in everyday life. The benefits of the study 
outweigh the risks. 
 
 
 

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References 
 
1.  
Palermo TM, Schwartz L, Drotar D, McGowan K. Parental report of health-related quality of life 
in children with sickle cell disease. Journal of Behavioral Medicine. 2002;25(3):269-283. 
2. 
Hassell KL. Population estimates of sickle cell disease in the U.S. American Journal of Preventive 
Medicine. 4// 2010;38(4, Supplement):S512-S521. 
3. 
National Heart  Lung and Blood Institute. What is Sickle Cell Disease? 2015; 
http://www.nhlbi.nih.gov/health/health-topics/topics/sca/. Accessed September 14, 2015. 
4. 
Reddin CDRC, Cerrentano E, Tanabe P. Sickle Cell Disease Management in the Emergency 
Department: What Every Emergency Nurse Should Know. Journal of Emergency Nursing. 7// 
2011;37(4):341-345. 
5. 
Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease -- Life expectancy and risk 
factors for early death. New England Journal of Medicine. 1994;330(23):1639-1644. 
6. 
Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C. Outcome of sickle cell anemia: A 4-decade 
observational study of 1056 patients. Medicine. 2005;84(6):363-376. 
7. 
Modi AC, Pai AL, Hommel KA, et al. Pediatric self-management: A framework for research, 
practice, and policy. Pediatrics. 2012;129:e473-e485. 
8. 
van den Tweel XW, Hatzmann J, Ensink E, et al. Quality of life of female caregivers of children 
with sickle cell disease: a survey. Haematologica. 2008;93(4):588-593. 
9. 
Raphael JL, Dietrich CL, Whitmire D, Mahoney DJ, Mueller BU, Giardino AP. Healthcare 
utilization and expenditures for low income children with sickle cell disease. Pediatric Blood & 
Cancer. 2009;52(263-7). 
10. 
Jacob E, Pavlish C, Duran J, Stinson J, Lewis MA, Zeltzer L. Facilitating pediatric patient-
provider communications using wireless echnology in children and adolescents with sickle cell 
disease. Journal of Pediatric Health Care. 2013;27(4):284-292. 
11. 
Ruggiero KJ, Price M, Adams Z, Stauffacher K, McCauley J, Danielson CK. Web intervention for 
adolescents affected by disaster: Population-based randomized controlled trial. Journal of the 
American Academy of Child & Adolescent Psychiatry. 2015;54(9):709-717. 
12. 
Ruggiero KJ, Bunnell BE, Andrews AR, Davidson TM, Hanson RF, Danielson CK. Protocol 
development and pilot evaluation of a tablet-based application to improve quality of care in child 
mental health treatment. JMIR Research Protocols. in press. 
13. 
Hudson SM. Hospital readmissions and repeat emergency department visits in children with 
medical complexity: An integrative review. Journal of Pediatric Nursing. 2013;28(4):316-339. 
14. 
Hudson SM, Mueller M, Hester WH, Magwood GS, Newman SD, Laken MA. At-risk 
characteristics for hospital admissions and ED visits. Journal for Specialists in Pediatric 
Nursing. 2014;19:183-193. 
15. 
Hudson SM, Newman SD, Hester WH, Magwood GS, Mueller M, Laken MA. Factors influencing 
hospital admissions and emergency department visits among children with complex chronic 
conditions: a qualitative study of parents' and providers' perspectives. Issues in Comprehensive 
Pediatric Nursing. 2014;37(1):61-80. 
16. 
Hudson SM, Magwood GS, Laken MA, Mueller M, Newman SD. A mixed methods analysis of the 
place-related risk and protective factors for hospital admissions and emergency department visits 
among children with complex chronic conditions. The Online Journal of Rural Nursing and 
Health Care. In press;15(2):(December 2015 issue). 
17. 
Sandelowski M. Whatever happened to qualitative description? Res Nurs Health. 2000;23:334-
340. 
18. 
Glasgow RE, Vogt TM, Boles SM. Evaluating the public health impact of health promotion 
interventions: the RE-AIM framework. American Journal of Public Health. 1999;89(9):1322-
1327. 
19. 
Hsieh H, Shannon SE. Three approaches to qualitative content analysis. Qualitative Health 
Research. 2005;15(9):1277-1288. 
20. 
NVivo qualitative data analysis software [computer program]. Version 102012. 

Version 4.0;    Rev. 09/25/18 
 
Page 17 of 17 
 
21. 
Varni JW, Thissen D, Stucky BD, et al. PROMIS Parent Proxy Report Scales for children ages 5-7 
years: an item response theroy analysis of differential item functioning across age groups. Quality 
of Life Research. 2014;23:349-361. 
22. 
Irwin DE, Gross HE, Stucky BD, et al. Development of six PROMIS pediatrics proxy-report item 
banks. Health and Quality of Life Outcomes. 2012;10(22). 
23. 
Panepinto JA, Torres S, Bendo CB, et al. PedsQL Sickle Cell Disease Module: Feasibility, 
reliability, and validity. Pediatric Blood & Cancer. 2013;60:1338-1344. 
24. 
Panepinto JA, Torres S, Bendo CB, et al. Pe