MULTIsite Feasibility of MUSIc Therapy to Address Quality Of Life in Sickle Cell Disease (MULTI-MUSIQOLS)
Phase: NA
Conditions: Sickle Cell Disease
Sponsor: University of California, Irvine

MULTIsite feasibility of MUSIc 
therapy to address Quality Of
Life in Sickle cell disease 
(MULTI-MUSIQOLS)

PREFACE
The Clinical Intervention Study Protocol Template is a suggested format for clinical trials 
sponsored by the National Center for Complementary and Integrative Health (NCCIH).
Investigators are encouraged to use this format, as appropriate, when developing protocols for 
their studies. Large multi-site observational studies will also benefit from this protocol template.
Note that instructions and explanatory text are indicated by italics and should be replaced in 
your protocol with appropriate text. Section headings and template text formatted in regular 
type should be included in your protocol document as provided in the template.
The goal of this template is to provide a general format applicable to all single- and multicenter 
clinical intervention trials (e.g., drug, surgery, behavioral, nutritional, device, etc).
As you can see the version number and date are on the bottom of each page. When making 
changes to an approved and “final” protocol, please provide a summary of the changes, with the 
date, at the front of the protocol.

MULTIsite feasibility of MUSIc therapy to address Quality Of 
Life in Sickle cell disease (MULTI-MUSIQOLS)
Principal Investigator:
Jeffery Dusek, PhD 
Professor in Residence
Department of Medicine, General Internal Medicine
University of California – Irvine
Director of Outcomes Research
Susan Samueli Integrative Health Institute
University of California – Irvine
Coretta Jenerette, PhD, RN, AOCN, ANEF, FAAN 
Senior Health Equity Scholar
Professor & Thelma Shobe Endowed Chair 
University of California San Francisco School of Nursing
Supported by:
The National Center for Complementary and Integrative Health
1R01AT012508-01
Study Intervention Provided by:
NA
Sponsor of IND (IDE):
NA

Tool Revision History
Version Number: 4
Version Date: 12Feb2025
Summary of Revisions Made:
1) Changed timing of iPad handoff to following randomization
2) Added that study team has the option to provide transportation assistance to help participants attend the 
baseline consent visit if needed.
Version Number: 3
Version Date: 12Sep2024
Summary of Revisions Made:
1) Removed the REDCap referral option. Providers will use email to refer patients to the study because this 
method is more likely to be used
2) Add Mind/Body pain management and transportation questionnaire to gauge and document inclusion 
exclusion criteria not captured elsewhere and to document the need for transportation assistance
3) Change MyChart to MyCAP because MyCAP is more accessible and has more features that the study team 
would like to utilize
4) Added that Prisma will use a paper consent as per their institutional requirements
Version Number:
Version Date:
Summary of Revisions Made:
Version Number:
Version Date:
Summary of Revisions Made:

TABLE OF CONTENTS
MULTIsite feasibility of MUSIc therapy to address Quality Of Life in Sickle cell disease (MULTI-
MUSIQOLS)…………………………………………………………………………………………...…….
1
Title Page: ................................................................................................................................................3
Tool Revision History.............................................................................................................................4
TABLE OF CONTENTS............................................................................................................................4
STUDY TEAM 
ROSTER…………...……………………………………………………………………….………….….6
PARTICIPATING STUDY 
SITES…………………………………………………………………………….………………………..7
PRECIS…………………………………………………………………………………………………………….8
1. STUDY OBJECTIVES........................................................................................................................10
1.1
Primary Objective....................................................................................................................10
1.2
Secondary Objectives .............................................................................................................10
2. BACKGROUND AND RATIONALE...................................................................................................11
2.1
Background on Condition, Disease, or Other Primary Study Focus .......................................11
2.2
Study Rationale.......................................................................................................................13
3. STUDY DESIGN.................................................................................................................................15
4. SELECTION AND ENROLLMENT OF PARTICIPANTS...................................................................21
4.1
Inclusion Criteria .....................................................................................................................21
4.2
Exclusion Criteria ....................................................................................................................22
4.3
Study Enrollment Procedures .................................................................................................23
5. STUDY INTERVENTIONS ..................................................................................................................26
5.1
Interventions, Administration, and Duration .............................................................................26
5.2
Handling of Study Interventions ...............................................................................................30
5.3
Concomitant Interventions .......................................................................................................31
5.4
Adherence Assessment ...........................................................................................................32
6. STUDY PROCEDURES ......................................................................................................................32
6.1
Schedule of Evaluations...........................................................................................................32
6.2
Description of Evaluations........................................................................................................34
7. SAFETY ASSESSMENTS ..................................................................................................................43
7.1
Specification of Safety Parameters..........................................................................................45
7.2
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters.................45
7.3
Adverse Events and Serious Adverse Events..........................................................................45
7.4
Reporting Procedures ..............................................................................................................46
7.5
Follow-up for Adverse Events ..................................................................................................46
7.6
Safety Monitoring .....................................................................................................................47
8. INTERVENTION DISCONTINUATION................................................................................................47
9. STATISTICAL CONSIDERATIONS....................................................................................................47

9.1
General Design Issues Primary Objective................................................................................47
Secondary Objectives..........................................................................................................................48
9.2
Sample Size and Randomization .............................................................................................48
9.3
Definition of Populations ..........................................................................................................49
9.4
Interim Analyses and Stopping Rules ......................................................................................49
9.5
Outcomes and Data Analysis...................................................................................................49
10. DATA COLLECTION AND QUALITY ASSURANCE .......................................................................53
10.1
Data Collection Forms .............................................................................................................53
10.2
Data Management....................................................................................................................53
10.3
Quality Assurance....................................................................................................................54
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY ..........................................................................58
11.1
Institutional Review Board (IRB) Review .................................................................................58
11.2
Informed Consent Forms .........................................................................................................58
11.3
Participant Confidentiality.........................................................................................................58
11.4
Study Discontinuation...............................................................................................................58
12. COMMITTEES...................................................................................................................................59
13. PUBLICATION OF RESEARCH FINDINGS.....................................................................................59
14. REFERENCES ..................................................................................................................................59
1

STUDY TEAM ROSTER
MPI’s:
Jeffery Dusek, PhD 
Professor In Residence 
Department of Medicine 
General Internal Medicine
University of California- Irvine
Irvine, CA 92697
949-824-8841
jdusek@hs.uci.edu
Director of Outcomes Research
Susan Samueli Integrative Health Institute
University of California- Irvine
Irvine, CA 92697
 949-824-8841
jdusek@hs.uci.edu
Coretta Jenerette, PhD, RN, AOCN, ANEF, FAAN 
Senior Health Equity Scholar
Professor & Thelma Shobe Endowed Chair 
Department of Community Health Systems
University of California San Francisco School of Nursing 
2 Koret Way, Ste N505
San Francisco, CA 94143 
415-502-4242
Coretta.Jenerette@ucsf.edu
Co-I’s:
Samuel N. Rodgers-Melnick, MPH, LPMT, MT-BC 
University Hospitals Connor Whole Health 
Cleveland Medical Center
11000 Euclid Avenue 
Wearn 548A 
Cleveland, Ohio 44106
216-844-7727
Samuel.RodgersMelnick@UHhospitals.org
Site PI’s:
Amma Owusu-Ansah, MD 
Director,
Sickle Cell Anemia Center
Rainbow Babies and Children's Hospital 
11100 Euclid Avenue
Cleveland, Ohio 44106
216-844-3345
Amma.Owusu-Ansah@UHhospitals.org
Alison Karasz, PhD 
Professor,
Department of Family Medicine and Community Health 
University Campus

University of Massachusetts Chan Medical School 
55 North Lake Avenue
Worcester, Massechusetts 01655
347-843-5652
Alison.Karasz@UMassmed.edu
Alan R. Anderson, MD
Associate Professor of Clinical Pediatrics,
University of South Carolina School of Medicine (Greenville) 
Director, Comprehensive SCD Program
Prisma Health-Upstate 
Greenville, South Carolina 
864-455-8898
Alan.Anderson@prismahealth.org
Shaista Malik, MD, PhD, MPH, FACC 
Professor,
School of Medicine 
University of California, Irvine 
City Tower, Suite 400
Mail Code: 4080
Irvine, California 92697
714-456-6699
smalik@hs.uci.edu
Biostatistician:
Jessica Tobin, PhD, MS
Senior Data Analyst 
Susan Samueli Integrative 
Health Institute
856 Health Services Rd,
University of California, Irvine
Phone: 619-850-8815
jltobin@hs.uci.edu
Multi-Site Study Coordinator:
Ashwini Erande MPH, M.Sc
Senior Clinical Research Coordinator 
Susan Samueli Integrative Health Institute
856 Health Services Rd,
University of California, Irvine
Tel: 714-456-7025
aerande@hs.uci.edu
PARTICIPATING STUDY SITES
Case Western Reserve University/University Hospitals of Cleveland – Lead Site, 
Recruiting Site #1
Amma Owusu-Ansah, MD 
Director,
Sickle Cell Anemia Center
Rainbow Babies and Children's Hospital 

11100 Euclid Avenue
Cleveland, Ohio 44106
216-844-3345
Amma.Owusu-Ansah@UHhospitals.org
Prisma Health/University of South Carolina – Recruiting Site #2
Alan R. Anderson, MD
University of South Carolina School of Medicine (Greenville) 
Director, Comprehensive SCD Program
Prisma Health-Upstate 
Greenville, SC
864-455-8898
Alan.Anderson@prismahealth.org
University of California, Irvine – Data Coordinating Center
Shaista Malik, MD, PhD, MPH, FACC 
University of California, Irvine
City Tower, Suite 400 
Mail Code 4080
Irvine, CA 92697
714-456-6699
smalik@hs.uci.edu
University of Massachusetts Chan Medical School – Interviewing Center
Alison Karasz, PhD
University of Massachusetts Chan Medical School 
Department of Family Medicine and Community Health 
University Campus
55 Lake Avenue North 
Worcester, Massachusetts 01655
347-843=5652
Alison.Karasz@UMassmed.edu
PRÉCIS
Study Title
MULTIsite feasibility of MUSIc therapy to address Quality Of Life in Sickle cell 
disease (MULTI-MUSIQOLS)
Objectives
The objectives of this study are to (1) conduct a feasibility randomized control trial 
(RCT), to examine the data collection processes, and intervention (in-person music 
therapy [InMT], hybrid MT [HybMT], and hybrid health education [HybHE]) 
implementation overall and across 2 sites (University Hospitals/Case Western 
Reserve University [site 1] and Prisma Health/University of South Carolina [site 2]); 
and (2) evaluate the implementation of the InMT, HybMT, and HybHE interventions 
using both quantitative data (study records, stakeholder surveys) and qualitative data 
(interviews).

Design and Outcomes
This is a multi-site, multi-visit feasibility RCT of music therapy (MT) among 
adolescent and adult patients (aged 14 and older) with sickle cell disease (SCD).
Subjects will be randomized into one of three groups, either (1) InMT: 6 visits of in- 
person MT; (2) HybMT: 1 visit of in-person MT and 5 visits of virtual MT; or (3) 
HybHE: 1 visit of in-person health education and 5 visits of virtual health education.
Cohorts of 15 participants (10 at site 1 and 5 site 2) will be recruited each quarter for 
6 quarters to reach 90 participants. Cohorts will maintain a semi-structured 
recruitment, consenting, assessment, and intervention schedule.
Interventions and Duration
Three wellbeing programs for individuals with SCD will be compared: (1) InMT, (2) 
HybMT, and (3) HybHE. Each intervention includes 6 sessions. The treatment period 
for each group will be 6 to 8 weeks. Each weekly session will last up to one hour in 
all arms of the study. MT sessions in the InMT and HybMT arms will include the 
topics of SCD education and MT rationale, breathing exercises, relaxation, imagery, 
music making, and review and creation of a coping plan for future challenges. The 
HybHE group will use an adapted version of Project Patients Empowered and 
Educated Providers (PEEP). Covered topics include: science of SCD, identifying 
barriers in the Emergency Department, tools for navigating the healthcare system, 
healthcare based communication, and review and planning for future challenges.
Semi-structured qualitative interview topics will focus on participants’ perceptions of 
the interventions, perceived benefits and burdens of the interventions, and other 
barriers and facilitators to in-person and hybrid delivery.
Sample Size and Population
A total of 90 subjects will be randomized to either InMT, HybMT, or HybHE (1:1:1 
allocation). Patients must:
(1) Be aged 14 years or older;
(2) Have a diagnosis of SCD present in their electronic health record (EHR);
(3) Meet Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations 
Opportunities and Networks-American Pain Society Pain Taxonomy (AAPT) criteria 
for chronic SCD pain which includes:
(3a) A diagnosis of SCD confirmed by laboratory testing (present in EHR per 
eligibility criteria 2)
(3b) Reports of ongoing pain present on most days over the past 6 months either 
in a single location or in multiple locations (to be obtained at screening)
(3c) Displaying at least one of the following signs on clinical exam (to be obtained 
from providers’ clinical notes in the EHR

Palpation of the region of reported pain elicits focal pain or tenderness;

Movement of the region of reported pain elicits focal pain;


Decreased range of motion or weakness in the region of reported pain;

Evidence of skin ulcer in the region of reported pain;

Evidence of hepatobiliary or splenic imaging abnormalities (e.g., splenic 
infarct, chronic pancreatitis) consistent with the region of reported pain; or

Evidence of imaging abnormalities consistent with bone infarction or 
avascular necrosis in the region of reported;
(3d) There is no other diagnosis that better explains the signs and symptoms (to 
be obtained from providers following referral and pre-screening)
(4) Be able to speak and understand English;
(5) Have an email address and access to mobile device with a functioning data plan
(6) Reporting that pain interfered with daily activities at least 1-2 days in the past 
week
Patients will be unable to participate if they:
(1) Have a significant visual, hearing, or cognitive impairment
(2) Have previously participated in the MUSIQOLS single-site pilot study at 
University Hospitals in 2018
(3) Are currently engaging in mind-body therapies under the supervision of a 
healthcare professional specifically for pain management
(4) Have a planned major medical event in the next 14 weeks such as (but not 
limited to) childbirth, orthopedic surgery, gene therapy, or stem cell transplant (These 
criteria do not include blood transfusions, exchange transfusions, or other 
pharmacologic pain treatment).
Qualitative interviews will be conducted with 24 participants who received the 
interventions (with equal numbers across the InMT, HybMT and HybHE groups). 
Participants will be purposively sampled to include both sexes, younger and older 
participants, and distribution across sites in proportion to recruitment.
Stakeholder surveys and qualitative interviews will be conducted among 20 relevant 
staff stakeholders (10 per site), including healthcare providers & staff, music 
therapists and HybHE interventionists.
1. STUDY OBJECTIVES
1.1
Primary Objective
The primary objective of the study is to examine the feasibility of completeness of 
data collection, participant recruitment and rate, participant retention, as well as 
assessment of hybrid intervention implementation and home practice using study 
records across the two sites.
1.2
Secondary Objective

This study will include a secondary objective of conducting qualitative interviews to 
assess feasibility of implementation.
2. BACKGROUND AND RATIONALE
2.1
Background on Condition, Disease, or Other Primary Study Focus
Sickle Cell Disease (SCD) in the United States: Approximately 100,000 individuals 
live with SCD in the United States. SCD disproportionately affects minority 
populations, with 1 out of every 365 Black or African American births carrying the 
genetic condition.1, 2 Emergency department (ED) and inpatient admissions among 
individuals with SCD account for approximately $2.4 billion dollars in annual 
spending, exceeding ED-associated expenditure rates among individuals with 
congestive heart failure, HIV, and asthma.3
Pain in SCD: In addition to enduring unpredictable acute vaso-occlusive pain crises 
throughout their lives, many adults with SCD also suffer from chronic pain, defined 
as the presence of pain on most days in the past 6 months in one or more 
locations.4, 5 Chronic SCD pain often emerges in adolescence as a result of 
physiological complications including chronic sickle cell vaso-occlusion, 
inflammation, increased red blood cell adhesion, central sensitization, and opioid- 
induced hyperalgesia.5, 6 In the Pain in Sickle Cell Epidemiology Study (PiSCES), a 
longitudinal etiologic study of 232 adults with SCD, 54% reported having pain, pain 
crises, or utilization on more than half (51%) of 31,017 analyzed patient-days.
Estimates of chronic pain prevalence among adults with SCD range from 29% to 
100%, with a weighted mean of 65% within seven studies.7 Among 170 adults with 
SCD and chronic pain, 57.1% reported Grade III (highly disabling–moderately 
limiting) or Grade IV (highly disabling–severely limiting) chronic pain that was 
significantly associated with higher pain catastrophizing and lower chronic pain self- 
efficacy.8
Health-Related Quality of Life (HRQoL) in SCD: These physical and psychological 
challenges contribute to impaired HRQoL. In PiSCES, patients with SCD scored 
significantly worse than national norms on all HRQoL subscales except mental 
health.9 Specifically, HRQoL was equal to or worse than patients with other 
significant chronic conditions in many domains, and the more pain patients with SCD 
experienced, the worse their reported HRQoL.9 More recently, an integrative review 
of 22 studies also found that adults with SCD report worse HRQoL than the general 
population.10 Adults with SCD enrolled in a recent randomized controlled trial (RCT) 
of a web-based decision aid reported PROMIS pain interference, anxiety, 
depression, fatigue, and physical function scores 0.5–1 SD worse than population 
norms and worse than reference norms of PROMIS scores for individuals with 
cancer.4 Thus, new interventions are needed to improve overall HRQoL for 
individuals with SCD in addition to pain outcomes.
Need for Non-pharmacologic Pain Management: In their 2020 guidelines for pain 
management in SCD, the American Society of Hematology acknowledged that

pharmacologic approaches have limited effectiveness and that non-pharmacologic 
integrative approaches are beneficial but may have limited accessibility for 
individuals with SCD. These guidelines identified research priorities including 
determining which non-pharmacologic therapies are most acceptable and developing 
manualized, accessible, and developmentally appropriate interventions for chronic 
SCD pain.5 In a qualitative study exploring chronic pain and self-management, adults 
with SCD expressed (1) a preference for non-pharmacologic strategies, (2) that pain 
medications were not always effective and limited their ability to perform daily 
activities, and (3) a desire to learn new pain management strategies.11
Music Therapy (MT) for Pain Management and HRQoL: MT is the clinical and 
evidence-based use of music interventions to accomplish individualized goals within 
a therapeutic relationship by a credentialed professional who has completed an 
approved MT program.12 MT has demonstrated effectiveness for managing pain in 
patients with cancer,13-15 patients with chronic pain,16-18 and patients receiving 
palliative care.19, 20 A recent clinical effectiveness study comparing the MT 
experiences of Black and White patients with cancer found that Black patients with 
moderate-to-severe pain reported clinically meaningful pain reduction (2.1 units on 
the Edmonton Symptom Assessment Scale).14 Importantly, MT can be tailored to the 
unique cultural preferences of adults with SCD and provide opportunities for active 
engagement with music, a factor shown to be associated with reduced pain intensity 
among adults with acute pain.21 Our prior work described below has demonstrated 
the preliminary efficacy of MT for addressing acute pain, mood,22 and HRQoL23 
among adults with SCD.
Importance of Self-efficacy: Self-efficacy is a significant factor influencing health 
outcomes and self-care activities for individuals with SCD.24 A meta-analytic review 
of 86 studies examining its relationship to chronic pain outcomes found that self- 
efficacy had negative overall correlations with impairment, affective distress, and 
pain severity and identified it as an important protective factor for individuals with 
chronic pain.25 Self-efficacy is related positively to fewer physical and psychological 
symptoms26, 27 and improved quality of life28, 29 among individuals with SCD. In a 
recent study of 170 adults with SCD and chronic pain, investigators observed a 
negative relationship between chronic pain self-efficacy and chronic pain intensity (p
= 0.026) and chronic pain disability (p < 0.001).8 Furthermore, self-efficacy has been 
shown to improve in response to MT interventions among Black/African American 
individuals with chronic pain.16, 18, 23
Figure 1. Theory of Self-Care Management for Sickle Cell Disease (Jenerette et 
al.) Applied to MT
The revised Theory of Self- 
Care Management for 
Sickle Cell Disease (Fig.
130, 31) guides the proposed 
study. Dr. Jenerette’s 
(study MPI) theory focuses 
on vulnerability factors and

self-care management resources influencing health outcomes. In Figure 1, 
vulnerability factors (lack of SCD crisis cue recognition/response, number of acute 
pain episodes per year, and overprotection) negatively influence health outcomes 
(pain management experience, depressive symptoms, self-esteem, and perceived 
health-related stigma). Self-care management resources (self-efficacy, coping 
behaviors, social support, self-care ability, self-care actions, and assertive 
communications skills) positively mediate the relationship between vulnerability 
factors and health outcomes.
Our proposed study conceptualizes MT as a self-care management resource that 
can mediate the relationship between vulnerability factors and health outcomes. The 
proposed study conceptualizes pain interference as a vulnerability factor 
approximating pain crises. As noted in the theory, self-efficacy will be the self-care 
management resource measured. Finally, HRQoL will be measured as a health 
outcome. Based on our previous work22, 23 as Preliminary Data immediately below, 
MT can be considered a coping behavior that positively influences HRQoL.
Critical gaps in the current evidence that necessitate additional research.
To date, there is not enough quality evidence on non-pharmacologic treatments for 
chronic SCD pain, including treatments that are patient-centered, culturally relevant, 
and accessible.5 Few studies examined the impact of MT on HRQoL and self- 
efficacy for individuals with complex chronic pain. Prior studies investigating the 
feasibility and impact of MT among predominantly Black/African American patients 
with chronic pain lacked an active attention-control condition and post-intervention 
follow-up outcome measures.16, 18
2.2
Study Rationale
Pilot Study 1: RCT of a Single MT Session for SCD: In a three-arm RCT 
comparing (1) MT, (2) music listening, and (3) no music (control), we enrolled 
participants with SCD who received a single 20-minute electronic music 
improvisation session. Subjects were more likely to report a significant improvement 
in pain intensity (mean = -1.92 ± 1.88 units; OR = 5.12, p = 0.035) and mood (OR = 
11.60, p = 0.005) compared to the control group, whereas participants who received 
music listening were more likely to report mood improvement only (OR = 5.76, p = 
0.040). Qualitative data from this study supported the acceptability and feasibility of a 
single MT intervention for addressing pain intensity during an acute care SCD clinic 
visit.22
Pilot Study 2: Music Use Survey: In a cross-sectional study of 100 adults with SCD 
conducted in preparation for Pilot Study 3 (below), we found that adults with SCD (1) 
face significant challenges related to pain interference (mean = 61.13); (2) perceive 
music as being helpful for managing challenges, including mood (57%), sleep (48%), 
stress (47%), and pain (37%); (3) purposefully engage in music listening to manage 
pain (74%); and (4) would be interested in participating in MT services in inpatient 
(88%) and outpatient (81%) settings. The most common need reported in our study 
population was for reducing pain (47%), followed by helping with relaxation and 
sleep (44%). Additionally, there was a moderate positive correlation (rs = 0.516, p <

.001) between the number of strategies used alongside music and the perceived 
helpfulness of music for reducing pain.32
Pilot Study 3: RCT of a 6-session MT Intervention for SCD: Mr. Rodgers-Melnick, 
Drs. Dusek, and Jenerette recently conducted a pilot study designed to determine 
the feasibility, acceptability, and preliminary efficacy of a 6-session MT intervention 
as compared to waitlist control (WLC) for adults with SCD and chronic pain. Adults 
with SCD (ages 21–57; mean age 32.33) were randomized (1:1) to either (1) a 6- 
session in-person MT intervention (n = 12) or (2) WLC (n = 12). All participants 
completed measures of self-efficacy, HRQoL, and coping skills before and after their 
assigned study condition to explore preliminary efficacy. MT participants received in- 
person MT and were taught music exercises accessed via smartphone and 
subsequently interviewed to determine feasibility and acceptability. The enrollment 
rate in this study was 89%. All outcomes were completed at the 2-week follow-up 
(100%). Interviews revealed two overall themes related to MT participants’ 
experience: (1) participants learned new self-management skills and (2) MT 
improved participants’ ability to cope with pain. MT participants demonstrated 100% 
attendance. In preliminary analyses, MT participants demonstrated significant 
improvements (means ± SD) in self-efficacy (5.42 ± 5.43, p = 0.008, d = 1.20), 
PROMIS sleep disturbance (−1.49 ± 6.68, p = 0.023, d = −0.99), PROMIS pain 
interference (−2.10 ± 4.68, p = 0.016, d = −1.06), and ASCQ-Me social functioning 
impact scores (2.97 ± 6.91, p = 0.018, d = 1.05) compared to WLC participants.23
We found across all six MT sessions that most MT participants reported using music 
exercises at home almost every day (40%) or every day (35%). Fewer MT 
participants reporting using music exercises once or twice per week (12%), never 
(10%), or more than once per day (3%). See Figure 2 below for a demonstration of 
the recruitment feasibility and preliminary efficacy from this study.
Figure 2. Demonstration of Feasibility and Preliminary Efficacy 
from Preliminary Study.
Outcome
Music 
Therapy 
Mean ± SD
Waitlist 
Control 
Mean ± SD
p- 
valueb
Effect 
sizec
Sickle Cell 
Self-Efficacy 
Scale
5.42 ± 5.43
-0.50 ± 4.38
0.008
1.20
PROMIS
Sleep 
Disturbancea
-1.49 ± 6.68
4.63 ± 5.58
0.023
-0.99
PROMIS
Pain 
Interferencea
-2.10 ± 4.68
4.30 ± 7.12
0.016
-1.06

Other 
Preliminary 
Data: Recent 
multi-session
ASCQ-Me Social 
Functioning 
Impacta
2.97 ± 6.91
-4.28 ± 6.93
0.018
1.05
interventions 
with urban 
African
a T-scores b Student t-test comparing change scores between groups c Cohen’s d comparing change 
scores between groups
Americans with chronic pain have revealed positive effects of vocal MT on pain self- 
efficacy and participants’ ability to participate in social activities.16, 18 A meta-analysis 
of 14 RCTs found that music interventions were effective for reducing self-reported 
chronic pain and depressive symptoms, and patient-preferred music was more 
effective than music chosen by the research team.33
Virtual and/or Hybrid Delivery of Integrative Therapies: Due to the COVID-19 
pandemic, the UH MT program has been adapted for virtual delivery, with several 
virtual MT sessions being provided to adults with SCD.34 Other cancer centers have 
also described successful MT adaptations to the virtual environment.35, 36 A recent 
study exploring the feasibility of a mindfulness-based MT intervention for adolescents 
and young adults with cancer that transitioned from in-person to virtual delivery found 
significant improvements in perceived stress and non-significant changes in anxiety. 
Additionally, a greater number of virtual MT group participants (n=17) completed all 
four sessions (76.5% vs. 29.4%) than in-person MT group participants (n=17).37 
Other virtual MT approaches have been utilized to reduce barriers to accessing 
services within military veteran populations,38-41 parents of hospitalized infants in 
neonatal intensive care units,42 and teens with Asperger’s Syndrome who lacked 
access to in-person services due to residing in remote or rural communities.43, 44
Ezenwa and colleagues conducted a pilot RCT of a 12-minute tablet-based guided 
audio-visual relaxation among 28 adults with SCD, and found that guided relaxation 
significantly reduced pain index scores, 96.4% of participants completed the study 
protocol and questionnaire items, and participants shared benefits of using tablets to 
collect research data and access the intervention.45 Ezenwa conducted a follow up 
RCT with all 30 participants completing the study, and 83% of participants in the 
experimental group reported enjoying the study.46 As a co-investigator, Dr. Ezenwa 
will bring her knowledge on virtual delivery for both the HybMT and HybHE 
intervention delivery.
3. STUDY DESIGN
Type/design of trial
This is a multi-site, multi-visit feasibility RCT of three wellbeing interventions among 
patients aged 14 and older with SCD.
Specific unit(s) of assignment and unit(s) of observation

The unit of assignment is at the patient level. Specifically, patients with SCD enrolled 
from SCD centers will be randomly assigned to either InMT, HybMT or HybHE. The 
unit of observation is the patient.
Primary and secondary outcomes
The primary objective is to refine procedures for conducting a future fully-powered 
multi-site RCT. The secondary objective of the study is to examine the feasibility of 
completeness of data collection, participant recruitment and rate, participant 
retention, as well as assessment of hybrid intervention implementation and home 
practice using study records across the 2 sites. This study will include qualitative 
interviews to assess feasibility of implementation.
Study population and groups/arms including sample size
(1) The study population will be ninety (60 from site 1, 30 from site 2) individuals who
(1) are aged 14 and older; (2) are diagnosed with SCD (3) meet AAPT Diagnostic 
Criteria for Chronic SCD Pain as evidenced by (3a) a diagnosis of SCD confirmed 
by laboratory testing; (3b) reporting ongoing pain present on most days over the 
past 6 months either in a single location or in multiple locations; (3c) displaying at 
least one of the following on clinical exam from a provider: palpation of the region 
of reported pain elicits focal pain or tenderness, movement of the region of 
reported pain elicits focal pain, decreased range of motion or weakness in the 
region of reported pain, evidence of skin ulcer in the region of reported pain, 
evidence of hepatobiliary or splenic imaging abnormalities (e.g., splenic infarct, 
chronic pancreatitis) consistent with the region of reported pain, or evidence of 
imaging abnormalities consistent with bone infarction or avascular necrosis in the 
region of reported pain; (4) are able to speak and understand English; (5) have 
an email address and access to a mobile device with a functioning data plan; and
(6) report that pain interfered with daily activities at least 1-2 days in the past 
week. Individuals who (1) have significant visual, hearing, or cognitive 
impairments; (2) previously participated the in MUSIQOLS single-site pilot study 
at University Hospitals in 2018; (3) are currently engaged in mind-body therapies 
under the supervision of a healthcare professional specifically for pain 
management or (4) have a planned major medical event in the next 14 weeks 
such as (but not limited to) childbirth, orthopedic surgery, gene therapy, or stem 
cell transplant (these criteria do not include blood transfusions, exchange 
transfusions, or other pharmacologic pain treatment) will be ineligible for study 
participation.
Allocation of the study participants will be as follows:
InMT
HybMT
HybHE
Total
UH/CWRU
20
20
20
60
Prisma/USC
10
10
10
30
(2) Twenty-four participants (equal numbers across the InMT, HybMT and HybHE 
groups) will be contacted for brief qualitative interviews within 2-3 weeks of 
intervention completion.
(3) Twenty relevant staff stakeholders (SCD providers and staff, music therapists and 
HybHE interventionists), 10 at each site, will be contacted to participate in a brief 
survey and qualitative interviews approximately 16-26 weeks after enrollment 
begins.

Study location
Randomized Control Trial
Subjects will be recruited from: UH Seidman Cancer Center Adult SCD Clinic or UH 
Rainbow Babies and Children’s Hospital Sickle Cell Anemia Center (site 1) and 
Prisma Health Lifespan Comprehensive SCD Program (site 2). Interventions will be 
conducted at:

InMT: SCD center main campus, satellite campus, or another location 
preferred by the participant (e.g., community center) for all sessions.

HybMT: SCD main campus, satellite campus, or another location preferred 
by the participant (e.g., community center) for session 1. Secure telehealth 
platform (i.e., Zoom Health Professional) for sessions 2 – 6.

HybHE: SCD main campus, satellite campus, or another location preferred 
by the participant (e.g., community center) for session 1. Secure telehealth 
platform (i.e., Zoom Health Professional) for sessions 2 – 6.
Qualitative Interviews
Participant qualitative interviews will be conducted via a HIPAA-compliant secure 
telehealth platform (e.g. Zoom Health Professional or Doxy.me) or over the phone 
and will be audio and/or video recorded. Video recordings will be immediately 
deleted, and audio recordings will be transcribed. SCD providers and staff, music 
therapist, and HybHE interventionist interviews will happen via a HIPAA-compliant 
secure telehealth platform (e.g. Zoom Health Professional or Doxy.me) and will be 
audio and/or video recorded. Video recordings will be immediately deleted, and 
audio recordings will be transcribed. Investigators will stop conducting the 
qualitative interviews in each arm AFTER 8 interviews are completed.
Approximate duration of enrollment period and follow-up 
Randomized Control Trial
Subjects will be enrolled for 12 to 14 weeks (6 – 8 weeks for the intervention and 6 
weeks for the final follow-up measures). Each site will enroll for ~18 months.
Cohorts of up to 15 participants (10 at site 1 and 5 at site 2) will be recruited each 
quarter for 6 quarters to reach the goal of 90 participants. Cohorts will maintain a 
semi- structured recruitment, consent, assessment, and intervention schedule.
Qualitative Interviews
Participant interviews will take place during their 12 to 14 weeks of enrollment, 
approximately 2-3 weeks after their last intervention session. Provider enrollment will 
begin when they express interest in participating in the interview and will end after 
they complete their interview and survey.
Description of intervention and administration
Parent/guardians of minor participants will be encouraged to remain on site during the 
minor participants’ in-person sessions at the SCD center main campus, satellite campus 
or another location preferred by the participant (e.g., community center). However, the 
parent/guardian will be asked to remain outside of the session space.

Music Therapy Conditions (InMT and HybMT)
Participants in the InMT and HybMT conditions will receive either 6 in-person MT 
sessions (InMT) or 1 in-person and 5 virtual sessions (HybMT) over 6 weeks (see 
Table 1 below for descriptions of each session). Each MT session will last no longer 
than one hour. This 6-week treatment period may be extended to up to 8 weeks if a 
scheduling conflict prevents a participant from receiving the 6 MT sessions over 6 
consecutive weeks. In-person sessions will be delivered one-on-one at the SCD 
center main campus, satellite campus, or another location preferred by the 
participant (e.g., community center). Virtual sessions will be delivered over secure 
telehealth platform (e.g. Zoom Health Professional). If participants lack their own 
tablets, computers, or home internet, they will be provided with iPads preconfigured 
with data plans and headphones to facilitate receiving the intervention.
To begin each session, the interventionist will determine ability to participate (see 
form B.3.3) in a session by asking and documenting “Do you feel able to engage with 
us now, or would you like to try to participate at a later time/date?” If the participant 
says “No”, the session will not continue and will be rescheduled. If the participant 
says “Yes”, the session will continue. At the start and end of each MT session, the 
participant will complete 0-10 numeric rating scale measures of pain, stress, anxiety, 
and fatigue (see below for description). Each MT session will include (1) setting an 
agenda, (2) an explanation of the music exercise, (3) a demonstration of the music 
exercise in which the MT-BC will engage the participant in practicing the music 
exercise (e.g., breathing, progressive muscle relaxation, imagery), (4) time to 
process the participant’s response to the exercise, (5) time for the MT-BC to 
electronically deliver the music exercise to the participant and ensure that the 
participant has all materials necessary to use the exercise at home, and (6) a 
homework assignment for the participant to practice the music exercise taught in that 
session at least once per day until the following MT session. The genres of each 
music exercise (i.e., music-based breathing exercise, progressive muscle relaxation, 
imagery, and active music making) will be personalized to participants’ preferences 
(e.g., hip-hop, gospel, R&B, jazz, rock, and/or soul) based on the music preferences 
disclosed in the first session. Each music exercise lasts an average of 10.9 minutes. 
As the music exercises are being demonstrated, the MT-BC will simultaneously 
record the exercise using GarageBand for MacOS. Participants will record their use 
of the music exercises in weekly REDCap surveys delivered via text message. We 
will also use REDCap surveys or MyCap to remind participants about upcoming MT 
sessions and prompt them to confirm their upcoming attendance.
Participants will be provided with all necessary materials (e.g., instruments, audio 
files, headphones) needed to practice the music exercises at home, including 
instructions and personalized audio recordings of music exercises delivered via a 
secure Box folder, email, and/or Airdrop depending on the functions of the 
participant’s mobile device. Participants will not have to purchase their own musical 
or electronic materials to participate in the MT interventions. Participants will be able 
to contact the music therapist via secure message in MyCap or via email if they 
have any questions about using the music exercises during the study.

Explain pain mechanisms in SCD and rationale for how music helps to reduce pain
1) Education
Description
Session
3) Relaxation
Teach guided progressive muscle relaxation (PMR) exercise with music
5) Music Making
Teach active music making exercise
Table 1. Description of MT Sessions.
2) Breathe
Teach deep breathing exercise with music
4) Imagery
Teach music-based imagery exercise
6) Conclusion
Review previous MT exercises and make plan for coping with future challenges
Hybrid Health Education (HybHE)
The HybHE attention control condition will be adapted from Project PEEP: Patients 
Empowered and Educated Providers. The Sickle Cell Community Consortium 
developed Project PEEP with a grant from Global Blood Therapeutics. Project PEEP 
addresses unmet needs directly identified and prioritized by a collective of patients 
with SCD, caregivers, and community-based organizations. The objective is to 
provide the tools and resources to improve communication and increase positive 
patient-provider interactions to receive quality, timely care. For the proposed study, 
we will use modules from the curriculum developed for patients living with SCD. All 
modules were developed with input from individuals living with SCD. Dr. Bailey was 
a critical developer of the Project PEEP curricula, and she will serve as a consultant 
to assist with its use in this R01 feasibility pilot RCT.
Participants in the HybHE condition will receive 1 in-person health education session 
at the SCD center main campus, satellite campus, or another location preferred by 
the participant (e.g., community center) and 5 virtual sessions over secure telehealth 
platform (e.g. Zoom Health Professional). The 6 HybHE sessions will occur over 6 
weeks (see Table 2 below for descriptions of each session). Each HybHE session 
will last no longer than one hour. This 6-week treatment period may be extended to 
up to 8 weeks if a scheduling conflict prevents a participant from receiving the 6 
HybHE sessions over 6 consecutive weeks. If participants lack their own tablets, 
computers, or home internet, they will be provided with iPads preconfigured with data 
plans and headphones to facilitate receiving the intervention. Participants will be 
given iPads to receive the intervention and complete outcome measures.
As in the MT conditions, to begin each session, the interventionist will determine 
capacity to participate in a session by performing and documenting a modified global 
assessment including: (1) Is the subject alert and able to communicate with the 
investigator/study team? (2) Is the subject sufficiently comfortable as to be able to 
communicate? and (3) Is the subject reporting a current pain level that would prevent 
them from participating in today’s session? Each HybHE session will include (1) 
setting an agenda, (2) an explanation module, (3) time to review the module, (4) time 
for the HybHE interventionist to answer any questions, and (5) a homework 
assignment for the participant to reflect on the module and reflect on how the content

can be used to improve care-seeking. Participants will record their use of HybHE 
content in weekly REDCap surveys delivered via text message. We will also use 
MyCap to remind participants about upcoming HybHE sessions and prompt them to 
confirm their upcoming attendance.
Participants will be provided with all necessary materials to fully engage in HybHE 
(e.g., manual of modules) needed to practice the content of the modules at home. 
These materials will be delivered via a secure Box folder, email, and/or Airdrop 
depending on the functions of the participant’s mobile device. Participants will not 
have to purchase electronic materials to participate in the HybHE interventions.
Participants will be able to contact the HybHE interventionist via secure message in 
MyCap or via email if they have any questions about using the HybHE content during 
the study.
Table 2. Description of HealthED Sessions.
Reviews the science of SCD, focusing on blood, organs affected, labs, and the 
biology behind vaso-occlusive crises.
1) Science of SCD
Description
Session
2) Identifying Barriers in 
the Emergency 
Department
Introduces common barriers (supported by research) that patients with SCD 
experience in the ED.
3) Tools for Navigating the
Explores the healthcare infrastructure, chain of command, documenting care (both
Healthcare System
positive and negative) and the process of filing a complaint in a constructive and 
effective manner.
4) SBAR: Healthcare 
Based Communication for 
Patients (Part 1)
Introduces Situation, Background, Assessment, Recommendation (SBAR) and as 
an effective form of communication for patients when accessing medical care and 
covers Situation (S) and Background (B) of SBAR.
5) SBAR: Healthcare
Based Communication for
Reviews SBAR and covers Assessment (A) and Recommendation (R) of SBAR.
Patients (Part 2)
6) Conclusion
Review content from sessions 1-5 and make a plan to address future challenges.
Following the post-test assessment, the participants randomized to HybHE will 
receive access to a library of recordings from the MT intervention. Participants 
randomized to InMT or HybMT will receive access to the health education content. 
All participants will not be required to complete any additional assessments or 
perform any study activities during the time following the 6-week post-intervention 
assessment.
Remuneration
As acknowledgement of the participant’s time, participants will receive:

$20 for baseline data collection;

$20 for participating in session 1;

$10 for sessions 2, 3, 4, and 5;

$20 for session 6;


Those who complete at least 4 of 6 sessions will receive a $25 bonus;

$25 for completing follow-up data collection at post-intervention;

$25 for interview participation; and

$25 for completing follow-up date collection at 6-weeks post-intervention.
Thus, participants will be eligible to receive a possible maximum of $175-$200 per 
patient, given via ClinCard prepaid debit card.
If the participant does not already have one, a ClinCard prepaid debit card will be 
issued during the participant’s enrollment session by the study staff. Study staff will 
register the participant to the card and distribute a physical or virtual card to the 
participant. Participants will be provided with a Frequently Asked Questions guide, 
Cardholder Agreement, and Cardholder Information Sheet. Study staff will load 
funds onto the participant’s ClinCard according to the schedule above.
Randomization, blinding and any restrictions on randomization
A total of 90 subjects (60 from site 1, 30 from site 2) will be randomized to either 
InMT, HybMT or HybHE (1:1:1 allocation). Random assignments will be made by the 
study statistician in permuted blocks of size 3 and 6. The block size will also be 
randomly generated to minimize correct prediction of assignments and preserve 
approximate balance between groups, using the rand function in SAS. Administrative 
personnel from the Data Coordinating Center will prepare the randomization module 
using REDCap.
Study personnel that will be blinded to participant data, unless they will be involved 
with fidelity monitoring, are the MPIs, co-investigators, site PIs, DCC PIs, study 
biostatistician, and research assistants recruiting participants and following up to 
collect patient-reported outcomes. The MSC/site coordinator at UH will be 
unblinded for quality assurance. Prisma’s site coordinator and all interventionists 
will be unblinded to the randomization of the participants. However, they will be 
blinded to patient-reported outcomes (e.g., NRS, PROMIS-29 or PROMIS-25, and 
ASCQ-Me). Unblinded staff will not have access to data outside the session logs 
that they document and no involvement in data monitoring and analyses.
4. SELECTION AND ENROLLMENT OF PARTICIPANTS
4.1
Inclusion Criteria
Participants must meet all of the inclusion criteria to participate in this study.
A. Randomized Control Trial
Inclusion Criteria
1.
≥14 years of age
2.
Have a diagnosis of SCD present in their EHR
3.
Meet AAPT criteria for chronic SCD pain, which includes:
a) Diagnosis of SCD confirmed by laboratory testing (eligibility criteria 2)

b) Reporting ongoing pain present on most days over the past 6 months 
either in a single location or in multiple locations (upon screening)
c) Provider EHR documentation of at least one of the following signs
a.
Palpation of the region of reported pain elicits focal pain or 
tenderness
b. Movement of the region of reported pain elicits focal pain
c.
Decreased range of motion or weakness in the region of reported 
pain
d. Evidence of skin ulcer in the region of reported pain
e.
Evidence of hepatobiliary or splenic imaging abnormalities (e.g., 
splenic infarct, chronic pancreatitis) consistent with the region of 
reported pain
f.
Evidence of imaging abnormalities consistent with bone infarction 
or avascular necrosis in the region of reported pain
d) Per provider documentation, there is no other diagnosis that better 
explains the signs and symptoms
4.
Ability to communicate in English
5.
Has an email address and access to mobile device with a functioning data plan
6.
Reporting that pain interfered with daily activities at least 1-2 days in the past 
week
B. Qualitative Interviews
Inclusion Criteria
1.
Participants: Individuals who participated in the RCT
2.
Participants: Access to the internet and a device with videoconferencing 
capabilities
3.
Providers/Staff: Clinical providers in the SCD centers for at least 6 months 
including the study period at University Hospitals or Prisma Health (physicians, 
nurse practitioners, physician assistants, and registered nurses) OR music 
therapist and HybHE interventionist involved with the MULTI-MUSIQOLS study 
for at least 6 months
4.
Providers/Staff: 18 years of age or older
4.2
Exclusion Criteria
All candidates meeting any of the exclusion criteria at baseline will be excluded from 
study participation.
A. Randomized Control Trial
Exclusion Criteria
1.
Currently engaging in practicing mindfulness, meditation, MT, or other mind-body 
practices under the guidance of a healthcare professional for the purposes of pain 
management
2.
A planned major medical event within 14 weeks of the screening date, which 
could include: childbirth, orthopedic surgery, gene therapy trial, or stem cell 
transplant (these criteria do not include blood transfusions, exchange 
transfusions, or other pharmacologic pain treatment).
3.
Having a significant visual, hearing, or cognitive impairment

4.
Previously participated in MUSIQOLS single-site pilot study (STUDY20180101)
B. Qualitative Interview
Exclusion Criteria
1.
Participants: N/A
2.
Providers/Staff: N/A
4.3
Study Enrollment Procedures 
Recruitment Methods
Randomized Control Trial: Patients will be referred by members of the outpatient 
SCD team at participating sites (UH Seidman Cancer Center Adult SCD Clinic or UH 
Rainbow Babies & Children’s Pediatric Sickle Cell Anemia Center [site 1] and Prisma 
Health Lifespan Comprehensive SCD Program [site 2]). Providers will be able to 
email patient information to a secure research email monitored by the site’s study 
staff, comprised of the site’s study coordinator (SC) and research assistant (RA) or 
meet with study staff to review patient lists for upcoming outpatient clinic visits or 
inpatient care. Following the patient referral, the study staff from the respective SCD 
center will review the patient’s paper and/or electronic health record (EHR) to verify 
the patient’s initial eligibility (age, understanding of English language, and diagnosis 
of SCD). After meeting these initial criteria, the study staff will enter the patient 
information in the screening log in REDCap. The study staff will prepare Participant 
Eligibility Source Document forms for each initially eligible patient arriving for an 
appointment or who has been admitted to the hospital for that day. During daily 
huddles, weekly meetings, or while in the SCD center, study staff will meet with 
providers to complete the Participant Eligibility Source Document form for 
determining patient’s signs of SCD and AAPT category. The study staff will approach 
eligible patients, and their parent/guardian when necessary, at a convenient time 
during their next (1) regularly scheduled visit to the outpatient SCD center, (2) visit to 
an infusion center, or (3) inpatient admission prior to discharge.
If the patient and parent/guardian has time to discuss the study right then, the study 
staff will continue with recruiting procedures. If the patient and parent/guardian do 
not have time during their appointment, the study staff will return at a more 
convenient time that day or ask to set up another time to meet to discuss the study in 
person.
After a brief explanation of the study and patient approval, the study staff will 
continue to determine eligibility by (1) asking about duration, frequency, and 
interference related to their pain, and (2) confirming the patient’s access to an email 
address and mobile phone with a functioning data plan. If the patient meets all 
eligibility criteria and expresses interest in participating in the study the SC or RA will 
seek to obtain informed consent from adult patients and parents of minors, as well as 
signature from minors. If the adult patient is not interested in participating in the study 
or refuses to provide/confirm their phone number and email for follow up 
assessments and scheduling, a reason for refusal will be documented in REDCap by 
the study staff. If the minor patient is not interested in participating in the study or
they or their parent/guardian refuses to provide/confirm their phone number and 
email for follow up assessments and scheduling, a reason for refusal will be 

documented in REDCap by the study staff.
Qualitative Interview: Patient Participants: The consent will inform the patient that if 
they are randomized to receive InMT, HybMT, or HybHE a study team member may 
contact them to ask if they would like to participate in an additional interview, and 
that they may refuse to participate in the interview portion of the study without 
affecting their participation in the other portion of the research. They will be informed 
that the interview will be recorded and transcribed and that a study information sheet 
will be shared and reviewed with them prior to the start of the interview. Study staff 
will contact the patients who expressed interest in participating in the interview via 
phone and/or email within 2-3 weeks of their final session. Participants may decline 
to participate in the interview when contacted to schedule the interview without 
penalty of withdrawal.
SCD Provider & Staff, Music Therapist, and HybHE Interventionists: We will use staff 
rosters to identify physicians, advance practice providers, nurses and SCD center 
staff who have been employed by the SCD center at one of the two sites during the 
data collection period and to identify MULTI-MUSIQOLS music therapists and 
HybHE interventionists performing the intervention as part of the study. Stakeholders 
will be presented with a study information sheet explaining the interview objectives, 
procedures, benefits and risks. A verbal consent will be obtained to continue with the 
interview. Study staff who have been trained to conduct the qualitative interviews will 
contact these providers and staff by email, followed by phone, to invite them to 
participate.
Documentation of Reasons for Ineligibility
We will maintain a screening and enrollment log to document ineligibility reasons and 
non-participation of eligible candidates in REDCap.
Informed Consent Process
Randomized Control Trial: During the initial approach, the study staff will give a brief 
explanation of the study, the time commitment and answer any preliminary questions 
from the patient. If the patient and parent/guardian, when appropriate, is/are willing to 
continue with the recruitment procedures, at this point, study staff will complete the 
screening process by asking the patient about pain duration, frequency, and 
interference in relation to their SCD, and access to WiFi, devices and data plans. If 
eligibility is confirmed between 2 and 6 weeks away from each cohort’s intervention 
start date, study staff will set up an appointment with the patient (and 
parent/guardian, when necessary) at the SCD center or another location preferred by 
the participant (e.g., community center) to obtain consent/assent and baseline 
assessments within 2 weeks of the cohort intervention start date. If the eligibility is 
confirmed within 2 weeks of the cohort start date, study staff will continue directly to 
the consent/assent and baseline assessment process, time permitting. If a 
patient/parent/guardian does not have time during their screening visit to complete 
the consent and baseline assessments, an appointment will be scheduled to 
complete these documents at the patient/parent/guardian’s convenience within 2
weeks prior to the cohort intervention start date. If the patient/parent/guardian cannot 
meet within 2 weeks of the cohort intervention start date, study staff will attempt to 
schedule the consent/baseline assessment appointment within the first weeks after 
the cohort intervention start date. If the patient/parent/guardian still cannot meet 

during that time, then their recruitment will be held over to a subsequent cohort. If 
this delay occurs during the final study cohort, then the patient will not be able to 
participate in the study. If needed, the study staff will provide the patient with 
transportation assistance to attend the consent and baseline assessment visit.
Study staff at University Hospitals and Prisma will obtain electronic signature on the 
eConsent from the adult patient or the minor’s parent/guardian and the minor patient.
The Informed consent process will occur in a private treatment room or consult room 
out of the earshot of others to maintain privacy. Patients and parents/guardians will 
be provided with a hard copy of the consent form along with an identical electronic 
version to read along with the SC or RA. Patients, parent/guardians, and study staff 
will read through the informed consent document together at this time. The study 
staff will answer any questions the adolescent or adult patient or parent/guardian 
may have about the study and allow time for the patient and parent/guardian to 
summarize the study procedures to confirm understanding. If the patient or 
parent/guardian would like more time to consider participation in the study, they can 
take the consent form home to review and consider and then bring it to their next visit 
to the SCD Clinic. The adult patients ready to consent, will sign the electronic 
consent form in REDCap by “making their mark” on the signature line to indicate that 
they understand the document. After this is documented in REDCap by the study 
staff, the minor patient and the parent/guardian of the minor will sign the electronic 
consent form in REDCap by “making their mark” on the signature line to indicate that 
they understand the document.
A partial waiver of consent will be used to review the medical charts for pre- 
screening purposes. This waiver will only be used to access patients' PHI following 
the referral and prior to obtaining written informed consent. Patients will still be fully 
informed of study details prior to giving written consent and participating in research.
Qualitative Interviews: Participant Interviews Consent Process: Participants who are 
consented to participate in the RCT will be informed as part of that consent process 
that we may approach them to invite them to participate in an interview. The consent 
form will include language informing the patient that the interview will take place via a 
HIPAA-compliant commercial tele-health platform: (e.g. Zoom Health Professional or 
Doxy.me) and will be recorded and transcribed. There will also be an option for the 
participant to opt out of being contacted for the interview. Study staff will contact 
participants within 2-3 weeks after their final session to schedule the interview and to 
share the study information sheet to review. Participant contact with the research 
staff for qualitative interviews will be documented in REDCap with up to 5 attempts to 
schedule the qualitative interview. At the time of the interview, the interviewer will 
review the study information sheet with the participant. This document will explain 
that the interview will be recorded and transcribed, and will reiterate the voluntary 
nature of participation. The document will explain that if the participant continues with 
the interview, they are agreeing that they have read the information and that they 
voluntarily agree to participate and to be recorded for transcription purposes.
Provider/Interventionist Interview Consent Process: Identified providers/staff and 
interventionists will be contacted by study staff via email followed by phone and 
invited to participate in the interview. They will schedule the interview at the 
providers’ convenience. A study information sheet will be shared via email with the 
provider ahead of the interview, and will be reviewed at the beginning of the 

scheduled interview. This document will explain that the interview will be recorded 
and transcribed, and will reiterate the voluntary nature of participation. The document 
will explain that if the participant continues with the interview, they are agreeing that 
they have read the information and that they voluntarily agree to participate and to be 
recorded and transcribed.
Randomization
Randomized Control Trial: Randomization to Group
Random assignments will be made by the study statistician in permuted blocks of 
size 3 and 6. Randomization will be stratified by site and by group. The block size 
will also be randomly generated to minimize correct prediction of assignments and 
preserve approximate balance between groups, using the rand function in SAS. 
Administrative personnel from the Data Coordinating Center (DCC) will prepare the 
randomization module using REDCap. The SC or RA will enable randomization in 
REDCap for each participant after completion of the informed consent and baseline 
data collection.
After a patient completes the consent/assent and baseline assessment process, 
study staff will inform the respective site study coordinator (sSC). The sSC will 
randomize the participants into their intervention group using the REDCap tool. Once 
randomized, the sSC will contact the participant/parent/guardian to schedule the 
initial intervention session.
Qualitative Interview
During the informed consent process for the randomized trial, all participants will be 
asked if they would be willing to participate in a 30-to-60-minute qualitative interview 
via secure Zoom within 2-3 weeks of completing their assigned intervention.
We seek to enroll 24 participants equally across the 3 groups (n = 8 per group), and 
a comparable number by sex (males vs females), age group (≥30 vs < 30), and site 
(16 from UH and 8 from Prisma). 
5. STUDY INTERVENTIONS
5.1
Interventions, Administration, and Duration
HybMT and InMT
Randomized participants will be assigned to a single music therapist for the duration 
of their study intervention (6-8 weeks). At each site, two music therapists will be 
trained to provide the study intervention, with one therapist providing the HybMT 
interventions and the other providing the InMT interventions. We expect the 
distribution of participants to be:

At Prisma/USC

For 20 MT participants (10 InMT and 10 HybMT), one music 
therapist will provide the InMT interventions and the other will 
provde the HybMT interventions.
At UH/CWRU

For 40 MT participants (20 to InMT and 20 HybMT), one music 
therapist will provide the InMT interventions and the other will provde 
the HybMT interventions.
HybHE
Randomized participants will be assigned to a single HybHE interventionist for the 
duration of their study intervention (6-8 weeks). At each site, two graduate nursing 
students will be trained on the HybHE intervention, one being the primary 
interventionist and the second as a back-up to provide flexibility in coverage. We 
expect the distribution of participants to be:
At Prisma/USC

For 10 HybHE participants, the primary HybHE interventionist will be a 
dedicated interventionist to this study group.
At UH/CWRU

For 20 HybHE participants, the primary HybHE interventionist will be a 
dedicated interventionist to this study group.
To minimize the burden on study interventionist, cohorts will be recruited quarterly 
(i.e., 15 participants per quarter [Qtr]).
UH/CWRU (n = 10/Qtr)
Music therapist(s) providing 36 – 48 sessions/Qtr

InMT (n ~ 3 – 4, max = 4) x 6 sessions = 18 – 24 sessions/Qtr

HybMT (n ~ 3 – 4, max = 4) x 6 sessions = 18 – 24 sessions/Qtr 
Graduate nursing student providing 18 – 24 sessions/Qtr

HybHD (n ~ 3 – 4, max = 4) x 6 sessions = 18 – 24 sessions/Qtr
Prisma/USC (n = 5/Qtr)
Music therapist(s) providing 12 – 24 sessions/Qtr

InMT (n ~ 1 – 2, max = 2) x 6 sessions = 6 – 12 sessions

HybMT (n ~ 1 – 2, max = 2) x 6 sessions = 6 – 12 sessions 
Graduate nursing student providing 6 – 12 sessions/Qtr

HybHD (n ~ 1 – 2, max = 2) x 6 sessions = 6 – 12 sessions/Qtr
Receiving either intervention (i.e., InMT, HybMT, or HybHE) will not affect the 
patient’s usual care in that any medications, infusions, or most services will continue 
to be available under the direction of the patient’s care provider team. Study 
participants will be asked to refrain from receiving mindfulness, meditation, MT, or 
other mind-body practices for the purposes of pain management under the guidance 
of professionals not affiliated with the study while participating in the study 
interventions. Study participation will be noted in the patient’s EHR (i.e., flagged in 
Epic). Other MT providers within the departments at UH and Prisma will be advised 
to look for this notation and not approach study participants for additional services 

while they are actively participating in the study.

Parent/guardians of minor participants will be encouraged to remain on site during 
participant’s in-person sessions at the SCD center or another location preferred by 
the participant (e.g., community center). However, the parent/guardian will be asked 
to remain outside of the session space.
The study music therapists will adhere to the following approach:
Participants in the MT condition (either InMT or HybMT) will receive 6 MT sessions 
over 6 weeks (see Table 1 below for descriptions of each session). Each MT session 
will last no longer than one hour. This 6-week treatment period may be extended to 
up to 8 weeks if a scheduling conflict prevents a participant from receiving the 6 MT 
sessions over 6 consecutive weeks. The first session will be delivered one-on-one in- 
person at the SCD center main campus, satellite campus, or another location 
preferred by the participant (e.g., community center). The focus of this session will 
include building rapport, goal setting, understanding participants’ music preferences, 
providing education on pain and music analgesia, and providing education on how to 
engage in future virtual sessions.
For participants randomized to the InMT arm, subsequent sessions will take place at 
the SCD center main campus, satellite campus, or another location preferred by the 
participant (e.g., community center). For participants randomized to the HybMT arm, 
subsequent sessions will occur virtually via a secure telehealth platform (e.g. Zoom 
Health Professional). If participants lack their own tablets, computers, or home 
internet, they will be provided with iPads preconfigured with data plans and 
headphones to facilitate receiving the intervention.
At the start and end of each MT session, the participant will complete 0-10 numeric 
rating scale measures of pain, stress, anxiety, and fatigue (see section 6.1 for 
description). Each MT session will include (1) setting an agenda, (2) an explanation 
of the music exercise, (3) a demonstration of the music exercise in which the MT-BC 
will engage the participant in practicing the music exercise (e.g., breathing, 
progressive muscle relaxation, imagery), (4) time to process the participant’s 
response to the exercise, (5) time for the MT-BC to electronically deliver the music 
exercise to the participant and ensure that the participant has all materials necessary 
to use the exercise at home, and (6) a homework assignment for the participant to 
practice the music exercise taught in that session at least once per day until the 
following MT session. The genres of each music exercise (i.e., music-based 
breathing exercise, progressive muscle relaxation, imagery, and active music 
making) will be personalized to participants’ preferences (e.g., hip-hop, gospel, R&B, 
jazz, rock, and/or soul) based on the music preferences disclosed in the first session. 
Each music exercise lasts an average of 10.9 minutes. As the music exercises are 
being demonstrated, the MT-BC will simultaneously record the exercise using 
GarageBand for MacOS. Participants will report their use of the music exercises at 
the beginning of MT sessions 2-6, and the music therapist will note this in REDCap. 
We will also use REDCap surveys to remind participants about upcoming MT 
sessions and prompt them to confirm their upcoming attendance.

Explain pain mechanisms in SCD and rationale for how music helps to reduce pain; receive 
devices for hybrid session, as needed
1) Education
Description
Session
3) Relaxation
Teach guided progressive muscle relaxation (PMR) exercise with music
5) Music Making
Teach active music making exercise
Participants will be provided with all necessary materials (e.g., instruments, audio 
files, headphones) needed to practice the music exercises at home, including 
instructions and personalized audio recordings of music exercises delivered via a 
secure Box folder, email, and/or Airdrop depending on the functions of the 
participant’s mobile device. Participants will not have to purchase their own musical 
or electronic materials to participate in the MT interventions. Participants will be able 
to contact the music therapist via secure message in MyCap or via email if they 
have any questions about using the music exercises during the study.
Table 1. Description of MT Sessions.
2) Breathe
Teach deep breathing exercise with music
4) Imagery
Teach music-based imagery exercise
6) Conclusion
Review previous MT exercises and make plan for coping with future challenges
The HybHE interventionists will adhere to the following approach:
The HybHE control will be adapted from Project PEEP: Patients Empowered and 
Educated Providers. The Sickle Cell Community Consortium developed Project 
PEEP with a grant from Global Blood Therapeutics. Project PEEP addresses unmet 
needs directly identified and prioritized by a collective of patients with SCD, 
caregivers, and community-based organizations. The objective is to provide the tools 
and resources to improve communication and increase positive patient-provider 
interactions to receive quality, timely care. For the proposed study, we will use 
modules from the curriculum developed for patients living with SCD. All modules 
were developed with input from individuals living with SCD. Dr. Bailey was a critical 
developer of the Project PEEP curricula, and she will serve as a consultant to assist 
with its use in this R01 feasibility pilot RCT.
Participants in the HybHE condition will receive 6 HybHE sessions over 6 weeks 
(see Table 2 below for descriptions of each session). Each HybHE session will last 
no longer than one hour. This 6-week treatment period may be extended to up to 8 
weeks if a scheduling conflict prevents a participant from receiving the 6 HybHE 
sessions over 6 consecutive weeks. Like the HybMT group, the first session will be 
delivered one-on-one in person at the SCD center main campus, satellite campus, or 
another location preferred by the participant (e.g., community center). The focus of 
this session will include building rapport, goal setting, understanding the HybHE 
intervention, and providing education on how to engage in future virtual sessions.
For participants randomized to the HybHE arm, subsequent sessions will be 
delivered virtually via Zoom. If participants lack their own tablets, computers, or

home internet, they will be provided with iPads preconfigured with data plans and 
headphones to facilitate receiving the intervention. Participants will be given iPads to 
receive the intervention and complete outcome measures.
Each HybHE session will include (1) setting an agenda, (2) an explanation module,
(3) time to review the module, (4) time for the HealthED interventionist to answer any 
questions, and (5) a homework assignment for the participant to reflect on the 
module and reflect on how the content can be used to improve care-seeking. 
Participants will report their use of HybHE content to HybHE interventionists at the 
beginning of session 2-6. We will also use MyCap to remind participants about 
upcoming HybHE sessions and prompt them to confirm their upcoming attendance.
Participants will be provided with all necessary materials to fully engage in HybHE 
(e.g., manual of modules) needed to practice the content of the modules at home. 
These materials will be delivered via a secure Box folder, email, and/or Airdrop 
depending on the functions of the participant’s mobile device. Participants will not 
have to purchase electronic materials to participate in the HybHE interventions.
Participants will be able to contact the HybHE interventionist via MyCap or via email 
if they have any questions about using the HybHE content during the study.
Table 2. Description of HybHE Sessions.
Reviews the science of SCD, focusing on blood, organs affected, labs, and the 
biology behind vaso-occlusive crises; receive devices for hybrid sessions, as 
needed.
1) Science of SCD
Description
Session
2) Identifying Barriers in 
the Emergency 
Department
Introduces common barriers (supported by research) that patients with SCD 
experience in the ED.
3) Tools for Navigating the
Explores the healthcare infrastructure, chain of command, documenting care (both
Healthcare System
positive and negative) and the process of filing a complaint in a constructive and 
effective manner.
4) SBAR: Healthcare 
Based Communication for 
Patients (Part 1)
Introduces Situation, Background, Assessment, Recommendation (SBAR) and as 
an effective form of communication for patients when accessing medical care and 
covers Situation (S) and Background (B) of SBAR.
5) SBAR: Healthcare
Based Communication for
Reviews SBAR and covers Assessment (A) and Recommendation (R) of SBAR.
Patients (Part 2)
6) Conclusion
Review content from sessions 1-5 and make a plan to address future challenges.
5.2
Handling of Study Interventions
To ensure HybMT and HybHE participants will have access to a reliable means of 
study engagement, we plan to purchase up to 36 iPads that these participants will 
use during their study participation (if needed) and return at the end of their

intervention period (i.e., after session 6). These iPads will be equipped with cellular 
capacity to provide data bandwidth for engaging in videoconferencing in the absence 
of a stable WiFi connection if needed. The sSC will track the distribution of iPads 
within REDCap.
The participant’s need for a device will be assessed at recruitment by asking 
questions regarding (1) what devices they have access to at home, (2) whether they 
have reliable WiFi internet at home, (3) whether they currently have a data plan for 
their smartphone (if applicable), and (4) whether they have engaged in video 
conferencing at home before. The person conducting the informed consent visit will 
distribute the iPad (if needed) following randomization.
We will plan to purchase 2-month LTE data plans as needed to provide to 
participants whose WiFi and/or limited data plans prevent or hinder engagement in 
videoconferencing at home. The sSC will track the distribution of data plans within 
REDCap. The iPads will be pre-configured with these data plans when they are 
provided to participants during HybMT or HybHE session 1.
We will purchase 90 closed back-headphones equipped with microphones for all 
study participants to ensure consistent audio delivery. The sSC or RA will distribute 
headphones during the consenting and baseline assessment appointment.
We will provide HybMT patients with a small diatonic xylophone to facilitate 
participation in session 5 (music making) at home while engaging in the session 
virtually. This will be provided to HydMT participants during their in-person MT 
session and collected following their final HybMT session.
To alleviate the burden on participants traveling to participate in in-person consenting 
and in-person sessions, local bus passes, rideshare assistance, or mileage 
reimbursement and parking passes will be distributed as needed. If a 
patient/parent/guardian needs a bus pass to attend a consenting and baseline 
assessment appointment, passes will be provided during the recruitment session.
During the consenting and baseline appointment, bus passes or rideshare 
assistance will be available to those who express a need in order to attend the first 
in-person session for all study arms. During the first session, those who have been 
randomized to the InMT arm will receive bus passes based on their need or discuss 
the rideshare assistance and mileage reimbursement process. Site SC will track the 
disbursement of bus passes in REDCap.
5.3
Concomitant Interventions
5.3.1
Allowed Interventions
There are no restrictions for participants’ care teams to prescribe or administer 
medications or refer to most services. Participants have the ability to continue any 
SCD interventions in place prior to enrollment except when prohibited (see section 
5.3.3).

5.3.2
Required Interventions
For participants randomized into the InMT or HybMT arms, the 6-session MT 
intervention is required.
For participants randomized into the HybHE arm, the 6-session HybHE intervention 
is required.
5.3.3
Prohibited Interventions
Participants will be asked to not engage in a new practice of mindfulness, meditation, 
MT, other mind-body practices under the guidance of professionals for the purposes 
of pain management during their time participating in the study.
5.4
Adherence Assessment
Recruitment proportion will be deemed successful if 35% of eligible approached 
patients enroll in the study. Recruitment rate will be successful if we can recruit 10 
participants at site 1 and 5 participants at site 2 per quarter.
Individual attendance will be acceptable if a given participant attends 4 of 6 sessions 
in 8 weeks. These 4 sessions must include the first session and any 3 out the 4 
sessions between sessions 2-5. We anticipate a 70% attendance rate in each arm. 
We will consider retention to be successful if we retain 70% of participants until the 
final survey time point (6-week follow-up).
Individual session attendance will be deemed complete if the participant attends 2/3 
of the session including (1) the introduction (discussing experience with the MT or 
HybHE exercise over previous week, providing education on rationale for 
intervention); (2) setting of the agenda; and (3) the main intervention (e.g., co- 
creating the music for the intervention, customizing the place and imagery to 
participants' preferences, experiencing and recording the intervention). The last third 
of the intervention includes verbally processing the participant's experience of the 
intervention, delivering the digital file, and providing directions for use in the future. If 
this last third is not provided in the live session, the music therapist or HybHE 
interventionist will provide this information via email.
Home practice will be considered sufficient if 70% of participants practice 
intervention exercises at least once per week.
We will consider data quality/completeness to be successful if data completeness 
exceeds 90% in quality control review.
6. STUDY PROCEDURES
6.1
Schedule of Evaluations
Randomized Control Trial
Participants will enter their responses to the patient reported outcome (PRO) 
measures detailed below directly into REDCap using an iPad provided by the RA or 
SC (baseline) or using their own devices (post-intervention and 6-week follow-up). 
The study staff will hand the patient a tablet for confidential self-administration. Once

the patient completes the questionnaires, the answers will be masked so the 
research staff will not have access to the scores. The numeric rating scale (NRS) is a 
validated measure for acute pain intensity.47 It has been widely used within studies of 
integrative therapies48 and found to be more reliable than the visual analog scale in 
clinical trials, especially among patients of low socioeconomic status.48 Investigators 
in previous studies have also used the 0-10 NRS to measure other domains 
including anxiety in clinical effectiveness studies of nonpharmacologic interventions 
(e.g., acupuncture, massage therapy, and meditation)49-51 and stress in a 
randomized controlled trial of music therapy.52 Prior research among adults with 
sickle cell disease has also demonstrated that acceptability of the Edmonton 
Symptom Assessment Scale measures of fatigue and anxiety for outpatient symptom 
monitoring (0 – 10 scale).53 For all scales, questions will be phrased as “How much 
(stress, pain, anxiety, or fatigue) are you having right now?” with 0 signifying “none” 
and 10 signifying “worst possible.”
Data Collection Time Point
Variable
Measure 
source
Screening 
& Baseline
Pre + post- 
session
Post 
intervention
Post- 
intervention 
exercise use
6-week 
follow 
up
Treatment 
outcomes
Pain interference 
(primary)
Pain interference items 
from the PROMIS-29 
Profile (if age ≥ 18) or 
PROMIS-25 Pediatric 
Profile (if age < 18)
X
X
X
HRQoLa
PROMIS-29 Profile (if 
age ≥ 18) or PROMIS- 
25 Pediatric Profile & 
PROMIS Pediatric 
Sleep Disturbance 4a 
(if age < 18)
ASCQ-Me
X
X
X
Self-efficacy
SCSES
X
X
X
Pain intensity
NRS
X
Stress
NRS
X
Anxiety
NRS
X
Fatigue
NRS
X
Baseline 
variables
Participant and 
emergency 
contact 
information
EHR and self-report
X
Demographicsb
EHR and self-report
X
Music use
Music use 
assessmentc
X
EHR review
Clinical 
characteristicsd
EHR
X
X
Implementation 
outcomes
Acceptability
Likert scale
X
Use of MT 
exercises/HybHE
Self-report to 
interventionists (at
X
assignments at 
home during 
intervention
beginning of session)

Use of MT 
exercises/HybHE 
assignments at 
home post- 
intervention
REDCap surveys
X
X
X
aHRQoL domains include (1) PROMIS-29 Profile measures of physical function, anxiety, depression, fatigue, sleep disturbance, ability to 
participate in social roles and activities, pain interference and pain intensity OR PROMIS-25 Pediatric Profile measures of physical 
function, anxiety, depression, fatigue, peer relationships, pain interference and pain intensity and PROMIS Pediatric Sleep Disturbance 
4a; and (2) ASCQ-Me measures of pain impact, emotional impact, and social functioning impact. bDemographic variables include age, 
gender, education level, religious background, income, employment status, race, ethnicity, and marital status. cMusic use will be assessed 
using the survey developed by Rodgers-Melnick et al.32 dClinical characteristics include age, SCD type, insurance type, SCD 
complications (e.g., history of stroke, avascular necrosis), healthcare utilization (i.e., hospital admission, emergency department visit, or 
same-day pain infusion) at any hospital in last 12 months (baseline) and since randomization (6 weeks post-intervention), SCD treatment, 
and opioid prescriptions in last 14 weeks (baseline) and since randomization (6 weeks post-intervention)
Please see attached Screening Log to be reviewed during the screening process.
Please see attached Screening Questionnaires to be completed during the screening process. 
Please see attached Informed Consent documents
Please see attached Study Information Sheets for participant and provider interviews
Please see attached Demographics Questionnaire to be collected after subject agrees to participate.
Please see attached Baseline, Post-Intervention and 6-weeks Post-Intervention questionnaires to be 
collected at each time point, including Music Use Assessment at Baseline and Treatment Acceptability 
at 6-Weeks
Please see attached Pre + Post Session for NRS measures
Please see attached Post-intervention Exercise Use to be collected weekly.
Please see attached Interview Guides for semi-structured participant, provider and interventionist 
qualitative interview guides.
6.2
Description of Evaluations
6.2.1
Screening Evaluation
At each site, the study staff will work with the SCD center staff and providers to 
identify patients who may be eligible for the study. Study staff will be embedded in 
the SCD centers up to 4-5 days per week during active recruitment periods. As the 
schematic below shows, study staff will use the EHR to evaluate patient eligibility for 
patients on the clinic roster or referred through provider referral.

The study team will procure a Participant Eligibility Source Document form for each 
patient that pre-screens as eligible to obtain patient’s signs of SCD and AAPT 
category from SCD providers (i.e., hematologist or advanced practice provider). For 
patients who continue to be eligible, study staff will approach the patient at their next
(1) regularly scheduled visit to the outpatient SCD center, (2) visit to an infusion 
center, or (3) inpatient admission prior to discharge. Study staff will approach the 
patient and give brief details about the study, the time commitment, and answer any 
initial questions from the patient.
If the patient/parent/guardian has time to discuss the study right then, the study staff 
will continue with recruiting procedures. If the patient/parent/guardian do not have 
time during their appointment, the study staff will return at a more convenient time 
that day or ask to set up another time to meet to discuss the study in person.
After a brief explanation of the study and patient approval, the study staff will 
continue to determine eligibility by asking the patient to complete a REDCap survey 
assessing (1) duration, frequency, and interference related to their pain, and (2) the 
patient’s access to an email address and mobile phone with functioning data plan. If 
the patient meets all eligibility criteria and expresses interest in participating in the 
study, the SC or RA will seek to obtain informed consent from adult patients and 
parents of minors, as well as written assent from minors. If the adult patient is not 
interested in participating in the study or refuses to provide/confirm their phone 
number and email for follow up assessments and scheduling, a reason for refusal will 
be documented in REDCap by the study staff. If the minor patient is not interested in 
participating in the study or they or their parent/guardian refuses to provide/confirm 
their phone number and email for follow up assessments and scheduling, a reason 
for refusal will be documented in REDCap by the study staff.
Consenting Procedure
During the initial approach, the study staff will give a brief explanation of the study, 
the time commitment and answer any preliminary questions from the patient. If the 
patient and parent/guardian, when appropriate, is/are willing to continue with the 
recruitment procedures, at this point, study staff will complete the screening process 
by asking the patient about pain duration and frequency in relation to their SCD and 
access to WiFi, devices and data plans. If eligibility is confirmed between 2 and 6 
weeks away from each cohort’s intervention start date, study staff will set up an

appointment with the patient (and parent/guardian, when necessary) at the SCD 
center main campus, satellite campus, or another location preferred by the 
participant (e.g., community center) to obtain consent/assent and baseline 
assessments within 2 weeks of the cohort intervention start date. If the eligibility is 
confirmed within 2 weeks of the cohort start date, study staff will continue directly to 
the consent/assent and baseline assessment process, time permitting. If a 
patient/parent/guardian does not have time during their screening visit to complete 
the consent and baseline assessments, an appointment will be scheduled to 
complete these documents at the patient/parent/guardian’s convenience within 2 
weeks prior to the cohort intervention start date. If the patient/parent/guardian cannot 
meet within 2 weeks of the cohort intervention start date, study staff will attempt to 
schedule the consent/baseline assessment appointment within the first 2 weeks after 
the cohort intervention start date. If the patient/parent/guardian still cannot meet 
during that time, then their recruitment will be held over to a subsequent cohort. If 
this delay occurs during the final study cohort, then the patient will not be able to 
participate in the study.
UH and Prisma study staff will obtain an electronic signature on the eConsent from 
the adult patient or the minor’s parent/guardian and assent from the minor patient.
Prisma study staff will obtain a wet ink signature on their paper consent from the 
adult patient or the minor’s parent/guardian and assent from the minor patient.
Informed consent will occur in a private treatment room or consult room out of the 
earshot of others to maintain privacy. Patients and parents/guardians will be 
provided with a hard copy of the consent form along with electronic version to read 
along with the SC or RA. Patients, parent/guardians, and study staff will read through 
the informed consent document together at this time. The study staff will answer any 
questions the adolescent or adult patient or parent/guardian may have about the 
study and allow time for the patient and parent/guardian to summarize the study 
procedures to confirm understanding. If the patient or parent/guardian would like 
more time to consider participation in the study, they can take the consent form 
home to review and consider and then bring it to their next visit to the SCD Clinic.
Once ready to consent, the adult patients will sign the electronic consent form in 
REDCap by “making their mark” on the signature line to indicate that they 
understand the document. The minor patient and the parent/guardian of the minor 
will sign the electronic consent form in REDCap by “making their mark” on the 
signature line to indicate that they understand the document.
A partial waiver of consent will be used to review the medical charts for pre- 
screening purposes. This waiver will only be used to access patients' PHI following 
the referral and prior to obtaining written informed consent. Patients will still be fully 
informed of study details prior to giving written consent and participating in research.
Screening
All screening activities must be completed before consent and study enrollment. All 
screening activity will take place 1-6 weeks prior to the cohort intervention start date.
Inclusion Criteria
When Screening 
Occurs
1.
≥14 years of age
Pre-screening
2.
Have a diagnosis of SCD present in their EHR
Pre-screening

3a.
Per provider, the patient displays at least one of the 
following signs:

Palpation of the region of reported pain elicits focal
Pre-screening/ 
Study staff obtains 
information from
pain or tenderness

Movement of the region of reported pain elicits focal 
pain

Decreased range of motion or weakness in the 
region of reported pain

Evidence of skin ulcer in the region of reported pain

Evidence of hepatobiliary or splenic imaging 
abnormalities (e.g., splenic infarct, chronic 
pancreatitis) consistent with the region of reported 
pain

Evidence of imaging abnormalities consistent with 
bone infarction or avascular necrosis in the region of 
reported pain
provider
3b
Reporting ongoing pain present on most days over the past 
6 months either in a single location or in multiple locations
Patient facing
3c
Per provider documentation, there is no other diagnosis that 
better explains the signs and symptoms of pain
Pre-screening/ 
Study staff obtains 
information from 
provider
4.
Ability to communicate in English
Pre-screening
5.
Have an email address and access to mobile device with a 
functioning data plan
Patient facing
6.
Reporting that pain interfered with daily activities at least 1- 
2 days in the past week
Patient facing
Exclusion Criteria
When Screening 
Occurs
1.
Currently engaging in practicing mindfulness, meditation, MT, 
or other mind-body practices under the guidance of a 
healthcare professional for the purposes of pain management
Pre-screening
2.
Having a significant visual, hearing, or cognitive impairment
Pre-screening
3.
Previously participated in MUSIQOLS single-site pilot study 
(STUDY20180101)
Pre-screening
4.
Have a planned major medical event in the next 14 weeks 
such as (but not limited to) childbirth, orthopedic surgery, 
gene therapy, or stem cell transplant (these criteria do not 
include blood transfusions, exchange transfusions, or other 
pharmacologic pain treatment)
Pre-screening
6.2.2
Enrollment, Baseline, and/or Randomization
Enrollment
Subjects are considered enrolled once all screening criteria are met and the informed 
consent document has been signed. Only one electronic informed consent document 
will be used, as we have requested a partial HIPAA waiver for screening. The date of 
enrollment will be the date the consent form is signed.

Baseline Assessments

The Patient Reported Outcomes Measurement Information System
Adults: (PROMIS-29 Profile): PROMIS-29 measures include physical function 
(4 questions), anxiety (4 questions), depression (4 questions), fatigue (4 
questions), sleep disturbance (4 questions), ability to participate in social 
roles and activities (4 questions), pain interference (4 questions), and pain 
intensity (1 question). Adolescents: (PROMIS Pediatric Profile-25): PROMIS- 
25 measures include physical function (4 questions), anxiety (4 questions), 
depressive symptoms (4 questions), fatigue (4 questions), peer relationships 
(4 questions), pain interference (4 questions), and pain intensity (1 question) 
and PROMIS Pediatric Sleep Disturbance 4a. Most PROMIS measures elicit 
participant responses based on the 7 days prior using 5-point response 
options ranging from ‘‘never’’ to ‘‘always’’ in most measures and from 
‘‘without any difficulty” to ‘‘unable to do” for physical functioning measures.
Higher scores indicate greater severity of anxiety, depression, fatigue, sleep 
disturbance, and pain interference; greater ability to participate in social roles 
and activities; and less severity for physical function impairment. PROMIS 
measures are scored on a general population-based T-score metric with a 
mean of 50 and a standard deviation of 10.54, 55 Different PROMIS measures 
have been validated in the adult and pediatric populations and have been 
evaluated in patients with SCD.56-58

Sickle Cell Self-Efficacy Scale (SCSES): Self-efficacy will be measured using 
the Sickle Cell Self-Efficacy Scale (SCSES). The SCSES is a nine-item Likert 
scale originally developed for adults with SCD59 and revised in a follow up 
study for adolescents using a sample of 131 individuals age 11-19.27 Clay 
and Telfair reported a Cronbach’s alpha of 0.87 for the nine items, indicating 
good internal consistency as well as a significant association with personal 
health care items showing convergent validity.

Adult Sickle Cell Quality of Life Measurement Information System (ASCQ- 
Me): ASCQ-Me is a patient-reported outcome measurement system that 
addresses the physical, social, and emotional impact of SCD. This study will 
utilize the ASCQ-Me 5-item short forms for pain impact, emotional impact, 
and social functioning impact. ASCQ-Me is a valid measure and highly 
reliable for use with adults and adolescents with SCD.60-62 ASCQ-Me scores 
are calculated in the direction of overall health, with higher ASCQ-Me scores 
indicating better health.

Numeric rating scale: Participants will complete 0-10 (0 = none, 10 = worst 
possible) numeric rating scale (NRS) measures of pain, stress, anxiety, and 
fatigue prior to and following each session using a REDCap survey sent to 
their own devices via Twilio. These scores will be used to understand 
participants’ symptoms pre-session, post-session, and longitudinally over the 
course of the study; and determine which MT exercises are most beneficial 
for MT participants’ symptoms. Intervention facilitators will be blinded to 
participants’ NRS scores.

EHR Review: Study staff will conduct an EHR review that includes age at the 
time of recruitment, insurance type, SCD type, SCD complications, 
emergency department utilization in the past 12 months, hospital admissions 
in the past 12 months, same-day pain treatment at infusion center in the past

12 months, current disease modifying therapies, and detailed description of 
pain medications prescribed in the past 14 weeks.

Access to technology and contact information: Study staff will collect access 
to technology information from participants including (1) cell phone number
(2) cell phone carrier, (3) mobile device type, (4) email address, and (5) 
emergency contact information.

Mind/Body pain management and transportation questionnaire to gauge and 
document inclusion exclusion criteria not captured elsewhere and to 
document the need for transportation assistance.
Provide Technology
Immediately following the baseline assessment the study staff will (1) enroll the 
participant in MyCap, for communication between the study team and the participant,  
if the patient is not already enrolled, (2) demonstrate to the participant how to 
communicate with study personnel using chat features within MyCap, (3) provide the 
participant with headphones, (4) ensure the participant has a means by which to 
access Zoom, (5) ensure the participant can access the Box folder designated to 
them during their study participation, and (6) provide the participant with 
transportation assistance (if needed) to attend their first in-person session.
Randomization
Random assignments will be made by the assistant study statistician in permuted 
blocks of size 3 and 6. The only role of the assistant study statistician will be to 
handle the randomization. Accordingly, s/he will be aware of group assignment.  
Importantly, the primary study statistician will remain blinded to group assignment 
until all analyses are complete. Randomization will occur within 2 weeks of the cohort 
intervention start date. Site SC will be notified when the participant has signed the 
consent form. The sSC will complete randomization using the REDCap tool. The 
sSC will contact the participant to inform them of their study arm and set up their 
initial session.
6.2.3
Blinding
Study personnel that will be blinded to participant data, unless they will be involved 
with fidelity monitoring, are the MPIs, co-investigators, site PIs, DCC PIs, study 
biostatistician, and research assistants recruiting participants and following up to 
collect patient-reported outcomes.
The MSC/site coordinator at UH will be unblinded for quality assurance. Prisma’s site 
coordinator and all interventionists will be unblinded to the randomization of the 
participants. However, they will be blinded to patient-reported outcomes (e.g., NRS, 
PROMIS-29 or PROMIS-25, and ASCQ-Me). Unblinded staff will not have access to 
data outside the session logs that they document and no involvement in data 
monitoring and analyses.

6.2.4
Follow-up Visits
MT Session
Session Description
Evaluations completed
1) Education
Explain pain mechanisms in 
SCD and rationale for how 
music helps to reduce pain; 
receive devices for hybrid 
session, as needed

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed via 
REDCap survey)
2) Breathe
Teach deep breathing exercise 
with music

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed via 
REDCap survey)

Music exercise use in past week 
(asked by interventionist)
3) Relaxation
Teach guided progressive 
muscle relaxation (PMR) 
exercise with music

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed via 
REDCap survey)

Music exercise use in past week 
(asked by interventionist)
4) Imagery
Teach music-based imagery 
exercise

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed via 
REDCap survey)

Music exercise use in past week 
(asked by interventionist)
5) Music 
Making
Teach active music making 
exercise

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed via 
REDCap survey)

Music exercise use in past week 
(asked by interventionist)
6) Conclusion
Review previous MT exercises 
and make plan for coping with 
future challenges

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed via 
REDCap survey)

Music exercise use in past week 
(asked by interventionist)
HybHE Session
Session Descriptions
Evaluations completed during the 
session
1) Science of 
SCD
Reviews the science of SCD, 
focusing on blood, organs affected, 
labs, and the biology behind vaso- 
occlusive crises; receive devices 
for hybrid sessions, as needed.

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed 
via REDCap survey)

2) Identifying 
Barriers in the 
Emergency 
Department
Introduces common barriers 
(supported by research) that 
patients with SCD experience in 
the ED.

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed 
via REDCap survey)

Health education assignment use in 
past week (asked by interventionist)
3) Tools for 
Navigating the 
Healthcare 
System
Explores the healthcare 
infrastructure, chain of command, 
documenting care (both positive 
and negative) and the process of 
filing a complaint in a constructive 
and effective manner.

Ability to Participate 

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed 
via REDCap survey)

Health education assignment use in 
past week (asked by interventionist)
4) SBAR:
Healthcare 
Based 
Communication 
for Patients 
(Part 1)
Introduces Situation, Background, 
Assessment, Recommendation 
(SBAR) and as an effective form of 
communication for patients when 
accessing medical care and covers 
Situation (S) and Background (B) 
of SBAR.

Ability to Participate 

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed 
via REDCap survey)

Health education assignment use in 
past week (asked by interventionist)
5) SBAR:
Healthcare 
Based 
Communication 
for Patients 
(Part 2)
Reviews SBAR and covers 
Assessment (A) and 
Recommendation (R) of SBAR.

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed 
via REDCap survey)

Health education assignment use in 
past week (asked by interventionist)
6) Conclusion
Review content from sessions 1-5 
and make a plan to address future 
challenges.

Ability to Participate

Pre- and post-session NRS: pain; 
stress; anxiety; fatigue (completed 
via REDCap survey)

Health education assignment use in 
past week (asked by interventionist)
Post-intervention evaluation for all arms
Post intervention evaluations will be obtained 1-7 days post session 6 in each arm 
via REDCap (Twilio text). Participants will complete these evaluations at home:

PROMIS-29 (if age ≥ 18) or PROMIS-25 Pediatric Profile & PROMIS 
Pediatric Sleep Disturbance 4a (if age < 18)

Sickle Cell Self Efficacy Scale

ASCQ-Me: Pain Impact, Emotional Impact and Social Functioning Impact

Treatment acceptability
6.2.5
Completion/Final Evaluation
6-Week Post-intervention evaluation for all arms
The 6-week post intervention evaluations will be obtained 42-49 days post session 6 
in each arm via REDCap (Twilio text). Participants will complete these evaluations at 
home:

PROMIS-29 (if age ≥ 18) or PROMIS-25 Pediatric Profile & PROMIS 

Pediatric Sleep Disturbance 4a (if age < 18)

Sickle Cell Self Efficacy Scale

ASCQ-Me: Pain Impact, Emotional Impact and Social Functioning Impact

MT and/or mind/body intervention engagement outside of the protocol during 
the study
An EHR and prescription monitoring program review will be collected by study staff. 
The following data will be collected using the participant’s EHR:

Emergency department utilization since randomization date;

Hospital admissions since randomization date;

Same-day pain treatment at infusion center since randomization date; and

Detailed description of pain medications prescribed since randomization.
Early Termination
The study doctor or the sponsor can stop a subject’s participation at any time without 
their consent for the following reasons:

If it appears to be medically harmful to them;

If they fail to follow directions for participating in the study;

If it is discovered that they do not meet the study requirements;

If the study is canceled; or

For administrative reasons, including competitive enrollment (e.g. the target 
number of subjects has entered the study.)
6.3 Provider Feasibility Assessment and Interview
A recruitment email will be sent via REDCap. Providers, staff, and interventionists 
who are interested will click a link to the feasibility study information sheet. Those 
who wish to participate in the interview will click “yes” and be directed to the survey. 
We will also distribute a recruitment flyer to be posted in charting areas and 
workspaces at each SCD center, inviting providers and staff to participate. The flyer 
will include a QR code that links directly to the study information sheet. Those who 
wish to participate will click “yes” and be directed to the survey. Feasibility surveys 
will be completed online by interested participants at their convenience.

Demographic information including: gender, ethnicity, race, age, how long 
they have worked in the SCD center, occupation, contact with the MULTI- 
MUSIQOLS study and in what context

Suitability of the intervention to the applicable population
o
To what degree do you view the MT (or HealthED) intervention as 
useful or suitable for this population?” (1-very inappropriate—5-very 
appropriate)
7. SAFETY ASSESSMENTS
The investigative team will monitor the data for security, integrity, and patient safety. 
The study teams will meet at least every 2-4 weeks to assess for adherence to the 
protocol and review any safety events.
There is a slight risk a participant may not like the music interventions included in the 
study. In that event, they may leave the session space during an MT intervention or 
choose not to participate in the rest of the intervention. It is possible that the 
participant may not be comfortable wearing headphones used for the music 

interventions. If this occurs, the participant may ask the investigator to remove them.
There is a slight risk a participant may not be comfortable with the content of the 
HybHE intervention during one or more sessions. In this event, the participant may 
request skipping the topic or ending the session early.
If a participant experiences a serious adverse event (e.g., active suicidal ideation, 
stroke, loss of consciousness, etc.), during the HybMT or HybHE intervention, away 
from a medical facility, the interventionist will immediately call the local suicide 
prevention hotline (e.g., Frontline Cuyahoga County for site 1 or 988 Suicide and 
Crisis Lifeline for site 2) and/or 911 and notify dispatch of the participant's condition 
and location. Suicide prevention help lines will be contacted in the event of suicidal 
ideations and 911 will be contacted in the event of other medical emergencies. The 
interventionist will then notify the study coordinator via REDCap reporting who will 
also notify the participant’s clinical team (i.e., SCD team).
If a participant experiences a serious adverse event (e.g., active suicidal ideation, 
stroke, loss of consciousness, etc.), while in a medical facility, the interventionist will 
initiate the local site’s intervention protocol by contacting the clinical team at that site 
immediately. The interventionist will then notify the study coordinator of the adverse 
event via REDCap reporting. The study coordinator will also notify the participant’s 
clinical team (i.e., SCD team) if this is not the clinical team at the medical facility.
If a participant displays or reports other physical or psychological challenges during 
or related to a session, the individual will be referred to their respective healthcare 
provider. In all cases, the interventionist will notify the appropriate clinical team (e.g., 
SCD team) and report the adverse event (AE).
If any of the 4 items on the PROMIS-29 or PROMIS-25 Depression 4a scale 
completed during baseline, post-intervention, and/or 6-week post-intervention 
assessments are reported as “often” or “always,” then a suicidality assessment (i.e., 
PHQ-9 item #9) will be triggered to populate in the REDCap instrument. If any of the 
first 3 items on the ASCQ-Me Emotional Impact scale completed during baseline, 
post-intervention, and/or 6-week post-intervention assessments are reported as 
“often," “always,” "quite," or "very" then a suicidality assessment (i.e., PHQ-9 item 
#9) will be asked. If the participant affirms suicidal ideation (i.e., PHQ-9 item #9 ≥1), 
they will immediately receive a screen referring them to call 911 in case of 
emergency or contact their local suicide prevention hotline. An automatic text or 
email message will notify the sickle cell team at the participant’s site (including 
physicians, nurses, and social workers) of the participant’s score for the team to 
reach out and make further assessments. The study team (i.e., study coordinator, 
principal investigator) will be notified immediately via automatic text or email 
notification for AE reporting.
Monitoring of the study for AEs will be continuous throughout the study. In the event 
of an AE or serious adverse event (SAE), it will be reported to the UH IRB in 
compliance with UH IRB standards. The MSC will be conducting weekly quality 
assurance checks for the first two months of enrollment and then monthly for 
remaining months of enrollment.
There is no guarantee of direct benefit during the interventions. Those who 
participate in InMT or HybMT may enjoy listening to music or having MT delivered 
during sessions. Those who participate in HybHE may learn more about SCD. 

Participants may experience reduced symptoms of pain, anxiety, and stress after 
sessions.
There is no guarantee of direct benefit from participating in the qualitative interviews. 
The insights provided from the responses will help to improve design and 
implementation of the music therapy intervention.
The only alternative to participation is to not participate.
7.1
Specification of Safety Parameters
N/A
7.2
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters
N/A
7.3
Adverse Events and Serious Adverse Events
An adverse event (AE) is generally defined as any untoward medical occurrence in a 
subject during participation in the clinical study or with use of the experimental agent 
being studied. An adverse finding can include a sign, symptom, abnormal 
assessment (laboratory test value, vital signs, electrocardiogram finding, etc.), or any 
combination of these regardless of relationship to participation in the study.any 
unfavorable and unintended diagnosis, symptom, sign (including an abnormal 
laboratory finding), syndrome or disease which either occurs during the study, having 
been absent at baseline, or if present at baseline, appears to worsen. Adverse 
events are to be recorded regardless of their relationship to the study intervention.
A serious adverse event (SAE) is generally defined as any event that meets one or 
more of the following criteria:

Results in death

Is life-threatening (places the subject at immediate risk of death from the event 
as it occurred)

Results in inpatient hospitalization or prolongation of existing hospitalization

Results in a persistent or significant disability or incapacity

Results in a congenital anomaly or birth defect
An important medical event that may not result in death, be life threatening, or 
require hospitalization may be considered an SAE when, based upon appropriate 
medical judgment, the event may jeopardize the subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition.
The Office for Human Research Protections (OHRP) considers unanticipated 
problems involving risks to subjects or others to include, in general, any incident, 
experience, or outcome that meets all of the following criteria:

Unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied;

Related or possibly related to participation in the research ("possibly related" 

means there is a reasonable possibility that the incident, experience, or outcome 
may have been caused by the procedures involved in the research); and,

Suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized.
7.4
Reporting Procedures
RESPONSIBLE INDIVIDUALS
The site Principal Investigator (PI) is responsible for assessing all AE and SAEs. The 
site PI will monitor AE reporting and complete the AE PI Report in the MULTI- 
MUSIQOLS REDCap for events reported during the study enrollment period as 
reported in the EHR. Study staff and interventionists are responsible for reporting 
and documenting the events determined to be an AE or SAE, including any adverse 
events occurring during a session or reported by a subject’s physician, in the MULTI- 
MUSIQOLS subject AE Log and reporting these events to the Clinical Coordinating 
Center within the required timelines.
PROCEDURES
Reporting Adverse Events: The PI or their delegated research staff will review 
reported events to determine if they qualify as an AE/SAE and assign causality and 
severity/intensity in REDCap. Research staff will document AE on the MULTI- 
MUSIQOLS Subject AE and External AE Summary logs after becoming aware of the 
event. Subject AE logs will be stored in the individual subject’s REDCap record. The 
External Summary AE log must be provided to the Clinical Coordination Center upon 
request, including for Quality Assurance, sIRB Continuing Review, and Study Close 
Out.
Reporting Serious Adverse Events: Research staff will document SAE on the MULTI- 
MUSIQOLS Subject AE log after becoming aware of the event. The PI, or their 
delegated research staff, and a study physician will review, sign off on SAE and 
assign causality, and severity/intensity and determine if the event was unanticipated. 
Those evaluating SAEs will use the OHRP standards to identify unanticipated events 
and the definitions of AE/SAEs to characterize the event. If the event satisfies the 
UHCMC IRB requirements for reporting SAEs, it will be reported to the UHCMC IRB;
a.
Serious
b.
Unanticipated, and 
c.
Related to study product or study procedures
If the event is clarified as an SAE and deemed reportable to the IRB, delegated 
research staff will report event to the IRB within 5 days of being notified of event via 
the University Hospital’s Cleveland Medical Center’s (UHCMC) IRB’s “Reportable 
New information Smart Form” (RNI). If more information becomes available 
regarding the SAE, delegated research staff will inform and follow-up with IRB.
ANTICIPATED ADVERSE EVENTS
The study team anticipates study participants may experience medical, 
financial and/or emotional events during their enrollment period.  Examples 
of these events may include:


Severe medical event not related to study intervention necessitating long 
admission to ICU

Financial issues effecting housing, data access, device access, disruption 
to transportation access

Emotional response during sessions, feeling uncomfortable answering 
survey or interview questions, feeling overwhelmed with participating
7.5
Follow-up for Adverse Events
Delegated research staff are responsible for all follow-up associated with AEs and 
SAEs and reporting this information to the IRB until the AE occurs.
7.6
Safety Monitoring
The NCCIH requires that all Human Subjects research studies undergo independent 
monitoring, and NCCIH Program Officials will provide specific guidelines to the PI for 
the study. Accordingly, an Independent Monitoring Committee will be assembled by 
the MPIs with approval required by the NCCIH.
8. INTERVENTION DISCONTINUATION
Early Termination
The study doctor or the sponsor can stop a subject’s participation at any time without 
their consent for the following reasons:

If it appears to be medically harmful to the participant;

If they fail to follow directions for participating in the study;

If it is discovered that they do not meet the study requirements;

If the study is canceled; or

For administrative reasons, including competitive enrollment (e.g. the 
target number of subjects has entered the study.)

If the patient’s clinical condition worsens emergently as determined by 
physician.
9. STATISTICAL CONSIDERATIONS
9.1
General Design Issues 
Primary Objective
The primary objective is to refine research procedures for conducting a future fully- 
powered multi-site RCT
The study will examine the feasibility of the following across 2 sites:
1) data quality/completeness
2) screening rate
3) recruitment
4) retention
5) individual attendance
6) home practice

Secondary Objectives
This study will include qualitative interviews of patients and providers/staff to assess 
feasibility of implementation.
9.2
Sample Size and Randomization
Sample Size Justification
The aim of the R01 is to examine feasibility and acceptability across sites to inform a 
future, full-scale trial, rather than to power the proposed study for detecting statistical 
differences. The Adult Sickle Cell Disease (SCD) Clinic at University Hospitals (UH) 
Seidman Cancer Center provides comprehensive care to over 344 active adult 
patients residing in Northeast Ohio. There are 66 pediatric patients between the ages 
of 14-17 at UH. The Prisma Health Lifespan Comprehensive SCD Program provides 
comprehensive care to over 213 active adult patients with SCD in South Carolina. At 
Prisma, there are 50 pediatric patients between the ages of 14-17. By including 
children aged 14 and older, we would have 673 individuals eligible for participation.
Our screening success rate will be successful if we can enroll 35% of those 
approached for the study. To meet that rate, we would need to approach ~28 
participants at UH per quarter and ~14 at Prisma per quarter. In other words, over 
the course of the study we expect that

The research team at UH will need to approach 170 individuals to enroll 60 
participants (60/170 = 35%).

The research team at Prisma will need to approach 86 individuals to enroll 30 
participants (30/86 = 35%).
Therefore, our proposed recruitment goal of 90 subjects will require enrollment of 60 
at UH (10 per quarter) and 30 at Prisma (5 per quarter) over the 6 quarters (18 
months) of recruitment.
Recruiting over 18 months provides the opportunity to modify recruitment procedures 
(if necessary) and assess the impact of such modifications on attaining recruitment 
goals. Statistical differences in outcome variables between groups will not be 
investigated. However, preliminary investigation of the distribution of within-group 
changes will be assessed. Specifically, obtaining estimates of the standard deviation 
of change (from baseline) in clinical outcome measures (e.g., self-efficacy and pain 
interference) will be useful for power calculations for the subsequent trial. However, 
per published literature63-66 and NCCIH guidance,67 we will be using clinically 
important differences from the literature to calculate the sample size for the future, 
multi-site RCT (UG3/UH3).
Randomization
Randomization will occur within 2 weeks of the cohort intervention start date. Study 
staff will contact the sSC when the participant has signed the consent form. The sSC 
will complete randomization using the REDCap tool. The sSC will contact the 
participant to inform them of their study arm and set up their initial session
9.3
Definition of Populations
As this is a multi-site feasibility study, the intent is not to assess statistical significance 
across the three study groups. As such, the feasibility outcomes will be assessed with 
patients actually receiving their assigned intervention. Thus, an intent-to-treat population will
 not be used in this study.

9.4
Interim Analyses and Stopping Rules
This study will be stopped prior to its completion if: (1) the intervention is associated 
with adverse effects that call into question the safety of the intervention; (2) difficulty 
in study recruitment or retention will significantly impact the ability to evaluate the 
study endpoints; (3) any new information becomes available during the trial that 
necessitates stopping the trial; or (4) other situations occur that might warrant 
stopping the trial.
9.5
Outcomes and Data Analysis
Implementation and Treatment Outcomes
All data analyses will be preceded by extensive data checking and verification to 
identify and resolve the reasons for any missing values, inconsistencies, and out-of- 
range values. Although we anticipate little missing data based on our experience, we 
will carefully examine whether missingness is completely at random, at random or 
informative. Models proposed for analysis can handle incomplete data but do require 
at least that missingness be at random.
Descriptive statistics of primary and secondary outcomes will be calculated to assess 
their distribution overall and by sites as well as demographic characteristics (e.g. 
sex, age group, SCD type, household income, among others). The variables will be 
summarized using descriptive statistics (sample size, mean, standard deviation, 
median, minimum, and maximum) for continuous variables and by the number and 
percentage of patients for categorical variables.
Primary Outcomes. Evaluate the feasibility of research procedures.
Data quality and completeness. We will track completeness of data collection, and 
patterns and proportions of missing data at each time point. We will compare these 
proportions overall, across sites, and by demographics.
Recruitment and retention. Using study records and administrative data, we will track 
recruitment (proportion of eligible patients recruited), document recruitment rates 
(accrual per quarter), and rates of retention. To assess recruitment, we will track the 
number of eligible patients being referred from the SCD centers and the proportion 
who agree to participate. Basic demographics will be collected for all eligible 
patients, allowing us to identify subgroups who are more or less likely to participate. 
Similar approaches will be used to assess variation in rates of loss to follow-up at all 
data collection points.
We will measure aspects of recruitment, including percentage of enrollees out of 
the total number of patients invited to participate, the average time of recruitment, 
and the clinic from which participants are recruited. Retention in the study, attending 
the respective program, and completion of outcome measures at all time-points will 
also be measured. Reasons for study dropout will be tracked.
1. Data quality/completeness is 90% in quality control review.
2. Screening rate is 35%. This is defined as those who were enrolled (i.e., provide 
written informed consent) divided by those approached for the study who met 
eligibility criteria.
3. Recruitment is 90%. This translates into randomizing 81 of 90 (90%) participants 
who provided written informed consent

A final determination of “feasibility” for the study will be met if any 4 of the 6 
metrics described above are met.
4. Retention is 70%. The number of participants retained until the final survey time 
point (6-week follow-up).
5. Individual attendance is 70%. We will consider individual attendance to be 
acceptable if a given participant attends 4 of 6 sessions in 8 weeks. These 4 
sessions must include the first session and any 3 out of the 4 sessions between 
sessions 2-5. Individual session attendance will be deemed complete if the 
participant attends 2/3 of the session including (1) the introduction (discussing 
experience with the MT or HybHE exercise over previous week, providing education 
on rationale for intervention); (2) setting of the agenda; and (3) the main intervention 
(e.g., co-creating the music for the intervention, customizing the place and imagery 
to participants' preferences, experiencing and recording the intervention).
6. Home practice is 70%. If a given participant practices intervention exercises at 
least once per week, this will be coded as engaging in the minimum dose of home 
practice.
Secondary Aim. Evaluate the implementation of the InMT, HybMT, and HybHE 
interventions, using both quantitative data (study records, stakeholder surveys) and 
qualitative data (interviews).
2a. Assess implementation outcomes: feasibility, appropriateness, and 
acceptability using administrative, survey, and qualitative data as appropriate.
Feasibility is defined as the degree to which the intervention can be successfully 
implemented in the clinic, community, or home setting (in-person or virtual).
This is operationalized as recruitment; and attendance (the proportion of recruited 
participants who completed at least 4 of 6 InMT, HybMT or HybHE sessions which 
must include the first session and any 3 out of the 4 sessions between sessions 2-5). 
This outcome will be measured by a single question assessment: “Did participant 
receive four of six complete sessions which included the first session and any 3 out 
of the 4 sessions between sessions 2-5?”).
We will compare feasibility metrics between InMT and HybMT to determine which is 
more favorable and resulted in higher attendance proportion. Feasibility of the study 
will also be assessed qualitatively, through stakeholder interviews focusing on 
barriers and facilitators to implementation.
Appropriateness is defined as the perceived suitability of the intervention to the 
applicable population. Patient providers will be asked: “To what degree do you view 
the InMT, HybMT or HybHE intervention as useful or suitable for this population?” (1- 
very inappropriate—5-very appropriate). Perceptions of appropriateness will also be 
explored through qualitative interviews.
Acceptability is defined as perceptions of the palatability of an innovation, or 
satisfaction by stakeholders with aspects of an innovation. It is more specific than 
overall satisfaction with a service.68 For this study, acceptability among the adult 
SCD team is operationalized in our quantitative assessment as satisfaction with the 
InMT, HybMT and HybHE as delivered. Enrolled participants will be asked to 
answer two questions at treatment completion and at 6-week follow up: “How 
satisfied are you with how your pain was managed during your participation in the 

study” on the 5-point Likert scale (1-strongly dissatisfied—5-very satisfied). A second 
question is “Overall how satisfied are you with your treatment during your study 
participation?” on the same 5-point Likert Scale. Acceptability of the intervention will 
also be explored through in-depth semi-structured stakeholder interviews with InMT, 
HybMT and HybHE participants.
2b. Assess implementation processes, strategies, and barriers/facilitators to 
implementation using semi-structured stakeholder interviews (healthcare 
providers, MT and HealthED subjects, music therapists, and HealthED 
interventionists).
To further explore influences on implementation outcomes, including stakeholder 
experiences, processes, strategies, and barriers and facilitators to implementation of 
the intervention, we will use qualitative methods. We will conduct qualitative 
interviews with a broad range of relevant staff stakeholders.
The success of program implementation depends on many factors, as described in 
Damschroder, et al’s influential Consolidated Framework For Implementation 
Research (CFIR) framework.69 The CFIR includes 5 ‘domains’ influencing 
implementation: the intervention, inner and outer setting, individuals, and processes. 
We will use the CFIR domains to structure our inquiry and to make sure that our 
qualitative data collection instruments, coding system, and interim reports reflect the 
complex multiple levels of influence that will shape the conduct and outcomes of the 
MT intervention.
Qualitative Interviews. We will develop stakeholder lists with contact information, 
following consultation with local project leadership, then conduct 20 qualitative 
interviews with 10 stakeholder participants per site. This will include a broad range of 
relevant staff stakeholders, including SCD providers, staff, and music therapists In 
addition, 24 participants who received InMT, HybMT or HybHE (16 from UH and 8 
from Prisma) will be purposefully sampled to include multiple presenting complaints, 
both sexes and older and younger participants (< 30 vs ≥30). Interviews will be 
conducted via Zoom and focus on perceptions of the intervention, burden, feasibility, 
and other barriers and facilitators. Participants will receive $25 for interview 
participation. Interview recordings will be stored on a secure server immediately after 
each interview. Interviews will be professionally transcribed.
Qualitative Analysis. To analyze qualitative interview data, we will use QSR’s 
NVivo, a computer program that facilitates (1) the rapid organization and retrieval of 
thematically linked data; and (2) the use of quantitative grouping variables to classify 
cases and generate complex comparisons. Briefly, the Implementation analysis team 
will first conduct thematic analysis through an iterative process of coding subsets of 
data. Analytic memos will be created for each interview describing the major themes 
emerging in the transcript. Memos will be used to determine the emergence of data 
saturation. Next, the coded data will be retrieved and used to create case summaries 
of key themes related to implementation processes at each site. Finally, we will 
conduct comparative analyses both within and across sites using the matrix 
functionality in NVivo. Within-site analyses will include comparisons of relevant 
groups, including but not limited to gender and baseline self-efficacy and pain (high 
vs. low). In the cross-site analyses, we will examine differences in barriers, 
facilitators, and implementation processes across the two sites with the goal of 
generating inferences regarding important factors shaping differences in 
implementation outcomes. For example, presuming that the sites differ on rates of 

recruitment, we will examine our qualitative
data to generate hypotheses regarding the causes of this documented difference.
2c. Examine InMT, HybMT and HybHE providers’ fidelity to the respective 
intervention.
‘Fidelity’ in this study means that we will identify the proportion of patients who are 
treated in a manner consistent with the manualized InMT, HybMT and HybHE 
interventions. The treatment fidelity parameters will align with our previously 
published intervention.23 The treatment fidelity measures will include the dose 
(number of sessions) and the session delivery (was the intervention delivered as 
planned or cut short). To ensure treatment fidelity, investigators will implement 
strategies consistent with the NIH Behavior Change Consortium Treatment Fidelity 
Workgroup. These recommendations have previously been utilized in a NIH-funded 
multi-site MT intervention for adolescents and young adults undergoing stem cell 
transplant.70 Specifically, Mr. Rodgers-Melnick (InMT and HybMT Fidelity) and Dr. 
Jenerette (HybHE fidelity) will implement the following strategies detailed in the table 
below to ensure fidelity in interventionists’ training, treatment delivery, and treatment 
receipt.
Goal
Strategy
Recruit qualified 
personnel
InMT and HybMT: Ensure music therapists are board-certified and 
demonstrate core competencies in music performance, music recording, 
clinical documentation, and interpersonal skills.
HybHE: Ensure graduate nursing students are able to deliver the 
HealthED intervention.
Provide training covering study protocol, clinical needs of patients with 
SCD, therapeutic and technological intervention procedures, workflow and 
documentation procedures, and quality assurance.
Provide standardized 
training
InMT and HybMT: Conduct role playing exercises until adequate 
therapeutic, musical, and technological skills are displayed.
HybHE: Conduct role-play educational content delivery to ensure that the 
students can deliver the content consistently.
Monitor session dosage, length, and intervention procedures using 
REDCap.
Conduct external quality assurance (QA) monitoring of session audio 
recordings for the first 5 participants followed by every 5th participant. 
Investigators will complete QA checklists and review any discrepancies 
with music therapists/graduate nursing students.
Hold bi-weekly conference calls to discuss challenges, communicate 
updates, and answer questions of interventionists.
Ensure consistent 
treatment delivery
Monitor for therapist effects through qualitative interviews with 
participants.
InMT and HybMT: Train music therapists to use active questioning and 
behavioral observation to assess whether participants comprehend how to 
access music exercises.
HybHE: Train graduate nursing students to use active questioning and 
behavioral observation to assess whether participants comprehend 
educational content.
Ensure appropriate 
receipt of treatment
InMT and HybMT: Train music therapists to encourage participants to 
engage in music exercises following each session.
HybHE: Train graduate nursing students to encourage participants to 
review content and ask questions to reinforce and clarify content.
InMT and HybMT: Assess music exercise utilization through REDCap 
surveys.
HybHE: Assess educational module completion through REDCap 
surveys.

10. DATA COLLECTION AND QUALITY ASSURANCE
10.1
Data Collection Forms
Confidentiality will be maintained by collecting and storing patient data in a secure 
REDCap database.
Data Collection Form
Method of Collection
Blinding
Screening and Baseline
Questions
Study Staff enter into REDCap Blinded 
Demographics Questionnaire
Patient-Facing REDCap survey Blinded 
ASCQ-Me- Emotional Impact
Patient-Facing REDCap survey  Blinded
ASCQ-Me- Pain Impact
Patient-Facing REDCap survey Blinded 
aSCQ-Me- Social Functioning
Impact
Patient-Facing REDCap survey Blinded 
NRS- pain, stress, anxiety,
tiredness
Patient-Facing REDCap survey Blinded 
PROMIS-29 or PROMIS-25 +
Pediatric Sleep Disturbance
Patient-Facing REDCap survey Blinded 
SCSES
Patient-Facing REDCap survey Blinded 
Treatment Acceptability
Patient-Facing REDCap survey  Blinded
Interventionist enters into
REDCap and interventionist
Music Use Assessment
assessment
Unblinded
Clinical Characteristics
Study Staff enter into REDCap
Blinded
10.2
Data Management
The research team will build a comprehensive study management database. Our 
team has successfully used REDCap for multisite data collection for a number of 
single-site and multi-clinic studies.
Informed consents and HIPAA authorizations will be collected and stored 
electronically. Participant Eligibility Source Documents forms will be scanned and 
uploaded to the participant’s REDCap record while the physical copy will be kept by 
the study team in individual patient binders in locked filing cabinets of a secure, 
badge-access location at each site.
Screening data will be collected by the study staff through EHR data extraction prior 
to consenting. Baseline data will be collected by study staff directly from the 
participants. The data collected by study staff will be entered directly into an 
electronic data collection tool. There will be no hard copies of this data
Baseline, post-intervention, and 6-week post intervention assessments will be 
collected electronically sent to participants via REDCap Twilio function. All PROs will 
be entered directly by the participant on a tablet via REDCap or participant’s own 
smart device and will disappear from view once entered so neither the participant nor 
study staff will have access to the scores. There will be no hard copies of this data.
Use of music exercises or HybHE will be collected by the interventionist during each 
session. Data will be entered into individual subject’s REDCap records by the 
interventionist. Between post-intervention and 6-week post intervention, use of music 
exercises or HybHE will be collected electronically by REDCap survey sent to 

participants. There will be no hard copies of this data.
Clinical characteristics will be collected via EHR data extract and will be entered 
electronically by study staff at each site with HIPAA protected identifiers as limited 
datasets. The data extracted from EHR will be verified by MRN and date with our 
electronic platforms. EHR extracted data will include age, SCD type, insurance type, 
SCD complications, healthcare utilization at any hospital in last 12 months (baseline) 
and since randomization (6 weeks post-intervention), SCD treatment, and opioid 
prescriptions in last 14 weeks (baseline) and since randomization (6 weeks post- 
intervention).
All electronic data will be kept in password protected databases behind an electronic 
firewall at sites and then securely sent to the UCI Coordinating Center and 
maintained on password protected PCs by a designated data manager. Data in hard 
copy form will be stored in locked file cabinets within a secure, badge-access 
location at each site. Upon completion of study enrollment, members of the study 
team will verify the information contained within the database. After answering all 
queries in the database, the information contained will be locked and exported for 
analysis. Both the source (electronic data collection) data and exported databases 
will be stored as required by the respective rules and regulations (e.g., HIPAA 
authorizations will be maintained for at least six years).
10.3
Quality Assurance
10.3.1 Training
The site Study Coordinator (sSC) will ensure that all study personnel have completed 
all required institution-specific and protocol-specific trainings and that these trainings 
are documented appropriately on the Training Log. The sSC will also ensure that 
new personnel are appropriately documented on the Delegation of Responsibilities 
Log (DOR). While training should be completed and documented in real time, the 
Multi-Site Study Coordinator (MSC) will verify that all training is current and 
appropriately documented on a quarterly basis, as noted in section 10.3.2 below.
Institution-specific Training
All study staff will complete CITI or NIH Human Subjects training prior to commencement of study 
activities. The site staff is also required to receive Good Clinical Practice (GCP) training through 
CITI or the Society for Behavioral Health. Staff training certificates will be stored in the Regulatory 
Binder in REDCap and documented on the Training Log.
Protocol-specific Training
Below is a summary of required initial training by role for new study personnel.
PI, Study Coordinators, Research Assistants and anyone recruiting patients:

Review and express understanding of the Site Initiation Visit (SIV) training 
slides

Review and express understanding of the IRB protocol

Review and express understanding of the NCCIH protocol

Review and express understanding of the Informed Consents and Study 
Information Sheets


Review and express understanding of the MOP
Music Therapists and HybHE interventionists who are not recruiting patients:

Review and express understanding of the IRB protocol

Review and express understanding of the Informed Consents and Study 
Information Sheets

Review and express understanding of the MOP
Statistician

Review and express understanding of the IRB protocol
10.3.2 Quality Control Committee
N/A
10.3.3 Metrics
Quality Assurance (QA) activities will be conducted at each subject study visit, as 
well as on a monthly, quarterly and annual schedule. Additional QA activities and 
reviews will be conducted on an as-needed basis in response to staff or process 
changes.
The following tools will be used to document QA activities for this study:

MULTI-MUSIQOLS QA Essential Documents Review Tool

MULTI-MUSIQOLS QA Monthly Consent and Eligibility Data Review Tool

MULTI-MUSIQOLS QA Participant Data Review Tool

MULTI-MUSIQOLS QA Quarterly Review Tool

MULTI-MUSIQOLS QA Annual Review Tool
In addition the following checklists and reminders have been developed for this 
study’s QA process:

MULTI-MUSIQOLS Informed Consent Documentation

MULTI-MUSIQOLS Study Visit checklist

MULTI-MUSIQOLS Interview Visit Checklist

MULTI-MUSIQOLS Protocol Deviation Log

MULTI-MUSIQOLS Session Protocol Adherence Checklist 
Consenting Visit QA Activities:
The following is a detailed description of the Consenting Visit QA activities:

Prior to the consent and baseline assessment appointment, the SC or RA will 
verify that the most current IRB-approved study consent documents are 
available for use. If re-consenting is required throughout the subject’s 
participation in the study, the study staff will verify that the most current IRB 
approved consent is available prior to the study visit.

Study staff will review and complete the REDCap Eligibility Criteria form 
before study activities begin.

Study staff will document the consent process using the MULTI-MUSIQOLS 
IC Documentation Form. Before the subject leaves the appointment, study 

staff will review the consent documentation and confirm adherence to the 
consent processes described in the MOP.

Study staff will document in REDCap 1) the distribution of participant’s 
headphones; 2) participant’s enrollment in MyCap; 3) review of MyCap 
functions; 4) Zoom account access; 5) Box account access; and 6) 
distribution of bus passes.
Intervention Session QA Activities:

At the initial visit the interventionist will document in REDCap (1) download 
of applications, as needed; (2) review of tech functionality; and (3) review of 
how to download music, if needed.

At completion of all sessions, the interventionist will complete the Intervention 
Visit Checklist that captures the required elements of the visit.
InMT and HybMT Intervention QA Activities:

Interventionists will complete MT Intervention QA checklist within 24 hours of 
each session and upload recorded sessions to the Box account.

The intervention monitors will complete MT Intervention QA Monitoring 
Checklist within 7 days of recording upload for the first 5 participants at each 
site and every 5th participant or 60 days since last external QA (whichever 
comes first) thereafter.
HybHE Intervention QA Activities:

Interventionists will complete HybHE Intervention QA checklist within 24 
hours of each session and upload recorded sessions to the Box account.

The intervention monitors will complete HybHE Intervention QA Monitoring 
Checklist within 7 days of recording upload for the first 5 participants at each 
site and every 5th participant or 60 days since last external QA (whichever 
comes first) thereafter.
Qualitative Interviews Visit QA Activities:

Prior to confirming subject study visits, the site interviewer will verify that the 
subject is scheduled for the appropriate appointment.

During the visit, the interviewer will ensure that the subject still meets the 
eligibility requirements.

The interviewer will document the consent process using either the MULTI- 
MUSIQOLS Consent with Signature Form for the participants after obtaining 
participant signature or the MULTI-MUSIQOLS Consent with Signature 
Waiver Documentation Form for providers after obtaining verbal consents.

At visit completion, the interviewer will complete the Interview Visit Checklist 
that captures the required elements of the visit.
Monthly QA Activities
The following is a detailed description of the Monthly QA review activities, which will 
be documented on the QA Monthly Consent and Eligibility Data Review Tool

Consent Process Completion and Documentation: The site PI will review 
100% of the site’s executed consents using the QA Participant Data Review 
Tool.


Eligibility Criteria and Documentation: the site PI will review 100% of the 
Eligibility checklists and source documentation.
Quarterly QA Activities
The following is a detailed description of the Quarterly QA review activities, which will 
be documented on the QA Quarterly Review Tool.

Consent Process Completion and Documentation: The MSC or designee will 
review 100% of the site’s executed consents using the QA Participant Data 
Review Tool.

The MSC will use the QA Participant Data Review Tool to review completion 
and accuracy of the source documents and the eCRFs for 100% of subjects 
at the site every 3 months.

The MSC will cross-check eCRF data for accuracy and completeness every 3 
months. The MSC will also review query reports to confirm that all manual 
and automatic queries have been resolved.

Training Logs will be reviewed by the MSC every 3 months to verify training is 
current and properly documented. This will include a review for institution- 
specific and protocol-specific trainings.

The Site Regulatory Binders in REDCap are updated by the sSC when 
changes to licenses, certifications, credentials, IRB documents or CVs are 
made during the study. The sSC will review the Site Regulatory Binder every 
3 months to verify that all documents (paper and electronic) are maintained. 
This review will be documented and summarized in the MULTI-MUSIQOLS 
Essential Documents Review Tool. At least annually, the MSC will conduct a 
complete review of the each Site Regulatory Binder.
Annual QA Activities
The following is a detailed description of the Annual QA review activities, which will 
be documented on the MULTI-MUSIQOLS QA Annual Review Tool.

The procedures and processes to ensure protocol adherence among the
study personnel are set forth in the Manual of Procedures (MOP). The MOP 
is reviewed by the MSC every 12 months for applicability and accuracy.

This QA Plan will be reviewed for applicability and accuracy and updated as 
necessary every 12 months by the MSC. Additional QA needs identified at a 
study site will be communicated to the MSC. The MSC and MPI’s will 
evaluate the need to update the QA plan, tools, and logs.
10.3.4 Protocol Deviations
A protocol deviation is any alteration/modification to the IRB-approved protocol that 
is not approved by the IRB prior to its initiation or implementation. Protocol deviations 
may result in determinations of non-compliance, serious or continuing.
1.
Minor Protocol Deviation: An incident involving noncompliance with the protocol 
but one that typically does not have a significant effect on the subject’s rights, 
safety, welfare, or on the integrity of the resultant data.
2.
Major Protocol Deviation: A more serious incident involving noncompliance with 
the protocol usually involving critical study parameters. Major protocol deviations 
generally affect the subject’s rights, safety, or welfare, or the integrity of the study 
data. A major protocol deviation can also be called a protocol violation.

Per UH IRB, protocol deviations must be reported by the PI or their designated 
research staff to the IRB within 5 days for major deviations, and at continuing review 
for minor deviations. Deviations are reported electronically by the MSC or designee 
using the appropriate category on the UHCMC IRB’s RNI form.
Research staff will document the protocol deviation on the MULTI-MUSIQOLS 
Protocol Deviation Log after becoming aware of the event. The site PI or their 
delegated research staff will review and sign off on the deviation and designate it as 
major or minor. The site PI or delegated staff is responsible for reporting the 
deviation to the MSC within 3 days for major deviations and quarterly for minor 
deviations. The MSC is responsible for all follow-up associated with protocol 
deviations and reporting this information to the UH IRB.
10.3.5 Monitoring
Each site will maintain the QA tools/logs either in a QA binder (for paper documents) 
or electronic folder. Site SCs will be responsible for site-specific QA activities. The 
MSC will be responsible for QA activities at the lead study site and will provide 
oversight for QA activities for the entire study.
Each sSC will provide a Quality Assurance Summary Report to the MSC one month 
before the Data Safety and Monitoring Committee (DSMC) Report is due. The MSC 
will compile the site reports into a comprehensive, study-wide report that will be 
provided to NCCIH. The MSC will also summarize the information for inclusion in the 
DSMC Report. This summary will document the following:

QA activities completed since the prior report submittal, including:
o
Frequency of reviews
o
Number of charts reviewed
o
Items covered by the review

Identification of problem areas

Corrective Action Plan(s)
In addition, the PI will propose an independent monitoring committee (requires 
NCCIH approval) to overview the study from a data and safety perspective.
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY
11.1
Institutional Review Board (IRB) Review
This protocol and the informed consent document and any subsequent modifications 
will be reviewed and approved by the IRB or ethics committee responsible for 
oversight of the study.
11.2
Informed Consent Forms
A signed consent form will be obtained from each participant. For adult patients, only 
the participating patients themselves will be allowed to provide consent for inclusion 
into the study. No legally authorized representative (LAR) may enroll an adult patient 
into the study. For minor patients, the minor will provide written assent to participate 
in the study while their parent/guardian will provide consent for inclusion in the study. 
The consent form will describe the purpose of the study, the procedures to be 
followed, and the risks and benefits of participation. A copy will be given to each 
participant or legal guardian and this fact will be documented in the participant’s 
record.

11.3
Participant Confidentiality
Any data, specimens, forms, reports, video recordings, and other records that leave 
the site will be identified only by a participant identification number (Participant ID, 
PID) to maintain confidentiality.
All electronic data will be kept in password protected databases behind an electronic 
firewall at sites and then securely sent to the UCI Coordinating Center and 
maintained on password protected PCs by a designated data manager. The UCI 
Coordinating Center will securely share data collected at their site and those 
received from Case Western Reserve University (CWRU)/University Hospitals (UH), 
the lead site and IRB of record. Data shared with CWRU/UH will be stored in a 
password protected database behind an electronic firewall on a secure UH server.
Data in hard copy form will be stored in locked file cabinets within a secure, badge- 
access location at each site. Upon completion of study enrollment, members of the 
study team will verify the information contained within the database. After answering 
all queries in the database, the information contained will be locked and exported for 
analysis. Both the source (electronic data collection) data and exported databases 
will be stored as required by the respective rules and regulations (e.g., HIPAA 
authorizations will be maintained for at least six years).
Information will not be released without written permission of the participant, except 
as necessary for monitoring by IRB, the FDA, the NCCIH, and the OHRP
11.4
Study Discontinuation
The study may be discontinued at any time by the IRB, the NCCIH, the OHRP, the 
FDA, or other government agencies as part of their duties to ensure that research 
participants are protected.
12. COMMITTEES
The proposed 3-year project is designed to conduct and evaluate a feasibility study 
in 2 sites, in preparation for a definitive study of MT vs health education for pain and 
quality of life in patients with SCD.
To pursue these aims, we have assembled an experienced multidisciplinary team.
The Steering Committee will consist of Drs. Dusek and Jenerette as multi-PIs, as 
well as Drs. Karasz, Anderson, Malik, Owusu-Ansah and Mr. Rodgers-Melnick. Ms. 
Segall will also join these meetings. This team will meet monthly to oversee 
implementation with specific insights from the site’s SCD physician champions.
Site Research Teams will consist of the site PI, SCD physician champion, Study 
Coordinator, Research Assistant, HybHE trainer(s) and the study music therapist(s). 
These teams will meet regularly leading up to and during the implementation of the 
feasibility study at their site, under the direction of the site PIs.
Data Coordinating Center (DCC) will consist of the PI (Dr. Malik) of the DCC, the 
lead statistician (Dr. Ricks-Oddie), the TBD junior statistician and the DCC manager 
(Dr. Christodoulou).
13. PUBLICATION OF RESEARCH FINDINGS
Publication of the results of this trial will be governed by the policies and procedures 
developed by the Steering Committee. Any presentation, abstract, or manuscript will 
be made available for review by the sponsor and the NCCIH prior to submission.

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