Music Therapy in Patients Undergoing Pancreatic Surgery (MUSIC PUPS): A Mixed Methods Feasibility Study
Phase: NA
Conditions: Whipple Procedure, Distal Pancreatectomy, Acute Pain
Sponsor: University Hospitals Cleveland Medical Center

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[USE THIS BIOMEDICAL PROTOCOL TEMPLATE IF YOUR PROJECT INVOLVES ANY 
PHYSICAL CONTACT OR MEDICAL INTERVENTIONS WITH PARTICIPANTS]  
INSTRUCTIONS:

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
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making changes. 
PROTOCOL TITLE: Music Therapy in Patients Undergoing Pancreatic Surgery (MUSIC PUPS): A 
Mixed Methods Feasibility Study.
PRINCIPAL INVESTIGATOR:
Samuel N. Rodgers-Melnick, MPH, MT-BC 
UH Connor Whole Health
216-844-7727 
Samuel.RodgersMelnick@UHhospitals.org
UH FACULTY ADVISOR:
If the principal investigator’s primary role at UH is resident, fellow or student, identify a faculty 
advisor.
☒ N/A
Name 
Primary Department
Telephone Number 
Email Address
OTHER DEPARTMENTS INVOLVED IN THIS STUDY (IF APPLICABLE):    
☒  N/A   
VERSION NUMBER:
Include the version number of this protocol if assigned by an outside entity.
DATE: 
3/22/2024 

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Objectives 
The purpose of this study is to determine the feasibility and acceptability of: (1) a tailored music-assisted 
relaxation and imagery intervention; (2) biological sample collection; and (3) mobile device patient-
reported outcome (MDPRO) collection among adults hospitalized for pancreatic surgery experiencing 
acute pain.  
Background
Patients undergoing pancreatic surgery often experience high pain, stress, and anxiety that can 
contribute to poorer recovery and increased risk of opioid misuse. Interventions that reduce 
postsurgical anxiety, stress, and pain that are also accessible to a diverse population and individualized 
to each patient are needed to address this complex problem.
Music therapy has not been investigated specifically in patients undergoing pancreatic surgery. 
However, several music medicine and music therapy studies in similar populations support the efficacy 
of music interventions for addressing pain and symptom management in this population. A 2015 
systematic review and meta-analysis of 72 music medicine randomized controlled trials (RCTs) initiated 
before, during, or after surgery found that music interventions reduced postoperative pain (45 RCTs, 
SMD –0.77 [95% CI –0.99 to –0.56]), anxiety (43 RCTs, –0.68 [–0.95 to –0.41]), and analgesia use (34 
RCTs, –0.37 [–0.54 to –0.20]), and increased patient satisfaction (16 RCTs, 1.09 [0.51 to 1.68]) scores. 
Visual analog scale pain scores were reduced by an average of 23 mm (95% CI 16.9–29.9), and anxiety 
scores measured by the State Trait Anxiety Inventory were reduced by an average of 6.4 units (95% CI 
3.86–8.94). Compared to investigator-selected music, patient-chosen music demonstrated a slightly 
increased but non-significant reduction in pain as well as a non-significant reduction in analgesia use 
(Hole et al., 2015). A 2020 systematic review and meta-analysis found that perioperative music 
interventions significantly reduced postoperative opioid requirements (pooled SMD -0.31 [95% CI -0.45 
to -0.16], p < 0.001, I2 = 44.3, n = 1398) (Fu et al., 2020).
Within the music therapy literature, investigators have examined the effects of patient-preferred live 
music (PPLM) and active music engagement among patients undergoing other pancreatic surgeries. 
Among patients recovering from organ transplant surgery, various small RCTs have demonstrated the 
efficacy of PPLM delivered by a music therapist for reducing pain, stress, anxiety, nausea, and improving 
mood and relaxation (Bergh & Silverman, 2018; Crawford et al., 2013; Haack & Silverman, 2017; Hogan 
& Silverman, 2015; Madson & Silverman, 2010). In a study of 29 adults who received liver and kidney 
transplants, those who engaged in active music engagement (i.e., singing and/or instrument playing) 
with a music therapist reported significant reductions in pain and negative affect compared to control 
(Ghetti, 2011). In a RCT of 44 adult patients on a post-surgical oncology unit, patients who received 20-
30 minutes of PPLM (n = 24) reported significant improvements in affect (Global Mood Scale) compared 
to waitlist control (Merry & Silverman, 2021). Similar studies of PPLM on postsurgical oncology units 
support its efficacy for improving anxiety, relaxation, and pain (Chaput-McGovern & Silverman, 2012; 
Yates & Silverman, 2015).
Based on available literature, no prior music therapy studies have investigated the effects of music-
assisted relaxation and imagery (MARI) in patients undergoing pancreatic surgery. However, our prior 
work with this intervention supports its use with this population. In a RCT conducted at our institution, 
patients receiving palliative care (n = 99) reported clinically and statistically significant mean reductions 

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in pain intensity (-1.9 points on the 0-10 numeric rating scale) in response to a live 20 min MARI session 
provided by a music therapist (Gutgsell et al., 2013). In our more recent clinical effectiveness research, 
among a larger sample of hospitalized adults reporting moderate-to-severe levels (≥ 4/10) of pain, a 
single session of MARI was clinically effective for reducing mean scores of pain (-2.0 points, n = 416). 
Patients receiving MARI in this sample reported pain changes of ≤ -2 points in 50% of sessions. More 
specifically, a single music therapy session was clinically effective for reducing mean pain scores (-1.7 
points, n = 70) on a surgical oncology unit with pain changes of ≤ -2 points in 40% of sessions.
Despite several studies supporting the efficacy of music interventions for addressing the needs of 
surgical patients, biological mechanisms of action remain poorly understood. The most frequently used 
biomarkers in medical music intervention research have been stress biomarkers including plasma 
cortisol, salivary cortisol, and salivary α-amylase. While a handful of studies have found significant p-
values for the reduction of salivary cortisol and salivary α-amylase in response to music interventions, 
research using these biomarkers have been limited by non-standardized interventions, small samples, 
and variation in sample collection (Wong et al., 2021). Recent advances in functional genomic science 
provide an opportunity to understand gene expression mechanisms. Thus far, these approaches have 
been applied to mind-body therapies (Bhasin et al., 2013, 2018; Dusek et al., 2008), recreational music 
making (Bittman et al., 2005, 2013), and music listening (Kanduri, Kuusi, et al., 2015; Kanduri, Raijas, et 
al., 2015). In a study of 32 healthy volunteers (mean age = 40.8) exposed to a 1-hour stress induction 
protocol, group keyboard recreational music making (RMM) led to reversal of 19 out of 45 immune 
response-related gene expression markers in contrast to 6 out of 45 markers in the resting control group 
and 0 out of 45 in the ongoing stressor group (Bittman et al., 2005). In a similar study of 34 Caucasian 
adults (mean age = 67.7) with a history of ischemic cardiovascular disease, group keyboard RMM 
produced changes in expression of 12 pathways governing immune function and genetic information 
processing compared to 2 pathways in a quiet reading control (Bittman et al., 2013). However, gene 
expression approaches have not been utilized in the investigation of music therapy or in hospitalized 
adults.
To support future research of biological mechanisms and scalability in MT, new study protocols must be 
tested for feasibility and acceptability. Therefore, the purpose of this study is to determine the feasibility 
and acceptability of: (1) a tailored music-assisted relaxation and imagery intervention; (2) biological 
sample collection; and (3) mobile device patient-reported outcome (MDPRO) collection in adults 
hospitalized for pancreatic surgery experiencing acute pain.  
Inclusion and Exclusion Criteria
Inclusion Criteria
1.
Age range: from 50 to 80
2.
Subject is able to speak and understand English
3.
Patient is scheduled to undergo a Whipple procedure or Distal pancreatectomy at UH 
Cleveland Medical Center with a standardized pain regimen
4.
Patient reports pain intensity of 4/10 or above to research assistant on day 1 post-
surgery or any other day post-surgery through discharge
Exclusion Criteria
1.
Subject has a significant visual impairment that has not been corrected

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2.
Subject has a significant hearing impairment that has not been corrected
3.
Subject has a significant cognitive impairment that would prevent subject from 
participating in the study
Number of Research Participants
We will enroll 30 subjects at UH Cleveland Medical Center (UHCMC).
Recruitment Methods 
Patients will be referred by their surgical team prior to their scheduled surgery. A member of the 
surgical team will tell patients that there is a study they might be eligible for, share the patient flyer with 
them, and ask if a member of the study team can call them to tell them more about the study. If the 
patient agrees, the provider will email the study team with the patient’s name, medical record number 
(MRN), date of birth, and upcoming dates for pre-admission testing (PAT) and surgery (if date set). 
Following the outpatient referral, the research assistant (RA) will review the patient’s medical record to 
pre-screen for eligibility using the eligibility checklist.  If the patient meets initial eligibility criteria, the 
RA will approach the patient over the phone prior to the patient’s surgery to explain the study. If the 
patient is interested in participating, the RA will either (1) meet with the patient at the patient’s PAT 
appointment at UHCMC to obtain full written informed consent or (2) obtain written informed consent 
over Zoom for Healthcare, depending on the patient’s preference.
Setting
Initial consent will take place either in person at the PAT or via a HIPAA-compliant commercial tele-
health platform (i.e., Zoom for Healthcare) prior to the patient’s surgery. Most subsequent activities will 
occur at UH Cleveland Medical Center (UHCMC). Confirmation of eligibility (i.e., pain rated ≥4/10 and 
not admitted to intensive care unit [ICU]) and affirmation of consent to participate, data collection, 
sample collection, and the in-person MARI intervention will occur within participants’ private hospital 
rooms. We will conduct semi-structured interviews with participants via a HIPAA-compliant commercial 
tele-health platform (i.e., Zoom Healthcare) or over the phone 1 to 2 weeks after discharge from 
UHCMC. Following sample collection, blood samples will be temporarily stored within the Connor Whole 
Health research office in the Wearn building or in the -70 freezer in the Dahms Clinical Research Unit 
(DCRU) laboratory space in the Wearn building. Later, samples will be shipped to Manoj Bhasin’s lab at 
Emory University for long-term storage and subsequent analysis (Bhasin Systems Biomedicine lab, S335, 
1760 Haygood drive, Atlanta, 30322).
Consent Process
Consent will be obtained in writing by the RA and captured in UH REDCap. Initial informed consent will 
occur before the surgery date either during a PAT appointment in a private clinical or consult room out 
of the earshot of others to maintain privacy, or via a HIPAA-compliant commercial tele-health platform. 
Patients will be provided with a copy of the consent form to read prior to the discussion of the study. 
The RA will call the patient over the phone prior to their surgery to explain the study. If the patient is 
interested in participating, the RA will either (1) meet with the patient at the patient’s pre-admission 
testing (PAT) appointment at UHCMC to obtain full written informed consent or (2) obtain written 
informed consent over Zoom for Healthcare, depending on the patient’s preference. The RA will send a 
copy of the informed consent document to the patient for them to review ahead of the scheduled 

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informed consent visit. During the consent visit, the patient may ask any questions they have about the 
study. The RA will answer these questions. The participant’s understanding of the study will be 
documented in the Informed Consent Documentation form in REDCap.  
When all questions have been answered, the participant will sign the consent by “making their mark” on 
the signature line in REDCap to indicate that they understand the document. Patients may participate in 
the study one time. The study team will send a PDF copy of the signed consent form to the participant 
via email. A copy of the consent form will be uploaded into the Electronic Health Record.
On day 1 post-surgery, the RA will first check in with the treating physician and/or the clinical nurse prior 
to approaching the participant to ensure that there is no clinical reason why they think the participant 
should not participate at that time. Participants admitted in the ICU on day 1 post-surgery, or any other 
day post-surgery when the study team would initially approach to collect T0 data and provide MARI, will 
not be approached for further study participation and will be withdrawn from the study.
If the participant is not admitted in the ICU and the treating physician and/or the clinical nurse affirm 
that it is appropriate to approach the participant, then the RA will check in with the participant in their 
private room to confirm eligibility, specifically that (1) their pain level is at least a 4 on the 0-10 numeric 
rating scale, and (2) they affirm that they want to continue participation in the study. The RA will also 
confirm that the participant is not in too much pain to spend some time answering some questions and 
to meet with the music therapist.  
If the participant’s pain is too low or too high to participate, or if the provider or nurse give a clinical 
reason that the participant should not participate at that time, the RA will return again in 15 minutes to 
see if anything has changed. At that time, if 

the provider or nurse continue to give a clinical reason that the subject should not participate, 

the participant rates their pain < 4/10,

the participant indicates that they are in too much pain to participate at that time, or

the participant is not able to rate their pain due to cognitive or physical limitations,
then the RA will ask the participant if it is ok for the research team to return at another time to see if 
they meet study criteria and are willing and able to participate in study procedures. If the participant 
says yes, the RA will return at least 24 hours later and repeat the above steps. If applicable, the RA will 
return each day that the patient is admitted and study staff are available to repeat the above steps until 
either (1) the participant’s eligibility is confirmed and study procedures begin, (2) the participant says 
that they are no longer interested in participating in the study at all, (3) the participant becomes 
ineligible for any other reason (e.g. they are admitted to the ICU, or (4) the participant is discharged. 
Participants who change their mind about participating (reason 2), become ineligible for another reason 
(3), or are discharged will be withdrawn from the study. They may still receive music therapy services 
during their hospitalization after this withdrawal, but these will occur within routine clinical music 
therapy practice and no data on those sessions will be collected for this study.
The result of both the check in(s) with the provider and with the participant will be documented in 
REDCap. Participants that continue to meet eligibility criteria on day 1 post-surgery or another day 
through discharge, and are not withdrawn from the study for the reasons noted above will be 
considered to have “Initiated study procedures” following enrollment.

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Sharing of Results with Research Participants
☒  Results will not be shared with research participants
☒  Results will not be shared with research participants’ doctors
Study Design
We will conduct a single arm non-randomized trial to determine the feasibility and acceptability of: (1) a 
tailored music-assisted relaxation and imagery intervention; (2) biological sample collection; and (3) 
mobile device patient-reported outcome (MDPRO) collection among adults hospitalized for pancreatic 
surgery experiencing acute pain. See Attachment “MUSICPUPS_Schematic” for a graphic representation 
of the study design.
 
Study Procedures
Following consent, the RA will ask the participant if they prefer to use their own device or a study iOS 
device to listen to the MARI recording and respond to the MDPRO surveys. Then, the participant will 
receive education on how to access the MARI recording and to respond to the surveys based on the 
choice that they make. The RA will provide a link to education videos on Box.com and a written step-by-
step guide, as well as verbal education (see attached videos and step-by-step guides). For participants 
who choose to use their own device, the RA will create a Box folder for them prior to surgery and have 
them save a link to this folder on their device home screen before surgery. The RA will also ask 
participants who choose to use their own device if they would prefer to receive MDPRO invitations via 
text message or email. This will be recorded in REDCap.
Regardless of which device the participant chooses to use during admission, the RA will encourage them 
to bring their own headphones to use if that is most comfortable for them (e.g., their own Airpods). 
However, if they don't have headphones or want to use study headphones instead, study headphones 
will be provided. If the participant chooses to use their own device and study headphones, the RA will 
ask the participant if their device has a headphone jack. If it does, they will be provided a set of Apple 
earbuds during admission. If it does not, they will also be provided a dongle for lightning or USB-C 
adaptor.
During the consent visit, in addition to the patient education, the RA will ask the participant a series of 
questions to determine their preferences for music (e.g., genre, artists) and imagery (e.g., a place or 
time in which the participant feels comfortable). These responses will be recorded in REDCap. After the 
consent visit, the RA will share the participant’s music and imagery preferences with the board-certified 
music therapist (MT-BC) who is an IRB-approved member of the study team. 
Following the participant’s surgery, about an hour after eligibility and continued willingness to 
participate are established as described above, the RA will return to the participants room. This amount 
of time is necessary to coordinate with the MT-BC, who will not know if the participant is eligible and if 
they will be providing the MARI intervention until the RA checks in. Before collecting any data, the RA 
will ask the participant if their pain will permit them to continue and if they would like to proceed. If the 
participant responds affirmatively, the RA will document this in REDCap and then will proceed to collect 
baseline (Time 0) patient-reported outcomes (PROs) (i.e., 0-10 ratings of pain, stress, and anxiety) using 
a REDCap instrument administered on an iPad. The RA will not view the participant’s PRO responses. If 

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the participant is currently utilizing a patient-controlled analgesia (PCA) pump, the RA will collect 
measures of medication usage from the PCA pump. The RA will also collect a peripheral blood sample 
using a Spot On Sciences HemaSpot-HF. The research team chose the HemaSpot HF because it is an 
efficient and less invasive means of collecting capillary blood. Using the HemaSpot HF also poses less risk 
and discomfort to these patients who recently underwent major surgery. Following baseline measure 
collection, the RA will leave the participant’s room.
Following Time 0, the MT-BC will deliver a standardized 30-minute MARI intervention, personalized to 
the participant’s music and imagery preferences. Prior to the intervention, the MT-BC will verify the 
participant’s music and imagery preferences discussed with the RA during the consent visit. During the 
MARI intervention, the MT-BC will provide live guitar accompaniment personalized to the participant’s 
music preferences and read from a standardized script directing the participant to relax muscles of the 
body, practice deep breaths, and explore a relaxing place. This intervention will be recorded live. 
Following the MARI intervention, the MT-BC will briefly process the participant’s experience by asking 
them how the experience was for them and to describe in their own words how they are feeling after 
the MARI intervention (please see the attachment “MUSIC PUPS Post MARI Debriefing” for more 
details). The recorded MARI track will be exported to a Box folder that the participant can access via an 
app on a study iOS device (e.g., iPod touch, iPhone), or via a web link that is saved as a shortcut on the 
home screen of the participant’s own device. In either case, the participant’s MARI use will be tracked in 
Box. 
Immediately following the MARI intervention and post-intervention processing, the MT-BC will leave the 
participant’s room. The RA will then enter the participant’s room again. The RA will confirm that the 
participant is not in too much pain to continue and would like to continue with study procedures, 
documenting this in REDCap, before collecting post-intervention PROs and peripheral blood smear 
measures (Time 1). After collecting these measures, the RA will wait in the participant’s room for 15 
minutes. At 15-minutes post-intervention (Time 2), the RA will again collect PROs and a final peripheral 
blood smear measure. 
After the final PRO and peripheral blood smear collection, the RA will ensure that the participant knows 
how to access the MARI recording and enter MDPRO measurements using the study iOS device or their 
own device, and that they have headphones and, if applicable, a dongle, in order to listen to the 
recording. The RA will instruct the participant to listen to the MARI intervention 3x/day and complete 3 
MDPRO measurements each day until discharge. If the participant elects to use a study iOS device, it will 
be locked to the participant’s tray table to prevent it from being lost or stolen during the participant’s 
hospitalization.
Following the collection of blood samples and PROs, the RA will conduct a review of the participant’s 
medical record to collect data on the participant’s demographics, clinical characteristics, and pain 
medications administered pre-intervention. The RA will enter this data into REDCap. Following sample 
collection, blood samples will be temporarily stored within the Connor Whole Health research office in 
the Wearn building or in the -70 freezer in the DCRU laboratory space in the Wearn building. Later, 
samples will be shipped to Manoj Bhasin’s lab at Emory University for long-term storage and subsequent 
analysis (Bhasin Systems Biomedicine lab, S335, 1760 Haygood drive, Atlanta, 30322).
The RA will meet with each participant every day, Monday through Friday, until discharge to 
troubleshoot any barriers to MARI use or MDPRO collection. Each day, before any troubleshooting or 

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collecting any data, the RA , like on day one, will (1) check in with the treating physician and/or the 
clinical nurse; (2) ask the participant if their pain level will permit them to participate; and (3) ask the 
participant if they still want to participate in study procedures. If the participant responds affirmatively 
to continuing study procedures, the RA will document this in REDCap and then proceed with 
troubleshooting and data collection. The RA will record any barriers to MARI use and/or MDPRO 
collection (i.e., forgot, technical difficulties, off the floor for a procedure) as well as the participant’s self-
reported use of MARI in the last 24 hours. From Day 2 (i.e., the day after the live MARI intervention) 
until the participant is discharged from the hospital, participants using a study iOS device will receive 
three notifications per day (i.e., morning, afternoon, and evening) on the iOS device to complete 
MDPRO measures, and participants using their own device will receive three email or text invitations 
(per their preference) to complete the MDPRO measures. The participant’s use of the MARI recording 
will be tracked using file utilization measures available within Box.com. No PHI will be entered into the 
Box.com folder. The RA will also track the participant’s use of pain medications (recorded in the EHR or 
on the PCA). All data will be stored in REDCap.
On the day of the participant’s discharge from the hospital, the RA will collect the study iOS device, if 
applicable. For those that don’t already have the link on their own device, the RA will provide the 
participant with the MARI recording via email and a Box.com link to allow the participant to access the 
recording post-discharge. If desired, the RA will also provide the recording via a compact disk. Following 
discharge, the study coordinator will arrange a time for the participant to complete a semi-structured 
interview over Zoom. One to two weeks after the participant’s discharge from the hospital, researchers 
will meet with the participant over a HIPAA-compliant commercial tele-health platform to complete a 
semi-structured interview (see Appendix for interview guide). If the participant is expected to be 
discharged over the weekend, the RA will provide the MARI recording resources on the Friday before 
the weekend in which the participant is to be discharged.
Blood sample procedures
All HemaSpot-HF will be prelabeled with a Study ID (e.g., 1,2,3,4, 5), the appropriate study time series 
(i.e., Time 0, Time 1, or Time 2), and a line for the research assistant to write the date and time the 
sample was collected.
When collecting the blood sample, the research assistant will follow Spot On Sciences’ procedure which 
can be viewed here (https://www.youtube.com/watch?v=rm8_jfOwlus). These procedures are as 
follows: 
1)
Put on a pair of protective gloves; 
2)
Clean and sanitize a tray table on which to place the HemaSpot materials; 
3)
Lay out the materials from the HemaSpot kit on a tray table in the participant’s room; 
4)
Clean the participant’s finger using an alcohol wipe; 
5)
Remove the cap from the lancet and position the end against the inside tip of the middle or 
ring finger; 
6)
Press the lancet firmly on the participant’s finger until it activates with a click; 
7)
Wipe away the first drop of blood with a sterile gauze; 
8)
Position the lanced finger over the center of the HemaSpot; 
9)
Provide gentle pressure on the end of the finger, and let three drops of blood drip from the 
finger onto the center of the HemaSpot; 
10) Wait one minute for the wicking process to complete; 
11) Bandage the participant’s finger; 

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12) Close the HemaSpot firmly ensuring that the latch is secure.
These steps will occur at Time 0, Time 1, and Time 2, with the RA sampling a different finger from the 
participant at each time. The RA will note any challenges to blood sample collection (e.g., participant 
discomfort, device malfunction, participant refusal) and record these in REDCap following the 
procedure.
Following blood sample collection, the RA will ensure that the samples are properly labeled and their 
collection are noted in REDCap. The three samples will be placed in a secure padded envelope and 
locked in the Connor Whole Health Research Office in Wearn 548 or in the DCRU lab in the Wearn 
building until they are shipped to the Emory lab for analysis via UPS.
Suicidal Ideation, Acute Anxiety and Adverse Event Mitigation Plan
If a patient reports suicidal ideation while admitted at any point during the study, study staff will 
immediately contact the clinical care team and make a note in the patient’s EHR. If the patient reports 
an anxiety score greater than or equal to 7/10 on the numeric rating scale during the study, study staff 
will make a note in the patient’s EHR documenting the patient’s anxiety score. The clinical care team will 
follow their intervention protocol to address the patient’s situation. 
 
Interview procedures
Interviews will take place over a HIPAA-compliant commercial tele-health platform (i.e., Zoom for 
Healthcare) or over the phone one-to-two weeks after the participant is discharged from the hospital. 
During that interview, a researcher will ask the participant about their experience in the study and what 
they thought about the MARI intervention. The researcher conducting the interviews remotely will be in 
a private room when interviewing the participants and will be certified in human subject protection and 
GCP, researched credentialed if applicable, and on the study personnel table. The interview will take 
about 30 minutes and will be recorded and then transcribed by hand.  
Study Timeline
Data to be Collected for your study 
(AFTER consent and HIPAA Authorization have been obtained)
Demographics
Pre-
Screening
Consent 
& 
Education
Time 0
MARI
Time 1
Time 2
Day 2 to 
discharge
Interview
Estimated time 
requirement of visit
15 min
25-40 
min
5 min
30 min
5 min
5 min
15 min
3x/day
30 min
Data Collection
X
X
X
X
X
Consent process
X
Mobile device 
education
X
Music therapy 
intervention
X
X

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1.
Age
2.
Sex
3.
Race
4.
Ethnicity
5.
Marital status
Clinical characteristics
1.
Principal diagnosis
2.
Secondary mental health diagnoses (if applicable)
3.
Other services provided during hospitalization (e.g., art therapy, psychiatry, spiritual care, 
palliative care, social work)
4.
Admission date
5.
Pain medications administered (name, route, quantity, dose, time)
6.
Surgery date
7.
Surgery type
8.
Significant surgical complications
9.
Hospital floor
10. MARI intervention date
11. Music preferences
12. Imagery preferences
13. Discharge date
Patient reported outcomes pre-intervention (Time 0), post-intervention (Time 1) and 15-minutes post-
intervention (Time 2), and three times per day (i.e., morning, afternoon, and evening) until the 
participant is discharged.
1.
Pain (0-10)
2.
Stress (0-10)
3.
Anxiety (0-10)
Feasibility measures
1.
Reasons for not completing MARI intervention (if applicable)
2.
Reasons for not completing peripheral blood smear (if applicable)
3.
Dates/times of accessing the MARI recording during participant’s hospitalization
4.
Self-reported use of MARI recording during participant’s hospitalization
5.
Reasons for not using MARI recording (if applicable)
6.
Reasons for not entering MDPRO data (if applicable)
7.
Reasons for study withdrawal (if applicable)
Semi-structured interview
1.
Audio recording
2.
Transcript

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Biological samples pre-intervention (Time 0), post-intervention (Time 1), 15-minutes post-intervention 
(Time 2).
1.
Peripheral blood sample
Data Analysis Plan
In anticipation of a dropout rate of 33% following admission to the hospital (i.e., participants either not 
ever meeting pain criteria or choosing not to participate), we decided on a sample size of 30 participants 
with a plan to complete study procedures among the first 20 participants meeting full eligibility criteria.  
We based our sample size of 20 and definition of feasibility on prior research examining the feasibility of 
biological sample collection with music therapy (Holochwost et al, 2020). We have no prior experience 
using the HemaSpot HF for sample collection nor with delivery of the MARI intervention to this 
population and plan to start with a small sample size in order to refine procedures for a larger study. We 
hypothesize a 75% feasibility threshold for complete live MARI intervention delivery, PRO collection, and 
biological sample collection. We would consider failure to be completing less than 15/20 MARI 
interventions, 15/20 complete sets of PROs at Time 0, Time 1, and Time 2, 80% of MDPRO measures 
over the duration of the participant’s hospitalization, and 45/60 blood sample collections. 
We will use descriptive statistics (e.g., counts, percentages, mean, standard deviation, and median) to 
summarize participants’ demographics and clinical characteristics (obtained from EHR), as well as 
feasibility measures including rates of enrollment, attrition, intervention participation, MARI recording 
use, biological sample collection/viability, and PRO collection. We will determine the feasibility of 
biological sample viability by quantifying whether individual participants provided enough biological 
samples for eventual testing. No formal hypothesis tests (e.g., linear mixed effects models) will be 
conducted on changes in PRO data as this is a feasibility study.
Blood sample analysis plan
We are not collecting genetic data. We are not performing any genetic profiling. We are performing 
gene expression analysis, and this is different from genetic profiling. This is a pilot study to collect 
information in preparation for an appropriately powered study. To establish procedural elements, it is 
necessary to test procedures including the MARI intervention, peripheral blood sampling, and mobile 
device patient-reported outcome collection as these have not been utilized in prior studies with this 
population. We have already consulted with statisticians and based on our previous findings in music 
intervention, we need 87 pre- and post-measures on subjects for the fully powered study. After this 
pilot study, we intend to launch a multi-center feasibility study in collaboration with other institutions.
We will plan on conducting the following gene expression analyses as specified for all three-time points 
(Time 0, Time 1, and Time 2). The gene expression analysis will be performed at Bhasin Systems 
biomedicine lab at Emory University.  
A large part of the human genome is transcribed into various forms of RNA, and the global gene 
expression profile (GEP) changes measure expression changes in genes over time due to an intervention. 
Accordingly, our long-term goal of this line of research will be to examine whether pain intensity 
changes after the MARI intervention are associated with specific changes in gene expression profiles 
(GEP) and pathophysiologic pathways that correspond with the elicitation of the relaxation response 
(Bhasin et al., 2013, 2018; Dusek et al., 2008). 

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Our prior work was conducted among healthy adults (Bhasin et al., 2013; Dusek et al., 2008) or 
hypertensive patients (Bhasin et al., 2018) living in the community using PaxGene tubes to collect whole 
blood.  In the intervening years, the technology of dried blood spot (DBS) collection of samples has 
improved and has been used for GEP analysis.  
Thus, for the current feasibility study with 30 pancreatic surgical patients with acute post-operative pain, 
we are primarily interested in understanding the feasibility of collecting the HemaSpot samples from this 
population and whether the samples collected will be of sufficient quality to allow for gene expression 
profile testing.  The HemaSpot sample will be sent to Dr. Bhasin’s lab at Emory University for RNA 
sequencing based transcriptome profiling.  The transcriptome profiling will be performed using paired-
end RNA sequencing that allows for the measurement of the expression profile of ~30,000 human genes 
with high sensitivity and specificity. Briefly, sequencing libraries of Poly A selected mRNA will be generated 
from the double-stranded cDNA using the Illumina TruSeq kit according to the manufacturer's protocol. 
High-quality libraries will be sequenced on an Illumina Novaseq 6000 to achieve comprehensive coverage 
of measuring the expression of all genes. The assay can only measure the expression of genes but cannot 
reveal the identity/race/gender of the subjects. 
The Raw sequencing data will be processed to remove any adaptor, PCR primers, and low-quality 
transcripts. After alignment, the gene expression levels will be normalized and compared among the 
baseline and post-intervention samples to identify genes that are significantly modulated by the 
intervention. The comparison will be performed by implementing linear data modeling algorithms 
comparing the mean and variance among the groups. We will perform a focused analysis on immune and 
inflammatory response-related genes as our previous analyses depicted that mind-body interventions 
deliver beneficial effects by affecting these pathways. Additionally, to understand the detailed mechanism 
of intervention, we will perform pathways enrichment and interactive network analysis.  
Although the size of the feasibility proposal is small, we contend that it is worth conducting the GEP for 
each of the 30 participants across the 3-time points.  However, with the small sample it will be beyond 
the scope of our study to confidently compare the GEP from T0 to T1 to T2. That type of analysis would 
be conducted in a future randomized trial with a comparison group.
Once the dried spots arrive at Emory University, two will be processed for RNA extraction, followed by 
library preparation and whole genome RNA sequencing to measure a profile of 30,000 genes. Lab 
technicians will extract RNA from the dried blood spots (DBS) and prepare RNA sequencing (RNAseq) 
libraries. This process will occur in three steps: (1) RNA extraction and isolation, (2) RNAseq library 
preparation, and (3) Sequencing.
1.
RNA extraction and isolation. The RNA will be quantified using Qubit (Thermo Fisher Scientific) 
and quality assessed by RNA bioanalyzer chips (Agilent). See attachment “NEB Protocol” for 
more details on RNA extraction and isolation.
2.
RNAseq library preparation. The lab technicians will use the New England biolabs kits. First, they 
will remove ribosomal RNAs using ribosomal depletion kit (NEB#E6310) and then prepare the 
RNAseq library using the NEBNext® Ultra™ II Directional RNA Library Prep with Sample 
Purification Beads (NEB#E7765). The technicians will quantify the library using qubit and 
checking the quality HS DNA bioanalyzer chips (Agilent). See attachment “RNA Extraction and 
Isolation from HemaSpot” for more details on the RNAseq library preparation protocol.

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3.
Sequencing. Once the RNAseq libraries are made, the lab technicians will sequence them using 
NextSeq 500/550 mid output kits – 150 cycles (Illumina).
Qualitative analysis plan
Interviews will take place via a HIPAA-compliant commercial tele-health platform (i.e., Zoom for 
Healthcare) and be recorded then transcribed by hand. The RA, who will not conduct any interviews, will 
proof transcripts against the original recordings for accuracy. The transcribed interviews will be 
imported into the qualitative software program NVivo for analysis. At least two individuals experienced 
in qualitative data analysis will perform a line-by-line review and coding of each transcript 
independently using a constant comparative method of qualitative data analysis (Hseih & Shannon, 
2005). The initial coding will consist of reading the narrative text and highlighting words or phrases that 
capture the experience with music therapy. Text will be coded as themes as identified from the 
narratives and will be organized into meaningful categories and subcategories. In the final step, a table 
with categories and subcategories of data, along with definitions for each category, will be constructed 
consistent with study objectives. All data from the interviews that appear to be directly related to the 
study aims will be extracted. 
Strategies to optimize validity will include reviewing the coding among all coders, refining the coding 
until there is agreement. Members of the research team will review findings for accuracy of generated 
themes, interpretations of the data, and conclusions. 
Risks to Research Participants
The participant may not like the MARI intervention included in the study. In that event, participants may 
ask the MT-BC to stop the intervention and choose not to participate in the rest of the intervention. The 
probability of this event is low, however, as it has not occurred in any prior music therapy studies and its 
occurrence is rare in music therapy practice. It is possible that the participant may experience 
discomfort providing peripheral blood samples via finger prick. A breach in participants’ privacy and 
confidentiality may occur as a result of participating in this research study. 
Provisions to Protect the Privacy Interests of Research Participants
All attempts will be made to ensure participants’ privacy. The referrals will come from the participant’s 
medical team. The participant’s name will only appear on the consent form and the linking log. The 
linking log that identifies the participant’s study ID to identifiable data will be stored on a password-
protected, encrypted computer or secure server. All data that is stored in REDCap will identify the 
participant by the number assigned to them at the beginning of the study. Informed consent will occur 
in a private clinical room or consult room out of the earshot of others to maintain privacy.
Only aggregate data will be presented or published and will be presented such that individuals cannot 
be identified. Only IRB-approved study personnel will have access to participant data. All study 
personnel will be required to be certified in the protection of human subjects throughout the study.
Identifiable information will not be reused or disclosed to any person or entity outside of University 
Hospitals other than those identified in the protocol, except as required by law, for authorized oversight 
of the research study, or as specifically approved for use in another study by the IRB.
Potential Benefit to Research Participants

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Although not guaranteed, there is the possibility that the MARI intervention may reduce pain, anxiety 
and stress after their surgery. Furthermore, future surgical patients may benefit from the knowledge 
gained from this study.
Withdrawal of Research Participants
The study doctor or the sponsor can withdraw participation of research participants at any time without 
their consent for the following reasons:

If the patient is admitted to the ICU following surgery and remain admitted to the ICU on the 
day when study procedures would typically begin.

If, after the first day participation, the participant’s clinical condition deteriorates enough that 
they are transferred to the ICU.

If it appears to be medically harmful to the subject;

If the subject fails to follow directions for participating in the study;

If it is discovered that the subject does not meet the study requirements;

If the study is canceled; or 

For administrative reasons, including competitive enrollment - the target number of subjects has 
entered the study.
Alternatives to Participation
Instead of participating in this research study, patients can continue to work with their care team to 
manage their pain.
Costs to Research Participants
There is no cost to participate in this study.
Research Participant Compensation
Participants who complete the semi-structured interview will receive a $25 gift card.
Provisions to Monitor the Data to Ensure the Safety of Research Participants
The study PI will monitor the study to ensure data integrity and the safety of the participants. The study 
coordinator will review the data for discrepancies on a regular basis and will review the study records 
for compliance with IRB requirements. The study team will hold regular weekly meetings to review study 
progress and any issues that may come up regarding data integrity and completeness.

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