Feasibility and Acceptability of a Biofeedback Based Virtual Reality Intervention to Manage Postoperative Pain in Children and Adolescents After Surgery
Phase: NA
Conditions: Pain, Pain, Postoperative, Pain, Acute, Surgery
Sponsor: Vanessa Olbrecht

Feasibility and Acceptability of Technology-Based Interventions in the 
Perioperative Setting 
 
 
NCT04943874 
 
 
September 8, 2022 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 1 of 25 
HRP-503  v.12.10.18 
PROTOCOL TITLE:  
Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
PRINCIPAL INVESTIGATOR: 
Name: Vanessa A. Olbrecht, MD, MBA 
Department/Center: Anesthesiology 
Telephone Number: 
Email Address: Vanessa.Olbrecht@nationwidechildrens.org 
VERSION NUMBER/DATE: 
Version 8.0 
Date: August 18, 2022 
 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
1 
#2 – 08/31/21 
IRB Requested Modifications 
 
2 
#3- 01/12/22 
Include Biometric identifiers in section#27 
Y 
3 
#4 – 03/21/22 
Change inclusion criteria from > 2 days to at 
least one night in the hospital post-op and 
study duration to up to 3 months 
Y 
4 
#5 – 04/25/22 
Change device name to Oculus/Meta Quest; 
change in-person daily visit to in-person visit 
and as needed 
Y 
5 
#6 – 05/18/22 
Exclusion criteria regarding opioids or 
benzodiazepines changed from “currently 
using” to “chronically using” 
Addition of possible study communications 
via text under Economic Burden to Subjects 
 
6 
#7- 06/17/2022 
Changing Aim #1 enrollment from 20 to 32 
and the overall enrollment number for the 
study from 90 to 102 
Y 
7 
#8 – 08/18/2022 Include statement that de-identified data will 
be shared with a statistician at CCHMC 
 
 
 
 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 2 of 25 
HRP-503  v.12.10.18 
1.0 
Study Summary 
 
Study Title 
Feasibility and acceptability of technology-based interventions in 
the perioperative setting 
Study Design 
Feasibility/acceptability study; single-blinded, randomized, 
controlled trial. 
Primary Objective 
To develop and refine a VR-BF treatment protocol for 
preoperative education and training and postoperative delivery of 
VR-BF in children and adolescents undergoing surgery. 
Secondary 
Objective(s) 
To collect pilot data for R01 application and to gather data on 
outcomes that will be assessed in the future randomized clinical 
trial (pain, anxiety, opioid consumption, efficacy of VR-BF). 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
Biofeedback-based virtual reality (VR-BF, intervention), Manage 
My Pain application (active control) 
IND/IDE #  
NA 
Study Population 
Aim 1: up to 32 adolescents (12-18 years) undergoing surgery 
anticipated to cause moderate to severe pain requiring 
management by the Acute Pain Service; Aim 2: 70 adolescents 
(12-18 years) scheduled to undergo surgery anticipated to cause 
moderate to severe pain requiring management by the Acute Pain 
Service randomized to 1 of 2 treatment arms (VR-BF or Manage 
My Pain application).   
Sample Size 
Up to 102 patients (minimum 82) 
Study Duration for 
individual 
participants 
Up to 3 months 
Study duration: 3 years (12/2024) 
Study Specific 
Abbreviations/ 
Definitions  
VR, virtual reality 
VR-BF, virtual reality-based biofeedback 
VR-D, distraction-based virtual reality 
HR, heart rate 
HRV, heart rate variability 
BF, biofeedback 
NRS, numerical rating scale 
CCHMC, Cincinnati Children’s Hospital Medical Center 
 
2.0 
Objectives 
Aim 1 (Phase 1). Refine a treatment protocol for preoperative education and training and 
postoperative application of VR-BF in children and adolescents undergoing surgery. We 
will collect qualitative feedback (regarding content, usability, perceived benefits) via 
questionnaires and a semi-structured interview and sensitivity to change of key physiological 
parameters (heartrate variability, respiratory rate) from 12-32 patients (12-18 years) undergoing 
surgery anticipated to cause moderate to severe pain. Purposive sampling will be used to obtain a 
representative sample of a broad patient population. Treatment protocol refinement using iterative 
methodology will allow us to define the trial protocol, including frequency and duration of (1a) 
preoperative education and training and (1b) postoperative administration of VR-BF. 
 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 3 of 25 
HRP-503  v.12.10.18 
Aim 2 (Phase 2). Conduct a pilot randomized controlled trial to assess the feasibility and 
acceptability of perioperative use of VR-BF in children and adolescents undergoing 
surgery. Seventy children and adolescents (12-18 years) scheduled for surgeries anticipated to 
cause moderate to severe pain will be randomized to receive VR-BF or active control 
(commercially available Manage My Pain application). Manage My Pain is engaging but lacks 
specific instruction in behavior change techniques, a key feature of VR-BF. It is included as the 
control arm to confirm appropriateness for use in the future efficacy trial. Specifically, (2a)  
Feasibility will be assessed by rates of study recruitment, enrollment and randomization, 
retention, and adherence. Target goals will be set at 80% for each assessment. (2b) Acceptability 
will be assessed by treatment/study burden, satisfaction, treatment credibility, and tolerability. It 
is essential that both treatment arms are feasible and acceptable for use in an efficacy trial. 
 
Our central hypothesis is that preoperative education and training combined with independent, 
self-directed, repeated postoperative use of VR-BF will be feasible and acceptable in this 
population. This proposal addresses key components necessary for the design of a large-scale, 
clinical efficacy trial. 
 
3.0 
Background 
There have been many attempts to enhance analgesia by combining various groups of 
medications while deemphasizing the use of opioids. Despite these attempts, the percentage of 
patients experiencing severe pain after surgery has essentially remained the same for the last 20 
years.6,7 Many children are initially exposed to opioids to treat pain,1 and surgery is typically the 
point of their initial opioid exposure.58-60 Just five days of opioid use can increase the risk of 
persistent use, and use for more than eight days may increase that risk nearly 50-fold.58,61 
 
Children and adolescents are at risk of persistent pain5,60,62,63 and opioid use65 after surgery. 
Chronic postsurgical pain (CPSP) is defined as pain extending beyond that expected from 
surgery. A recent study identified an approximate 20% incidence of CPSP in children.5 While 
80% of these patients recover without issue, about 20% maintain a reduced quality of life due to 
persistent pain.5 Children are not just at risk of developing CPSP; they are also at risk of 
persistent opioid use after surgery,58,59 as opioids have long been the cornerstone of postoperative 
pain management.64 A study of opioid-naïve patients (13-21 years) who underwent one of 13 
surgeries found persistent opioid use in 4.8% of adolescents compared to 0.1% in a matched, 
nonsurgical cohort.58 In a study assessing patients with chronic pain using opioids, more than 
25% of patients transitioned to chronic use after receiving opioids for surgery.65 Novel, 
nonpharmacologic strategies are needed to reduce the risk, adverse consequences, and long-term 
impact of persistent pain and opioid use. 
 
Mind-body therapies, like biofeedback (BF), provide sustained pain reduction,8-18,22,66-71 and 
have the potential to reduce pain and opioid use after surgery, but there are barriers to 
their routine use in postoperative72,73 and inpatient settings.74 BF reduces pain8,75 by teaching 
patients to modify the behavioral responses that influence their pain and by changing their brain’s 
perception of that pain, resulting in improved physical, mental, and emotional health.19,20 By 
slowing breathing during BF, patients increase their heartrate variability (HRV),76 which activates 
the parasympathetic nervous system to increase vagal tone, resulting in pain reduction.19,20 
Implementation of BF, however, is fraught with barriers, particularly with respect to the 
availability of trained providers in inpatient and acute settings.8,9,77 Further, application of BF 
uses various computerized instruments to provide instantaneous data to patients to teach and 
reinforce physiological self-regulation. Because BF is so resource-intensive, widespread 
application has not been possible.78 As such, BF is not available to help manage pain in children 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 4 of 25 
HRP-503  v.12.10.18 
after surgery. In order to increase availability,79 novel strategies are needed to deliver this 
effective therapy at point-of-care. Biofeedback-based virtual reality (VR-BF) has the potential to 
reduce pain and opioid requirements and to fill the unmet need for alternative, effective mind-
body therapy for children with acute postoperative pain by increasing accessibility and 
acceptability of BF therapy. 
 
Distraction-based virtual reality (VR-D) transiently reduces pain by redirecting attention 
but is insufficient to manage prolonged pain associated with surgery. VR has been used to 
temporarily reduce pain in multiple clinical situations.25-28,32-34,36,46,49 Most studies assess the 
application of VR-D to minimize pain during acutely painful procedures in adults33,34,36,40,41,48,80-83 
and children26,32,39,84-86 by redirecting attention. Without VR, distraction alone provides little 
benefit in pain reduction,87 with no lasting or significant impact.49,50 The improved efficacy of 
VR-D to temporarily reduce pain compared to distraction alone is related to the immersion 
created by VR.44,88 Studies using VR to help manage postoperative pain shows pilot effectiveness 
in adults to transiently reduce pain after a single session.89,90 Our unpublished pilot work marks 
the first study to assess the impact of VR-D on pediatric postoperative pain. Results of our study 
were similar to the results of these two adult studies.91 Although VR-D is more effective than 
distraction alone, transient pain reductions associated with VR-D are insufficient to treat 
prolonged pain experiences, including postoperative pain. 
 
VR-based delivery may enhance BF, making this therapy more engaging and relevant92 and 
increase its accessibility.78 Administering BF in diverse clinical settings has several challenges, 
including a lack of engagement, a dependence on administration by a trained clinical provider, 
and a lack of motivation for repetition.78,93 Using VR to deliver mind-body therapies, like BF, can 
increase their accessibility while enhancing acceptability, motivation,47 and adherence52 
compared to methods without VR.78 Combined, these two therapies could be accessible and 
useful in many clinical settings,78,92 including in the management of acute postoperative pain. VR-
BF has the potential to avoid many of the common challenges of administering conventional 
mind-body therapies, allowing its widespread dissemination for postsurgical care. 
 
VR-BF has not yet been employed in perioperative care, therefore no defined treatment 
protocols for preoperative training and postoperative application of VR-BF exist. The 
literature supports the use of education and training to master and optimize the success of mind-
body techniques.19,20,78,94 Studies of VR-based mind-body interventions support teaching patients 
about the role of the autonomic nervous system on stress and pain and teaching patients how to 
alter their physiological response prior to the VR sessions.52,55,78 Classically, BF is done in 
weekly sessions with a clinical psychologist coupled with daily, 10-minute home practice 
sessions.20 In studies of adult and pediatric migraine patients, home practice between formal 
sessions enhanced BF efficacy.95,96 For postsurgical pain, our pilot work (CCHMC IRB #2018-
2892) showed that initiating mind-body training after surgery, while the patient is experiencing 
considerable pain and fatigue, is not optimal. Providing preoperative education and training and 
enabling technique mastery prior to the pain and stress caused by surgery may improve efficacy 
and enhance acceptability of VR-BF.19,20,56,57 Aim 1a will refine a VR-BF preoperative education 
and training protocol and help define the number and duration of sessions needed before surgery. 
 
VR-BF is a new therapy. Optimal frequency and duration of therapy sessions have not been 
established. Although the standard duration of a BF session is about ten minutes,20,97 VR-D 
sessions range from five80 to ten33,81,98 to 30 minutes.82,90 Frequency of BF sessions have ranged 
from just one97 to six weekly sessions.20 Published studies of VR-D to manage pain primarily use 
VR during acute pain from procedures such as cystoscopy,83 IV placement,32 dressing changes or 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 5 of 25 
HRP-503  v.12.10.18 
acute burn care,24,26,31,33,36,38,40,42,45,46,48,82 dental procedures,34,35 episiotomy repair,81 or during 
labor.98 Like our unpublished pilot studies,91,99 the single study applying VR-D in adults after 
surgery used one postoperative session.90 The variability of treatment regimens used in the 
literature does not provide a model for VR-BF dosing. Aim 1b will help determine the 
appropriate frequency and duration of VR-BF to help identify the appropriate “dose” of therapy 
following surgery. 
 
This proposed study seeks to establish measurable milestones that have not been addressed 
in prior studies. Aim 1 will refine a treatment protocol for preoperative education and training 
and postoperative application of VR-BF in children and adolescents for Aim 2, the pilot 
feasibility and acceptability trial. By understanding the key components of VR-BF and 
demonstrating feasibility and acceptability of the trial design, we will optimize design and 
execution of a large-scale, randomized, controlled efficacy trial comparing VR-BF to active 
control in this patient population. Before conducting this efficacy trial of VR-BF versus active 
control, it is imperative to assess factors that will impact the VR-BF intervention105 and, 
consequently, the efficacy of VR-BF to reduce pain and opioid use. This study will answer 
“whether the future trial can be done, should be done, and, if so, how.”106 
 
PILOT DATA (CCHMC IRB #2018-2892) 
Recruitment data. In FY2020, a total of 25,122 surgeries were performed at Cincinnati 
Children’s Hospital. Of those, 952 patients were followed by the Acute Pain Service for 
management of moderate to severe postoperative pain. Between November 2018 and March 
2020, we conducted two pilot studies using VR-D and biofeedback-based VR (VR-BF). We 
screened 550 patients. Based on eligibility criteria, 95 (17%) were ineligible. We approached 235 
patients after surgery. Of those approached, 82% were interested in the study and 43% were 
successfully recruited and 
completed the study. Despite 
being interested, many eligible 
patients declined enrollment 
due to feeling tired, being in too 
much pain, or needing to 
participate in other clinical care. 
This pilot data informed our 
decision to recruit patients 
preoperatively in efforts to 
increase recruitment and 
enhance buy-in for this therapy 
with preoperative education 
and training. Ultimately, we 
believe this strategy will also 
enhance efficacy as technique 
practice and mastery are likely 
necessary components of 
efficacy. 
 
Reduction of pain and anxiety 
with VR-D. Children and adolescents (8-18 years) being managed by Cincinnati Children’s 
Hospital Acute Pain Service for moderate to severe pain after surgery were screened for 
eligibility. Over seven months, we enrolled 50 patients to participate in a single, 10-minute 
postoperative VR-D session (Table 1). After consent, patients were asked to complete surveys for 
Variables 
VR-D 
VR-BF 
Age – mean (SD), years 
15.6 (2.5) 
14.6 (3.2) 
Sex – male/female (n) 
31/19 
32/19 
Race (%) 
 
 
 Caucasian 
88% 
80% 
 Non-Caucasian 
12% 
20% 
Surgery type (%) 
 
 
 Abdominal 
38% 
37% 
 Pectus/chest  
34% 
41% 
 Orthopedic 
28% 
22% 
Baseline NRS scores – mean (SD) 
 
 
 Pain intensity (0-10) 
4.68 (2.09) 
5.11 (1.74) 
 Pain unpleasantness (0-10) 
5.39 (2.50) 
5.73 (2.30) 
 Anxiety (0-10) 
1.79 (2.52) 
2.05 (2.50) 
Table 1. Characteristics of VR-D, VR-BF patients. 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 6 of 25 
HRP-503  v.12.10.18 
trait measures: (a) pain catastrophizing (Pain Catastrophizing Scale for Children, PCS-C)107 and 
(b) anxiety sensitivity (Child Anxiety Sensitivity Index, CASI).108,109 Children played one of three 
games (all provided a similar distraction-based experience) for ten minutes. Patients were asked 
to rate their pain intensity, pain unpleasantness, and anxiety using the numerical rating scale 
(NRS)110,111 immediately and 15 and 30 minutes after the VR session. Pain intensity decreased by 
about 1 point immediately following the session (p<0.0001), and this change remained significant 
at 15 minutes (0.4 points, p=0.02) but not at 30 minutes. Pain unpleasantness decreased 
significantly (1.5 points, p<0.0001) immediately following the VR-D session and this change 
remained significant at 15 (0.8 points, p=0.0008) and 30 minutes (0.33 points, p=0.0001) 
following session completion. We found only minimal associations of VR-D with anxiety. 
Anxiety decreased from baseline by about 1 point immediately following the session (p<0.0001) 
and remained lower at 15 minutes (0.4 points, p=0.0014) but was no longer significant at 30 
minutes. Levels of pain catastrophizing and anxiety sensitivity were not associated with changes 
in pain and anxiety. No patients experienced adverse effects related to VR-D. Small, transient 
changes in pain and anxiety were associated with a single, 10-minute postoperative VR-D 
session. These results informed our decision to explore integration of a mind-body therapy with 
VR using a commercially available VR application. 
 
Reduction of pain and anxiety with VR-BF. In a follow-up study, patients (n=51) were 
recruited from the Acute Pain Service over 8 months (Table 1) using the same eligibility criteria 
used in the VR-D pilot study. The same approach was used as 
described above but instead of receiving a single, 10-minute VR-D 
session, patients underwent a single, 10-minute session using 
Mindful Aurora, an application that engages patients in guided 
relaxation and slow breathing. Moderate changes in pain intensity 
and pain unpleasantness and small changes in anxiety were found to 
be associated with the VR-BF session (Figure 2). Pain intensity 
decreased by about 1 point immediately (p=0.002) and 30 minutes 
(p= 0.028) following VR-BF but was not significant at 15 minutes. 
Pain unpleasantness decreased by about 1.5 points immediately 
(p=0.001), 1.1 points at 15 (p=0.025), and 2 points at 30 minutes 
(p=0.001) following VR-BF. Anxiety decreased by about 0.9 points 
immediately following VR-BF (p=0.008); changes were not 
significant at 15 or 30 minutes. Anxiety sensitivity was associated 
with greater reductions in pain intensity (Beta (SE) = -0.06 (0.03), 
p=0.0426) and pain unpleasantness (Beta (SE) = -0.09 (0.04), 
p=0.0111). Pain catastrophizing was not associated with changes in 
outcomes. No patients experienced adverse effects related to VR-BF. 
Small, transient changes in pain and anxiety were associated with a 
single postoperative VR-BF session. These results highlighted the 
need for preoperative education and training and multiple sessions 
after surgery to likely produce greater and more sustained 
reductions in pain.20,78,112 
 
Patient and family satisfaction. Qualitative data from our pilot 
studies indicated high levels of patient and family satisfaction. Survey data showed 94% of 
patients in the VR-D pilot and 96% of patients in the VR-BF pilot would “recommend friends or 
family to try VR during their visits.” Although the survey data clearly expressed the 
overwhelming positive attitude that patients had toward VR, it was unable to capture the 
magnitude of patient engagement and satisfaction best told through patient experiences. An 
Figure 2. Changes in           
pain following VR-BF. 
Figure provided for 
graphical purposes only. 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 7 of 25 
HRP-503  v.12.10.18 
adolescent male completely bed-ridden due to abdominal pain was able to sit up for the first time 
while using VR in our study. Because he felt that VR was the only intervention to help his pain, 
his family purchased a VR headset for use during his rehabilitation. Acceptance and appreciation 
of VR treatment by families has been near universal. According to survey data of parents of 
enrolled patients, 95% of parents from the VR-D and 100% of parents from the VR-BF pilots 
would recommend VR to friends or family. Parents consistently exhibited tangible changes in 
emotion and disposition when watching their child use VR. Fatigue and stress were suddenly 
replaced by relief and excitement. In addition to enthusiastic patient and family feedback, 
surgeons have also been highly engaged, with one expressing that “this innovative therapy will 
help transform how we deliver postoperative care at our institution.” Another, while initially 
skeptical, received so much positive feedback from his patients enrolled in our studies that he has 
engaged us to apply VR to patients in one of his NIH-funded trials. These anecdotal reports of 
improvements in pain, mood, and positive reports from patients, families, and providers show 
high acceptance of VR therapy. This level of engagement will be crucial for integration of VR-BF 
into postoperative pain management. 
 
4.0 
Study Endpoints 
Primary endpoint: Successful accrual of patients and completion of study  
 
Secondary endpoints: Refinement of VR-BF platform; protocol for preoperative education 
training in and postoperative delivery of VR-BF; feasibility and acceptability data for clinical 
efficacy trial design; preliminary assessment of efficacy trial outcomes. 
 
Safety endpoints: NA 
 
5.0 
Study Intervention/Investigational Agent 
Description: The VR headsets (Oculus/Meta Quest) used in this study are minimal risk 
devices, and because they are considered a relaxation device by the FDA, they are not 
regulated. The Oculus/Meta Quest have been used in prior studies without any reported 
adverse events (CCHMC IRBs #2019-1090, 2020-0258, 2020-0612). FOREVR VR is a 
device developed by the research team approved for research use by the Equipment and 
Standards Committee at Cincinnati Children’s Hospital. It is a noninvasive device that 
measures respiratory rate (via chest movement) and heart rate using an ear clip. This 
device also bears minimal risk. It has also now been approved for clinical use at CCHMC 
by this same committee. 
 
Back-Up Intervention: Should there be technical challenges with FOREVR VR, we will use 
HeartMath Inner Balance as a back-up means to collect heart rate and use data 
(www.heartmath.com), a commercially available biofeedback device. HeartMath Inner Balance is 
also considered a non-invasive device and uses an ear clip to collect heart rate data (analogous to 
FOREVR VR). There is minimal risk with the use of this device.  
Drug/Device Handling: All equipment will be kept in a secured area in a locked 
cabinet/office to be used only on subjects by authorized study team members. 
 
6.0 
Procedures Involved* 
Table 2 (below) summarizes the measures and goals of this proposal.  
 
Overall experimental design. We hypothesize that the use of VR-BF in children undergoing 
surgery resulting in moderate to severe pain will be feasible and acceptable. Findings from this 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 8 of 25 
HRP-503  v.12.10.18 
pilot trial will inform design of a large-scale efficacy trial of VR-BF versus active control in this 
patient population. The goals of this study are to define the approaches for effective training in 
and delivery of VR-BF and to conduct a pilot clinical trial to assess the feasibility and 
acceptability of VR-BF in managing moderate to severe postoperative pain in children and  
adolescents. This pilot 
study will be conducted in 
two phases: Phase 1 (Aim 
1) will refine our VR-BF 
intervention allowing us 
to create a treatment 
protocol for VR-BF. 
Phase 2 (Aim 2) will 
conduct a pilot clinical 
trial assessing feasibility 
and acceptability of the 
intervention. Phase 2 will 
inform development of a 
manual of procedures for 
efficacy trial design and 
provide key pilot data for 
future extramural grant 
applications.  
 
Study population. Subjects will be recruited when scheduled for surgery at Nationwide 
Children’s Hospital. We will coordinate recruitment efforts with surgeons who perform surgeries 
that require pain management by the Acute Pain Service. We will screen patient lists provided by 
the surgical schedulers as well as operating room schedules to identify potentially eligible 
patients prior to their scheduled surgery. Messages assessing interest in the study will be sent 
through MyChart. We anticipate recruiting 1 patient per week. We are confident that we can 
successfully recruit and enroll our full cohort of up to 102 patients: up to 32 for Aim 1 (minimum 
12 patients) and 70 for Aim 2.  
 
Blinding. Although patients will not be blinded to the intervention they receive, patients and 
families will be blinded with respect to the study arms. Therefore, the consent will describe the 
study as assessing technology-based interventions for the management of pain without specific 
detail about VR-BF (FOREVR VR) or Manage My Pain or indicate the use of any device, such as 
a headset. Once assigned to a group, patients will receive a handout describing the intervention 
with instructions and information about what participation entails. We will also blind data 
collection by using a study number for each patient and will not indicate in which arm the patient 
is enrolled in data collection forms. The biostatistician will be blinded to the patient groups 
during analysis.  
 
Study Materials 
Self-reported measures. Patients will be asked to complete a survey at the end of study 
participation as well as participate in a semi-structured interview. Parents will also be asked to 
complete a survey. The questionnaires will be completed through the Research Electronic Data 
Capture (REDCap) database.  
 
 
 
Measures 
Goal(s) 
Aim 1 
(Phase 1) 
a 
Questionnaires, semi-structured interviews, use of 
VR-BF, sensitivity to change of physiological 
parameters (HR and respiratory rate) 
Refined VR-BF 
treatment protocol 
 
VR-BF dose 
 
b 
Questionnaires, semi-structured interviews, use of 
VR-BF, sensitivity to change of physiological 
parameters (HR and respiratory rate) 
Aim 2 
(Phase 2) 
a 
Rates of recruitment, enrollment and randomization, 
retention, adherence; qualitative data assessed with 
questionnaires and semi-structured interviews; pain, 
anxiety, and opioid consumption; physiological 
parameter achievement (HR and respiratory rate) 
Feasibility and 
acceptability of VR-
BF and active control 
in perioperative setting 
 
VR-BF dose 
finalization 
 
Pilot data for R01 
application 
b 
Treatment/study burden, satisfaction, treatment 
credibility, and tolerability; qualitative data assessed 
with questionnaires and semi-structured interviews; 
physiological parameter achievement (HR and 
respiratory rate) 
Table 2. Proposed outcome measures and goals for Aims 1 and 2. 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 9 of 25 
HRP-503  v.12.10.18 
VR headset. Participants will use the Oculus/Meta Quest VR headset with the FOREVR VR 
device. When necessary, we will use the software supplied by Invincikids (Mindful Aurora 
application) with the Oculus/Meta Quest. 
 
The Oculus/Meta Quest VR devices are non-invasive, relaxation devices that are commercially 
and widely available to deliver mobile (untethered) VR content to the patient; they are not FDA 
regulated. Both devices are all-in-one headsets, so no additional hardware is required to deliver 
the VR experience. These devices have audio capabilities built into the headset to deliver 
instructions and application sounds, creating an immersive experience. We have used these 
devices in multiple IRBs since 2018 without any adverse events. Each VR headset will be cleaned 
with an alcohol or peroxide wipe according to infection control standards following use of the 
device by the patient as well as prior to use for each patient and may undergo further cleaning 
with UV light using the Cleanbox (https://cleanboxtech.com/).  
 
VR session. All participants will receive a device tutorial at the start of the study which will entail 
teaching them how to use the device and introducing them to the VR-BF software. They will be 
taught how to sync their breathing with the application. Patients will be instructed to remove the 
device should any discomfort or side effects occur, such as motion sickness, dizziness, or nausea.  
 
FOREVR VR. FOREVR VR is the result of the collaboration between our research team, 
engineers at the Digital Experience (DX) Center at Cincinnati Children’s Hospital, and 
programmers at House of Moves, an animation and motion capture studio in Los Angeles, 
California. FOREVR VR integrates real-time patient physiological data into a gamified 
environment using a chest strap (to monitor respiration) and an ear clip (adapted from HeartMath, 
see below) to measure heart rate. This technique is effective in reducing respiratory rate, and 
consequently, increasing heartrate variability.20,97 This increased heartrate variability increases 
vagal tone, resulting in activation of the parasympathetic response and decreased pain.97 
 
VR-BF content. We currently have two game options for use with the FOREVR VR device. The 
first is a 360-video shot in Eden Park (a public park in Cincinnati, OH) that starts out as a stand-
still, black and white image that adds color and eventually motion as the participant achieves 
target heart rate and respiratory rate targets. The second is a blooming flower scene that starts 
with a clean, blank scene that allows the participant to have a flower appear and fully bloom as 
he/she achieves target physiological parameters.  
 
We are currently finalizing the Mysterious Island game with House of Moves which we plan on 
using for the study once it becomes available. In this game, participants will be transported to a 
beautiful tropical island in which the participant will use breath to explore the island. As the 
patient breathes in, they will make a small rise in the VR world upwards and breathing out will 
propel forward movement. The motions are small and gentle to minimize the risk of motion 
sickness. The entire VR space syncs with the patient’s breathing. During the course of the 
experience, the participant will travel through a sunny island full of palm trees, caves, and 
tropical flowers. The user will move towards a beach to watch the sunset. The user will also 
encounter several tropical animals and birds. The VR world will combine a total of 3 locations: a 
tropical island and trail going to the entrance of a cave, the cave, and a beach. On the tropical 
path, the user will encounter a waterfall, up to 5 different tropical birds, and 2 different animals 
(hippo and monkey). This experience in its entirety will take up to 10 minutes.   
 
Back-Up Technology. This is the first study to use FOREVR VR. Although we anticipate success 
with its use, we appreciate the difficulties of using any new technology. We therefore have a 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 10 of 25 
HRP-503  v.12.10.18 
back-up plan in place using existing technology. Should it be necessary, we will use the 
Oculus/Meta Quest with the Mindful Aurora application and monitor heart rate/heart rate 
variability with the commercially available HeartMath Inner Balance device 
(www.heartmath.com). HeartMath is a program that is used clinically at Cincinnati Children’s 
Hospital to teach biofeedback and that can document a patient’s use of the application and heart 
rate/heart rate variability. The Inner Balance device integrates directly with a participant’s smart 
phone device. HeartMath products are currently used in over 500 institutions. From a research 
perspective, they have been used in over 11,500 subjects resulting in over 400 peer-reviewed 
publications. Analogous to FOREVR VR, it uses an ear clip to measure heart rate. It stores 
information about use and performance in an application that is accessible to the research team. 
Dr. Williams, one of the co-investigators, is an expert in the use of HeartMath for biofeedback.  
 
In this scenario, the Mindful Aurora application would be used to deliver the VR content. This 
application acts as an escape for patients as well as a tool to help them learn slow breathing and 
relaxation techniques. It transports patients to an alpine meadow. With the help of a 10-minute 
relaxation narrative, study participants will observe the world transition from day to night while 
focusing on paced breathing. The goal of the application is to have participants mirror the rate of 
their breathing with the virtual world around them, which includes changes in floating butterflies 
and swaying trees to assist in the pacing of their breathing. This technique is effective in reducing 
respiratory rate, and consequently, increasing heartrate variability.20,97 This increased heartrate 
variability increases vagal tone, resulting in activation of the parasympathetic response and 
decreased pain.97 This is the same application that has been used to deliver VR-BF content in 
CCHMC IRB #2018-2892, 2019-1090, and 2020-0258. 
 
Manage My Pain. Control patients in Aim 2 will use the Manage My Pain application 
analogously to VR-BF per the protocol developed in Phase 1. This commercially available 
application is designed to assist patients with recognizing and reflecting on their pain and is 
highly engaging. It is available for iPhone, Android, and laptop download and is approved for 
children 12 years of age and older. In an assessment of commercially available pain applications, 
Manage My Pain was found to be appropriate for adolescents and had a high engagement score 
(4.2/5) as well as an excellent functionality rating (4.5/5).114 While it scored high overall 
(application quality score 4.06/5), it lacks the immersion and specific instruction in behavior 
change techniques,114 which are key features of VR-BF. 
 
Device Tracking. Participants in Phase 1 as well as those randomized to the VR group in Aim 2 
will receive a VR headset and FOREVR VR device to take home. During the first visit, these 
patients and families will be told that they will be given temporary possession of this equipment. 
To help increase our ability to retrieve these devices, they will be asked to sign a Device 
Agreement form. We will plan to collect the devices in the first postoperative clinic visit. If this is 
not possible, we will provide patients with a prepaid label and box to mail the device back to us. 
Other arrangements may be made with families for device retrieval as necessary. 
 
Study Procedures 
Aim 1: We will accomplish Aim 1 using an iterative study design eliciting data through 
questionnaires and semi-structured interviews of pediatric patients scheduled to undergo surgery 
anticipated to have moderate to severe pain with a length of stay at least one night in the hospital 
post-op. We will use a grounded theory114,115 and thematic analysis116 approach to study design, 
data collection, and analysis.  
 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 11 of 25 
HRP-503  v.12.10.18 
Research Design. We will recruit up to 32 patients (minimum 12 patients, 12-18 years) 
scheduled for surgery anticipated to cause moderate to severe pain with admission of at least one 
night in 
the 
hospital 
post-op to 
participate 
in Aim 1 
(Figure 2). 
Purposive 
sampling will be used to select a representative patient group according to age, sex, and race. We 
anticipate recruiting about 1 patient per week. Patients will be identified when scheduled for 
surgery. They will receive scripted instruction on the Oculus/Meta Quest and a tutorial on the 
biofeedback application. Once device and content education are complete, patients will receive 
manual-based training on the benefits of HRV BF.56 They will be given the appropriate 
equipment and instructed to complete an independent daily, 10-minute session (based on the 
standard duration of a BF session) and record each session in a log. Patients will bring the 
equipment to the hospital on the day of surgery for continuation into Aim 1b. After surgery, 
patients will have free use of VR-BF. They will be instructed to undergo, at minimum, one daily, 
10-minute session. They will also be instructed to freely use VR-BF, particularly when in pain. 
They will use a log to record their VR-BF usage (date, time, and duration). Patients will be visited 
daily, or more or less frequently as applicable/needed, to assist with log completion and any 
issues. On the day of discharge, a study team member will conduct a detailed, semi-structured 
interview. Patients may take the VR-BF device home for up to two weeks for home pain 
management; a similar log will be used to document home use. We will enroll 4 patients at a time 
and analyze data to refine the protocol in an iterative fashion; this process will be repeated until 
12 patients are enrolled. If further data is required for protocol refinement, we will continue 
recruiting patients in groups of 4 as necessary until a maximum number of 32 patients is reached.  
 
Study measures. Qualitative data will be collected using questionnaires and a semi-structured 
interview to collect feedback on the FOREVR VR platform content and usability, preoperative 
VR-BF education and training, postoperative application of VR-BF, and perceived efficacy. 
Review of patient daily use obtained from FOREVR VR will provide quantitative data about 
frequency and duration of VR-BF use. As mentioned below, we will assess sensitivity to change 
of physiological parameters (HRV, respiratory rate) to different frequencies and durations of VR-
BF use (dose).117 This data will assist us in determining an appropriate dose (frequency and 
duration) of VR-BF for training and postoperative pain management to be trialed in Phase 2. 
Iterative refinements to the VR-BF treatment protocol will be made throughout Aim 1 based on 
this data. Refinements will be documented, tracked, and applied by the study team. 
 
Aim 2: We will conduct a pilot clinical trial to assess the feasibility and acceptability of the VR-
BF protocol defined in Aim 1. Feasibility will be assessed by rates of recruitment, enrollment and 
randomization, retention, and adherence. Acceptability will be assessed by treatment/study 
burden, satisfaction, treatment credibility, and intervention tolerability. Qualitative data will also 
be used to assess feasibility and acceptability.  
 
Patient Groups. Seventy patients with the same inclusion/exclusion criteria described in Aim 1 
will be randomized to 1 of 2 groups in a 1:1 ratio: VR-BF or attention control condition using a 
web-based application (www.randomizer.org). The randomization scheme will be generated prior 
to the start of the study and patients will be randomized based on subject number. We will use the 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 12 of 25 
HRP-503  v.12.10.18 
protocol generated in Phase 1 to apply either the VR-BF or control condition. Control patients 
will use the Manage My Pain application analogously to VR-BF per the protocol developed in 
Phase 1. Like the VR-BF group, patients will receive scripted instruction on the benefits of mind-
body therapy. We will recruit a total of 70 patients to participate, with 35 in each group. Both 
patient groups will receive a handout detailing the intervention and what they can expect with 
participation in the study.  
 
Research Design (Figure 3). Eligibility, recruitment, and study procedures will follow those 
described in Aim 1 but VR-BF or the control condition will be applied both pre- and 
postoperatively according to the 
protocol refined in Phase 1. 
Figure 3 summarizes Aim 2 
design. During the preoperative 
visit with our study team, 
patients randomized to the 
control group will download the 
Manage My Pain application 
onto their device. If patients do 
not have a personal device, we will ask a parent to download the program onto his or her phone or 
computer. We will provide explicit instructions on how to use the application and what features 
should be used. Patients will also be instructed on how to create a daily report documenting each 
day’s use of the application prior to surgery. These daily reports will be returned to our study 
team. Like the VR-BF group, patients will receive scripted instruction on the benefits of mind 
body therapy, will be instructed to use the application for at least 10-minutes per day for seven 
days prior to surgery, and will be asked to complete a daily report using the application each day. 
On the day of surgery, a study team member will visit each participant to document possession of 
the FOREVR VR platform (intervention group), to collect reports, and to any answer questions.  
 
After surgery, as in Aim 1, a trained CRC will visit patients daily or as needed while hospitalized. 
Control group patients will complete a daily application-generated usage report (date, time, 
duration); VR-BF patients will have this information, along with HRV and respiratory rate data, 
obtained from the device. To help determine what outcomes may be impacted by VR-BF for 
future trial development, patients will also be asked to document pain and anxiety scores before 
and after each VR-BF or application session using the NRS.110,111 Patients will self-report and 
document these scores before each session and then immediately, 15 minutes, and 30 minutes 
after session completion. All pain scores and opioid consumption (in morphine equivalents 
mg/kg/day) will be collected from EPIC, the electronic medical record, for each 24-hour period 
during study enrollment; anxiety scores are not documented by the nursing staff so only self-
reported scores will be used. Documented pain scores will also help finalize the “dose” of VR-BF 
to be used in the efficacy trial as we will assess for correlation, if any, between pain score and use 
of VR-BF. At the final study visit prior to discharge, patients will answer a questionnaire and 
engage in a semi-structured interview soliciting qualitative feedback about their experience with 
the intervention or control to finalize the study protocol for the clinical efficacy trial. Participants 
will be given the option to take the VR-BF platform home or continue using the Manage My Pain 
application for up to two weeks after discharge. If this option is selected, patients will complete a 
daily log/report documenting use, pain scores, and opioid consumption. During the first 
postoperative clinic visit, VR-BF and reports/logs will be collected and questions about home use 
will be asked, answered, and recorded. Parents will also be asked to complete a survey about their 
experience and opinions. If patients cannot be met during the first postoperative clinic visits, 
other arrangements will be made to collect the information and equipment. 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 13 of 25 
HRP-503  v.12.10.18 
 
Data Collection (Table 3). Feasibility. Recruitment: The number of patients screened per month 
will be recorded and assessed for eligibility; reasons for ineligibility will be recorded. If 80% of 
patients do not meet criteria, we will adjust criteria as necessary. Enrollment and randomization: 
Enrollment and randomization will be defined as agreeing to participate in the study and being 
willing to be randomized. We will record the number of eligible patients approached and enrolled 
each month. We will collect reasons for refusal to enroll, including unwillingness to be 
randomized. If rates are not maintained at 80%, we will adjust strategies accordingly. Retention: 
We will define retention as the number of patients who complete the study by participation in the 
last study visit for both arms. We will collect reasons for dropout. If > 80% retention is not 
maintained, we will evaluate reasons for dropout. Adherence: We will define adherence to 
preoperative training as completion of the education and training session with the study team and 
completion of > 5/7 daily sessions. Adherence to postoperative VR-BF/app use will be defined as 
completion of > 5/7 daily sessions. Our target will be > 80% completion. We will collect reasons 
for failure. 
Questionnaires 
and the semi-
structured 
interview will 
also assess 
feasibility using 
measures based 
in the 
literature.119 
Acceptability. 
Treatment/Study 
Burden: Burden 
will be  
assessed by 
collecting data 
on daily log 
completion, 
data from 
questionnaires, 
and 
participation in 
the interview. 
We will collect 
reasons for drop 
out to better 
understand 
treatment and 
study burden. 
We anticipate > 75% of patients will complete all study measures, with completion of daily logs 
defined as completion of > 5/7 daily logs. Satisfaction: Satisfaction will be assessed by 
questionnaire and the semi-structured interview. Development of these qualitative assessments 
are based on reported measures of acceptability.102,119 Treatment credibility: We will define 
treatment credibility as patient perception of treatment efficacy as measured by survey and 
interview. Tolerability: We will record the number of adverse effects (minor, moderate/severe)  
 
Measures 
Definition 
Benchmarks 
Additional 
Data 
Feasibility  
Recruitment 
Number of patients 
screened per month 
> 80% will meet 
eligibility criteria 
Reasons for not 
meeting criteria 
Enrollment and 
randomization 
Number of patients 
approached who agree 
to enroll in the study 
and be randomized to a 
treatment arm 
> 80% of those 
approached will agree 
to enroll and be 
randomized 
 
Reasons for 
refusal, including 
unwillingness to 
be randomized  
Retention  
Number of participants 
who complete the study 
as defined by 
participation in the last 
study visit 
> 80% retention 
Reasons for 
dropout 
Adherence 
Treatment-specific 
adherence 
> 80% will complete 
> 1 session per day 
for > 5/7 days (preop) 
and > 1 session per 
day (postop) 
Reasons for 
failure 
 
 
 
 
 
Acceptability  
Burden 
Percent completion of 
daily logs/reports, 
percent completion of 
questionnaires and 
interview 
> 80% completion of 
all study measures 
Reasons for 
failures 
Satisfaction 
Patient/parent 
satisfaction  
NA 
Questionnaires, 
semi-structured 
interview 
Credibility 
Perception of efficacy 
NA 
Questionnaires, 
semi-structured 
interview 
Tolerability 
Number and percent of 
patients experiencing 
AEs 
< 1% will experience 
a serious AE 
Reasons for not 
tolerating 
therapy, AEs 
Table 3. Feasibility and acceptability outcome measures and benchmarks. 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 14 of 25 
HRP-503  v.12.10.18 
from therapy. We anticipate a very low rate (<1%) of adverse events. We will collect qualitative 
acceptability data using questionnaires and the semi-structured interview using measures based in 
the literature.102,119   
 
Additional Data Collection   
The following data may be collected in the CRF: (a) type and duration of anesthesia and surgery 
where applicable; (b) anxiety and pain scores (both intensity and unpleasantness as well as pain 
medications used to treat the patient (including doses and number of rescues); (c) satisfaction 
with VR device/comments; (d) desire for study team to return; (e) any critical or adverse events. 
Survey data will be captured directly into REDCap or paper forms.  
We will also collect descriptive data from the health record for each patient, such as age, sex, 
race, ethnicity, ASA status, type of surgery, diagnosis at surgery, underlying medical conditions, 
medications taken prior to surgery, and treatment history. We will record VR experience, 
presentation order, and any use of corrective lenses. Anxiety and pain will be collected with 
numerical rating scale (NRS) prior to and after the VR intervention for patients in all 3 cohorts. 
Additional outcome measures will be pulled from EPIC regarding narcotic/medication 
consumption during hospitalization, all pain assessments during the hospitalization, and length of 
stay. We will collect all heart rate, respiratory rate, and FOREVR VR usage from the FOREVR 
VR device (or HeartMath if necessary).  
 
7.0 
Data and Specimen Banking* 
NA 
 
8.0 
Sharing of Results with Subjects* 
NA 
 
9.0 
Study Timelines* 
Each individual subject will have a participation period of no more than 3 months depending on 
timing of initial preoperative visit. Patients will be approached before surgery, have a study visit 
in person or virtual before surgery, and participate in practice sessions for 1 week prior to 
surgery. They will participate in the study during their hospitalization and may opt to continue 
participation for up to 2 weeks following hospital discharge. 
 
 
We anticipate a total of up to 3 years to fully enroll all study subjects. 
 
 
We anticipate completion of primary analysis by the end of year 3 (12/24). 
 
10.0 Inclusion and Exclusion Criteria* 
Screening: Surgery patient lists and the operating room schedules will be 
screened for eligible patients based upon basic eligibility criteria such as age and 
surgical procedure. 
 
Inclusion/Exclusion: 
Inclusion criteria. Patients will be eligible if they are: 
• 
Between the ages of 12 and 18 years, inclusive 
• 
Able to read, understand, and speak English 
• 
Scheduled to undergo surgery at NCH anticipated to cause moderate to severe pain with 
staying at least 1 night in the hospital post-op. 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 15 of 25 
HRP-503  v.12.10.18 
• 
Require postoperative pain management by the Acute Pain Service 
• 
Own or have access to a mobile device or computer for study participation 
 
Exclusion criteria. Patients will be ineligible if they: 
• 
Are less than 12 years of age or older than 18 years of age 
• 
Are non-English speaking 
• 
Have a history of significant developmental delay, psychiatric conditions associated with 
hallucinations or delusions, or significant neurological disease, especially epilepsy/seizure 
disorder 
• 
Have a history of significant motion sickness 
• 
Have a history of chronic pain 
• 
Are chronically using opioids or benzodiazepines for the management of pain 
• 
Are actively experiencing nausea or vomiting 
• 
Have any conditions that preclude their ability to use the virtual reality (VR) headset, such as 
craniofacial abnormalities or surgeries of the head and neck 
• 
Previous participation in this study 
Children (ages 12-18 years) will be included in this study. No other vulnerable 
populations will be included. 
 
11.0 Vulnerable Populations* 
We will include children, and will not include pregnant women, and prisoners as they are 
not part of our usual patient population. 
 
This study presents no more than minimal risk as it only requires use of VR-BF or 
computer application and completing questionnaires and interviews. 
 
Study staff will discuss the study with the parents and children together, review the 
consent form with them, answer any questions, and obtain parental permission and assent 
from those children able to provide it. 
 
12.0 Local Number of Subjects 
Total number of subjects to be accrued locally: up to 102 
We anticipate a > 80% recruitment and retention rate 
 
 
13.0 Recruitment Methods 
Patient Recruitment. Participants who are being managed by the Acute Postoperative Pain 
Service for the management of moderate to severe postoperative pain will be recruited 
continuously throughout the course of the study until enrollment numbers for each cohort are met.  
Once the family agrees that this is a study that they want to hear more about, a team member will 
describe the study procedures and verify eligibility criteria.  Specifically, a team member will 
explain the study in greater detail and invite them to participate in the study. If the family is 
interested in proceeding to the consenting phase of the study, a team member will review the 
consent and assent in detail and cover all required elements of consent. The team member will 
answer any questions and verify understanding of the consent by asking questions about the study 
to the parent and child. The research coordinator will give the family adequate time to review the 
consent/assent form in full on their own. It will be made clear to the family that participation is 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 16 of 25 
HRP-503  v.12.10.18 
completely voluntary, non-participation will not result in any consequences to them, and they are 
free to withdraw at any time for any reason. 
 
Consenting/Assenting Procedures and Considerations. Due to needing subjects to begin study 
participation prior to surgery, we are requesting permission to consent by phone. Consent for 
participation will be done via an e-consent platform conducted through an application (REDCap 
or another  NCH supported application or with a paper informed consent form (ICF) provided 
ahead of time. A member of the study team will arrange for a time to discuss the study with the 
parent/LAR over the phone and answer any questions they may have about study participation. 
Informed consent will be documented by the person obtaining consent and parents/LAR will be 
asked to sign via the e-consent platform or if using the paper ICF, to bring the original version of 
the ICF with them to the training appointment.  (see Section 12 for further detail). 
Subject/parent/guardian identity will be verified with documentation in EPIC. 
 
Requirements. A signed consent form will be obtained from the participant. For participants who 
cannot consent for themselves, such as those below the legal age, a parent, legal guardian, or 
person with power of attorney, must sign the consent form; additionally, the participant's assent 
must also be obtained if he or she is able to understand the nature, significance, and risks/benefits 
associated with 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 of the signed consent form will 
be given to the participant, parent, or legal guardian, and this fact will be documented in the 
participant’s record. 
 
Procedure. The approved, HIPAA compliant informed consent/assent will be provided to the 
study participant and the parents for review. The consent will be completed through the Research 
Electronic Data Capture (REDCap) database or on paper forms (if eConsent is unavailable at the 
time of consent). After allowing adequate time for review, the participant and parents will have 
the opportunity to ask questions and receive answers. When all questions have been answered, the 
consent and/or assent will be signed, and a signed copy will be provided to the participant and 
parents. This will all be conducted before any study measures interventions are undertaken. 
 
Phone Consent. Due to needing subjects to begin study participation prior to surgery, we are 
requesting permission to consent by phone in order to have time to have subjects be trained on the 
technology prior to the scheduled surgery. Potential subjects may schedule surgery over the 
phone or at an in-person visit however subjects who are in person may not be available for 
approach due time constraints or already being overwhelmed with information regarding the 
surgery.    
 
Documentation of Ineligibility. Screen failures will be documented on the source worksheets with 
the supporting data accompanying the eligibility screening form. Documentation of ineligibility 
or non-participation for each consented participant will be maintained in an electronic database 
(e.g., REDCap). Reports detailing the reasons for screen-failure and non-participation of eligible 
participants will reviewed by the study team to determine if the exclusion criteria require revision 
in order to make the study accessible to families and study participants. 
 
Payment. Patients may receive a stipend for participation, not to exceed a total of $100 per 
patient. For time and inconvenience, the subject will receive up to $100 - $50 for completing all 
pre-surgery activities and an additional $50 when the device is returned. There is no difference in 
how subjects will be compensated based on the phase of the study they are in. 
 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 17 of 25 
HRP-503  v.12.10.18 
Subjects will be issued a debit card specially designed for clinical research. When a study visit is 
completed, funds will be approved and automatically loaded onto the card. 
 
14.0 Withdrawal of Subjects* 
We do not anticipate any withdrawal of subjects or early termination. 
 
15.0 Risks to Subjects* 
There are minimal physical risks to participants and enrollment in this study will not alter their 
management. All patients will receive pain management per the Acute Pain Service during the 
duration of the study.  
 
Clinical Care. Enrolled patients will receive the same care and attention in the postoperative 
period or during their hospital stay as those non-enrolled patients. Patients will be given the 
opportunity to end participation in the study at any time.  
 
VR Headset. VR headsets used in this study are minimal risk devices, and because they are 
considered a relaxation device by the FDA, they are not regulated. Risks specific to this research 
study are minimal or absent with the greatest risk being motion sickness while the headset is in 
place113 and a theoretical risk of inducing seizures (0.025% in pediatric data supplied by a similar 
Samsung device). Should motion sickness occur, the participant will be instructed to remove the 
device to ensure resolution of symptoms; we will exclude patients with a history of seizure 
disorder or other relevant neurological conditions. Other adverse events will be defined using 
standard criteria. The researchers shall monitor the patient while the device is applied. Serious 
adverse events, although unanticipated, will be reported using routine avenues. The Starlight 
Xperience device was used in our pilot study (CCHMC IRB #2018-2892) without any 
documentation of adverse effects. We have since purchased new headsets, the Oculus Quest and 
Oculus Quest 2, which have been used in prior studies without any reported adverse events 
(CCHMC IRBs #2019-1090, 2020-0258, 2020-0612). We will continue updating to newer 
versions of the Oculus/Meta Quest as they become available when new equipment is required. 
 
FOREVR VR. This device has been approved for both research and clinical use by the 
Equipment and Standards Committee at Cincinnati Children’s Hospital. It is a noninvasive device 
to measure respiratory rate (via chest movement) and heart rate using an ear clip. This device is 
also considered a minimal risk device. This is the first study to use FOREVR VR. 
 
HeartMath Inner Balance. If FOREVR VR is unable to be used, we will use HeartMath Inner 
Balance as a back-up means to collect heart rate and use data (www.heartmath.com), a 
commercially available biofeedback device. HeartMath Inner Balance is also considered a non-
invasive device and uses an ear clip (analogous to FOREVR VR) to collect heart rate data. There 
is minimal risk with the use of this device.  
 
We do not anticipate any psychological, social, legal, or economic risks to this study. We also do 
not anticipate risk to others who are not subjects in this study. 
 
16.0 Potential Benefits to Subjects* 
Individual study participants may derive direct benefit from participation in the study as the 
addition of VR or Manage My Pain may enhance standard pain management strategies and result 
in decreased pain intensity and unpleasantness and anxiety at the time of participation in the 
study. Participants may also have a longer lasting benefits, but these are currently unexplored, 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 18 of 25 
HRP-503  v.12.10.18 
and this exploration will be part of future studies. Should VR show to be a useful tool to augment 
pain control, we hope that this technology will ultimately be offered to all pediatric patients 
coming in for surgery to assist with postoperative pain control. Participation in the study may also 
decrease medication consumption; however, this potential benefit will be assessed in subsequent 
studies using the treatment protocol developed in this proposed work. Patients may receive a 
stipend for participation, not to exceed a total of $100 per patient. 
 
17.0 Data Management* and Confidentiality 
Aim 1: 
Data analysis. Statistical analysis will be done using SAS 9.4 (Cary, NC). Demographic and 
baseline characteristics will be summarized for all patients (categorical variables: frequency and 
percent; continuous variables: mean + standard deviation (SD) or median and interquartile range 
(IQR)).  
 
Qualitative analysis. Qualitative data will be collected via questionnaires and a semi-structured 
interview (see Appendix 1 for the interview guide and Appendix 2 for the questionnaires) 
conducted by a trained CRC. The interview script creates a framework for the discussion with 
further probing based on patients’ responses to elicit a rich and informative description of their 
experiences and perceptions. Interviews will be recorded, assigned an identification number to 
anonymize content, and transcribed for coding. Each transcript will be independently reviewed by 
two trained coders and line-by-line content will be analyzed using a priori themes evaluating the 
acceptability and satisfaction with content (understanding, difficulty level, ease of use), feasibility 
of practice (both at home after preoperative training and after surgery), and perceived helpfulness 
in reducing pain and distress after surgery. Results will be analyzed and reviewed by the study 
team after each cohort of four patients has completed Aims 1a and 1b so that iterative changes 
can be made to refine the protocol (e.g., improvements to the education component, involvement 
of parents, device adjustments, recommendations for duration and frequency of use 
postoperatively, etc.) before the next group of four patients is enrolled.  
 
Quantitative analysis (dose). Data will be collected on number of daily practice (preoperative) 
and therapy (postoperative) sessions completed by each patient, duration of each session, and 
changes in HRV and respiratory rate parameters over time. We will also assess the total daily 
dose of sessions by totaling the duration of all sessions per day and assessing the mean and 
variability of the daily dose. These quantitative data together with quantitative responses from the 
questionnaires and interviews will be summarized using frequency and percent for categorical 
variables and mean + SD or median and IQR for continuous variables. For variables measured 
multiple times per participant (duration of each practice/therapy session, changes in HRV and 
respiratory rate), within- and between-subject summary measures of location and variability will 
be derived and examined. 
 
Sample size. No statistical power analysis was done to determine the sample size for Aim 1. 
Rather, sample size determination was based on our extensive pilot work and clinical experience 
with the population along with the team’s expertise in protocol refinement studies in intervention 
development.  
 
Anticipated outcomes. At the end of Phase 1, we anticipate having a refined treatment protocol 
for preoperative education and training, and postoperative application of VR-BF. This protocol 
will be piloted in Phase 2. Results from Aim 1 will provide a preliminary study protocol and 
manual of procedures for the clinical efficacy trial that will be finalized at the end of Aim 2. 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 19 of 25 
HRP-503  v.12.10.18 
 
Aim 2: 
Data analysis. Phase 2 is a single-center, randomized, two-arm, parallel-group, single blinded 
trial to assess the feasibility and acceptability of the treatment protocol designed in Aim 1. We 
will ensure study transparency, describing recruitment, enrollment, and outcomes in a 
Consolidated Standards of Reporting Trials (CONSORT) diagram106,120 and provide detailed 
descriptions of the intervention and active control. Demographic and baseline characteristics will 
be summarized for all patients and within each study group (categorical variables: frequency and 
percent; continuous variables: mean + SD or median and IQR). 
 
Quantitative analysis. We will assess measures of feasibility and acceptability for each arm.  
Feasibility. We will calculate descriptive data on 1) How many patients are screened per month; 
2) Percentage of patients meeting eligibility criteria; 3) Percentage of eligible patients 
approached, enrolled, and randomized; 4) Percentage of patients completing Phase 2; and 5) 
Percentage of patients adhering to preoperative education and postoperative application of VR-
BF as defined in the study measures. For each measure, the rates, variances, and two-sided 95% 
confidence interval (CI) will be reported. Each CI will be examined to determine if the 
hypothesized value of 80% is contained within the interval. This data will also be used to 
generate a diagram of participant flow. Because this is a feasibility study, we will not conduct 
statistical tests on the clinical outcomes collected for exploratory purposes (pain and anxiety 
ratings, opioid use). We will analyze this data using descriptive measures stratified by treatment 
arm. Acceptability. We will calculate descriptive data on 1) Treatment/study burden: number and 
percentage of patients completing all study measures; 2) Tolerability: number and percentage of 
patients experiencing AEs; and 3) Any quantitative data of satisfaction and treatment credibility 
from questionnaires and semi-structured interviews. For each of these measures, the rates, 
variances, and two-sided 95% CI will be reported. The CI for treatment/study burden will be 
examined to determine if the hypothesized value of 80% is contained within the interval. 
Qualitative treatment credibility and parent/patient satisfaction data will be assessed qualitatively 
as described below. 
 
Dosing. To finalize VR-BF dosing prior to the efficacy trial, data will be collected on the number 
of daily practice (preoperative) and therapy (postoperative) sessions completed by each patient, 
duration of each session, changes in HRV and respiratory rate, and achievement of target HRV 
and respiratory rate parameters. We will also assess the total daily dose of sessions by totaling the 
duration of all sessions per day and assessing the mean and variability of the total daily dose. 
Achievement of target physiological parameters will be assessed by calculating the percentage of 
time a patient spends within specified targets for each session. Consistency in achieving target 
HRV and respiratory rate parameters will be defined as a binary outcome (yes/no) when the target 
range is achieved >75% of the time during use (by session and by day). We will run descriptive 
statistics on duration of each session stratified by sessions achieving consistency (or not) and on 
frequency and duration of daily use by days achieving consistency (or not). Mean duration per 
session and mean duration and frequency per day in the group achieving consistency will be used 
to guide minimal dosing in the efficacy trial. Exploratory analysis. We will examine the 
association of VR-BF dose (frequency and duration of use) with the change in target 
physiological parameters to help identify the minimal dose (frequency and duration of use) 
required to reach consistency in achieving these targets. We will also examine the correlation 
between pain score reduction and VR-BF use (frequency and duration). We will calculate mean 
changes in pain score before and after VR-BF and mean frequency and duration of VR-BF use for 
each patient. We will visualize any correlation using a scatter or box plot and quantify the 
correlation using Spearman or Pearson correlation coefficients between two continuous variables 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 20 of 25 
HRP-503  v.12.10.18 
and two sample t-tests or Wilcoxon rank-sum tests, as appropriate, between a continuous and 
categorical variable. Regression on changes in pain score will be used to examine linear or 
nonlinear correlations between pain reduction and VR-BF use. The same analysis will be repeated 
for opioid use (mg/kg/day) and patient-reported anxiety scores. 
 
Qualitative analysis. From the questionnaires and semi-structured interviews, we will compile 
data on satisfaction, credibility, and tolerability as well as additional feasibility data. This 
qualitative data will be analyzed in the same way as in Aim 1. 
 
Sample size. Seventy subjects will be enrolled and randomized to one of two study arms: 
intervention and active control. As this is a pilot feasibility and acceptability study, no 
confirmatory hypothesis testing will be done. Our sample size is based on estimation of two-sided 
CIs for one proportion with exact formula of the binomial probabilities. To estimate a 95% CI 
with targeted width of 0.22 and an assumed proportion of 80%, we will need a sample size of 70 
(35 per group), resulting in a total of 56 patients (28 per group) included in the analysis after 80% 
retention. 
 
Anticipated outcomes. We anticipate creating a final VR-BF study manual that will define study 
procedures for an efficacy trial and provide key pilot data for future grant applications. By the 
end of Phase 2, we expect to have 1) A defined patient population with clearly delineated 
eligibility criteria; 2) A clearly delineated preoperative education and training protocol for VR-
BF/active control; 3) A dosing strategy (frequency, duration) for postoperative administration of 
VR-BF/active control; 4) Feasibility and acceptability data for VR-BF/active control; and 5) A 
preliminary assessment of key outcome measures (pain, anxiety, opioid consumption) to be 
evaluated in the efficacy trial. 
 
Data Safety: 
Data confidentiality will be maintained by data being stored in a password protected computer 
and any hard copies of patient information stored in a locked office. Data will be transmitted to a 
password-protected Nationwide Children’s computer for further analysis. Data held in REDCap is 
deemed secure. All individuals using and interacting with this data will be trained appropriately 
and a member of the study team. Any data transmission will occur via secure emails (not 
personal). Proper agreements have been executed to cover the sharing of de-identified data from 
REDCap with a statistician at CCHMC. Data will be de-identified by selecting the option to 
export data directly from REDCap with all known identifier fields (date, name, address, MRN, 
etc.) removed. The exported data set will then be shared with CCHMC. Data will be stored for the 
duration of the study and analysis/presentation up to the time period specified by the IRB.  
 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
Although this is considered a minimal risk study, we have created a Data Safety Monitoring Plan 
that has been approved by the NIH. It will be uploaded separately. 
 
19.0 Provisions to Protect the Privacy Interests of Subjects 
Subject information will not be given to any other investigators. Subjects and their 
information will be closely monitored and guarded by study staff; there will be limited 
access to patients and their information by trained study staff; and subject information will 
only be shared and discussed between study staff specific to this study.  
 
20.0 Compensation for Research-Related Injury 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 21 of 25 
HRP-503  v.12.10.18 
NA 
 
 
21.0 Economic Burden to Subjects 
Some study communications such as appointment reminders may be done through text 
messaging and the subject would be responsible for any message and data rates may 
apply. Subjects will be given the option to communicate via email or phone if  they could 
potentially incur costs due to text messaging.    
 
22.0 Consent Process 
Children will be identified from the operating room schedule and surgery patient lists. Parents 
and children will be provided with oral and written information about the research project and a 
signed consent will be obtained from the participant. For participants who cannot consent for 
themselves, such as those below the legal age, a parent or legal guardian must sign the consent 
form; additionally, the participant’s assent will also be obtained if he or she is able to understand 
the nature, significance and risks/benefits associated with the study. The consent form will 
describe the purpose of the study, the procedures to be followed, and the risks/benefits of 
participation. A copy of the signed consent form (including assent where appropriate) will be 
given to the participant, parent or legal guardian and a copy will be placed in the patient’s 
medical record. Patients will be contacted prior to surgery and told about the study. If interested, 
consent may be signed electronically (see below) or may be obtained during the first preoperative 
study visit. 
 
Participants may choose to complete an electronic consent by using an application (e.g., 
REDCap) supported by Nationwide Children’s Hospital in compliance with HIPAA designed to 
protect PHI in the electronic transfer and storage of the consent form. Participants that choose to 
complete the electronic consent will have the opportunity to review the consent form and talk 
with research staff. If the potential participant agrees to participate, they will have an opportunity 
to check a box stating that that agree to provide their consent / parental permission / assent. There 
will also be fields for their typed name and their signature, along with witness fields. Once the 
electronic form has been submitted, a copy of the signed form will be provided to the participant. 
Electronic consents will be maintained within the application. In the event electronic consent is 
not available papers consent forms will be used. 
 
Subjects and participants will be informed during the consent process (and included in written 
form) that their consent/assent in the study is fully voluntary and that they may withdraw at any 
time with no consequence or penalty. The consent process will follow the SOP: Informed 
Consent Process for Research (HRP-090). Parental permission will be obtained from one parent, 
even if the other parent is alive, known, competent, reasonably available, and shares legal 
responsibility for the care and custody of the child as this is a minimal risk study. If a parent is 
not available or the legal guardian, consent may be obtained from one legal guardian or an 
individual with the ability to consent for the child. This ability to consent will be verified with 
documentation in the patient’s medical record. As this study involves children of the age of 
assent, appropriate assent will also be obtained per the SOP: Legally Authorized Representatives, 
Children, and Guardians (HRP-013) and will be documented via signature of the subject 
participating in the study. 
 
23.0 Process to Document Consent in Writing 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 22 of 25 
HRP-503  v.12.10.18 
We will follow SOP: Written Documentation of Consent (HRP-091) to obtain consent for 
this study. 
 
24.0 Setting 
All research will be conducted on Nationwide Children’s Hospital premises. 
 
25.0 Resources Available 
The study team will devote an adequate amount of time each week to ensure 
recruitment and enrollment timelines and goals are met.  
Most study visits will occur in the Clinical Research Services area, 6th floor, 
Tower Building which is dedicated clinical research space with 6 exam rooms, a 
CLIA waived lab for processing specimens, EKG, crash cart and all other 
necessary equipment to conduct a variety of study visits. Studies requiring 
ancillary services including but not limited to lab, radiology imaging, physical 
therapy, cardiac diagnostics and/or behavioral health assessments will be seen in 
those areas for those portions of the study. 
 
Should a subject exhibit signs requiring medical attention, the study doctor will be 
called immediately to assess required follow-up. Any subject experiencing 
suicidal ideation (verbally or through a response on the CSSRS), the psychology 
on call service would be contacted for a more thorough evaluation and if 
necessary a referral for treatment. 
 
A delegation of authority will be maintained for all studies involving informed 
consent. The delegation of authority clearly outlines each person’s role and 
responsibilities in the study. All study staff listed on the delegation of authority 
will be trained on the protocol, procedures, duties and any subsequent 
amendments per ICH and federal regulatory requirements. Documentation of all 
training will be kept in the study administrative binder and managed by the 
regulatory coordinator or study coordinator assigned to the study. 
 
26.0 Multi-Site Research* 
 
NA 
 
27.0  Protected Health Information Recording 
 
1.0 
Indicate which subject identifiers will be recorded for this research. 
☒  Name 
☒  Complete Address 
☒  Telephone or Fax Number 
☐  Social Security Number (do not check if only used for ClinCard) 
☒  Dates (treatment dates, birth date, date of death) 
☒  Email address , IP address or url 
☒  Medical Record Number or other account number 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 23 of 25 
HRP-503  v.12.10.18 
☐  Health Plan Beneficiary Identification Number 
☐  Full face photographic images and/or any comparable images (x-rays) 
☐  Account Numbers 
☐  Certificate/License Numbers 
☐  Vehicle Identifiers and Serial Numbers (e.g. VINs, License Plate Numbers) 
☐  Device Identifiers and Serial Numbers 
☒  Biometric identifiers, including finger and voice prints 
☒  Other number, characteristic or code that could be used to identify an 
individual 
☐  None (Complete De-identification Certification Form) 
 
2.0   
Check the appropriate category and attach the required form* on the Local 
Site Documents, #3. Other Documents, page of the application.  (Choose one.) 
☒  Patient Authorization will be obtained. (Include the appropriate HIPAA 
language (see Section 14 of consent template) in the consent form OR attach 
the HRP-900, HIPAA AUTHORIZATION form.) 
☐  Protocol meets the criteria for waiver of authorization. (Attach the HRP-901, 
WAIVER OF HIPAA AUTHORIZATION REQUEST form.) 
☐  Protocol is using de-identified information. (Attach the HRP-902, DE-
IDENTIFICATION CERTIFICATION form.) (Checked "None" in 1.0 above) 
☐  Protocol involves research on decedents. (Attach the HRP-903, RESEARCH 
ON DECEDENTS REQUEST form.) 
☐  Protocol is using a limited data set and data use agreement. (Contact the 
Office of Technology Commercialization to initiate a Limited Data Use 
Agreement. 
 
*Find the HIPAA forms in the IRB Website Library, Templates. 
 
Attach the appropriate HIPAA form on the “Local Site Documents, #3. 
Other Documents”, page of the application. 
 
3.0    How long will identifying information on each participant be maintained? 
Identifying data will be retained for 6 years after the research is complete as this 
meets both HIPAA & OHRP regulations. 
 
4.0 
Describe any plans to code identifiable information collected about each 
participant. 
Each subject will be assigned a unique study number.  Only subject initials and/or 
study number will be used when sending data for analysis. 
 
5.0 
Check each box that describes steps that will be taken to safeguard the 
confidentiality of information collected for this research: 
X Research records will be stored in a locked cabinet in a secure location 
X Research records will be stored in a password-protected computer file 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 24 of 25 
HRP-503  v.12.10.18 
X The list linking the assigned code number to the individual subject will be 
maintained separately from the other research data 
X Only certified research personnel will be given access to identifiable subject 
information 
 
6.0 
Describe the provisions included in the protocol to protect the privacy 
interests of subjects, where "privacy interests" refer to the interest of 
individuals in being left alone, limiting access to them, and limiting access to 
their information. (This is not the same provision to maintain the 
confidentiality of data.) 
Subject information will not be given to any other investigators. Subjects and 
their information will be closely monitored and guarded by study staff; there will 
be limited access to patients and their information by trained study staff; and 
subject information will only be shared and discussed between study staff specific 
to this study. 
 
Confidential Health Information 
 
1.0 
Please mark all categories that reflect the nature of health information to be 
accessed and used as part of this research. 
 
☒  Demographics (age, gender, educational level) 
☒  Diagnosis 
☐  Laboratory reports 
☐  Radiology reports 
☒  Discharge summaries 
☒  Procedures/Treatments received 
☒  Dates related to course of treatment (admission, surgery, discharge) 
☐  Billing information 
☒  Names of drugs and/or devices used as part of treatment 
☒  Location of treatment 
☐  Name of treatment provider 
☐  Surgical reports 
☒  Other information related to course of treatment 
☐  None 
 
2.0 
Please discuss why it is necessary to access and review the health information 
noted in your response above. 
This information is necessary to conduct the research and achieve the aims of the study.  
 
3.0 
Is the health information to be accessed and reviewed the minimal necessary 
to achieve the goals of this research?  ☒ Yes    ☐ No 
 
4.0 
Will it be necessary to record information of a sensitive nature? ☐ Yes ☒ No 

Feasibility and Acceptability of Technology-Based Interventions in the Perioperative 
Setting 
 
 
 
V8 – 08/18/22 
Page 25 of 25 
HRP-503  v.12.10.18 
 
5.0 
Do you plan to obtain a federally-issued Certificate of Confidentiality as a 
means of protecting the confidentiality of the information collected?  ☒ Yes 
☐ No