Physical and Psychological Measures of Pain in Acute Orthopedic Injuries: Use of At-home Virtual Reality
Phase: NA
Conditions: Injuries, Injury Arm, Injury;Sports, Injury, Knee, Injury Wrist, Injury, Ankle, Injury Foot, Injury, Hand, Injury Finger, Injury Leg
Sponsor: Massachusetts General Hospital

 
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Protocol Title: Physical and psychological measures of pain in acute 
orthopedic injuries: use of at-home virtual reality 
 
Protocol Identifier: NCT05552430 
 
Version Date: 6.22.23 
Download 
 
 

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Institutional Review Board 
Intervention/Interaction Detailed Protocol 
 
 
Principal Investigator: 
Ryan A. Mace, PhD 
 
Project Title: 
Physical and psychological measures of pain in acute orthopedic 
injuries: use of at-home virtual reality 
 
Version Date: 
 
6/22/23 
 
 
 
For Intervention/Interaction studies, submit a Detailed Protocol that includes the following sections.  If 
information in a particular section is not applicable, omit and include the other relevant information.   
 
 
1. 
 Background and Significance 
 
Acute orthopedic musculoskeletal injuries are prevalent and costly. Musculoskeletal injuries (e.g., 
fractures, dislocations; also known as traumatic injuries) are the leading cause of adult hospitalizations.1 
Many patients develop chronic pain and disability despite recovery of bones and soft tissue.2 An 
estimated 1.75 billion people globally have some form of chronic musculoskeletal pain.3 These patients 
pose a major public health problem and are costly to the healthcare system due to multiple surgeries 
and medical appointments.4 
The care of patients with orthopedic musculoskeletal injuries follows an outdated model that does not 
address the multifactorial influences on recovery. Catastrophic thinking about pain, pain anxiety, 
depression are established risk factors for disability and pain in patients with musculoskeletal injuries, 
regardless of the severity, location or type of injury.5 Referrals to address the multifactorial influences 
on recovery are often done after multiple unsuccessful medical procedures (surgery, injections, opioids), 
when patients have become invested in a medical cure, pain has already become chronic, and 
treatments are generally less efficacious. 
Cognitive-behavioral and mind-body approaches show promise but have limitations. Small to moderate 
effects have been found for depression, pain bothersomeness, and pain catastrophizing in mixed 
etiology pain6,7 including among orthopedic patients.8,9 The goal of these approaches is to “confront” 
rather than “avoid” by teaching adaptive coping skills thereby preventing the transition toward chronic 
pain and disability.10,11 However, access to these approaches remain poor due to stigma of mental 
health treatment, reluctance toward psychosocial issues in orthopedic departments, lack of trained 
providers, health insurance limits, and burdens associated with travel and treatment time.12,13 Because 
of the scope of acute orthopedic pain and the national opioid epidemic,14 there is an urgent need for 
effective, accessible, low-risk treatments that are acceptable to patients.  
Virtual reality (VR) can eliminate barriers to pain management15 but has not been tested in acute 
orthopedic patients. Most VR studies have focused on distraction to increase pain tolerance limits16 and 
provide temporary relief17 and do not include pain self-management skills training.18A recent double-

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blind RCT of an at-home skills-based VR (RelieveVRx) for chronic low back pain found superiority for all 
primary outcomes (pain intensity, pain-related interference, mood, and stress) and reduced over-the-
counter analgesic use versus a immersive VR control.19 However, there were no changes in several 
intervention targets (pain catastrophizing, pain self-efficacy, pain acceptance) and clinically important 
outcomes (prescription opioid use). Additional research is needed to characterize the mechanisms and 
treatment effects of skills-based VR for preventing chronic pain and disability after acute orthopedic 
injury.  
In this Borsook Project, we propose to conduct the first pilot study of skills-based VR for acute 
orthopedic injury. We will evaluate the feasibility, signals of improvement, and pain modulation 
mechanisms of an established skills-based program (RelieveVRx) for acute orthopedic injury. RelieveVRx 
is advantageous for this study because it: 1) is FDA-approved for chronic lower back pain but untested in 
acute orthopedic injury; 2) can be self-administered by patients at-home, 3) is the first to integrate 
multiple proven behavioral pain management strategies (e.g., education, diaphragmatic breathing, 
relaxation training, cognition and emotion regulation), 4) is interactive using biofeedback, and 5) the 
headset collects digital markers of the VR user experience and pain management skills practice. There is 
immense potential for a VR network modulating system to radically shift our approach to preventing 
chronic pain and disability as an effective, low-risk non-pharmacological intervention for acute 
orthopedic injury. If successful, skills-based VR could be easily administered in the clinic or at home, 
adapted to other pain conditions, and scaled using digital therapeutics.  
 
2. 
Specific Aims and Objectives  
 
My long-term goal is to evaluate the biopsychosocial mechanisms by which skills-based VR promotes 
recovery after acute orthopedic injury. Our guiding hypotheses that we will test in subsequent studies is 
that skills-based regulates autonomic (relaxation), affective (mood and situational anxiety), and 
evaluative (subjective pain and enjoyment ratings) responses associated with acute pain16 while also 
promoting pain self-management skills thus preventing the progression to chronic pain and disability. To 
accomplish this goal, we will: 1) evaluate a-priori feasibility markers of the self-administered, skills-
based, at-home VR program and data collection procedures; 2) explore within-group signals of 
improvement in multiple measures of pain and pain-related outcomes; 3) identify digital markers of pain 
modulation induced by skills-based VR to target in subsequent fully-powered trials, and 4) identify 
signals of tissue blood perfusion and oxygenation on the head using non-invasive Functional near-
infrared spectroscopy (fNIRS) during normal extremity movements and while using the VR. 
 
3. 
General Description of Study Design 
 
My approach follows the NIH Stage Model20 and NCCIH framework,21 which specify testing feasibility 
and identification of putative intervention targets before conducting an efficacy trial.22–24 We will 
conduct a mixed-methods feasibility pilot and with individual exit interviews (N=10) following 
procedures for successful orthopedic behavioral intervention trials from our group.25,26 Participants will 
be patients with acute orthopedic musculoskeletal injuries who are at risk for chronic pain and disability 
(PCS ≥ 20 and PASS-20 ≥ 40) and meet inclusionary/exclusionary criteria. With a trained RA, we will 
recruit patients from Mass General Brigham Orthopedics Departments (Orthopedic Trauma at MGH and 
Brigham and Women’s Hospital, Sports Medicine Services, Hand & Arm Services) through established 
partnerships on active trials (~220 patients/year meet criteria) through our IRB-approved study flyer. 

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The skills-based VR will be self-administered by patients at-home over an 8-week period. The primary 
outcome for the pilot will be a-priori Go/No-Go feasibility markers (feasibility, acceptability, fidelity, 
credibility, expectancy, satisfaction) of the VR program and data collection procedures to increase the 
success of subsequent trials. To inform outcomes and mechanisms of action, we will integrate four 
quantitative assessment techniques: 1) multi-modal assessment (following IMMPACT criteria for pain 
trials)27 of pain intensity, pain-specific coping (catastrophizing, self-efficacy, acceptance), disability, 
physical function, and emotional function (depression, anxiety, stress); digital markers (VR use data, 
smartphone pain survey) for tracking dynamics of pain during the 8-week intervention; non-invasive 
fNIRS placed on the head (tissue blood perfusion and oxygenation) for brain activity during extremity 
movement and use of VR. Participants will travel to the clinic at baseline to pick up the VR equipment 
and complete the study assessments (self-reports and non-invasive fNIRS). Participants will return to the 
clinic after the 8-week intervention to repeat the assessment and drop off the VR. Given that skills-
based VR has not been tested in this population, 30 min individual exit interviews will be critical for 
understanding patients’ perception of: 1) the rationale and helpfulness of the skills; 2) the VR user 
experience; 3) barriers and facilitators to treatment adherence; 4) burden of the study procedures and 
data collection. The deliverables of this pilot study include: refined study protocol; preliminary 
feasibility; within-group signals of improvement; assessment of biomarkers; assessment of non-invasive 
fNIRS tissue perfusion and oxygenation; training in VR and mechanistic-based data collection; 
subsequent NIH proposal. 
 
4. 
Subject Selection 
 
4a. Inclusion and Exclusion Criteria 
The eligibility criteria is consistent with our IRB-approved intervention study for acute orthopedic injury 
(protocol #: 2020P000095) and guidelines for VR studies for pain.12,18,19 
Eligible patients must meet the following inclusion criteria: 
1) Outpatient adults in the Level 1 Trauma Center 
2) Age 18 or older 
3) Able to meaningfully participate meaningfully (English fluency and literacy) and stable living 
situation  
4) Acute upper or lower extremity musculoskeletal injury (e.g., fracture, dislocation, rupture) in the 
acute phase or repeated injury. 
5) Pain Catastrophizing Scale ≥20 or Pain Anxiety Symptom Scale-20 ≥40 
6) Has access to internet (Wi-Fi or wireless) 
7) Willing to participate and comply with the requirements of the study protocol, including virtual 
reality program and questionnaire completion  
8) Free of concurrent psychotropic medication for at least 2 weeks prior to initiation of treatment, 
OR stable on current psychotropic medication for a minimum of 6 weeks and willing to maintain 
a stable dose (i.e., no psychotropics or stable for >6 weeks) 
9) Cleared by orthopedic surgeon for study participation 
 
One or more of the following exclusion criteria will render a patient ineligible: 
1) Current or prior diagnosis of epilepsy, seizure disorder, dementia, migraines, or other 
neurological diseases that are contraindicated for VR 
2) Medical condition predisposing to nausea or dizziness  

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3) Hypersensitivity to flashing light or motion 
4) Vision or severe hearing impairment 
5) Injury to eyes, face, or neck that impedes comfortable use of virtual reality 
6) Diagnosed with a medical illness expected to worsen in the next 3 months (e.g., malignancy) 
7) Other serious injuries that occurred with the orthopedic injury or surgical complications (e.g., 
infection, need for repeat surgery) 
8) Current or prior untreated mental illness, substance use disorder, or suicidal ideation 
9) Self-reported pregnancy 
10) Currently in litigation or under Workman’s Comp 
11) Practice of cognitive-behavioral therapy, yoga/meditation, or other mind body techniques once 
per week for 45 minutes or more within the last 3 months  
 
4b. Local Recruitment Procedures 
 
We will recruit patients with acute orthopedic musculoskeletal injuries who are at risk for chronic pain 
and disability (PCS ≥ 20 and PASS-20 ≥ 40) and meet inclusionary/exclusionary criteria. With a trained 
RA, we will recruit patients from the MGB Orthopedics Departments through established partnerships 
on active trials (~220 patients/year meet criteria). Recruitment will follow a standardized protocol 
developed specifically for the MGH Orthopedics Department consistent with prior recommendations, 
28,29 and informed by our prior IRB-approved study (protocol #: 2020P000095).25,30 We anticipate that 
potential participants will be identified through daily screening of Epic admission reports by the trained 
RA. The RA will next notify the medical staff (medical assistant) who will alert the surgeons. The surgeon 
will introduce study to the potential participants at the end of the medical visit if time allows. If the 
surgeon does not have time to introduce the study or if additional follow up to discuss the study is 
needed, the RA will contact referrals via telephone to provide details and conduct a phone screen using 
an IRB-approved script. We will also distribute our flyer, after getting approval from site leadership, to 
orthopedic clinics within the larger MGB infrastructure (such as Brigham & Women's Orthopedic Trauma 
Department) to expand our recruitment and maximize the geographic diversity in our sample. We will 
not be approaching these participants in-person, but they could complete a self-reported survey for 
screening and will receive a call from a RA with more information. All forms of recruitment, including 
patient flyers, will be submitted for IRB approval prior to use.  
 
5. 
Subject Enrollment 
 
A trained RA will contact all referrals via telephone. The research assistant will make 3 attempts to 
contact referred potential participants before discontinuing. During the screening call, the RA will 
provide study details to participants and assess eligibility. The RA will be available to answer any 
questions from potential participants. The RA will review the consent form with eligible participants who 
express interest and intent to participate in the study. All participants will sign a REDCap-integrated e-
consent form prior to study procedures. Individuals who do not meet study criteria or are not interested 
in participating will be offered a resource sheet with relevant health and mental health information for 
patients with acute orthopedic musculoskeletal injuries who are at risk for chronic pain and disability. 
The RA will maintain a detailed and updated log of all screening attempts for study data reports (i.e., % 
participants eligible, approached, recruited, enrolled). The principal investigator will review all cases in 
weekly meetings. 
 

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6. 
STUDY PROCEDURES 
 
6a. Assessments 
 
There are two assessment periods: pre-intervention (week 0) and post-intervention (week 8). Following 
consent, participants will complete a battery of assessments via a secure REDCap link. Participants will 
have the option to complete post-intervention assessments in-person or remotely. All assessments are 
reliable, valid, and were selected according to our prior studies in this population and (protocol #: 
2020P000095) and guidelines for VR studies for pain.12,18,19 Only trained study staff will have access to 
the assessment data. Participants’ data will be identified by an ID number only, and a link between 
names and ID numbers will be kept separately under lock and key. Participants will have a password-
protected account for downloading the data. 
 
The self-report assessments include: 
 
1) Demographic factors (potential moderators): to assess age, gender, biological sex, 
race/ethnicity, educational level, employment status, occupation, income, marital status, 
mental health history, current psychotropic/pain medication intake. Pre-intervention only.   
2) Clinical factors (potential moderators): to assess pain location, medical procedures and pain 
medications throughout study, medical comorbidities. Pre, post (chart review and self-report). 
3) Credibility and Expectancy questionnaire (primary feasibility marker): to assess treatment 
credibility and expectancy. Pre-intervention only.  
4) PROMIS Physical Function (secondary outcome): to assess one's ability to carry out activities 
that require physical actions, ranging from self-care to social and work. Pre, post. 
5) Short Musculoskeletal Functional Assessment questionnaire (secondary outcome): to assess 
disability specific to musculoskeletal injury and pain. Pre, post. 
6) Numerical Rating Scale (secondary outcome): to assess pain intensity. Pre, post.  
7) PROMIS Sleep Disturbance Scale (secondary outcome): to assess problems with sleep and sleep 
quality. Pre, post.  
8) Pain Catastrophizing Scale (secondary outcome) to assess catastrophic thinking about pain. Pre, 
post. 
9) Pain Anxiety Scale (secondary outcome):  to assess pain-specific anxiety. Pre, post. 
10) Center for Epidemiologic Study of Depression (secondary outcome): to assess depression. Pre, 
post. 
11) Defense and Veterans Pain Rating Scale (secondary outcome): to assess pain interference. Pre, 
post. 
12) Pain Self-Efficacy Questionnaire (secondary outcome): to assess confidence to engage in 
physical activity despite pain. Pre, post. 
13) Chronic Pain Acceptance Questionnaire (secondary outcome): to assess ability to engage in 
meaningful activities despite pain. Pre, post.  
14) Cognitive and Affective Mindfulness Scale (secondary outcome): to assess state of mindfulness 
taught during the program. Pre, post. 
15) Measure of Current Status (secondary outcome): to assess general coping ability taught during 
the program. Pre, post.  
16) Patient’s Global Impression of Change (secondary outcome): to assess perceptions of overall 
improvement in pain and physical function during the program. Post-intervention only 

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17) Client Satisfaction Questionnaire (primary feasibility marker): to assess satisfaction with 
treatment. Post-intervention only.  
18) Motion Sickness and Nausea (primary feasibility marker): to assess adverse experiences with VR. 
Post-intervention only. 
19) System Usability Scale (primary feasibility marker): to assess global user experience of the VR. 
Post-intervention only. 
20) Program Feedback: to assess satisfaction with the study procedures, VR device, and study team. 
Post-intervention only.  
 
After the self-reports, the trained RA will set up the non-invasive fNIRS. fNIRS monitors brain activity by 
recording changes in detectoxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentration. It is 
a flexible, portable, easy to use, and sensationless imaging technique for detecting objective pain 
signatures in the brain. fNIRS is currently being used by other investigators on MGB IRB-approved 
studies (NCT05258591). Participants will be asked to sit on a chair and wear an elastic fNIRS system 10-
20 cap on their head during normal extremity movements and while using the VR. The cap will have 8 
mounted optodes (4 on each hemisphere) that will be located over the prefrontal cortex. The cap size 
will be determined by participants' circumstance of head (measurement tape will be position right 
above eyebrows and inion). The cap will be positioned at the proper location by the research team and, 
to make sure the participant is comfortable, transmitters and receivers pressure will be adjusted based 
on participants’ feedback.  
We will compensate participants $25 for completing the pre-intervention and $25 for completing the 
post-intervention assessments ($50 total).  
 
6b. Intervention Period 
 
Enrolled participants that completed the baseline assessments will progress to the intervention period. 
Participants will receive the RelieveVRx program loaded in a Pico G2 4k head-mounted VR device at no 
cost. The Pico G2 4K device is commercially available, widely used, inexpensive, have minimal visual 
latency, and are easier for participants to use than many other devices (Figures 1 and 2). Importantly, 
the Pico G2 4k headset only records module completion and time. It does not collect or store biometric 
data on participants (e.g., eye tracking, breathing). 
 

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Figure 1. Participant view of RelieveVRx program. 
 
Figure 2. Pico G2 4k head-mounted VR device and controller. 
The package will also include a study welcome letter from the PI, patient-friendly instructions, a charger, 
and a pre-paid envelope to return the VR after the intervention period. Participants will be instructed to 

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self-administer 1 module of at-home VR (RelieveVrx) daily for 8 weeks. The RA will monitor participant 
completion of the device use in Curebase (modules completed, time worn) and daily logs (sent by Twilio) 
in REDCap. Curebase is a password-protected, HIPAA- compliant, online platform used in prior studies of 
RelieveVRx.18,19 The RA will contact participants to problem-solve barriers to VR use after 24 hours of 
non-wear.  
The standardized 8-week VR program (RelieveVrx) delivers a multifaceted combination of pain relief 
skills training through a prescribed sequence of daily immersive experiences. The modules are informed 
by evidence-based principles of CBT, mindfulness, and pain neuroscience education. Each VR module is 
2-16 minutes in length (average of 6 minutes). The VR treatment modules were designed to minimize 
triggers of emotional distress or cybersickness. Participants will complete the following RelieveVrx 
treatment modules: 
• 
Pain education: visual and voice-guided lessons establish a medical and scientific rationale for 
the VR exercises and behavioral medicine skills for pain relief.  
• 
Relaxation/Interoception: scenes that progressively change from busy/active to calm in order to 
train users to understand the benefits of progressive relaxation. User exhalation is measured by 
the microphone embedded in the Pico G2 hardware, offering biofeedback-enhanced relaxation 
exercises. 
• 
Mindful escapes: high-resolution 360 videos with therapeutic voiceovers, music, guided 
breathing, and sound effects designed to maximize the relaxation response and participant 
engagement.  
• 
Pain distraction games: interactive games to train the skill of shifting focus away from pain. 
Participants will receive text messages from Twilio, an MGH-approved smartphone app that our team 
has successfully used in similar R34 and U01 intervention development trials, to deliver daily study 
reminders and biweekly pain surveys (intensity and pain interference) during the intervention 
period.18,19 Participants will be informed of texting risks and provide consent for text messaging in 
writing or verbally if preferred. Participants will have the opportunity to ask questions about texting 
with study staff. Approval of text messaging and/or opting out of text messaging will be recorded in 
each participant’s file. Participants may opt-out of the text message contact option at any point. This 
notification procedure was informed by prior orthopedic and pain participants in focus groups and exit 
interviews.30–32  
After the 8-week intervention period, the RA will contact participants again to schedule a return visit. 
The RA will repeat the assessment procedures for the self-reports and the non-invasive fNIRS. After 
completing the post-intervention assessments, participants will be invited to participate in individual 
exit interviews (30 min). The PI will conduct the exit interviews with an IRB-approved semi-structured 
interview script. If study participants are unable to schedule a 90-minute visit, post-tests and exit 
interviews may be conducted virtually at an alternate time. The purpose is to gather detailed feedback 
on intervention components, measures, procedures, and user experience with the VR.  
 
7. 
Risks and Discomforts 
Patients will be informed that the foreseeable physical risks from this research study are minimal. They 
will be informed that there is some risk of breach of privacy/confidentiality associated with the use of 
text messaging, videoconferencing, and virtual reality. We specifically selected the Pico G2 4k headset 
because, in contrast with other commercial VR (e.g., Oculus, owned by Facebook), it does not collect 

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personal information on participants (e.g., demographics, biometrics, tracking/location). They will also 
be informed of the unlikely situation that they might feel uncomfortable with the topic of pain 
management and informed to contact the who will provide help, as needed. The PI is an experienced 
clinical psychologist who has specific expertise with orthopedic injury and pain. They will also be 
informed that they may feel uncomfortable completing various psychological questionnaires and that 
they may find it time-consuming to participate in the 8-week program.  
Risk to participating in the VR program are minimal. Patients have a small risk of experiencing motion 
sickness or mild nausea when initially adjusting to the VR. In a recent double-blind efficacy trial that 
tested the RelieveVRx program used in this study, only 5 of 75 participants (6.7%) reported initial motion 
sickness.19 All of the cases of motion sickness were mild and quickly resolved without further issues. All 
referring clinicians will be asked to document that there are no medical contraindications for 
participating in VR. For patients not referred from clinics, we will ensure that this information is 
collected prior to enrollment. We will comprehensively assess safety during enrollment using guidelines 
for VR studies of pain.18,19 This includes: current or prior diagnosis of epilepsy, seizure disorder, 
dementia, migraines, or other neurological diseases; medical condition predisposing to nausea or 
dizziness; hypersensitivity to flashing light or motion; vision or severe hearing impairment; injury to 
eyes, face, or neck that impedes comfortable use of VR. We will be encouraged to contact the PI and RA 
as soon as possible in the unlikely event of any problems with device safety or adverse events during 
their treatment.  
In the unlikely event that a participant is determined to be in distress or actively suicidal and at risk for 
self-harm during any study procedure, we will use a standardized protocol for assessing and monitoring 
risk developed by the PI that has been successfully used in other remote trials. In this protocol, the RA 
would contact the PI and the appropriate clinical intervention would be executed. In case we are unable 
to contact the participant we will contact their safety contacts. In case suicidality is determined during 
the intervention or control sessions, the PI will perform safety procedures in real time. We do not expect 
this unlikely event to occur, as there were no previous occurrences in our previous studies. Further, we 
set serious mental illness and current suicidal ideation as exclusion criteria to further reduce the chance 
that enrolled participants would express harm towards themselves or others during the study.  
There are no risks or discomforts with the fNIRS. Participants will wear the device with an elastic cap to 
avoid irritation caused by skin placement. Participants may temporarily experience discomfort and/or 
frustration while performing normal extremity movements during the brain activation scan. 
As mentioned above, we will be using secure email to communicate with participants. All email 
communication with participants will be encrypted using the send secure function. To further protect 
participants’ confidentiality, we will discourage participants from communicating about medical issues 
by non-secure email.   
8. 
Benefits 
 
No direct benefit is anticipated. Participants may improve their ability to cope with pain and improve 
their mood, pain, and disability. Information gained through this study may lead to a better 
understanding the importance of delivery method of mind body interventions. The potential benefits 
from this study far outweigh the potential risks. The data collected as part of this study may ultimately 

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help researchers and clinicians develop novel digital therapeutics to better care for patients with acute 
injuries to prevent chronic pain and disability. 
 
9. 
Statistical Analysis 
 
We will not test for efficacy of the VR program, in line with guidelines for feasibility studies33,34 and the 
NIH Stage Model20 and NCCIH framework.21  Instead, we will calculate frequency and proportions to 
assess feasibility Go/No-go benchmarks consistent with virtual pilot studies of mind-body interventions 
(see table below).35–40 Power analysis is not appropriate for small feasibility pilot studies. The sample 
size of 10 is appropriate for early feasibility testing and achieving thematic saturation in the exit 
interviews. 35–40Participants who drop-out will be counted as not meeting applicable feasibility criteria. If 
these benchmarks are not met, revisions will be necessary prior to an efficacy trial.39 106 Exploratory 
analyses: I will calculate paired t-tests, effect sizes of improvement, and exploratory correlations for 
each quantitative measure.41 
 
We will analyze qualitative data from the exit interviews using NVIVO 12 using the framework 
method42,43 and a hybrid inductive-deductive approach.44,45 This will include predetermined themes105 
while allowing for inductive flexibility where themes and codes are induced by data to allow for novel 
ideas to optimize the VR program.87,103 We will code the raw qualitative data and the RA will perform 
reliability coding. The PI resolve discrepancies with the RA to achieve sufficient reliability (kappa > .80). 
We will use the qualitative feedback to improve the study procedures for subsequent trials. 46,47 
 
10.   Monitoring and Quality Assurance 
 
Study data will be maintained in a locked filing cabinet and on password protected computers.  
Questionnaires and self-reported responses will not become part of the patient’s medical record and 
will not contain medical record numbers or names.  Hardcopies of study related data and forms will be 
Feasibility markers 
Acceptable 
Excellent 
Credibility and Expectancy  
>70% score over scale midpoint 
≥ 80% score over scale midpoint 
Client Satisfaction Score 
> 70% score over scale midpoint 
≥ 80% score over scale midpoint 
Feasibility of recruitment 
> 70% approached participate 
≥ 80% of approached participate 
Acceptability of treatment 
> 70% attend 6 out of 8 weeks 
≥ 80% attend 6 out of 8 weeks 
Adherence to pain survey 
> 70% of biweekly surveys  
≥ 80% of biweekly surveys 
Feasibility of assessments 
> 70% have no measures missing 
≥ 80% have no measures missing 
System Usability 
> 70% score over scale midpoint 
≥ 80% score over scale midpoint 
Motion Sickness/Nausea 
> 70% score below scale 
midpoint 
≥ 80% score below scale midpoint 
Other Adverse Events  
Minimal  
None 

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stored in a lockable file cabinet.  Patient information will remain confidential by keeping identifying 
information (name, medical record number, and subject number) in a separate locked file cabinet.  Only 
the investigators and study staff specified on the consent form will have access to this information. 
 
Adverse Event Monitoring: Throughout the study subjects will be monitored for the occurrence of 
events defined as any undesirable experience or unanticipated risk. Lack of effect of treatment is not 
considered an event. All adverse events will be reported on an adverse event form. The PI has the 
responsibility of reporting serious adverse events (death, life threatening illness or injury, serious injury, 
or permanent disability) to PHRC within 24-72 hours of notification. 
 
A unique anonymous identifier will be assigned to each subject; subsequently, all data collected will be 
associated exclusively with this identifier. This includes all questionnaires administered over the course 
of the study, as well as pain surveys and VR use data. 
 
Electronic information will be stored in REDCap (Research Electronic Data Capture), a free, secure, and 
HIPAA-compliant web-based application hosted by the Partners HealthCare Research Computing 
Enterprise Research Infrastructure & Services (ERIS) group (based at the PHS Needham corporate 
datacenter). Data will be stored on password protected computers that will be always stored in secure 
locations. Paper data files (with coded subject identification) will be stored in a locked filing cabinet. 
Only research staff will have access to these data locations. 
 
The VR program, RelieveVRx, will transmit data when participants wear the Pico headset (treatment 
modules completed, time worn) via Curebase. Curebase is a password-protected, HIPAA- compliant, 
online platform. Curebase is used by the developer of the RelieveVRx, Applied VR, for clinical trials. 
Virtual reality use data transmitted by Curebase will be encrypted with a unique identifier and stored in 
a secure encrypted cloud-based software (AWS) and a password-protected Excel database. The 
database will have a participant number and no personal identifiers associated with the virtual reality 
use data.  
 
The exit interviews will be audio recorded for transcription and qualitative analysis. The audio 
recordings will be stored on a password protected drive and deleted once transcribed. The 
transcriptions will be de-identified. 
 
Data from this study will be stored for three years after the publication of all study results, at which time 
all paper data files will be shredded, and computer files will be deleted.  
 
11.   Privacy and Confidentiality 
 
☒ Study procedures will be conducted in a private setting 
☒ Only data and/or specimens necessary for the conduct of the study will be collected 
☒ Data collected (paper and/or electronic) will be maintained in a secure location with appropriate 
protections such as password protection, encryption, physical security measures (locked 
files/areas) 
☒ Specimens collected will be maintained in a secure location with appropriate protections (e.g. 
locked storage spaces, laboratory areas) 
☒ Data and specimens will only be shared with individuals who are members of the IRB-approved 
research team or approved for sharing as described in this IRB protocol 

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☒  Data and/or specimens requiring transportation from one location or electronic space to 
another will be transported only in a secure manner (e.g. encrypted files, password protection, 
using chain-of-custody procedures, etc.) 
☒   All electronic communication with participants will comply with Mass General Brigham secure 
communication policies 
☒ Identifiers will be coded or removed as soon as feasible and access to files linking identifiers 
with coded data or specimens will be limited to the minimal necessary members of the research 
team required to conduct the research 
☒ All staff are trained on and will follow the Mass General Brigham policies and procedures for 
maintaining appropriate confidentiality of research data and specimens 
☒ The PI will ensure that all staff implement and follow any Research Information Service Office 
(RISO) requirements for this research 
☒ Additional privacy and/or confidentiality protections: We specifically selected the Pico G2 4k 
headset because, in contrast with other commercial VR (e.g., Occulus, owned by Facebook), it 
does not collect personally information on participants (e.g., demographics, biometrics, 
tracking/location). 
 
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47.  Onken LS, Carroll KM, Shoham V, Cuthbert BN, Riddle M. Reenvisioning Clinical Science: Unifying 
the Discipline to Improve the Public Health. Clinical Psychological Science. 2013;2(1):22-34. 
doi:10.1177/2167702613497932 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
APPENDIX A 
 
Data Monitoring Committee / Data and Safety Monitoring Board 
Appendix 
 
 
 
• 
To be completed for studies monitored by Data Monitoring Committee (DMC) or Data and Safety 
Monitoring Board (DSMB) if a full DMC/DSMB charter is not available at the time of initial IRB 
review. 
• 
DMC/DSMB Charter and/or Roster can be submitted to the IRB later via Amendment, though these 
are not required.  
 
A Data Monitoring Committee (DMC) or Data and Safety Monitoring Board (DSMB) will be convened for 
safety monitoring of this research study.  The following characteristics describe the DMC/DSMB 
convened for this study (Check all that apply): 
 
☐ The DMC/DSMB is independent from the study team and study sponsor. 
 
☐ A process has been implemented to ensure absence of conflicts of interest by DMC/DSMB 
members. 
 
☐ The DMC/DSMB has the authority to intervene on study progress in the event of safety 
concerns, e.g., to suspend or terminate a study if new safety concerns have been identified or 
need to be investigated.   
 
☐ Describe number and types of (i.e., qualifications of) members: 
Click or tap here to enter text. 

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☐  Describe planned frequency of meetings: 
Click or tap here to enter text. 
 
☐ DMC/DSMB reports with no findings (i.e., “continue without modifications”) will be submitted 
to the IRB at the time of Continuing Review. 
 
☐ DMC/DSMB reports with findings/modifications required will be submitted promptly (within 5 
business days/7 calendar days of becoming aware) to the IRB as an Other Event.