Virtual Reality Distraction for Reduction in Acute Postoperative Pain
Phase: NA
Conditions: Postoperative Pain
Sponsor: The Cleveland Clinic

 
Page 1 
September 1, 2021 
 
 
 
 
Virtual Reality Distraction for Reduction 
in Acute Postoperative Pain 
NCT: NCT04416555   
 
Sabry Ayad, MD; and Colleagues 
 
Departments of General Anesthesiology, Regional Practice, 
and OUTCOMES RESEARCH, Cleveland Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
1 INTRODUCTION 
1.1 Background 
A.  Postoperative Pain 
B. Opioid Analgesics and side effects 
C. Multimodal Analgesia 
D. Virtual Reality 
E. Rationale of the Study 
 
2 STUDY OBJECTIVES 
 
3 METHODS and STUDY DESIGN 
A. Study Overview 
B. Setting and Population 
Inclusion Criteria 
Exclusion Criteria 
C. Withdrawal Criteria 
D. Protocol 
E. Measurements 
F. Data Analysis 
G. References 
 
 
 
 
 

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1. INTRODUCTION 
1.1 Background 
 
A. Postoperative Pain Management 
Despite more and more surgeries being moved to the outpatient realm, the scope 
of inpatient postoperative pain management remains large1. As the American population 
ages and life expectancy increases, major orthopedic hip arthroplasties are increasingly 
common. The American Academy of Orthopedic Surgeons projects that by 2030, primary 
total hip replacement will grow by 171%2. 
In this era of healthcare, opioids comprise the first line of treatment in acute 
postoperative pain yet in the interest of patient safety this reliance should shift.  
Depending on opioids alone can leave patients dissatisfied, still in pain and have the 
potential for abuse. A 2016 review of current management of postoperative pain revealed 
an unmet need for better therapy3. 
 
B. Opioid Analgesics and Side Effects    
Opioids are effective yet a recent survey showed a majority of patients reported 
moderate to severe pain after adequate narcotic analgesics4.  Most patients in this survey 
had at least one side effect with the most common being drowsiness, constipation, and 
nausea. Respiratory depression is a serious side effect and puts these patients at risk of 
harm. Receiving narcotic analgesics also places patients at risk for abuse: either misuse 
by family members, addiction or tolerance. Acute tolerance requires patients to increase 
opioid dose for comparable effect and, although controversial, there is even a concept of 
opiate-induced hyperalgesia5 In opiate induced hyperalgesia, studies show a paradoxical 
response where patients treated with more opioids become more sensitive to pain and 
have higher opioid requirements. In this era of the opioid crisis, multiple advisory boards 
have issued education regarding proper opioid prescribing6. Current recommendations 
call for using opioids only when necessary and at the lowest possible dose. 

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           C. Multimodal Analgesia 
Multimodal treatment plans provide an advantage for acute postoperative pain 
based on the theory that the total narcotic dose will decrease and side effects be 
consequently reduced.  A recent multi-society guideline defines multimodal analgesia as 
having three parts: (1) the pre-, intra- and post-operative use of pharmacological and 
interventional techniques with the primary aim of decreasing acute pain; (2) use of these 
same techniques to decrease postoperative opioid needs; and, (3) reducing the risk of 
persistent incisional pain3. As defined above, postoperative analgesia starts 
preoperatively. Planning for each patient may start with education about various 
interventions.  One such intervention may be use of Virtual Reality (VR). This distraction 
technique has been shown to be a safe and effective adjunctive therapy for acute pain in 
multiple randomized controlled studies7. 
 
D. Virtual Reality 
Virtual Reality (VR) is a technology that provides an immersive multisensory 
experience that simulates a user's physical presence in a software and hardware  
environment in a way that allows the user to interact with it. The VR enviroment studied 
here is interactive software and a goggle headset unit that gives users the sensation of 
being in a scenario and controlling certain actions with their body movements. Patients 
views the immersive environment through light-weight head-mounted goggles that gives 
feedback on certain movements including breathing exercises. The goggles provide a 
stereo visual image creating a sense of space and depth, and is thus three dimensional. 
A motion tracker in the goggles measures the position of the head and aligns the visual 
image accordingly. Although VR has been studied for more than 2 decades, recent factors 
have  converged to make this intervention worth studying, namely the opioid crisis, 
decreasing cost of the device, and increasing quality and accessibility. 
VR allows users to have an immersive experience that modifies their immediate 
environment and experience ”presence” in the simulated environment8. The external 
environmnet is excluded. The exact mechanism of action remains unknown, but VR is a 
distraction technique that fully engages patient’s auditory, visual, and propioception 

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senses8. The theory is that full engagement in a VR environment may restrict the mind’s 
ability to simultaneously processing painful stimuli. There is so far limited understanding 
of possible biological and psychological mechanisms of action9.  
A 2017 study evaluated hospitalized patients who had both somatic and visceral 
pain, and identified several factors that may preclude safe and effective VR use8. 
Concerning conditions include active neurologic conditions, epilepsy, facial injuries, 
ventilator dependence, nausea or vomiting, and excessive fraility. Although the trial 
protocol limited treatments to 15-minute sessions, some patients nonetheless became 
dizzy or nauseated. 
 A recent feasibility study of immersive VR in hospitalized patients showed that 
although treatments were apparently analgesic and reduced anxiety, many patients were 
unwilling to use VR or ineligible10. Among eligible patients, the elderly were least likely to 
participate, possibly because they had difficulty adopting to the novel technology. 
Several systematic reviews summarize available studies of clinical efficacy of 
virtual reality for pain reduction. Malloy and colleagues9 evaluated controlled trials with 
either between-subjects or mixed model designs, in which VR analagesia was compared 
with at least one alternative intervention, placebo, standard care, or no-treatment. Using 
fairly strict criteria, the investigators identified 11 studies that point to the effectiveness of 
VR in reducing pain. VR was effective for experimental pain and for burn care, but results 
for sharp pain were less consistent. The authors point to a pattern in the literature 
suggesting that immersive VR technology is better than non-immersive technology for 
relief of pain. Recently Chan and her group did a systematic review and meta-analysis of 
randomized trials for clinical pain and although considerably heterogeneity in studies they 
found -0.49 (95%CI -0.83 to -0.41, p=0.006) standard mean reduction in pain score11. 
Another meta-analysis, by Kenney et al., also concluded that VR reduces clinical pain12. 
 
E. Rationale of the study 
Previous VR studies have identified clinically meaningful reductions in pain scores; 
however, they did not evaluate opioid consumption which is a clinically meaningful 

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outcome. Opioid-related complications including respiratory depression and nausea and 
vomiting will also be assessed to include cost-effectiveness aspect.  
Clinically, opioid-related complications are important from a patient safety 
perspective, and economically. One barrier to use VR in the perioperative period is that 
the units have been relatively expensive and cumbersome to use. Improvements in 
software, hardware and a reduction in cost have been developed that make VR a viable 
non-pharmacologic adjunct in the treatment of pain. Our trial will provide data for use in 
a future economic analysis of VR technology in postoperative patients. 
 
2. Study Objectives 
Using a randomized controlled design, our goal is to estimate the effect of VR on 
postoperative analgesia and opioid consumption.  
Specifically, we propose to test the primary hypothesis that the use of Applied VR 
software in Pico G2 4K headsets decreases acute postoperative pain scores (with a 1 
point difference considered clinically important)  compared to sham treatment on a 0-10 
scale 15 minutes after each use in the first 48 hours after surgery or hospital discharge, 
whoever comes first. 
  
Our secondary hypotheses are that the use of VR over the initial two postoperative days 
or until hospital discharge: 
1) reduces average pain scores (with 1 point being considered clinically important); 
2) reduces postoperative opioid consumption (with a 25% reduction being 
considered clinically important). 
On an exploratory basis, we will test the additional hypotheses that use of VR over the 
initial two postoperative days or until hospital discharge: 1) improves patient mobility; and, 
2) reduces the need for nausea and vomiting treatments (ondansetron, dexamethasone, 
or metoclopramide).  
 

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3. Method and Study Design 
A. Study Overview 
The proposed trial will be conducted with IRB approval and registered at 
ClinicalTrials.gov before the first patient is enrolled. Written informed consent will be 
obtained from participating patients. The randomized, blinded, controlled trial will evaluate 
the effect of AppliedVR software on postoperative pain, opioid use, and opioid-related 
complications after elective primary total hip arthroplasty.  
Participating patients will be randomly assigned to video headset analgesia (video 
headset featuring a relaxation program with three dimensional video experience and 
binaural audio) or sham video headset (identical video headset mimicking a void theater 
where a 2D content will be displayed on a “ virtual screen” in front of the user ). The 
headset will not be labeled with the terms “VR,” “virtual reality,” or “Pico.” The study will 
be performed at two Cleveland Clinic hospitals. 
 
Pico G2 4K VR googles (left) and a sample image of the video headset analgesia 
software displayed (right) 

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Diagram of the sham video mimicking a void theater with a screen showing 2D content 
(left) and a sample image of the sham video headset displayed (right) 
B. Setting and Population 
Inclusion criteria: 
(1) Written informed consent; 
(2) Men or women 18-85 years old; 
(3) American Society of Anesthesiology Physical Status 1-3; 
(4) Scheduled for elective, primary total hip arthroplasty; 
(5) Anticipated hospitalization of at least 1 night; 
(6) Expected to require parenteral opioids for postoperative pain; 
(7) Able to use IV PCA systems. 
Exclusion criteria:  
(1) Use of more than 30 mg/day of oral oxycodone (or equivalent);  
(2) Greater than 12 weeks of current and continued opioid use; 
(3) History of seizures, epilepsy, motion sickness, stroke, dementia; 
(4) Non-English speaking;  
(5) Women who are pregnant or breastfeeding; 
(6) History of illicit substance use disorder. 
 
C. Withdrawal Criteria  
 Patients are free to withdraw from study at any time. Patients will also be removed from 

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study at any time for adverse events or if deemed necessary for their safety. Patients 
should be asked if they want to fully withdraw from the study, or only stop the intervention 
and answer the surveys and allow collect other data that may apply. 
 
D. Protocol 
Patients will be randomized to either sham video headset group or video headset 
analgesia group. Study coordinators will be assigned to either randomize and program 
headsets, or to assess patients’ during sessions. All enrolled patients will receive 
education by research team who will demonstrate how to adjust the headset strap, 
activate the device, and adjust the volume following a predetermined script with the goal 
of making patients feel comfortable using the device on their own. Patients will be assured 
they will receive the routine pain control in addition to video headset experience.  
Anesthetic management will follow pre-established clinical and institutional 
guidelines. Anesthesia will be at attending anesthesiologist’s discretion; usually that will 
be spinal anesthesia without intrathecal opioids. Intraoperative and postoperative opioids 
will also be given at the discretion of the attending anesthesiologist. Prophylactic 
antibiotics will be given per surgical routine. Other intraoperative and postoperative 
medications may be used and include anti-inflammatory medications, gabapentin, 
pregabalin, ketamine, or lidocaine patches. Clinicians will be encouraged to give a single 
dose of dexamethasone (4-8 mg) for PONV prophylaxis. Inhaled steroids will be permitted 
as necessary to treat reactive airway disease. 
Patients will be randomized in a 1:1 ratio to either relaxation program the morning 
of the first postoperative day, before start the intervention. Randomization will be based 
on computer-generated codes with random blocking and no stratification. Allocation will 
be concealed by a web-based system. The use of the video headset will be offered 
postoperatively while patients are awake between 8 AM to 4 PM. Each session will have 
a maximum duration of 8 minutes. We will target 3 session per day, with at least 
one hour separating each treatments. Treatments will continue for two postoperative 
days or until hospital discharge, whichever comes first. 
The study device is a Pico G2 4K headset, but all labels will be masked to reduce 

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the risk of unblinding. A member of the research team will program the headsets to either 
one of the two different relaxation programs and will explain to patient how to set up and 
use the device. The sham video group will watch a 2D conventional video projected in a 
virtual screen mimicking a void theater in the same headset, whereas the treatment group 
will have a full immersive experience with three-dimensional video and binaural audio. 
Other research team members and healthcare providers will be blinded to intervention 
assignment and pain assessment will be done by the blinded study coordinator. Patients 
will not use the video headset device during physical therapy or while ambulating and use 
of the headset will be restricted to the hospital. 
Patients will be allowed to receive prophylactic anti-emetics during intraoperative 
time based on the risk assessment for nausea and vomiting. Postoperative anti-emetics 
for symptomatic treatment will also be allowed; ondansetron will be the first choice. 
Patients will be followed-up by phone call one week after hospital discharge to ask 
them the Pain Outcomes Questionnaire Short Form (POQ-SF). No more than 3 attempts 
should be accomplished to contact the patients for the one-week post-discharge follow-
up. 
 
E. Measurements 
Demographic and Background Information 
Demographic data to be obtained includes height (cm), weight (kg), age (years), 
sex, ASA physical status classification, and self-declared ethnicity. Patients will be 
questioned for social history (tobacco) and medical history (pulmonary disease, kidney 
disease, diabetes mellitus, neurological disease, chronic pain conditions, illegal drug 
usage, alcohol abuse, myocardial infarction, previous surgery or stent placement and 
medications usage). Available preoperative laboratory tests and medication list will be 
recorded.  
Standard anesthesia monitoring will be used. Data obtained from electronic 
medical records for intraoperative variables will include: duration of surgery, 
intraoperative opioid consumption and antiemetic medications.   
Data for variables for the day of surgery as a baseline will be obtained from 

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electronic medical records for opioid consumption in PACU and ward; pain scores before 
surgery, in PACU and ward; requirement of oxygen in PACU and ward; nausea and 
vomiting, requirement of antiemetics, requirement of naloxone, and adverse events. 
Patient interaction with presented video content will be characterized using eye-tracking 
metrics. 
 
Outcomes  
All postoperative assessment will be made by an investigator who is strictly blinded to 
treatment allocation, and actual treatment (e.g., full immersion or sham distraction).  
Primary Outcome 
1. Pain Scores. We will assess pain using NRS scores (0-10, with 10 being worst) 
immediately before and 15 minutes after each intervention with the device, 
starting on postoperative day one (POD1) and until end of postoperative day two 
(POD2) or hospital discharge, whichever occurs first.  
 
Secondary Outcomes 
1. Total opioid consumption.  We will measure total opioid consumption, 
converted to morphine milligram equivalents (MME), starting at the first pre-
intervention pain score measurement, postoperative day one (POD1), and until 
the end of postoperative day 2 (POD2) or hospital discharge, whichever occurs 
first. 
2. Pain scores. We will capture all pain score measurements done every 4 hours 
by standard of care starting at the first pre-intervention pain score measurement, 
POD1, and end of postoperative day two or hospital discharge, whichever occurs 
first, using NRS scores (0-10, with 10 being worst). Only the pain scores from 
routine nurse assessments will be used here (pain scores measured as a part of 
the primary outcome won’t be included). 
3. Perception of video system usability.  Patient’s perception of video system 

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usability will be assessed using a validated questionnaire (System Usability 
Scale13)  once after the last intervention with the device and before hospital 
discharge. The System Usability Scale is scored from 0 to 100 and higher scores 
are related with devices that are easier to use. 
4. Post discharge pain outcomes.  Patients will be called one week after hospital 
discharge to assess post discharge pain outcomes using a validated 
questionnaire (Pain Outcomes Questionnaire Short Form14) which evaluates five 
domains (pain, mobility, activities of daily living, vitality, negative affect and fear). 
The Pain Outcomes Questionnaire Short Form is scored from 0 to 190 and 
higher scores are related with worst pain outcomes. 
 
Tertiary Outcomes 
1. Anti-emetic medications. We will record use of anti-emetic medications, and the 
outcome variable will be calculated as the number of anti-emetic medications 
administered starting at the first pre-intervention pain score measurement, POD1, 
until end of postoperative day two or hospital discharge, whichever occurs first. 
2. Patient mobility score.  We will measure patient mobility using physical therapy 
daily postoperative assessment (“6 Clicks” Basic Mobility Inpatient Short Form 
questionnaire15) starting at the first pre-intervention pain score measurement, POD1, 
until end of postoperative two or hospital discharge, whichever occurs first. The 
“6 Clicks” Basic Mobility Inpatient Short Form questionnaire is scored from 6 to 24 
and higher scores are related with lower levels of functional impairment. 
 
F. Data Analysis 
We will assess the balance between randomized groups on baseline variables using the 
standardized difference (i.e., difference in means or proportions divided by the pooled 
standard deviation).  For all analyses we will adjust for baseline variables having absolute 
standardized difference <0.1016. The analyses will be carried out using a modified 
Intention-to-Treat approach. More specifically, all patients who receive the treatment for 

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any duration of time will be included in the analysis. For example, if a patient chose to 
withdraw on POD 2, their measurements from POD1 would still be used in the analysis. 
We’ll only exclude patients who didn’t receive any treatment at all either due to refusal or 
because they chose to withdraw.  
Primary outcome. We will assess the effect of VR on NRS pain score after each study 
treatment over postoperative days one and two using a linear mixed effects model on the 
series of post-VR pains scores while adjusting for the corresponding pre-VR pain score, 
with time and randomized group as fixed effect categorical variables.  We will adjust for 
within-subject correlation across the pains scores using either an autoregressive AR (1) 
or unstructured correlation matrix, whichever has better fit (lower AIC, BIC). We will 
assess the group-by-time interaction, but even if significant (P<0.15) the primary result 
will be made collapsing over time. 
Secondary Outcomes 
1. Total opioid consumption.  We will assess the effect of VR on log-transformed 
total opioid consumption starting at the first pre-intervention pain score 
measurement, POD1, and until end of postoperative day 2 or hospital discharge, 
whichever occurs first, using a linear regression model. 
2.  Pain scores. We will assess the effect of VR on pain score over time starting at 
the first pre-intervention pain score measurement, POD1, and until end of 
postoperative day 2 or hospital discharge, whichever occurs first, using a linear 
mixed effects regression to account for within-subject correlation. Only the pain 
scores from routine nurse assessments will be used here (pain scores from Aim 
1 won’t be used). 
3. Perception of video system usability.  We will assess the effect of VR on 
perception of video system usability as measured by the System Usability Scale 
using a Wilcoxon rank-sum test and report the median difference (along with the 
95% CI) estimated using the Hodges-Lehmann approach. 
4. Post discharge analgesia.  We will assess the effect of VR on analgesia scores 
one week after discharge using a Wilcoxon rank-sum test and report the median 

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difference (along with the 95% CI) estimated using the Hodges-Lehmann 
approach. 
 
 
Tertiary Outcomes 
5. Anti-emetic medications. We will assess the effects of VR on the number of 
times a patient required anti-emetic medication within starting at the first pre-
intervention pain score measurement, POD1, and until postoperative day 2 or 
hospital discharge, whichever occurs first, using a Wilcoxon rank-sum test, and 
report the median difference (along with the 95% CI) estimated using the 
Hodges-Lehmann approach. 
6. Patient mobility score.  We will assess the effect of VR on patient mobility 
scores(s) during the postoperative day one (POD1), and until end of 
postoperative day 2 or hospital discharge, whichever occurs first, using a 
Wilcoxon rank-sum test, and report the median difference (along with the 95% 
CI) estimated using the Hodges-Lehmann approach. 
 
Interim analyses. We will use a group sequential design to conduct interim analyses at 
each 25% of the planned enrollment to assess efficacy and futility of the intervention using 
a gamma spending function. Specifically, we will maintain the overall alpha level 
(monitoring efficacy) at 0.05 using gamma parameter of -4 [similar to O’Brien Fleming], 
and power at 90% (monitoring beta, type II error) using gamma parameter of -1 [more 
aggressive].  Under the alternative hypothesis (assuming a true difference of 1 point) the 
cumulative probability of crossing an efficacy (and futility in parentheses) boundary at the 
1st through 4th analyses will be 0.08 (0.017), 0.36 (0.038), 0.71 (0.065) and 0.90 (0.10).   
  
Sample Size Considerations.   We base the sample size to have 90% power at the 0.05 
significance level to detect a difference of 1 point or more between VR and placebo on 
the serial post-intervention NRS measurements in our linear mixed effects model.  If we 

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assume a SD of 1.5 points (taking into account the within-subject correlation in the 
repeated measures design), a total of 98 patients (49 per group) would be needed, and 
after adjusting for interim analyses, a total of 113.  This sample size will also be sufficient 
for detecting moderate effect sizes in most of the other outcome variables.   
 
Interim Pilot Study to Re-Assess variability.  
We plan to re-estimate the sample size at the first interim analysis. For the 
outcome, the variance (𝜎2) and ICC (𝜌) will be estimated from the enrolled patients. 
Further, the correlation coefficient (𝑟) between pre-intervention and post-intervention pain 
scores was also estimated. The variance for the outcome (𝜎2) will be estimated for each 
of the pain score measurements separately and the most conservative (i.e., highest 
variance) option will be selected. Correlation coefficient was calculated in a similar 
manner and the lowest one was selected.   For estimating ICC (𝜌) a linear mixed effects 
model will be set up. We’ll obtain estimates of between subject variance (𝜎𝑏
2) and total 
variance (𝜎𝑡
2) from the model and estimated ICC as 𝜎𝑏
2/𝜎𝑡
2. 
Such a re-assessment “nuisance” parameters, does not affect the statistical 
properties of the design (i.e, does not increase type I error or decrease power). Keeping 
everything else the same as initially planned (90% power at the 0.05 significance level to 
detect a difference (Δ) of 1 point or more, 4 total analyses), we will calculate the new 
sample size using the equation below17,18, where n is the number of observations required 
per group and m is the average cluster size. The total variance will be estimated by 
calculated by estimating the total variance for each observation separately and selecting 
the most conservative (i.e., highest variance) option. Correlation coefficient will be 
calculated in a similar manner.  The number of patients required per group (N) would then 
be n/m. 
 
 
 

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If an increase in the total sample size is deemed necessary, the primary analysis will be 
carried out using the efficacy/futility boundaries for the new sample size. 
 

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Addendum. 
 
A. Pain Outcomes Questionnaire Short Form14 (POQ-SF) 
 
01. On a scale of 0 to 10, with 0 being no pain at all and 10 being the worst possible pain, 
how would you rate your pain on AVERAGE on the LAST WEEK? 
← 
No pain 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
Worst possible pain 
 
 
 
 
 
 
 
 
 
 
 
 
 
02. Does pain interfere with your ability to walk? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
03. Does your pain interfere with your ability to carry/handle everyday objects such as a 
bag of groceries or books? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
04. Does your pain interfere with your ability to climb stairs? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
05. Does your pain require you to use a cane, walker, wheelchair or other devices? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
06. Does your pain interfere with your ability to bathe yourself? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
07. Does your pain interfere with your ability to dress yourself? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 

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08. Does your pain interfere with your ability to use the bathroom? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
09. Does your pain interfere with your ability to manage your personal grooming (for 
example: combing hair, brushing teeth, etc.)? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
10. Does your pain affect your self-esteem or self-worth? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
11. How would you rate your physical activity? 
← 
Significant 
limitation in basic 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
→ 
Can perform 
vigorous activities 
without limitations  
  
12. How would you rate your overall energy? 
← 
Totally worn out 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
Most energy ever 
 
13. How would you rate your strength and endurance today? 
← 
Very poor 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
Very high 
 
14. How would you rate your feeling of depression TODAY? 
← 
Not at all depressed 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
Extremely 
depressed 
 
15. How would you rate your feelings of anxiety TODAY? 
← 
Not at all anxious 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
Extremely anxious 
 
16. How much do you worry about re-injuring yourself if you are more active? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
 

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17. How safe do you think it is for you to exercise? 
← 
Not safe at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
Extremely safe 
 
18. Do you have problems concentrating on things TODAY? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
19. How often do you feel tense? 
← 
Not at all 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 → 
All the time 
 
 
Pain Outcomes Questionnaire Short Form14 (POQ-SF) scoring template 
Pain 
Self-report of pain intensity 
Item 1 
Mobility 
Self-report of pain-related impairment in mobility 
Item 2 + item 3 + Item 4 + Item 5 
Activities of Daily Living (ADL) 
Self-report of pain-related impairment in completing ADL 
Item 6 + Item 7 + Item 8 + Item 9 
Vitality 
Subjective sense of impairment in activity and energy levels 
30 – (Item 11 + Item 12  + Item 13) 
Negative Affect 
Self-report of dysphoric affect and associated symptoms 
Item 10 + Item 14 +Item 15 + Item 18 + Item 19 
Fear 
Pain-related fear and avoidance 
(10 – Item 17) + Item 16 
TOTAL SCORE: 0 (best score) to 190 (worst score) 
 
 
 
 
 

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B. Boston University AM-PAC “6 Clicks” Basic Mobility Inpatient Short Form15 
 
How much difficulty does the patient currently have… 
Unable 
A lot 
A little 
None 
1. Turning over in bed (including adjusting bedclothes, sheets and 
blankets)? 
□ 
□ 
□ 
□ 
2. Sitting down on and standing up from a chair with arms (e.g. 
wheelchair, bedside commode, etc.) 
□ 
□ 
□ 
□ 
3. Moving from lying back to sitting on the side of the bed? 
□ 
□ 
□ 
□ 
How much help from another person does the patient 
currently need… 
Total 
A lot 
A little 
None 
4. Moving to and from a bed to a chair (including a wheelchair)? 
□ 
□ 
□ 
□ 
5. Need to walk in hospital room? 
□ 
□ 
□ 
□ 
6. Climbing 3-5 steps with a railing? 
□ 
□ 
□ 
□ 
 
Boston University AM-PAC “6 Clicks” Basic Mobility Inpatient Short Form scoring 
How much difficulty does the patient currently have… 
Unable 
A lot 
A little 
None 
1. Turning over in bed? 
1 
2 
3 
4 
2. Sitting down on and standing up from a chair with arms? 
1 
2 
3 
4 
3. Moving from lying back to sitting on the side of the bed? 
1 
2 
3 
4 
How much help from another person does the patient currently need… 
Total 
A lot 
A little 
None 
4. Moving to and from a bed to a chair? 
1 
2 
3 
4 
5. Need to walk in hospital room? 
1 
2 
3 
4 
6. Climbing 3-5 steps with a railing? 
1 
2 
3 
4 
TOTAL SCORE: 
Sum of the scores for each of six questions above 
6 (worst outcome) to 24 (best outcome) 
06: ±100% of functional impairment 
10: ±77% of functional impairment 
15: ±58% of functional impairment 
19: ±42% of functional impairment 
24: ±0% of functional impairment 
 

Virtual Reality Distraction for Reduction in Acute Postoperative 
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September 1, 2021. Protocol Amendment 
3.1. 
21 
C. System Usability Scale assessment13 
 
01. I think that I would like to use this product frequently 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
02. I found the product unnecessarily complex 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
03. I though the product was easy to use 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
04. I think that I would need the support of a technical person to be able to use this product 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
05. I found that the various functions in this product were well integrated 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
06. I thought that there was too much inconsistency in this product 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
07. I would imagine that most people would learn to use this product very quickly 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
08. I found the product very awkward to use 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
09. I felt very confident using the product 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
10. I need to learn a lot of things before I could get going with this product 
Strongly disagree 
□ 
Disagree 
□ 
Neutral 
□ 
Agree 
□ 
Strongly agree 
□ 
 
 

Virtual Reality Distraction for Reduction in Acute Postoperative 
Pain 
 
 
 
 
September 1, 2021. Protocol Amendment 
3.1. 
22 
System Usability Scale assessment scoring 
 
Strongly 
disagree 
Disagree 
Neutral 
Agree 
Strongly 
agree 
SCORE 
I think that I would like to use this product 
frequently 
1 
2 
3 
4 
5 
(score) – 1 
I found the product unnecessarily complex 
1 
2 
3 
4 
5 
5 – (score) 
I though the product was easy to use 
1 
2 
3 
4 
5 
(score) – 1 
I think that I would need the support of a 
technical person to be able to use this product 
1 
2 
3 
4 
5 
5 – (score) 
I found that the various functions in this product 
were well integrated 
1 
2 
3 
4 
5 
(score) – 1 
I thought that there was too much inconsistency 
in this product 
1 
2 
3 
4 
5 
5 – (score) 
I would imagine that most people would learn to 
use this product very quickly 
1 
2 
3 
4 
5 
(score) – 1 
I found the product very awkward to use 
1 
2 
3 
4 
5 
5 – (score) 
I felt very confident using the product 
1 
2 
3 
4 
5 
(score) – 1 
I need to learn a lot of things before I could get 
going with this product 
1 
2 
3 
4 
5 
5 – (score) 
TOTAL SCORE: 
0 (worst outcome) to 100 (best outcome) 
Sum of the scores for each statement and multiply by 22.5 
55 raw score: P25%, 68 raw score: P50%, 75 raw score: P75%  

Virtual Reality Distraction for Reduction in Acute Postoperative 
Pain 
 
 
 
 
September 1, 2021. Protocol Amendment 
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23 
G. REFERENCES 
 
1.  Hall MJ, Schwartzman A, Zhang J, Liu X. Ambulatory Surgery Data From Hospitals 
and Ambulatory Surgery Centers: United States, 2010. Natl Health Stat Rep. 
2017;(102):1-15. 
2.  Sloan M, Premkumar A, Sheth NP. Projected Volume of Primary Total Joint 
Arthroplasty in the U.S., 2014 to 2030. J Bone Joint Surg Am. 2018;100(17):1455-
1460. doi:10.2106/JBJS.17.01617 
3.  Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of Postoperative 
Pain: A Clinical Practice Guideline From the American Pain Society, the American 
Society of Regional Anesthesia and Pain Medicine, and the American Society of 
Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and 
Administrative Council. J Pain Off J Am Pain Soc. 2016;17(2):131-157. 
doi:10.1016/j.jpain.2015.12.008 
4.  Gan TJ, Habib AS, Miller TE, White W, Apfelbaum JL. Incidence, patient satisfaction, 
and perceptions of post-surgical pain: results from a US national survey. Curr Med 
Res Opin. 2014;30(1):149-160. doi:10.1185/03007995.2013.860019 
5.  Richebé P, Capdevila X, Rivat C. Persistent Postsurgical Pain: Pathophysiology and 
Preventative Pharmacologic Considerations. Anesthesiology. 2018;129(3):590-607. 
doi:10.1097/ALN.0000000000002238 
6.  Soffin EM, Waldman SA, Stack RJ, Liguori GA. An Evidence-Based Approach to the 
Prescription 
Opioid 
Epidemic 
in 
Orthopedic 
Surgery. 
Anesth 
Analg. 
2017;125(5):1704-1713. doi:10.1213/ANE.0000000000002433 
7.  Dascal J, Reid M, IsHak WW, et al. Virtual Reality and Medical Inpatients: A 
Systematic Review of Randomized, Controlled Trials. Innov Clin Neurosci. 2017;14(1-
2):14-21. 
8.  Tashjian VC, Mosadeghi S, Howard AR, et al. Virtual Reality for Management of Pain 
in Hospitalized Patients: Results of a Controlled Trial. JMIR Ment Health. 
2017;4(1):e9. doi:10.2196/mental.7387 
9.  Malloy KM, Milling LS. The effectiveness of virtual reality distraction for pain reduction: 
a 
systematic 
review. 
Clin 
Psychol 
Rev. 
2010;30(8):1011-1018. 
doi:10.1016/j.cpr.2010.07.001 
10.  
Mosadeghi S, Reid MW, Martinez B, Rosen BT, Spiegel BMR. Feasibility of an 
Immersive Virtual Reality Intervention for Hospitalized Patients: An Observational 
Cohort Study. JMIR Ment Health. 2016;3(2):e28. doi:10.2196/mental.5801 

Virtual Reality Distraction for Reduction in Acute Postoperative 
Pain 
 
 
 
 
September 1, 2021. Protocol Amendment 
3.1. 
24 
11.  
Chan E, Foster S, Sambell R, Leong P. Clinical efficacy of virtual reality for acute 
procedural pain management: A systematic review and meta-analysis. PloS One. 
2018;13(7):e0200987. doi:10.1371/journal.pone.0200987 
12.  
Kenney MP, Milling LS. The effectiveness of virtual reality distraction for reducing 
pain: A meta-analysis. Psychol Conscious Theory Res Pract. 2016;3(3):199-210. 
doi:10.1037/cns0000084 
13.  
Kortum P, Peres SC. Evaluation of Home Health Care Devices: Remote Usability 
Assessment. JMIR Hum Factors. 2015;2(1):e10. doi:10.2196/humanfactors.4570 
14.  
Clark ME, Gironda RJ, Young RW. Development and validation of the Pain 
Outcomes 
Questionnaire-VA. 
J 
Rehabil 
Res 
Dev. 
2003;40(5):381-395. 
doi:10.1682/jrrd.2003.09.0381 
15.  
Jette DU, Stilphen M, Ranganathan VK, Passek SD, Frost FS, Jette AM. Validity 
of the AM-PAC “6-Clicks” inpatient daily activity and basic mobility short forms. Phys 
Ther. 2014;94(3):379-391. doi:10.2522/ptj.20130199 
16.  
Austin PC. Balance diagnostics for comparing the distribution of baseline 
covariates between treatment groups in propensity-score matched samples. Stat 
Med. 2009;28(25):3083-3107. doi:10.1002/sim.3697 
17.    Rutterford, Clare, Andrew Copas, and Sandra Eldridge. Methods for Sample Size 
Determination in Cluster Randomized Trials. International Journal of Epidemiology 
44, no. 3 (June 2015): 1051–67. https://doi.org/10.1093/ije/dyv113. 
18. Clifton, Lei, Jacqueline Birks, and David A. Clifton. “Comparing Different Ways of 
Calculating Sample Size for Two Independent Means: A Worked Example.” 
Contemporary Clinical Trials Communications 13 (November 29, 2018). 
https://doi.org/10.1016/j.conctc.2018.100309.