Trial Outcomes & Findings for Pragmatic Comparative Effectiveness Trial of Evidence-based, On-demand, Digital Behavioral Treatments for Chronic Pain (NCT NCT04933474)

Last Updated: 2026-01-21

Results Overview

\[Alternative Title: Proportion of Participants with \>=2 Change in Average of 7 Daily Pain Intensity Questionnaires\] The change from study baseline to week 8 in daily pain intensity was measured using the standard 11-point numeric rating scale (NRS) with a 24-hour recall. Daily pain NRS was measured for 7-days during baseline and again during the final week of the study (week 8). This outcome is the baseline vs. week 8 difference-in-difference in 7-day average NRS pain intensity scores, dichotomized into if the minimally clinically importance difference (MCID) of 2 is achieved. NRS is positively scored, where higher scores indicate worse pain intensity. The difference from baseline is reported as Baseline - Week 8, therefore a higher difference corresponds to improvement of symptoms (reduced pain intensity). The difference-in-difference is dichotomized into if the MCID of 2 is achieved, reported as the proportion of participants by arm.

Recruitment status

COMPLETED

Study phase

Target enrollment

330 participants

Primary outcome timeframe

From baseline to end of treatment at Week 8

Results posted on

2026-01-21

Participant Flow

Participants were recruited from four clinical sites: Cedars-Sinai Medical Center (CA), Ochsner Health System (LA), University of Alabama at Birmingham (AL), and Bendcare (FL). Patient cohort search engines identified individuals with chronic pain, and their zip codes were matched with 2010 USDA RUCA data. Enrollment activities were conducted remotely, by telephone and electronic surveys. Recruitment spanned from 3/29/2022 to 2/28/2024 with final analyzable sample N=330 (N=300+30 replacements).

Of 2,804 participants screened, 367 underwent the informed eConsent process and enrolled in the Screening Week. Of the 367 participants, 330 successfully met inclusion criteria and were randomized to one of two treatment arms.

Participant milestones

Participant milestones
Measure	painTRAINER (2D mHealth Intervention) Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management. Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR Therapy (3D VR Intervention) Participants will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward chronic pain management. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes. Skills-based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html
Overall Study STARTED	161	169
Overall Study Follow-Up Complete	129	153
Overall Study COMPLETED	127	152
Overall Study NOT COMPLETED	34	17

Reasons for withdrawal

Reasons for withdrawal
Measure	painTRAINER (2D mHealth Intervention) Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management. Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR Therapy (3D VR Intervention) Participants will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward chronic pain management. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes. Skills-based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html
Overall Study Discontinued Intervention Prior to End of Follow-up	2	1
Overall Study Lost to Follow-up	19	9
Overall Study Life Burden - unable to participate	6	2
Overall Study Disease Burden - unable to participate	4	1
Overall Study Surgery/Hospitalization	1	2
Overall Study Dissatisfied with Intervention	1	1
Overall Study Withdrew interest in participation	1	0
Overall Study Had previously enrolled in the study	0	1

Baseline Characteristics

Pragmatic Comparative Effectiveness Trial of Evidence-based, On-demand, Digital Behavioral Treatments for Chronic Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	painTRAINER (2D mHealth Intervention) n=161 Participants Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR (3D VR Intervention) n=169 Participants Participants will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed.VR experiences last between 2-16 minutes. Participants will use the Pico G24K VR audio and visual head-mounted device, loaded with EaseVRx+. It does not require a smartphone or personal computer to operate and comes with an orientation-tracked controller. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view.	Total n=330 Participants Total of all reporting groups
Age, Continuous	54.4 years STANDARD_DEVIATION 12.0 • n=37 Participants	55.4 years STANDARD_DEVIATION 12.9 • n=44 Participants	54.9 years STANDARD_DEVIATION 12.5 • n=40 Participants
Sex: Female, Male Female	112 Participants n=37 Participants	122 Participants n=44 Participants	234 Participants n=40 Participants
Sex: Female, Male Male	49 Participants n=37 Participants	47 Participants n=44 Participants	96 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=37 Participants	10 Participants n=44 Participants	24 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	142 Participants n=37 Participants	156 Participants n=44 Participants	298 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=37 Participants	3 Participants n=44 Participants	8 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=37 Participants	3 Participants n=44 Participants	5 Participants n=40 Participants
Race (NIH/OMB) Asian	0 Participants n=37 Participants	4 Participants n=44 Participants	4 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	17 Participants n=37 Participants	25 Participants n=44 Participants	42 Participants n=40 Participants
Race (NIH/OMB) White	129 Participants n=37 Participants	134 Participants n=44 Participants	263 Participants n=40 Participants
Race (NIH/OMB) More than one race	13 Participants n=37 Participants	2 Participants n=44 Participants	15 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	1 Participants n=44 Participants	1 Participants n=40 Participants
Education Did not complete Secondary School or Less than High School	5 Participants n=37 Participants	2 Participants n=44 Participants	7 Participants n=40 Participants
Education Some Secondary School or High School Education	20 Participants n=37 Participants	23 Participants n=44 Participants	43 Participants n=40 Participants
Education High School or Secondary School Degree Complete	50 Participants n=37 Participants	65 Participants n=44 Participants	115 Participants n=40 Participants
Education Associate's or Technical Degree Complete	38 Participants n=37 Participants	40 Participants n=44 Participants	78 Participants n=40 Participants
Education College or Baccalaureate Degree Complete	34 Participants n=37 Participants	25 Participants n=44 Participants	59 Participants n=40 Participants
Education Doctoral or Postgraduate Education	14 Participants n=37 Participants	14 Participants n=44 Participants	28 Participants n=40 Participants
Employment Not employed	98 Participants n=37 Participants	102 Participants n=44 Participants	200 Participants n=40 Participants
Employment Part-time employment	12 Participants n=37 Participants	17 Participants n=44 Participants	29 Participants n=40 Participants
Employment Full-time employment	51 Participants n=37 Participants	50 Participants n=44 Participants	101 Participants n=40 Participants
Household Income Less than $10,000	13 Participants n=37 Participants	8 Participants n=44 Participants	21 Participants n=40 Participants
Household Income $10,000-$24,999	22 Participants n=37 Participants	30 Participants n=44 Participants	52 Participants n=40 Participants
Household Income $25,000-$34,999	18 Participants n=37 Participants	15 Participants n=44 Participants	33 Participants n=40 Participants
Household Income $35,000-$49,999	20 Participants n=37 Participants	32 Participants n=44 Participants	52 Participants n=40 Participants
Household Income $50,000-$74,999	24 Participants n=37 Participants	20 Participants n=44 Participants	44 Participants n=40 Participants
Household Income $75,000-$99,999	19 Participants n=37 Participants	24 Participants n=44 Participants	43 Participants n=40 Participants
Household Income $100,000-$149,999	21 Participants n=37 Participants	13 Participants n=44 Participants	34 Participants n=40 Participants
Household Income $150,000-$199,999	8 Participants n=37 Participants	7 Participants n=44 Participants	15 Participants n=40 Participants
Household Income $200,000 or more	4 Participants n=37 Participants	5 Participants n=44 Participants	9 Participants n=40 Participants
Household Income Prefer not to answer	12 Participants n=37 Participants	15 Participants n=44 Participants	27 Participants n=40 Participants
Participant Enrollment by Site Cedars-Sinai Health System	30 Participants n=37 Participants	33 Participants n=44 Participants	63 Participants n=40 Participants
Participant Enrollment by Site Ochsner Health	54 Participants n=37 Participants	56 Participants n=44 Participants	110 Participants n=40 Participants
Participant Enrollment by Site University of Alabama at Birmingham (UAB)	29 Participants n=37 Participants	32 Participants n=44 Participants	61 Participants n=40 Participants
Participant Enrollment by Site Bendcare	46 Participants n=37 Participants	47 Participants n=44 Participants	93 Participants n=40 Participants
Participant Enrollment by Site Other	2 Participants n=37 Participants	1 Participants n=44 Participants	3 Participants n=40 Participants

PRIMARY outcome

Timeframe: From baseline to end of treatment at Week 8

Population: All analyses were performed by study arm using an Intent-to-treat (ITT) population defined as all randomized participants across each treatment arm. Participants that provided at least 4 out of 7 possibly daily responses at Week 8 were included in the analysis.

Outcome measures

Outcome measures
Measure	painTRAINER (2D mHealth Intervention) n=125 Participants Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR (3D VR Intervention) n=153 Participants Participants will use the Pico G2 4K VR audio and visual head-mounted device. It is a standalone VR headset that comes with an orientation-tracked controller and does not require a smartphone or personal computer to operate. It supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. Patients will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes.
Change From Baseline to Week 8 in Daily Pain Intensity Difference is greater than or equal to 2	40 Participants	35 Participants
Change From Baseline to Week 8 in Daily Pain Intensity Difference is less than 2	85 Participants	118 Participants

SECONDARY outcome

Timeframe: From baseline to end of treatment at Week 8

Population: All analyses were performed by study arm using an Intent-to-Treat (ITT) population, defined as all randomized participants. Participants who completed the PROMIS-PI instrument at Week 8 were included in the analysis.

The Patient-Reported Outcomes Measurement Information System Pain Interference (PROMIS-PI) scale, version 4a, measures the consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Items are rated on a 5-point Likert scale from "not at all" (1) to "very much" (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10). PROMIS-PI is positively scored, where higher scores indicate worse pain interference. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced PI).

Outcome measures

Outcome measures
Measure	painTRAINER (2D mHealth Intervention) n=127 Participants Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR (3D VR Intervention) n=153 Participants Participants will use the Pico G2 4K VR audio and visual head-mounted device. It is a standalone VR headset that comes with an orientation-tracked controller and does not require a smartphone or personal computer to operate. It supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. Patients will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes.
Change in Patient-Reported Outcomes Measurement Information System Pain Interference 4a (PROMIS-PI) T-score	-4.5 T-score Standard Deviation 6.3	-3.2 T-score Standard Deviation 6.0

SECONDARY outcome

Timeframe: From baseline to end of treatment at Week 8

Population: All analyses were performed by study arm using an Intent-to-Treat (ITT) population, defined as all randomized participants. Participants who completed the PROMIS Anxiety instrument at Week 8 were included in the analysis.

The Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale, version 4, assesses self-reported perceptions of fear, anxious misery (worry, dread), hyperarousal, and somatic symptoms related to arousal. Items are rated Items are rated on a 5-point Likert scale from "never" (1) to "always" (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10). PROMIS-Anxiety is positively scored, where higher scores indicate worse anxiety. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced anxiety).

Outcome measures

Outcome measures
Measure	painTRAINER (2D mHealth Intervention) n=127 Participants Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR (3D VR Intervention) n=153 Participants Participants will use the Pico G2 4K VR audio and visual head-mounted device. It is a standalone VR headset that comes with an orientation-tracked controller and does not require a smartphone or personal computer to operate. It supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. Patients will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes.
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety T-score	-0.3 T-score Standard Deviation 7.6	-0.6 T-score Standard Deviation 7.6

SECONDARY outcome

Timeframe: From baseline to end of treatment at Week 8

Population: All analyses were performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants. Participants that completed PSEQ-2 at Week 8 were included in the analysis.

The Pain Self-Efficacy Questionnaire (PSEQ-2) is a two-item instrument designed to assess the extent to which people in pain believe they are presently able to work and live a normal life, despite pain. "Work" includes housework and paid and unpaid work. Items are rated on a 7-point Likert scale from "not confident at all" (0) to "completely confident" (6), with a raw score calculated by a sum of the 2 items ranging from 0 to 12. PSEQ-2 is positively scored, where higher scores indicate greater self-efficacy. The difference from baseline is reported as Week 8 - Baseline, therefore a positive difference corresponds to improvement of symptoms (greater self-efficacy).

Outcome measures

Outcome measures
Measure	painTRAINER (2D mHealth Intervention) n=127 Participants Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR (3D VR Intervention) n=153 Participants Participants will use the Pico G2 4K VR audio and visual head-mounted device. It is a standalone VR headset that comes with an orientation-tracked controller and does not require a smartphone or personal computer to operate. It supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. Patients will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes.
Change in 2-item Pain Self-Efficacy Questionnaire (PSEQ-2)	1.5 units on a scale Standard Deviation 2.7	0.6 units on a scale Standard Deviation 2.8

SECONDARY outcome

Timeframe: From baseline to end of treatment at Week 8

Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants. Participants who completed the briefPCS instrument at Week 8 were included in the analysis.

Self-reported pain catastrophizing was measured using the 4-item Pain Catastrophizing Scale (briefPCS) questionnaire. Pain catastrophizing is a negative mental state regarding actual or anticipated pain, and includes aspects of rumination, magnification, and sense of helplessness. Pain catastrophizing is a highly potent prognostic indicator for acute analgesic use, and acute and chronic pain outcomes, yet is also highly modifiable with behavioral treatment that enhances pain self-regulation via evidence-based skills. Items are rated on a 5-point Likert scale from "not at all" (0) to "all the time" (4), with a raw score calculated by a sum of the 4 items, ranging from 0 to 16. briefPCS is positively scored, where higher scores indicate greater levels of pain catastrophizing. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced pain catastrophizing).

Outcome measures

Outcome measures
Measure	painTRAINER (2D mHealth Intervention) n=127 Participants Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR (3D VR Intervention) n=153 Participants Participants will use the Pico G2 4K VR audio and visual head-mounted device. It is a standalone VR headset that comes with an orientation-tracked controller and does not require a smartphone or personal computer to operate. It supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. Patients will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes.
Change in 4-item Pain Catastrophizing Scale (briefPCS)	-1.8 units on a scale Standard Deviation 3.5	-1.7 units on a scale Standard Deviation 3.2

SECONDARY outcome

Timeframe: From baseline to end of treatment at Week 8

Population: Participants that responded to the medication use questionnaire in at least 4 out of 7 days administered during Baseline and during Week 8 were included in the each respective analysis.

Opioid medications are commonly prescribed for pain analgesia. Participants self-reported their prescription and over-the-counter pain medications, daily for 7 days, at baseline (days -6 to 0) and during Week 8 of the study (days 50-56). The questionnaire contains lists of opioids and non-opioids. Responses were categorized based on whether or not an individual reported the use of an opioid medication on at least one of the daily surveys during baseline and during week 8; responses are reported as the proportion of individuals who reported the use of an opioid and who completed at least 4 daily questionnaires during the specified time period, divided by the total number of individuals who completed at least 4 daily questionnaires during the time interval, by arm. A smaller proportion at week 8 corresponds to a decrease in the frequency of opioid use in the observed sample.

Outcome measures

Outcome measures
Measure	painTRAINER (2D mHealth Intervention) n=161 Participants Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR (3D VR Intervention) n=169 Participants Participants will use the Pico G2 4K VR audio and visual head-mounted device. It is a standalone VR headset that comes with an orientation-tracked controller and does not require a smartphone or personal computer to operate. It supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. Patients will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes.
Change in Weekly Opioid Use (Use or No Use) Baseline:Used Opioid in Past 7 Days	67 Participants	67 Participants
Change in Weekly Opioid Use (Use or No Use) Week 8: Used Opioid in Past 7 Days	44 Participants	45 Participants

Adverse Events

painTRAINER (2D mHealth Intervention)

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Skills-based VR (3D VR Intervention)

Serious events: 4 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	painTRAINER (2D mHealth Intervention) n=161 participants at risk Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR (3D VR Intervention) n=169 participants at risk Participants will use the Pico G2 4K VR audio and visual head-mounted device. It is a standalone VR headset that comes with an orientation-tracked controller and does not require a smartphone or personal computer to operate. It supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. Patients will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes.
Hepatobiliary disorders Kidney Stones	0.62% 1/161 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.00% 0/169 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Surgical and medical procedures Hysterectomy	0.00% 0/161 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.59% 1/169 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Hepatobiliary disorders Kidney Infection	0.00% 0/161 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.59% 1/169 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Nervous system disorders Hospitalization for pain	0.00% 0/161 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.59% 1/169 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Cardiac disorders Heart transplant	0.00% 0/161 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.59% 1/169 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Musculoskeletal and connective tissue disorders Lumbar Sprain	0.62% 1/161 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.00% 0/169 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Blood and lymphatic system disorders Leg Swelling	0.62% 1/161 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.00% 0/169 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.

Other adverse events

Other adverse events
Measure	painTRAINER (2D mHealth Intervention) n=161 participants at risk Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences. painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.	Skills-based VR (3D VR Intervention) n=169 participants at risk Participants will use the Pico G2 4K VR audio and visual head-mounted device. It is a standalone VR headset that comes with an orientation-tracked controller and does not require a smartphone or personal computer to operate. It supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. Patients will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed. VR experiences last between 2-16 minutes.
Nervous system disorders Cybersickness	0.00% 0/161 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	20.7% 35/169 • Number of events 52 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Psychiatric disorders Video Game Anxiety	0.00% 0/161 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	4.7% 8/169 • Number of events 13 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Infections and infestations COVID-19	1.9% 3/161 • Number of events 3 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.59% 1/169 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Musculoskeletal and connective tissue disorders Pain flare-up/Spasms	2.5% 4/161 • Number of events 4 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.59% 1/169 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Infections and infestations Flu/Head cold	2.5% 4/161 • Number of events 4 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.00% 0/169 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/161 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	7.1% 12/169 • Number of events 18 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Musculoskeletal and connective tissue disorders Muscle soreness and stiffness	0.00% 0/161 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.59% 1/169 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Infections and infestations Strep Throat	0.62% 1/161 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.00% 0/169 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Musculoskeletal and connective tissue disorders Hip Swelling	0.62% 1/161 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.00% 0/169 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.
Infections and infestations Shingles	0.00% 0/161 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.	0.59% 1/169 • Number of events 1 • Adverse event data were collected during participants' 8-week follow-up period. Adverse events (AEs) were collected via weekly questionnaires, participant communications, and free-text responses. This low-risk trial focused on chronic pain, with most AEs involving initial VR side effects and intermittent pain flare-ups. For side-effects reported in the SSQ survey, only side-effects reported at moderate or above were logged. Mild AEs requiring treatment were upgraded to moderate, and ER visits/hospitalizations were reported as severe/serious.

Additional Information

Samuel Eberlein

Cedars-Sinai Medical Center

Phone: 310-423-6721

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place