ABSTRACT Millions of Americans undergo surgery each year with fewer than half of patients reporting adequate postoperative pain relief and approximately 75% reporting moderate to severe postoperative pain. Gaps in postoperative pain management that lead to the unnecessary introduction and over-prescription of opioids continue to exacerbate the opioid crisis. Data from the US Center for Disease Control (CDC) revealed that even a single day of opioid therapy can predict up to a 6% increase in the risk of the patient developing a dependency within a year. appliedVR plans to combine its existing success with Virtual Reality (VR)-based technology to provide acute perioperative pain management through a new software-based VR medical device, RelieVRx™. In Phase I, we developed therapeutic virtual reality content focused on strategies for substance abuse. RelieVRx is intended to prevent the onset of Opioid Use Disorder (OUD) via enhanced opioid sparing techniques. Initial clinical studies have shown our content has reduced patient’s pain scores not only while the patient is actively utilizing the device, but also following the treatment. In Phase II, we will improve the functionality of the device, conduct two clinical trials to validate the use of RelieVRx™ for pain management after total hip or knee arthroplasty, and prepare a report of our findings to the FDA for class 2 SaMD clearance. In Aim 1, we will optimize the backend infrastructure (e.g., storage, access to data, delivery of content) of the RelieVRx™ platform to improve content storage, distribution and FDA-compliant data collection. In Aims 2 and 3, we will conduct two 100 patient trials to assess the efficacy of RelieVRx for acute pain management after total hip or knee arthroplasty in partnership with the Cleveland Clinic and Geisinger Health System, respectively. Lastly, in Aim 4, we will prepare the materials/reports garnered through our studies for a de novo submission to the FDA for class 2 SaMD clearance. Over $13 billion in annual healthcare dollars go to treating addiction associated with postoperative pain management. Annually an estimated 2.6 million people undergoing surgery will become persistent opioid users. As a non-opioid alternative intended to reduce postoperative pain and reduce the need for and utilization of opioids in the postoperative setting, RelieVRx stands to change the course of the opioid epidemic and dramatically improve the state of surgical outcomes for millions of patients, doctors, and caregivers.

PROJECT NARRATIVE Millions of Americans undergo surgery each year with fewer than half of patients reporting adequate postoperative pain relief, which can lead to the unnecessary introduction and over- prescription of opioids and subsequent Opioid Use Disorder (OUD). These clinical studies will drive the development of Virtual Reality-based adjunctive therapies as an opioid sparing method for acute postoperative pain management. Thus, our technology will have broad societal impact for reducing the incidence of OUD in the United States.