Clinical Insights: Virtual Reality - An Emerging Paradigm in Healthcare

Page 1

August 2022


Contents

3 | INTRODUCTION 3 | UNDERSTANDING VIRTUAL REALITY (VR) What is VR? How Does VR Work? How is VR Being Used? Augmented Reality (AR) and Mixed Reality (MR) The Digital Care Landscape

5 | THE VR INDUSTRY Funding Influencers

6 | THE VALUE OF VR Pediatric Intervention Mental Health Treatments Chronic Pain Treatment Virtual Rehabilitation VR in Training and Education Inequities in Health

11 | CLINICAL TRIAL EVIDENCE 16 | THE POTENTIAL RISKS OF VR 17 | REGULATORY TRENDS 18 | MAGELLAN’S PERSPECTIVE 19 | SUMMARY 20 | REFERENCES Visit magellanrx.com to view more insights!

Contributors Maryam Tabatabai, PharmD Vice President, Clinical Information, Magellan Rx Management Caroline Carney, MD, MSc, FAPM, CPHQ Chief Medical Officer, Magellan Health Chera L. York Medical Writer, Magellan Rx Management Kristin D. Brown-Gentry, MS Director, Clinical Outcomes and Analytics, Magellan Rx Management Brooke D. Hunter, MS Senior Health Outcome Specialist, Magellan Rx Management Lou Parrott, MD, PHD ABPM Certified Addiction Medicine Vice President, Medical Director, Magellan Healthcare Gerald Busch, MD MPH Medical Director, Clinical Center of Excellence Lead, Magellan Healthcare


INTRODUCTION As the era of digital health comes into focus, the transformation encompasses a broad scope of categories including, telehealth, wearable devices, wellness applications (apps), and digital therapeutics.1 Digital therapeutics are used as preventive medicine and for medical intervention, delivered directly to the patient and built on evidenced-based information.2 Virtual Reality (VR) is part of the digital therapeutics spectrum and is an emerging and rapidly evolving technology. In 2019, Time magazine listed VR as one of the 12 Innovations That Will Change Health Care and Medicine in the 2020s.3 Though some treatments are available on an outpatient basis, it is primarily applied in larger teaching and research institutions and not yet considered a part of routine care. VR has existed for several decades, but only recently has it advanced enough for commercial readiness and application.

Dating back to 1962 and the advent of the Sensorama (which allowed theater goers to experience multisensory simulation), major optical advances took place in the 1970’s and 80’s, including the National Aeronautics and Space Administration’s (NASA) development of a head-mounted device with gloves.4, 5

UNDERSTANDING VR What is VR? Defined by the International Research Journal of Engineering and Technology (IRJET), VR is “the use of computer modeling and situations which help a person in interacting with an artificial 3D environment.”6 VR technology constructs an artificial environment allowing participants to engage and interact much like they would in the physical world, only in a virtual form with the use of a virtual headset. VR’s potential as a clinical tool is quickly changing from science fiction to conceivable medical treatment. The umbrella of Medical Extended Reality (MXR) encompasses VR and Augmented Reality (AR).7 How Does VR Work? As VR use expands and is extended into new disciplines of study and application, researchers continue to investigate how VR works. It is suggested that VR creates embodied simulation, similar to the brain. Neuroscientists know in order for the brain to regulate and control the body in the physical world, it constructs an embodied simulation of the body in order to predict and represent actions, concepts, and emotions. VR works similarly by maintaining a simulation of the body and the space around it. VR predicts sensory consequences of the users movements, creating the same scene they see in the physical world.8 For instance, a patient being treated for post-traumatic stress disorder (PTSD) with VR is able to become immersed in a simulated combat environment in which the simulated world changes in response to head or body movement. This allows exposure therapy to take place in a controlled environment, including the emotional intensity of the scenes promoting the retrieval, confrontation, and processing of traumatic events.9 Furthermore, individuals being treated for pain with VR are able to feel a sense of presence when immersed in strong and effective virtual environments. This allows distraction from the physical world where they feel the pain, supporting previous research around the theory of distraction that demonstrates the efficacy of cognitive engagement in the reduction of pain.10, 11 How is VR Being Used? VR is currently being practiced in a number of disciplines such as mental health, pain management, rehabilitation, training, education, and pediatric care. Vigorous studies are also underway for potential efficacy in the treatment of Alzheimer’s disease, depression, addiction, and other illnesses.12, 13, 14 Its healthcare functionality is made possible by the swift speed of technological advances in the past 10 years, constructing a more immersive and accessible platform. Further, the United States (US) Food and Drug Administration (FDA) is playing a critical role through regulatory controls and marketing pathways to ensure devices and rapidly developing technologies are safe and effective for treatment.15 Ensuring checks and balances is key considering many of the companies spurring innovation in healthcare are new to the medical device industry. 3


Augmented and Mixed Reality AR and Mixed Reality (MR) fall within the spectrum of MXR including VR. They are also becoming important tools in the future of VR healthcare. AR is a semi-immersive experience which integrates computer-generated images into the physical world, such as a filter on a social media app or a visualization tool that helps medical staff draw blood.16, 17 Further, MR allows the user to interact with the physical and virtual worlds simultaneously, combining elements of both VR and AR.18 The National Aeronautics and Space Administration (NASA) recently created an MR software that allows AR MR engineers and scientists to have virtual meetings and even walk on Mars.19 MR is already being used through the use of MR headsets that allow doctors to make hospital rounds with the ease of receiving patient data (such as test results) in real time through a holographic image transferred onto the MR headset visor. Additionally, hospital staff outside of the patient room can see what the physician is seeing on a computer screen, allowing an entire team to engage in rounds remotely.20 As the technology advances at an accelerated pace, AR and MR can sometimes be difficult to differentiate. Although distinct differences currently exist, future advancements could likely converge the technologies into one universe.

MXR

The Digital Care Landscape The quick adoption of digital care during the COVID-19 crisis contributed to a healthcare system reshaped by the pandemic. Digital care, including telehealth services, represents a wide array of care including, provider-to-patient and provider-to-provider communication, along with utilization of virtual agents and wearable devices.21 Heavy utilization of digital care during the pandemic and beyond have demonstrated the value and need for convenient and accessible care. VR, AR, and MR have the potential to further leverage telehealth services as the technology is studied and covered by payers and the medical community. As healthcare transforms and evolves in the age of digital health, the Metaverse may signal the beginning of a whole new virtual approach to healthcare delivery. The Metaverse, hypothesized to be the next internet, will harness the technologies of virtual, augmented, and mixed realities to create online environments and telemedicine outlets for treatment.22 Rehabilitation, physical therapy, cognitive therapy, and support groups already exist in the Metaverse allowing patients to gather virtually. As the face and location of healthcare change, we may experience it in a new dimension.

NOTABLE MILESTONES

2016

1956

First VR surgery is live-streamed

Sensorama introduced

1982

FDA’s Center for Devices and Radiological Health (CDRH) established

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2021

FDA grants first approval for a VR system for chronic pain

2018

Facebook unveils the Oculus Quest wireless headset


THE VR INDUSTRY Funding Private and public funding have grown for clinical trials in the US and around the world, including those sponsored by the National Institute of Health (NIH). The NIH is currently involved in multiple trials studying the effectiveness of VR in the treatment of pain, post-traumatic stress disorder (PTSD), anxiety, and other illnesses that may benefit from VR therapy.23, 24, 25, 26 Notably, the National Institute on Aging (NIA) awarded tech company, Rendever, a $2 million grant in August 2021 for mental health research.27 There is a brisk market of tech companies committed to the advancement of VR technology and obtaining funds is rising rapidly. California-based, AppliedVR, acquired $36 million in public funding to continue building its pharmacy platform aimed at replacing traditional pharmaceuticals and/or surgery for pain management.28 A pioneer in at-home VR treatment, XRHealth, raised $10 million through funds from the American Association of Retired Persons (AARP), crowdfunding, and others to expand VR treatment in the Metaverse.29 Osso VR raised $66 million in March 2022 to broaden access to surgical education after securing $14 million in funding from private investors in 2020.30 The Swiss digital neurotherapy company MindMaze, raised more than $340 million to aid in global commercialization of products that focus on motor skills and cognitive function treatment.31 Influencers As VR technology sees prolific growth, the potential in the healthcare industry looks promising. Meta’s (formerly Facebook) acquisition of Oculus and its VR technology in 2014 prompted an increased interest among tech startups in the development of numerous healthcare related uses.32 The release of the VR headset, the Oculus Rift in 2016, marked a significant shift in the history of VR technology and considerable growth followed, putting the technology in the hands of consumers as well as teaching and research institutions and not just software companies.33 The World Health Organization (WHO), Harvard, and Johns Hopkins are just a few of the research and educational organizations working with VR companies to develop healthcare uses. Multiple tech startups, as well as long-established companies, are currently involved in VR healthcare development and application. COMPANY AppliedVR

DEVICE/SYSTEM

CLINICAL UTILITY

RelieVRx Chronic pain treatment (formally EaseVRx)

FDA STATUS FDA-Cleared, De Novo Approval

ImmersiveTouch®34 ImmersiveTouch®

Training, education, and surgical planning

FDA-Cleared, 510(k) Approval35

Meta36

Meta Quest 237

Surgical training

N/A

MindMaze

MindMotion GO & MindMotion PRO

Virtual rehabilitation

FDA-Cleared, 510(k) Approval

Microsoft

HoloLens

Patient treatment

N/A

Novarad

OpenSight®

Training, education, and surgical planning

FDA-Cleared, 510(k) Approval

Osso VR

Osso VR

Training and education

N/A

Penumbra

REAL® system38

Virtual rehabilitation

FDA-Cleared, 510(k) Approval39

PrecisionOS

InVisionOS

Training, education, and surgical planning

FDA-Cleared, 510(k) Approval

Rendever

Rendever

Mental health treatment

N/A

NEUROSYNC

EYESYNC®40

Analyzes eye-tracking impairment

FDA-Cleared, 510(k) Approval41

XRHealth

XRHealth

Mental health treatment & virtual rehabilitation N/A

Not an all-inclusive list.

5


THE VALUE OF VR Pediatric Intervention Managing pain, fear, and anxiety remain difficult in the pediatric population as they are often under-recognized and undertreated. Patient distress is common during treatment and procedures. This can especially be true with the intense pain experienced by burn and cancer patients who endure ongoing testing and treatment.42 Additionally, immediate pain and distress are not the only concerns. It is well documented that patients experience long term sequelae from inadequate pain management creating a negative impact on their future psychological health, including increased pain sensitivity over the course of their lives.43 Managing pain with the use of sedation and analgesia have been routinely used over the last 40 years, but experts have voiced serious concerns about the adverse effects of combining opioids with benzodiazepines for pain and anxiety control.44 Non-pharmacologic interventions have been somewhat effective including cognitive behavioral therapy (CBT), guided imagery, relaxation techniques, toy distraction, and hypnosis, but new and effective interventions are needed. Multiple clinical trials demonstrate that pediatric patients receiving VR intervention have statistically significantly reduced pain and anxiety as opposed to those treated with standard care. Recent studies examining VR intervention as a tool for pain and anxiety reduction in the pediatric population include a study comparing the effectiveness of VR intervention to conventional care in children receiving peripheral intravenous catheter placement, and a study examining the use of VR intervention among hematology, oncology, and blood marrow transplant patients undergoing painful and distressing procedures.,45, 46 Both studies suggest VR intervention can be clinically significant in reducing pain and anxiety. The use of VR is increasingly applied in children’s hospitals, such as Stanford Children’s Health where AR and VR software are part of a patient’s care plan to engage and distract them during painful procedures. The Childhood Anxiety Reduction Through Innovation and Technology (CHARIOT) program at Lucile Packard Children’s Hospital Stanford has composed a team of physicians, engineers, researchers, and child life professionals in an effort to implement new non-traditional immersive technologies for young patients.47 The hospital uses VR during treatment as a means to decrease pain and stress, for example, by offering AR goggles for patients in the pre-op so they can watch movies and play games prior to being wheeled back for surgery, and by using VR games in the intensive care unit (ICU). A study published in the Journal of the American Medical Association (JAMA) in June of 2021, suggests VR may be effective in reducing pain during dressing changes for pediatric burn patients. The intense pain associated with burn dressing changes is often worse than the initial burn injury and highdose opioids are routinely required. As well, a direct relationship between pain and anxiety exists amid pediatric burn patients leading to increased anxiety over the course of treatment and creating long-term challenges.48 Amidst the increased application and positive outlook of VR in the pediatric population, there is a lack of clinical professional guidelines and quantitative studies looking at the effects on children. Preliminary results show improvements in anxiety and pain symptoms with little side effects, but the possible impact on vision, brain development, and issues with stimulus intensity are all considerations for further investigation.49, 50 This is a greater concern in younger children given brain neuroplasticity for development in the early years of life. Evidence shows excessive exposure to screen time negatively impacts brain development, including a connection between increased screen time and diminished language, literary, and executive functions of the brain in preschool-aged children.51 Coordination may be negatively impacted due to VR’s influence on the brain’s interpretation of sensory stimulus such as vision and vestibular balance.52 Additionally, studies have investigated electronic media use and sleep disturbances, depression, and anxiety.53 Age appropriateness is likely to be more critically reviewed as utilization grows and more studies are completed. Currently, some manufacturers of VR headsets do not recommend them for children younger than 13 years.54, 55 Furthermore, cau-

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tion should be used regarding material that may be inappropriate or harmful to children. Meta Quest recently announced VR parental supervision tools to be implemented over the next several months while using the Quest headset. A paper published in Pediatrics suggests instead of using VR to fix a child’s impairment, it could be utilized as a tool to gain more insight and awareness of the difficulties the child may experience due to the impairment.56 Mental Health Treatment An estimated 52.9 million adults suffer from mental illness, according to a 2020 survey by the Substance Abuse and Mental Health Services Administration (SAMHSA). This equates to 1 in 5 American adults. Moreover, US young adults, ages 18 to 25 years old, were reported to have the highest prevalence of mental health illness.57 One of the biggest challenges today is the rising demand for mental health treatment and a shortage of available providers.58 As the pandemic unfolded, the need to provide continuity of care remotely quickly became a necessity and telehealth appointments offered mental healthcare delivery outside of a traditional face-to-face setting. In fact, early studies show the potential benefits of this viable option, including improved accessibility for low-income, racial, and ethnic minority adults and children.59 Mental health treatment at a distance has the potential to break down the barriers of high cost and limited accessibility. As virtual-based treatment moves into mainstream medicine, more is understood about its potential as a mental health treatment. One of the advantages of VR in mental health treatment may be utilization of VR for mental health assessment and exposure therapy, which is traditionally performed in a lab or clinic rather than a real-world setting. Through VR software, real-world settings designed to closely resemble surroundings of daily life offer insight into triggering stimuli such as anxiety, paranoia, fear, and cravings. This gives therapists the ability to provide highly controlled environments for assessment and obtain real-time feedback to implement therapeutic strategies.60 Virtual reality exposure therapy (VRET) shows promise as a scalable tool for anxiety disorders and is already being used in panic disorder and phobia treatment.61, 62 Considerable research indicates efficacy for exposure-based therapy for anxiety, but it remains a treatment gap and is underutilized due to patient fears and therapists’ concern for only having limited control in real-life stimuli scenarios.63 A virtual environment allows more control regarding the insertion of stimuli, contexts, and tasks not possible in in vivo exposure therapy. Smartphone-based VR apps such as EASYHEiGHTS (created to treat Acrophobia) are low cost and can be accessed with a VR headset and conventional smartphone, enabling patients to receive treatments in a therapist’s office or even in their own home. This option removes the difficulty of patients, for instance, having to stand on a tall building for acrophobia treatment, also removing the extra liability for clinicians conducting treatment in a real-world setting. Evidence shows patients are more willing to receive exposure therapy when they can do so in the comfort of a therapy office or their home rather than in the physical world.64 There is activity in PTSD using exposure therapy. PTSD, caused by traumatic life events, affects 3.6% of US adults.65 Studies show VRET produced a significant reduction in PTSD symptoms, including sustained improvements at 6- and 12-month follow-ups.66 Created at the University of Southern California (USC) Institute for Creative Technologies, BraveMind, a clinical, interactive, and VR based exposure therapy tool is currently being used by numerous hospitals and universities to treat PTSD.67 Autism Spectrum Disorder (ASD) researchers and therapists have been using VR since the mid-1990’s in an effort to help patients with autism practice being in stressful situations, combat phobias, and prepare for public speaking.68 A research initiative recently investigated the efficacy of VR incorporated with CBT resulting in marked improvements in specific phobias among children with ASD.69 With hopes of reducing depression and loneliness, Rendever has created an innovative engagement VR platform to assist seniors suffering from social isolation.70 They are currently working with senior living communities and hospitals including the University of Cincinnati (UC) and the National Institute on Aging (NIA) to help bridge the distance between seniors and family members living apart. Moreover, they have created platforms allowing seniors to explore far away cities, travel back to their childhood homes, and even fulfill lifelong bucket list items.71 7


Of notable importance to mental health practitioners is a small January 2022 published study that compared face-to-face interaction with VR interaction suggesting participants reported a slight preference to face-to-face interaction overall, but when asked to disclose negative information 30% of the participants preferred to interact with an avatar rather than a real person.72 Preliminary study results suggest VR can be an effective treatment for individuals suffering from certain mental health disorders. Notably, some users may require VR-created platforms with special accommodations, such as programs designed around impaired cognition, memory, and language skills, or for individuals with mental health conditions that involve dissociative states or hallucinations. Chronic Pain Treatment According to a Centers for Disease Control and Prevention’s (CDC) survey in 2019, 20.4% of adults in the US reported having chronic pain.73 Persistent pain has also been linked to depression and anxiety and can become an overlapping symptom. The CDC and the Centers for Medicare & Medicaid Services (CMS) recommend non-opioid and non-pharmacologic therapies as first-line treatments. Both agencies have raised concerns in response to the increasing rate of opioid abuse and overdose deaths.74 A randomized comparative effectiveness trial conducted at Cedars Sinai revealed VR significantly decreased pain in hospitalized patients and was most effective in patients experiencing severe pain. The patients, using VR goggles, engaged in virtual environments that included swimming with dolphins, and reported a 24% drop in pain scores.75, 76 Seeking non-pharmaceutical solutions for pain management, AppliedVR received De Novo approval from the US FDA in November 2021 for the first VR therapeutic to treat chronic low back pain.77 RelieVRx (formally EaseVRx), a prescription-use medical device, is an immersive VR system based on cognitive therapy methods delivered in an 8-week program and has been proven to improve chronic pain outcomes.78 A trial conducted in 2020 looked at 179 adults experiencing non-malignant chronic low back pain and reported a substantial reduction in pain, mood, and stress suggesting that home-based VR programs could open up access to effective non-pharmacologic on-demand treatments for chronic low back pain.79 Access to treatment and therapists remain obstacles for patients with pain, further exacerbated by COVID-19. A new and promising option for chronic pain sufferers is on-the-spot VR treatment, including automated behavioral programs. One such company, XRHealth, provides virtual treatment rooms inside the Metaverse. Patients can go to the website, choose a therapist, order a VR headset, and begin personalized occupational therapy (OT), physical therapy (PT), or mental health therapy. XRHealth is covered under some insurance plans and offers out-of-pocket plans.80 Virtual Rehabilitation Telerehabilitation, or rehabilitation through VR, has been gaining traction for a number of years due to the growing advancement of hardware and software technologies designed to treat patients with a range of conditions, including chronic pain associated with injury or illness, traumatic brain injury (TBI), spinal cord injury, stroke, Parkinson’s disease, multiple sclerosis (MS), Alzheimer’s disease and dementia, and cerebral palsy (CP).81, 82, 83 Telerehabilitation methods are being implemented as alternatives to multiple traditional therapies like PT and OT. Although the benefits of PT have long been established, between 50% and 70% of patients who would benefit from PT are unable to receive therapy due to limited access.84 This number is believed to have been higher during the COVID-19 pandemic. Traditional therapies are helpful for recovery, but novel approaches have been suggested to improve patient compliance and outcomes. The use of VR in rehabilitation may offer potential positive advantages for patients.85 Noteworthy advantages of VR-assisted rehabilitation have been reported in the literature including, improved patient engagement and motivation, post-stroke functional recovery and increased mobility, and quality of life in Parkinson’s patients.86, 87 Multiple clinical trials demonstrating VR’s

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effectiveness in treating symptoms associated with Parkinson’s disease have been completed with promising results, including studies focused on balance, postural control, and gait disorders to prevent falls.88 VR environments provide interactive and customized platforms that allow patients to elicit realistic reactions that can be used to track patient performance, which is essential in recording patient progress.89 MindMaze, a company specializing in neurorehabilitation and enhancing the recovery potential of patients with neurological diseases, received FDA clearance for 2 gamified neurorehabilitation systems.90 MindMotion GO received FDA-clearance in May 2018 and can be used in inpatient, outpatient, or home settings and offers rehabilitation through upper and lower limb, and hand or trunk exercises.91 MindMotion Pro received FDA-clearance in May 2017 and was designed exclusively for inpatient acute stroke patients with upper limb hemiparesis.92 VR in Training and Education The complexity of the ever-changing healthcare system and pressure to ensure learning objectives are met through standardized medical training is an ongoing challenge and a potential opportunity for medical educators. The use of VR in training and education offers the ability to train personnel in a controlled environment while minimizing risks to a real patient. Communication skills and simulation-based training have become increasingly more important as a part of the clinical learning experience.93 Dramatic developments have taken place in the drive for better educational tools, including internet and mobile device options. A growing number of hospitals are implementing VR systems to train residents, assist surgeons in surgical planning, and educate patients. Partnering with hospitals and institutions such as Yale University and University Hospitals Cleveland Medical Center, PrecisionOS received FDA 510(k) clearance for the InVisionOS tool for surgical planning in November 2021.94, 95 Further, Stanford University, Department of Neurosurgery is now utilizing Surgical Theater’s medical visualization platform Precision XR. The platform transforms patient’s 2D scans and data into a 360-degree 3D view, allowing surgeons to explore a patient’s anatomy in a way never before possible. Stanford surgeons can reconstruct a patient’s brain through 3D imaging which allows greater visualization, surgical mapping, and planning to improve surgical accuracy and create safer procedures.96, 97 In 2019 George Washington University Hospital became the first hospital in the US to perform surgery using the AR system OpenSight, ushering in what has been called a revolution in pre-surgical planning. This followed Microsoft’s release of a newer version of the HoloLens, the HoloLens 2, which was granted 501(k) clearance for use with OpenSight for surgical planning which renders 2D, 3D, and 4D images in an interactive display and directly onto a patient’s body allowing surgeons to more accurately plan and perform surgeries with precise accuracy.98, 99 According to a recent randomized controlled trial from University of California Los Angeles’s (UCLA) David Geffen School of Medicine, participants using the Osso VR platform improved their overall surgical performance by 230% compared to conventional training methods.100, 101 Osso VR technology combined with Oculus headsets uses customized training platforms to provide reimagined surgical training. The platform allows dozens of hospital staff to collaborate and train in virtual operating rooms and has been demonstrated to accelerate learning memorization.102 Doctors from around the world recently collaborated in a 24-hour surgery facilitated by Microsoft featuring 12 holographic surgeries, including a shoulder replacement in South Africa and a knee procedure in the United Arab Emirates (UAE).103 Moreover, VR is assisting medical students and practicing physicians to create awareness and a better understanding around the patient-doctor relationship, including patient empathy. A study published in 2018 demonstrated VR immersion training as an effective tool to help medical students and other healthcare providers (HCPs) develop empathy for older adults dealing with vision and hearing loss and Alzheimer’s disease.104 The training is currently being used at the University of New England. Additionally, the recently developed mobile app, HealthVoyager, is designed to help 9


physicians enhance medical comprehension for patients and families following surgery or medical procedures and is currently being used at the Boston Children’s Hospital.105, 106 Early studies demonstrate the importance and potential of VR in improving performance and decreasing medical training costs. While the advantages of VR come into focus, the possible limitations such as overdependence on technology, reduced classical training and standardization in training should be a part of the dialogue. Inequities in Health Structural racism in the healthcare system has been evidenced in multiple studies and continues to affect the wellbeing of all people, but specifically those who have been historically marginalized in society. Socioeconomic status and long-established residential segregation remain two strong determining factors of racial health disparity.107 It is important to consider how evolving healthcare technologies like VR may impact the future of healthcare equality. During the COVID-19 pandemic disparities in the healthcare system were profoundly visible as mortality and hospitalization rates were significantly higher among marginalized populations. As the healthcare system adapted to reach individuals who needed care amid the threat of a burgeoning pandemic, telehealth and remote care implementation exploded, emphasizing what is widely known as the digital divide: the inequality between those who have access to technology and those who do not.108 Access obstacles to digital health tools like video enabled smartphones and limited broadband access are common in vulnerable populations with low social economic status and limited health or English literacy and could create an even greater barrier to the potential beneficial application of VR in healthcare.109 Although the pandemic established telehealth as an effective way to reach patients that may have been unreachable otherwise, technology access and literacy remain a challenge. Thus a continued investment in broadband access is warranted. The fact that VR technology is not widely available cannot be overlooked. Not only could individuals face barriers in obtaining access to the technology, but entire communities, including the healthcare organizations that serve them may lack the means to obtain or adopt the technology. As these challenges and the solutions to them unfold, researchers are learning how VR could be used as a catalyst to understand racial bias. VR is currently being implemented as a training tool to better understand the cultural and social needs of patients, and although study in this area has just begun there is potential for VR to become a tool to increase empathy and give users a more positive perspective when interacting with people from different ethnic or social economic backgrounds. Stanford University recently conducted a preliminary study suggesting that individuals who were able to imagine themselves in someone else’s circumstances report feeling empathetic, however individuals who actually experience someone else’s circumstances through VR had longer lasting empathy and the experience even motivated prosocial behaviors.110 While promising, the field is still underexplored regarding using technological means to bolster empathy as a step towards equality. Although the benefits of VR are recognized in this paper, as the technology becomes more commonly used by HCPs it could inadvertently leave underserved populations vulnerable if they are unable to access the growing wave of technology, in lieu of traditional methods to see and treat patients. This discussion acknowledges current healthcare disparities and how new technologies such as VR may positively or negatively impact select populations.

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CLINICAL TRIAL EVIDENCE The products that are identified as VR technology are quite broad. There is a proliferation of rapidly evolving development in this space, extending from VR, AR, and MR devices to software systems and digital applications. This paper looks at the spectrum of products that fall under these categories, but the primary focus is on physical devices using immersive and tracking features. A literature search was performed limited to FDA-approved devices. Studies considered most relevant for the analysis included free full-text studies with clinical endpoints, published in English. These studies are summarized below. This is not an all-inclusive list. Medications (drugs and biologics) have prescribing information readily posted to the FDA website. For medical devices though, the CDRH Freedom of Information (FOI) Reference Sheet outlines what is releasable through the FOI process from the FDA. For example, for 510(k) premarket notification, labeling is only releasable through the FOI staff after pre-disclosure notification.111 Further, bench and clinical data are not releasable. Hence, specific prescribing information and evidence could not be accessed for evaluation. General device labeling provisions are summarized in the FDA’s General Device Labeling Requirements.112

AUTHOR

TRIAL DESIGN

OBJECTIVE

SAMPLE SIZE

ADVERSE EVENTS & SAFETY

AUTHOR'S CONCLUSION

785 observations were recorded; 47 exercises had sufficiently good fit to the Rasch model; 6 items showed underfit (outfit mean square values > 1.5); 1 item showed underfit but was kept in the analysis; 3 items had negative point-biserial correlations; the final model included 47 exercises for persons with low to moderate balance ability

No serious adverse events occurred during training; 2 falls from the chair (without injuries) occurred, which is comparable to conventional balance training

An adequately fitting Rasch model for the VR exercises was identified with a hierarchical order of VR balance exercises for stroke and MS patients with low to moderate balance ability; results provide guidance in the selection of VR balance exercises for stroke and MS patients

Participants showed 5.3% improvement in motor function post intervention and 15.4% at 1-month follow-up relative to baseline, which was a clinically significant improvement for 3 participants. A significant improvement in active range of motion (AROM) for the shoulder was observed

No severe adverse events were reported, however, some participants did report very low levels of pain, stress, and fatigue following each training session

Demonstrated how the use of a dedicated VR system can be used to deliver high rehabilitation doses and intensive training in chronic stroke survivors; results indicated that task-specific VR training may help with further functional recovery in the chronic stage of stroke

INTERVENTION

RESULTS

Participants performed a training program that consisted of performing VR balance exergames with a movement recognition-based system

MindMotion GO Wiskerke, E, et al. (2022)

Longitudinal observational study

This study sought to apply the Rasch model to create a hierarchical order of existing VR balance exergames and to relate these exergames to the abilities of patients with neurological disorders (Multiple Sclerosis [MS] and stroke) to deliver challenge and variation

81

To evaluate the impact of a VR system for taskspecific upper extremity training after stroke in outpatient; study examined the impact on rehabilitation dose and training intensity, functional improvements, and safety and tolerance

10

Weekly for 3 weeks for MS patients, and 4 weeks for stroke patients Primary Endpoint: VR exercise scores & Berg Balance Scale scores

MindMotion PRO Perez-Marco D, et al. (2017)

Pilot study

Use of a novel VR system for taskspecific upper extremity training after stroke 10-session VRbased upper limb rehabilitation program (2 sessions/week) Primary Endpoint: Motor function (FuglMeyer Assessment for Upper Extremity)

11


CLINICAL TRIAL EVIDENCE continued AUTHOR

TRIAL DESIGN

OBJECTIVE

SAMPLE SIZE

INTERVENTION

RESULTS

ADVERSE EVENTS & SAFETY

AUTHOR'S CONCLUSION

7 participants (9.7%) from the EaseVRx group and 5 participants (6.7%) from the Sham VR group reported nausea and motion sickness during treatment

EaseVRx demonstrated high user satisfaction as well as clinically relevant symptom reduction for pain intensity and painrelated interference with activity, mood, and stress relative to sham VR. Homebased VR may provide access to effective on-demand non-pharmacologic treatment for chronic low back pain

RelieVRx Garcia LM, et al. (2021)

Double-blind, randomized, placebocontrolled trial

This study was a double-blind, parallel-arm, single-cohort, remote, randomized, placebocontrolled trial that evaluated a self-administered behavioral skills-based VR program in a sample of community-based individuals with self-reported chronic low back pain during COVID-19

179

Participants were randomized 1:1 to EaseVRx (immersive pain relief skills VR program) or Sham VR (2D nature content delivered in a VR headset) 1 VR program daily for 56 days Primary Endpoint: Initial self-reported pain intensity and pain interference with daily activities, mood, sleep, and stress

EaseVRx was superior to Sham VR for all primary outcomes (highestp=0.009) between groups, with Cohen’s d effect sizes ranging from 0.40 to 0.49; the pre-post effect sizes for EaseVRx ranged from 1.17 to 1.3

Garcia, L et al. (2022)

Double-blind, randomized, placebocontrolled trial

To assess durability of effects at 3-month followup

188

Participants were randomized 1:1 to EaseVRx (immersive pain relief skills VR program) or Sham VR (2D nature content delivered in a VR headset)

Results indicate that sustained benefits for both groups were observed, with therapeutic VR providing additional benefits over Sham VR for 1 VR program daily for pain intensity and 56 days multiple indices of pain-related Primary Endpoint: interference (effect Initial self-reported sizes ranged from pain intensity and pain drm=0.56 to 0.88) interference with daily at 3-month followactivities, mood, sleep, up and stress at 3-month follow-up

No adverse events of any type, including nausea and motion sickness were reported

Therapeutic VR demonstrated clinically meaningful benefits and superiority over Sham VR sustained to 3-months posttreatment

Garcia, L et al. (2022)

Double-blind, randomized, placebocontrolled trial

To assess durability of effects at 6-month followup

188

Participants were randomized 1:1 to EaseVRx (immersive pain relief skills VR program) or Sham VR (2D nature content delivered in a VR headset)

Results indicate that therapeutic VR maintained significant and clinically meaningful effects at 6-month followup and sustained superiority to sham 1 VR program daily for VR for reducing 56 days pain intensity and pain-related Primary Endpoint: interference with Initial self-reported activity, stress, and pain intensity and pain sleep (ds=0.44 to interference with daily 0.54; p<0.003) activities, mood, sleep, and stress at 6-month follow-up

No adverse events of any type, including nausea and motion sickness were reported

Therapeutic VR demonstrated clinically meaningful benefits and superiority over Sham VR sustained out 6-months posttreatment

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CLINICAL TRIAL EVIDENCE continued AUTHOR

TRIAL DESIGN

OBJECTIVE

SAMPLE SIZE

ADVERSE EVENTS & SAFETY

AUTHOR'S CONCLUSION

INTERVENTION

RESULTS

Participants were randomized 1:1 to either an IVR training platform that provided a case-based training module for reverse shoulder arthroplasty (RSA), or a control group

The IVR group had significantly higher OSATS scores on average relative to the control group (15.9 [2.5] versus 9.4 [3.2] 95% CI, 3.3 to 9.7; p<0.001)

N/R

Surgical training with IVR resulted in significantly better learning efficiency, knowledge, and skill transfer

ICCs for the standard deviation of tangential error score were 0.86 (95% CI=0.82 to 0.9) and 0.88 (95% CI=0.84 to 0.91) at pre- and post-practice, respectively; the absolute mean differences between pre- and post-practice scores ranged from 0.02 (0.05) for horizontal gain to 0.1 (0.5) for standard deviation of tangential error

N/R

The ICC scores support visual synchronization measurement reliability; Eye-Sync goggles have the potential for use in assessing ocularmotor function for sideline evaluation of concussion

InVisionOS Lohre, R et al. (2020)

Block randomized, interventioncontrolled clinical trial

To evaluate the efficacy of immerssive VR (IVR), to improve learning effectiveness in surgical residents, and to validate a VR rating scale by calculating correlations to real-world performance

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Participants were allowed to repeat the training module indefinitely Primary Endpoint: Objective Structured Assessment of Technical Skills (OSATS)

EYE-SYNC® Sundaram, V., et al. (2019)

Prospective cohort study

Assessment of the reliability and effectectiveness of exercise on dynamic visual performance measures of ocular-motor function using a portable visual assessment system (EyeSync)

150

Performed eyetracking using EyeSync goggles 3 times consecutively prior to athletic practice and 3 times post practice Primary Endpoint: Gaze error outcomes between target position and actual gaze position to assess dynamic visual synchronization; reliability was assessed based on intraclass correlation coefficient (ICC) and differences in mean pre- and post-practice scores

13


CLINICAL TRIAL EVIDENCE continued AUTHOR

TRIAL DESIGN

OBJECTIVE

SAMPLE SIZE

INTERVENTION

RESULTS

Participants underwent circumferential tumor border tracing

11 patients undergoing craniotomy were included in the study (5 patient procedures were rated as having an excellent correspondence degree, 5 had an adequate correspondence degree, 1 had poor correspondence); both raters had consensus on the rating in all cases; AR tracing was possible in all cases

ADVERSE EVENTS & SAFETY

AUTHOR'S CONCLUSION

Open Sight Ivan, ME et al. (2021)

Prospective pilot study

Prospective pilot study investigating the feasibility of using the OpenSight application with an AR headmounted display to map out the borders of tumors in patients undergoing elective craniotomy for tumor resection, and to compare the degree of correspondence with monitor and wand-based neuronavigation stations (MWBNS) tracing

11

To evaluate the learning retention for neurosurgical fellows and residents of thoracic pedicle screw placement on a highperformance AR and haptic technology workstation

51

All participants underwent the procedure twice: 1) once with a surgeon wearing HoloLens AR glasses running the commercially available OpenSight application registered to the patient, and 2) once with using the StealthStation S8 MWBNS Primary Endpoint: Both tumor border tracings were compared by 2 blinded board-certified neurosurgeons and rated as having an excellent, adequate, or poor correspondence degree based on a subjective sense of the overlap; objective overlap area measurements were also determined

N/R

Augmented reality head-mounted displays (ARHMD) with OpenSight in a cranial neurosurgery operating room is feasible without interrupting workflow. Additional work will need to be conducted to assess the reliability and accuracy of preoperative tumor border identification for incision planning using AR versus standard navigation

ImmersiveTouch Luciano, CJ et al. (2011)

Single cohort training study

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Participants under went a 5-minute training session for thoracic pedicle screw placement, and were then tested on skill acquisition 5-minute training session Primary Endpoint: Euclidean distance in mm from the target drilling spot to the actual drilling spot, and failure rate measured as a collision with the spine surface

N/R 12.5% failure rate, a 2-proportion z test yielded p=0.08; for performance accuracy, an aggregate Euclidean distance deviation from entry landmark on the pedicle and a similar deviation from the target landmark in the vertebral body yielded p=0.04 from a 2-sample t test where the rejected null hypothesis assumes no improvement in performance accuracy (from the practice to the test sessions), and the alternative hypothesis assumes an improvement

Assessed the performance accuracy on the stimulator to the accuracy reported in literature from retrospective evaluations of similar placements; the observed failure rates, which measured the collision between the drill and virtual spine model, were indicative of performance improvement from the practice to the test sessions


CLINICAL TRIAL EVIDENCE continued AUTHOR

TRIAL DESIGN

OBJECTIVE

SAMPLE SIZE

INTERVENTION

RESULTS

Neurosurgery residents participated in individual simulator practice on the library of brains including visualizing the 3-D location of the catheter within the brain immediately after each insertion for a ventriculostomy

Simulator cannulation success rates increased after intervention, and live procedure outcomes showed improvement in the rate of successful cannulation on the first pass; however, the incidence of deeper, contralateral (simulator) and third-ventricle (live) placements increased after intervention; residents reported that simulations were realistic and helpful in improving procedural skills such as aiming the probe, sensing the pressure change when entering the ventricle, and estimating how far the catheter should be advanced within the ventricle

ADVERSE EVENTS & SAFETY

AUTHOR'S CONCLUSION

ImmersiveTouch continued Yudkowsky, R et al. (2013)

Pre-post

Evaluate the impact of simulationbased practice with a library of virtual brains on neurosurgery residents’ performance in simulated and live surgical ventriculostomies

16

A single 2 to 3 hour practice session Primary Endpoint: Performance of participants on novel brains in the simulator and during actual surgery before and after intervention was analyzed using generalized linear mixed models

N/R

Simulator practice with a library of virtual brains representing a range of anatomies and difficulty levels may improve performance; thereby, potentially decreasing complications due to inexperience

15


THE POTENTIAL RISKS OF VR Although the barriers of cost and access to technology for underserved populations cannot be ignored, the latest breakthroughs have extended accessibility of some apps to anyone with a smartphone and a VR headset. Despite technological advances providing the impetus for a great expansion in studying the effectiveness of VR, there is still much to learn, including the limitations and possible adverse effects of the technology. Importantly, studies are beginning to emerge detailing research on the brain-health consequences of spending too much time using digital technology.113 Cybersickness Patient tolerability can sometimes be an issue and cybersickness (simulator sickness) remains a challenge for some individuals. Symptoms include dizziness, headache, and nausea, notably more prevalent in women, children, and the elderly population.114, 115, 116 The exact etiology of cybersickness is unknown, but possible causes appear consistent with the causes of motion sickness including, a mismatch of sensory information between the eyes and the inner ear, loss of postural control (awareness of presence in space), and eye movement theory (excessive eye muscle movement).117 Evidence shows that 60% to 95% of users experience some degree of cybersickness.118 Headset Discomfort The headsets can also be uncomfortable when worn for long periods of time. A typical headset weighs nearly 2 pounds and early studies show it may contribute to muscle strain and discomfort.119 Surgeons have reported headset weight and weight distribution as a limiting factor during long surgeries.120 Injuries Injuries have also been reported, falling into two categories: overuse and accidents. Individuals may become disoriented and fall down or run into furniture, walls, or other people causing broken bones, concussions, and lacerations. Individuals can also experience overuse injuries such as musculoskeletal disorders of the neck, shoulder, and spine due to the weight of the device as mentioned above.121 The potential for unintended negative effects such as stimulus intensity, which could make a condition worse rather than better, are also being considered.122 Mental Health Impact There is also caution about the possible addictive properties of VR use. The WHO has classified video game addiction as an official mental health disorder in January 2022.123 “Gaming Disorder” is in the 11th Revision of the International Classification of Diseases (ICD-11) and defined as a pattern of ‘gaming behavior (“digital-gaming” or “video-gaming”) characterized by impaired control over gaming, increasing priority given to gaming over other activities to the extent that gaming takes precedence over other interests and daily activities, and continuation or escalation of gaming despite the occurrence of negative consequences. Furthermore those that suffer from photosensitive epilepsy could be at risk for seizures while using VR apps that require a greater field of vision.124 VR stimulates the eyes whole field of view, affecting a larger part of the brain, hence triggering a seizure.125 Privacy Privacy protection is of concern as well. Since VR headsets are able to collect more data (eye movement, eye focus, and body movement) than a traditional screen, they may present further opportunities for profiling, predatory behavior, and security breaches.126 Individual privacy as well as personal health information protection concerns can grow as virtual spaces become more common. Hence, safeguarding data and privacy and having appropriate frameworks are key. There are currently organizations working to ensure privacy and safety for MRX frameworks.127 16 MAGELLANRX.COM


There is more to learn and potential hurdles to overcome. This includes the possible repercussions of reduced face-to-face communication, technology illiteracy, HCP and student anxiety or reluctance to learn a new technology, and the possible negative impact of overuse. The impacts described for VR can also apply to AR.

REGULATORY TRENDS While there is a plethora of digital health options such as wellness apps, Medical Extended Reality (MXR) such as VR/AR that undergoes regulatory review has to be validated through the US Food and Drug Administration (FDA) clearance process.128 The US FDA classifies medical devices based on the risk associated with the device. There are also different premarket pathways for a device to undergo regulatory review under the FDA’s Center for Devices and Radiological Health (CDRH).129

DEVICE CLASSIFICATION: Class I

Class II

Class III

low risk devices that are generally exempt from premarket notification or clearance. General controls apply.

moderate risk devices with greater regulatory control than Class I. General and special controls apply. Premarket notification is generally required but is sometimes exempt.

high risk devices and require a Premarket Approval (PMA) before they are marketed. General and special controls apply.

EXAMPLES dental floss, nasal swabs, and manual stereoscopes

EXAMPLES endoscopes, powered wheelchair, and digital cognitive behavioral therapy

EXAMPLES coronary stents and breast implants

PREMARKET PATHWAYS: De Novo Premarket Pathway • Intended for low to moderate risk devices of a “new” type where a predicate device does not exist. AppliedVR’s RelieVRx (formerly EaseVRx) is a Class II device that was cleared through the De Novo pathway. º De Novo is a risk-based classification process, therefore benefit versus risk is described as an assurance of safety and effectiveness for the intended use.130

510(k) also called Premarket Notification (PMN) • Used to show a device to be marketed is safe and effective and substantially equivalent to a legally marketed or predicate device. 510(k) is the most common type of premarket submission for medical devices. Most 510(k) submissions are for Class II devices. º A 510(k) device is considered substantially equivalent to a predicate if it: » has the same intended use and same technological characteristics OR » has the same intended use, different technological characteristics and does not raise different questions of safety and effectiveness and submitted data shows device is as safe and effective as the legally marketed device. º Once a 510(k) has been created for a device, subsequent companies can submit a 510(k).131

Premarket Pathway (PMA) • The FDA’s most stringent device marketing application. It is reserved for highest risk devices (Class III) and has the highest data requirements than any other premarket pathway. º Given the level of risk associated with Class III devices, general and special controls alone are insufficient to assure safety and effectiveness. PMA has significant data requirements including clinical data and non-clinical laboratory studies.132


VR and prescription digital therapeutics are primarily Class II. Data requirements will depend on a number of factors including class, the premarket pathway, potential risk to patients, and any special controls. There is also another type of marketing application for a Humanitarian Use Device (HUD) called a Humanitarian Device Exemption (HDE). An HDE is a pathway to market medical devices for rare diseases or conditions.133 Of note, the FDA’s Breakthrough Device designation can be granted to VR. This designation is intended for devices that “provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.”134 An example is RelieVRx (formally EaseVRx) which was granted Breakthrough Device designation.135 The FDA also offers a Safer Technologies Program (STeP) for medical devices. STeP is a voluntary program for medical devices that are “reasonably expected to significantly improve the safety of currently available treatments or diagnostics that target an underlying disease or condition associated with morbidities and mortalities less serious than those eligible for the Breakthrough Devices Program.” SteP provides more timely access to medical devices and device-led combination products by expediting development, assessment, and review, while still preserving the statutory standards for the 3 premarket pathways.136 The Patient Engagement Advisory Committee (PEAC) is comprised of patients, caregivers, and patient organization representatives. This committee was established by the FDA to consider patient needs and experiences around medical devices. PEAC has provided considerations for VR/AR benefits, risks, and uncertainty.137 In addition to regulatory considerations, legislative authorities that allow for access to certain telehealth services are a notable trend. For example, during the pandemic the authority under the Ryan Haight Act was lifted so prescriptions for certain medications such as medication assisted therapies (MAT) for substance use disorders could be accessible via telehealth instead of an in-person visit. Looking ahead patient-centric digital health legislation can aid in fostering an environment of responsible access.138

MAGELLAN PERSPECTIVE – FOUR PILLARS Magellan Health supports fair and balanced reviews for new devices to the market. We have four primary tenants of practice, including education, evidence-based, safety, and access. Our overarching perspectives for VR are summarized in these four pillars:

Education & health literacy provide targeted education and increase health literacy for all stakeholders (patients, providers, payors, educators, etc.) in the private and public sectors, for multigenerational ages (young & old), increase patient engagement, and advance healthcare training

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Evidence-based recommendations & coverage ensure future coverage decisions are grounded in high-quality, validated evidence for devices that have undergone regulatory clearance, provide scalable value

Patient safety advocate for patients by encouraging responsible access to these technologies with security protections in mind and using privacy standards and vigilance for all, particularly for children and teens where studies show safety and efficacy

Access increase access to healthcare in a responsible manner, remove geographical, social, broadband, and language barriers, increase diversity in care by closing the healthcare equity gap for underserved communities, and improve healthcare staffing


SUMMARY While an abundant amount of research is being conducted, questions remain regarding the scalability of VR, the ethical aspects, and the longitudinal effects of quickly embracing the technology. Additionally, although MXR technology has the potential to create improved access to individuals through virtual care, it could also exacerbate current healthcare inequities due to inadequate broadband or device access, costs, and limited digital literacy. As VR technology becomes more accessible, the immersive and interactive learning environment is providing experiences never thought possible. The future of healthcare could look very different, greatly impacted by the digital age and VR technology potential. It is a rapidly changing landscape in part due to the rapid flow of technological advancement. The advancing technology spurring considerable interest in healthcare utility can be observed in the number of startup and established tech companies leading the market in research and development of potentially effective medical treatments. Considering the potential positive impact already demonstrated in the areas of pain management, rehabilitation, mental health treatment, training, and education, it is imperative to understand the importance of proper infrastructure, potential risks, standardization, balancing privacy with innovation, and training in order to successfully integrate the technology into practice. Further, representatives of specific user groups (such as pediatrics) could be involved in the design and development through interdisciplinary research teams to create appropriate VR interventions. As well, special attention to these groups should be considered since longitudinal and large randomized studies have not clearly defined the benefits and risks of the technology. MXR technology is new and continuing to be studied. The rapidly evolving and widely varied hardware and soft­ ware create an exciting yet challenging research environment as current research becomes quickly obsolete or irrelevant due to frequent introduction of new versions. There is keen interest in VR’s healthcare potential and research initiatives are currently benefiting from increased funding. Larger randomized controlled, and longer studies will be required to fully determine safety and efficacy in a multitude of treatment areas. This will be key in determining the potential positive and negative impacts of MXR and fostering mindful use of the technology.

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