Article In Brief
The FDA recently authorized the marketing of a prescription only virtual reality system that uses cognitive-behavioral therapy and other behavioral methods for the relief of chronic lower back pain. Clinicians want to know more about how it works and how much it costs before prescribing.
The US Food and Drug Administration has authorized the marketing of a virtual reality (VR) system, available by prescription only, that uses the principles of cognitive-behavioral therapy (CBT), mindfulness and other behavioral methods for the relief of chronic lower back pain.
The approval was based on a double-blind trial, published in February, involving 179 participants randomized either to the VR system or a control 2-D program that did not include training previously shown to improve chronic pain. Participants were instructed to use the devices at home for 56 sessions lasting two to 16 minutes each over an eight-week period.
At the conclusion of the treatment protocol, 66 percent of the participants using the VR system reported greater than 41 percent reduction in pain, versus 30 percent of control participants. In addition, 46 percent of the VR participants reported greater than 50 percent reduction in pain, compared to 26 percent of the control participants. The effect remained significant, but diminished, at three months post-treatment.
Christopher M. Loftus, MD, acting director of the Office of Neurological and Physical Medicine Devices in the FDA’s Center for Devices and Radiological Health, said in a prepared statement on November 16: “Today’s authorization offers a treatment option for pain reduction that does not include opioid pain medications when used alongside other treatment methods for chronic lower back pain.”
The leader of the trial, Beth B. Darnall, PhD, associate professor of anesthesiology at Stanford University and chief science advisor to AppliedVR, the company that developed and will market the device, said: “We have known for years that treatments that include CBT skills can be effective for relief of chronic pain, but they have not been easily accessible. Home-based virtual reality makes them more readily available. A clinician can write a prescription, the device arrives at the patient’s door, they put on the headset and they’re immediately self-treating.”
Neurologists and other physicians who specialize in pain treatment and research generally praised the quality of Dr. Darnall’s study and said that VR could be a useful tool for treating pain. But they expressed reluctance to begin prescribing the device, called EaseVRx, until they know more about it.
“It’s going to depend on the cost,” said Gary Franklin, MD, MPH, FAAN, a research professor of neurology at the University of Washington and medical director of the Washington state workers’ compensation program. “Most insurers will probably look at it, but if it costs, say, $3,000, then no, they probably won’t cover it.”
A spokesperson for AppliedVR said the company “isn’t able to provide pricing at this time.”
Published on February 22 in the Journal of Medical Internet Research, the study involved a national online convenience sample of individuals recruited via chronic pain organizations, Facebook advertisements, and outreach from medical clinics. A total of 1,577 people volunteered to participate, but 1,389 were excluded due to meeting the study’s threshold for depressive symptoms. After enrollment, nine individuals discontinued participation, five could not receive the VR device, one returned the device unopened and four withdrew for unknown reasons.
Of the 179 participants who received a device and participated, 76.5 percent were women, 90.5 percent were White, and 91.1 percent had at least some college education. Their average pain intensity was five on a scale of one to ten. Two-thirds of them had experienced back pain for five or more years.
Participants were sent a VR headset by mail, and were compensated with $6 per completed pain survey up to a possible total of $126. If they returned the headset and completed 16 or more of the surveys, they could also receive a new VR headset to keep.
The program offered by the EaseVRx device “incorporates evidence-based principles of CBT, mindfulness, and pain neuroscience education,” the study stated. For instance, during a deep-breathing exercise, users are directed to breathe toward the headset’s microphone. As they slowly exhale, they see 3D images of flowers blossoming. Narrated mindfulness exercises occur during immersive scenes of nature. During lessons about the neuroscience of pain, the device makes it appear that the user is diving into their body to better understand how pain is processed and controlled. CBT-inspired exercises in perspective-taking, distraction, and self-compassion are also included.
The sham treatment also includes a VR headset, but it presented only 2D nature footage accompanied by neutral music.
Data from both groups included self-reported and objective measures from the VR devices, beginning two weeks before the trial and continuing to day 56 of treatment. Levels of pain were measured using standard scales, such as the Defense and Veterans Pain Rating Scale, the Pain Catastrophizing Scale, and the NIH Physical Function and Sleep Disturbance short-form measures.
The primary outcomes were the between-group effect of EaseVRx versus the sham VR treatment across multiple time points, and the change in average pain intensity and pain-related interference with activity, stress, mood, and sleep from baseline to end-of-treatment at day 56.
The study found no serious adverse events in either group, and there were no significant differences between the active and sham groups at baseline on any measure.
All the primary outcomes favored the EaseVRx device (highest p value=.009), the study found. Between-group effect sizes ranged from 0.40 to 0.49, indicating a “moderately clinically meaningful” effect.
Both groups started the study with an average pain intensity of just over five out of ten. By day 56, the EaseRVx group’s average pain intensity had dropped to 2.9, compared with 4.0 in the sham treatment group.
The only between-group measures that did not reach statistical significance were for pain catastrophizing, pain self-efficacy, pain acceptance, and pain medicine use.
(The study measured the catastrophizing by asking participants the degree to which they agreed or not with statements such as: “It’s terrible and I think it’s never going to get any better,” or “I become afraid that the pain will get worse.” Pain acceptance was measured on an eight-item questionnaire that asks participants to rate the degree to which they agree with statements such as “I am getting on with the business of living no matter what my level of pain is.”)
The FDA granted EaseVRx a Breakthrough Device designation, and reviewed it through the De Novo pre-market review pathway, used for new devices with low-to-moderate risk.
Along with its authorization of EaseVRx, the FDA established requirements related to labeling and performance testing for any similar device. Any such device that can meet those standards will only have to demonstrate “substantial equivalence” to the Ease VRx device in order to receive authorization.
Natalia E. Morone, MD, MS, an associate professor of medicine at Boston University who studies body-mind treatments for pain, said she agrees with Dr. Darnall’s statement about the difficulty of finding therapists who deliver CBT or mindfulness training for pain relief.
“That argument is true,” Dr. Morone said. “And I’m impressed with the study. But I don’t see myself prescribing something that might cost hundreds of dollars or more without seeing the treatment itself. I would like to see some demonstrations of it.”
Dr. Morone added that she wished the study had had greater race, gender and socioeconomic diversity in its patient population.
Javeria A. Hashmi, PhD, an associate professor of anesthesia at Dalhousie University and a researcher in the pain management unit in NS Health, expressed surprise that the study found no benefit of the device on pain catastrophizing.
“Pain catastrophizing is one of the most important issues for chronic pain,” Dr. Hashmi said. “I’ve been studying this for 20 years, and normally pain catastrophizing goes hand-in-hand with pain intensity. CBT is beneficial for pain catastrophizing, so it’s shocking to me that it did not change over time.”
Charles Brock, MD, professor and senior vice chair in the department of neurology at the University of South Florida Morsani College of Medicine and chief of the neurology service at the James A. Haley Veteran’s Hospital, praised the study’s use of established pain measures and the inclusion of a sham VR device.
“Frequently when it comes to pain therapies, a treatment may sound beneficial and make sense physiologically, but you can’t be sure if it’s just a placebo effect,” said Dr. Brock, who works in the multidisciplinary chronic pain management service, among the most comprehensive in the VA system. “What’s helpful here is that they could distinguish a significant difference between their sham group and the treatment group.”
Dr. Franklin expressed concern that Dr. Darnall is associated with Applied VR and that some of the study coauthors work for the company. “There might be some bias in there,” he said.
His main reservation about the study, however, was that it excluded anyone with significant depression, which included nearly 90 percent of volunteers. “The vast majority of people with chronic pain have depression,” he said. “So these findings are limited to the relatively small number of people who don’t have any depression.”
Even so, he and the other researchers emphasized that any program offering CBT can offer significant improvement in symptoms of pain.
“There are at least 10 or 15 systematic reviews of CBT,” he said. “There’s nothing new here about whether CBT per se can be effective for chronic pain. We know it can. What’s new here is whether it can be delivered through a virtual reality device at home. It looks pretty promising.”
Dr Darnall is chief science advisor at AppliedVR and receives compensation for this role. Dr. Darnall receives royalties for four pain treatment books she has authored or coauthored. She is the principal investigator for two pain research awards from the Patient-Centered Research Outcomes Research Institute. Dr. Darnall received consultant fees from Axial Healthcare related to physician education for opioid prescribing and deprescribing (2019). Dr. Darnall has multiple NIH pain research grants, and is coinvestigator on two virtual reality research projects. Dr. Darnall serves on the board of directors for the American Academy of Pain Medicine and is on the board of directors for the Institute for Brain Potential. Dr. Darnall is a scientific member of the NIH Interagency Pain Research Coordinating Committee, and a former member of the Centers for Disease Control and Prevention (CDC) Opioid Workgroup (2020-2021) and is a current member of the Pain Advisory Group of the American Psychological Association. Dr. Hashmi had no relevant disclosures.