Background: Therapeutic virtual reality (VR) has emerged as an efficacious treatment modality for a wide range of health conditions. However, despite encouraging outcomes from early stage research, a consensus for the best way to develop and evaluate VR treatments within a scientific framework is needed.Objective: We aimed to develop a methodological framework with input from an international working group in order to guide the design, implementation, analysis, interpretation, and communication of trials that develop and test VR treatments.Methods: A group of 21 international experts was recruited based on their contributions to the VR literature. The resulting Virtual Reality Clinical Outcomes Research Experts held iterative meetings to seek consensus on best practices for the development and testing of VR treatments.Results: The interactions were transcribed, and key themes were identified to develop a scientific framework in order to support best practices in methodology of clinical VR trials. Using the Food and Drug Administration Phase I-III pharmacotherapy model as guidance, a framework emerged to support three phases of VR clinical study designs—VR1, VR2, and VR3. VR1 studies focus on content development by working with patients and providers through the principles of human-centered design. VR2 trials conduct early testing with a focus on feasibility, acceptability, tolerability, and initial clinical efficacy. VR3 trials are randomized, controlled studies that evaluate efficacy against a control condition. Best practice recommendations for each trial were provided.Conclusions: Patients, providers, payers, and regulators should consider this best practice framework when assessing the validity of VR treatments.

Numerous reports indicate that the incidence of posttraumatic stress disorder (PTSD) in Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) military personnel has created a significant behavioural healthcare challenge. These findings have served to motivate research on how to better develop and disseminate evidence-based treatments for PTSD. The current article presents the use of Virtual Reality (VR) as a clinical tool to address the assessment, prevention, and treatment of PTSD, based on the VR projects that were evolved at the University of Southern California Institute for Creative Technologies since 2004. A brief discussion of the definition and rationale for the clinical use of VR is followed by a description of a VR application designed for the delivery of prolonged exposure (PE) for treating Service Members (SMs) and Veterans with combat- and sexual assault-related PTSD. The expansion of the virtual treatment simulations of Iraq and Afghanistan for PTSD assessment and prevention is then presented. This is followed by a forward-looking discussion that details early efforts to develop virtual human agent systems that serve the role of virtual patients for training the next generation of clinical providers, as healthcare guides that can be used to support anonymous access to trauma-relevant behavioural healthcare information, and as clinical interviewers capable of automated behaviour analysis of users to infer psychological state. The paper will conclude with a discussion of VR as a tool for breaking down barriers to care in addition to its direct application in assessment and intervention.

Purpose: This paper details a brief history and rationale for the use of virtual reality (VR) technology for clinical research and intervention, and then focuses on game-based VR applications in the area of rehabilitation. An analysis of the match between rehabilitation task requirements and the assets available with VR technology is presented. Key messages and implications: Low-cost camera-based systems capable of tracking user behavior at sufficient levels for game-based virtual rehabilitation activities are currently available for in-home use. Authoring software is now being developed that aims to provide clinicians with a usable toolkit for leveraging this technology. This will facilitate informed professional input on software design, development and application to ensure safe and effective use in the rehabilitation context. Conclusion: The field of rehabilitation generally stands to benefit from the continual advances in VR technology, concomitant system cost reductions and an expanding clinical research literature and knowledge base. Home-based activity within VR systems that are low-cost, easy to deploy and maintain, and meet the requirements for “good” interactive rehabilitation tasks could radically improve users’ access to care, adherence to prescribed training and subsequently enhance functional activity in everyday life in clinical populations.

Posttraumatic stress disorder (PTSD) is a significant public health issue. Yet, there are limited treatment options and no data to suggest which treatment will work for whom. We tested the efficacy of virtual reality exposure (VRE) or prolonged imaginal exposure (PE), augmented with D-cycloserine (DCS) for combat-related PTSD. As an exploratory aim, we examined whether brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) moderated treatment response. Military personnel with PTSD (n = 192) were recruited into a multisite double-blind randomized controlled trial to receive nine weeks of VRE or PE, with DCS or placebo. Primary outcome was the improvement in symptom severity. Randomization was stratified by comorbid depression (MDD) and site. Participants in both VRE and PE showed similar meaningful clinical improvement with no difference between the treatment groups. A significant interaction (p = 0.45) suggested VRE was more effective for depressed participants (CAPS difference M = 3.51 [95% CI 1.17–5.86],p = 0.004, ES = 0.14) while PE was more effective for nondepressed participants (M = −8.87 [95% CI −11.33 to −6.40],p < 0.001, ES = −0.44). The main effect of DCS vs. placebo was not significant. Augmentation by MDD interaction (p = 0.073) suggested that depressed participants improved more on placebo (M = −8.43 [95% CI −10.98 to −5.88],p < 0.001, ES = −0.42); DCS and placebo were equally effective for nondepressed participants. There was an apparent moderating effect of BDNF Val66Met polymorphism on DCS augmentation (ES = 0.67). Met66 allele carriers improved more on DCS (ES = −0.25). FAAH 385 A carriers improved more than non-carriers (ES = 0.33), particularly those with MDD (ES = 0.62). This study provides a step toward precision therapeutics for PTSD by demonstrating that comorbid MDD and genetic markers may help guide treatment selection.ClinicalTrials.gov Identifier: NCT01352637.