Study design

This was a phase 2 clinical trial with a single arm experimental design (Supplementary Fig. 2) which evaluated the feasibility of a VR intervention to improve distress and anxiety symptoms for PBT patients at the time of clinical evaluation. While initially intended to be conducted in-person, due to the COVID-19 pandemic all aspects of this trial were conducted remotely via telehealth with participants using VR in their home.

Participants and recruitment

The study population was comprised of patients who were actively enrolled on the Neuro-Oncology Branch Natural History Study trial (NCT02851706) for primary central nervous system tumors [18]. Patients were screened for trial eligibility based on pre-defined criteria, which are outlined in Table 1. Potential patients were identified by screening for those scheduled for follow-up disease evaluation with subsequent review of their clinic notes in the electronic medical record and discussion with their clinicians. Patients were recruited during clinic or telehealth visits, as well as via email reach-outs using a study flyer. Interested patients who met eligibility criteria were consented remotely via telehealth.

Table 1 Eligibility criteria for VR trialVR intervention

Research staff demonstrated use of the VR headsets with the patients in a telehealth meeting prior to the initial intervention. Once all baseline assessments were collected, patients completed a brief, self-selected 5-min VR intervention under remote supervision by study staff. Staff remained in the telehealth meeting with the patients during the VR intervention so they could monitor for any technology issues or device-related AEs.

The VR headset used in this trial is the Pico G2 4K device, which is an immersive, lightweight, stand-alone headset that comes with an orientation-tracked controller and does not require a smartphone or a PC to function. This headset can be used via “gaze mode” or “controller mode” where the user can make selections on the screen by either directing their gaze at a particular item or by pointing at it using the remote controller. Additionally, there is a breath shield attachment on the front of the headset that can detect breathing patterns of the user and will change the virtual environment experienced if a breath-based scenario is chosen. The VR software loaded on the headset was designed by AppliedVR™ for use within clinical populations and aims to target unpleasant symptoms and promote relaxation. There are a total of 41 scenarios on the VR headset that fall within 3 main categories: (1) Dynamic Breathing, (2) Guided Relaxation, and (3) Instant Escape, shown in Fig. 1. While there are several interactive games on the VR device, participants were instructed not to choose these during the initial VR intervention since they tend to be more stimulating than anxiolytic.

Fig. 1

AppliedVR™ virtual scenarios on Pico G2 4K headset. The dynamic breathing scenarios, which make use of a breath shield attachment, guide the participant to take slow, deep breaths in order to slow the heart rate and induce relaxation as the environment seen changes based on the breathing pattern. Guided relaxation scenarios are meditative in nature and promote mindfulness and bringing attention to unhelpful thoughts and emotions that participants might be experiencing. Instant escape scenarios allow distraction through exploration of immersive environments, including ocean-based experiences, travel to various locations around the world, and interactive games

Following the initial VR intervention, patients had self-directed VR use for the 1 month period they were on study and could choose any scenario available on the headset. Study staff conducted weekly check-ins to help troubleshoot any technological questions, to ask about device-related AEs, and to ask how often they used VR during the previous week. Other members of the household, including caregivers, were permitted to use the VR headset and patients were asked to inform us if this occurred, though no data was collected from those individuals.

MeasuresFeasibility and acceptability

This study will be considered successful if the following feasibility and acceptability metrics are met: 80% of approached eligible patients agree to participate in the trial, 70% compliance with VR headset use during the initial intervention, 70% of PROs are completed, no grade 3 or higher device-related adverse effects (AEs) reported, and high patient satisfaction with the intervention, which is determined by responses obtained during the qualitative interview and the Was It Worth It (WIWI) questions.

Patient-reported outcomes

Study outcome measures were collected using validated, patient-reported instruments. Device-related AEs were a primary outcome, distress and anxiety symptoms were secondary outcomes, and loneliness, financial toxicity, and adjustment disorder were exploratory outcomes. Table 2 outlines additional details about the PROs instruments used in this trial.

Table 2 PROs measures included in trialQualitative assessment

A 7-item semi-structured questionnaire was used during a phone interview with trial participants 1 week following the initial VR intervention in order to assess patient satisfaction with the intervention, feedback about the device, adverse effects related to device use, and the patient’s experience during the COVID-19 pandemic related to their psychological health. The interview concluded with 4 yes/no WIWI questions that further assessed satisfaction with the VR intervention. The phone interviews were recorded and the content transcribed to allow for qualitative thematic analysis. For the purposes of this interim analysis, responses to the WIWI questions were used to report patient satisfaction and the results from qualitative thematic analysis will be reported elsewhere.

Correlative biomarkers

This trial has optional collection of salivary stress biomarkers, including salivary cortisol, dehydroepiandrosterone-sulfate, and salivary alpha amylase, which are collected by patients at their home with kits supplied by the study team. Due to restrictions related to the COVID-19 pandemic, no saliva has been collected to date.

Data management and monitoring

The PROs data from the questionnaires was collected via the Scribe electronic interface using links emailed to participants at the 4 study timepoints (baseline, immediate post-VR intervention, 1 week post-VR intervention, and 1 month post-VR intervention). All trial data was exported into a password-protected internal database and audited for errors by trained data analysts. To protect confidentiality, patient identifiers are stored in a separate location from the research data and only the key study personnel have access to identifying information.

Device-related AEs were assessed via the PRO-CTCAE questionnaires and through patient report during weekly check-ins with the study team. In the event that the participant reported any adverse effects, either during the intervention or with ongoing VR use at home, they were instructed to remove the VR headset and allow time to recover from the symptoms. If their symptoms persisted despite a break from using the device, their clinical team was notified, VR use was discontinued, and they completed follow-up PROs assessments, per investigator and clinician discretion.

Statistical analysis

To evaluate the feasibility of the VR intervention, descriptive statistics were used to summarize rates of recruitment and retention, data completion, compliance, device-related AEs, and patient satisfaction. Analysis of secondary and exploratory aims will be reported elsewhere following recruitment of the full cohort.