Brandon B

Whenever you see a claim that a device is efficacious in improving a clinical outcome, hopefully, that claim was a result of studies comparing one group of patients using the device to another group. Given that a claim requires a study with a comparator, let's chat about the comparisons that could be made for a virtual reality therapy program.

Much of my thought has been on VR comparators for clinical trials over the last 3 years. Ill start with nothing and move up from there.

Standard of care (nothing)

When you read a paper that says standard of care was used in the control group, know that it means nothing in addition to what the patient was going to get for their care was given. Most researchers know that this is not an ideal comparison and should not be part of the design of a trial unless there is a significant medical/ethical reason to provide nothing to the patient. One of the reasons that this is an issue is that the patient will know from the consent form that they were placed into a group that was given nothing for volunteering there time and effort toward the study. This will bias the results decreasing the validity of the claim that your VR program can improve clinical outcomes. Also its just not ethical to provide nothing especially when there are options available to them.

Waitlist

One alternative to is a waitlist controlled trial. This can improve the complete disappointment that a patient can have when they provided with nothing. It can still bias the results as the patient will know from the consent form that they will be given something at some point. Subconsciously a participant may assume that they should feel better during the period they are given something vs the period when not given something leading to a bias in the results. 

Non-head mounted device (TV/smartphone/Desktop/Game Console/etc.)

Providing a control group with a technology is helpful on many levels. There is a benefit above standard of care for the patient’s time and effort. Non-immersive technology has been shown to be beneficial in reducing pain but has been shown to reduce pain statistically significantly lower than VR(1). However, the challenge of participants discovering that they are in that control group is still present. Even if virtual reality is removed from the form and replaced with audiovisual experiences the potential risks of both devices will be different as virtual reality can cause specific side effects. For more info on VR side effects see my other post. 

[I am purposely focusing the discussion of passive and active content for the sections on using control programs with head mounted devices though the same could be said for non-head mounted devices.] 

Non-immersive content in head-mounted display

To be able to control for the novelty of the hardware the control group would need content within a VR headset. With identical hardware in each group the consent form can be ethically made in a way that the patient does not know which group they would be in.

Much of the head mounted device research within dentistry used 2-D content (movies and games) to reduce pain as the patient wouldn’t need to turn their head during the procedure which is critical for dental surgery(2-4). To translate the benefits of this research into modern headsets I worked with developers who then created a void theater to present 2-D content. These are neutral environments with a single floating TV in front of the user (see Figure 1). There are several different types of content that could be used in the floating display that are similar to the content that is used in the non-head mounted device:

·       Passive content

o  A non-engaging video (ShamVR or PlaceboVR see below)

o  Relaxing videos (i.e. - nature videos)

o  A video recording of the content in the primary intervention group. This has been done in a few VR clinical studies to control for the content presented to the participant(5).

·       Interactive content

Figure : A virtual movie theater like experience

Placebo VR (non-engaging 2D content)

In an initial efficacy trial, nonengaging content is ideal to assess the impact of the VR program vs a true placebo. A placebo is an intervention that lacks active substance or active ingredient. Even a nature video that is made with engaging music could lead to a decrease in pain perceived as it could be found to be engaging for the participant.

Immersive content in HMD (active comparator)

As part of a set of guidelines we put together for VR therapy research, we felt that the selection of the control should ultimately be based on the mechanism of action for the VR therapy program(6). The mechanism of action may not only hinge on being present within the VR world, but also having a successful biofeedback loop or effectively teaching skills that can be used outside the headset. If these other components are critical for the success of the treatment than an active comparator that lacks those features might be needed. For example, as VR therapy researchers focusing on chronic pain we wonder if skills-building programs are superior t0 VR programs currently being used for acute pain.