Virtually treatable<\/strong><\/p>\nImprovements in VR technology and falling costs are raising hopes that its use might become more widespread in medicine. \u201cVR has been used for 25 years, but only for very few conditions, in specialist centres,\u201d says Freeman. The technology has seen most use in delivering exposure therapy for post-traumatic stress disorder, and this is still the leading application. But it also has potential uses in depression, anxiety, phobias, obsessive\u2013compulsive disorder, eating disorders, addiction and psychosis.<\/p>\n
Freeman is currently investigating its use for treating schizophrenia. Initially, he used VR as a research tool to assess paranoia by presenting people with neutral social situations and seeing whether they perceived hostility. Now, he is aiming to use simulation to allow people to learn by experiencing real-world situations. \u201cThe really good treatments aren\u2019t talking therapies, they\u2019re action therapy,\u201d says Freeman. \u201cYou go into situations and learn how to think, feel and act differently.\u201d<\/p>\n
The gameChange clinical trial, which launched in July, is the largest trial of a VR therapy for schizophrenia so far. Participants first choose from six scenarios, such as visiting a pub or catching a bus, that were proposed by a patient group coordinated by mental-health charity The McPin Foundation in London, which promotes the involvement of people with mental-health conditions in research. The 432 participants then set some parameters for the session, including how challenging they want it to be, which affects the numbers and proximity of other people. Additional stressors can also crop up, such as the papers that blew into the air as I stood in the doctor\u2019s waiting room.<\/p>\n
After three hours of self-paced treatment, researchers will assess participants\u2019 avoidance and distress in real-life situations, and again at a six-month follow-up assessment. As with other digital therapeutics for mental-health disorders, however, the aim is to supplement clinicians, not replace them. \u201cWe need more therapists, not fewer,\u201d says Freeman. \u201cBut given the numbers of people who aren\u2019t getting the help they need, we\u2019re going to need solutions like VR.\u201d And with consumer systems becoming cheaper and more widespread, Freeman hopes that therapy could ultimately be delivered in a person\u2019s home. \u201cThat would be a very appealing way to access help,\u201d he says.<\/p>\n
<\/h2>\n Regulation questions<\/strong><\/p>\nAs digital treatments proliferate, the need for scrutiny of the various medical claims being made becomes ever more important. \u201cYou have the App Store, which has something like 300,000 health apps, but doctors are afraid they\u2019re going to recommend the wrong one,\u201d says Kvedar. \u201cSome of them have high-quality clinical research behind them, some do not, and the regulatory bodies in the United States are struggling to keep up with the volume to make sure no one is making false claims.\u201d<\/p>\n
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\nCatalia Health\u2019s Mabu uses AI to build relationships with patients, helping them to stick to drug plans.<\/span>Credit: Catalia Health<\/p>\n<\/figcaption><\/figure>\n <\/p>\n
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The DTA industry group, which companies join voluntarily, expects members to adopt certain principles and best practices, to reassure users that they take robust evidence and regulatory clearance seriously, says Coder. \u201cThat\u2019s part of our goal as an alliance, to ensure companies know that these are the standards for our industry,\u201d she says. These include publishing trial results with clinically meaningful outcomes in peer-reviewed journals, and incorporating adequate privacy and security protections.<\/p>\n
Digital therapeutics can also run into government regulation. In the United States, they usually fall under the Food and Drug Administration\u2019s (FDA\u2019s) definition of a medical device, which is anything other than a drug that is \u201cintended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease\u201d. Most must therefore follow the regulatory pathways set up for medical devices. In these cases, \u201cthe FDA applies regulatory oversight since they could pose a risk to patient safety should they not function as intended\u201d, says Coder.<\/p>\n
The precise path a digital therapeutic must take, and the level of clinical evidence its maker must provide, is dependent on the novelty of the product and how great a risk it poses should it malfunction. WellDoc\u2019s type 2 diabetes management tool, BlueStar, was granted FDA approval in 2010. Because BlueStar was similar to existing therapies, this involved providing evidence of \u2018substantial equivalence\u2019 to existing diabetes-management software, rather than new clinical evidence. Entirely new therapies, however, typically face bigger hurdles. Pear\u2019s reSET, for instance, had to submit results of a randomized controlled trial (RCT) through the FDA\u2019s\u00a0de novo<\/i>\u00a0approval pathway. The FDA approved it as a prescription-only product, a designation that is independent of the level of regulatory control a digital therapeutic requires.<\/p>\n
However, almost regardless of the type of claim being made, the FDA can exercise \u2018enforcement discretion\u2019 \u2014 waiving regulatory oversight if it decides a product is low risk. For example, apps that aim to prevent diabetes by helping people to change their diet and to exercise, such as Omada\u2019s programme, can be marketed in the United States without providing safety and efficacy evidence to the FDA.<\/p>\n
For those digital therapeutics that do have to take the long road, the process is not a rapid one. \u201cAn RCT takes about three years, in which time there\u2019s been new research and evidence published, and we have improvements,\u201d says Papadopoulou. \u201cAll the digital providers say it\u2019s too slow,\u201d she adds. \u201cThe digital world moves fast.\u201d Iteration after approval can also be a pain point. \u201cYou can\u2019t change your product so much that it\u2019s no longer doing what it was cleared to do,\u201d says Coder.<\/p>\n
The FDA\u2019s regulatory pathways for medical devices took shape in 1976, and the agency has acknowledged the need to modernize its procedures to better foster innovation, particularly in light of the iterative nature of digital products. In December 2017, the FDA issued new guidelines clarifying types of product that will no longer be deemed regulated medical devices, such as apps that promote general wellness. The guidelines also outline the kinds of change to existing software that will require fresh approval, and those that won\u2019t. Earlier that year, it also outlined a pilot scheme for a \u2018pre-certification\u2019 programme that assesses companies, rather than products. Pre-certified companies deemed to have demonstrated excellence in software development and validation could market lower-risk devices without further oversight, or through a more streamlined process. Real-world performance data, which are generally much easier to collect for digital therapeutics than for pharmaceuticals, could then be used to affirm a product\u2019s regulatory status, as well as supporting its evolution. The idea is being tested in a pilot scheme involving nine companies that are undergoing the new process alongside conventional review, to check that they produce the same decision. One of those participating is Pear, that in July became the first company to apply for authorization through the scheme, for Somryst.<\/p>\n
In the United Kingdom, the National Institute for Health and Care Excellence (NICE) assesses the clinical and economic efficacy of treatments. Although commissioners in the country\u2019s National Health Service (NHS) are not bound by NICE recommendations, they carry enormous weight. In an effort to accelerate NHS uptake of digital innovations, NICE, in collaboration with stakeholders such as NHS England and NHS Digital, published guidelines last year aimed at helping manufacturers to understand the kinds of evidence they should be providing, and what commissioners should be requesting. \u201cThe NHS has done a fantastic job with their evidence-for-effectiveness guidelines,\u201d says Coder. It provides guidance for classifying a product according to its function or the type of claim being made, with corresponding recommendations for minimal and ideal types of supporting evidence, as well as appropriate economic data.<\/p>\n
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