Risks and rewards of digital therapeutics in treating mental disorders 2 mins ago
More Americans than ever before are Madeline Stein & Michael SteinContributor suffering from mental and emotional distress. Madeline Stein is a first year In the U.S., the mental health problem is Doctorate student at Saybrook exacerbated by issues across infrastructure, University studying Applied government, and culture. However, because Psychophysiology within the College of Integrative Medicine the resources for those living with mental and Health Sciences. Michael Stein health issues are constrained, startups could (@MichaelStein16) is an attorney and angel investor, with a focus on have a big impact. technology companies that want to make the world a better place. In particular, we believe that digital therapeutic-approaches offer great promise in overcoming the problems inherent in traditional approaches to mental and behavioral therapy. Such problems relate to stigma, cost, and general inaccessibility of cost-effective treatments for the general population.
We are starting to see new energy behind innovators in the mental health space. Examples include Enlyte (discussed in greater detail below); Talkspace, an online therapy app that connects users with licensed therapists; Calm, a sleep and meditation app; and Feel, a wearable designed to monitor the userʼs emotional state. Other examples are listed in the Appendix at the back.
Each of these companies—whether they aim to provide easy access to mental health professionals, to promote overall mental wellness, or to better monitor the userʼs mental state—has the potential to be highly impactful as well as profitable.
In our view, the time is right to invest in mental health and digital therapeutics. In this paper, we provide an overview of the field of digital therapeutics for mental health, as well as the legal, regulatory and ethical issues that should be considered by entrepreneurs and investors.
Table of Contents
The big four mental health afflictions: Stress, anxiety, addiction, depression Stress Anxiety Addiction Depression The promise of digital therapeutics FDA regulatory environment: Software as a medical device Legislative exclusions of software (21st Century Cures Act) Mobile apps Intellectual property protection Example startup: Enlyte Reasons to invest in digital therapeutics Appendix: Example startups Pear Therapeutics Stop, Breathe & Think Pzizz Simple Habit Aura Health Pacifica 2Morrow
The big four mental health afflictions: Stress, anxiety, addiction, depression
Image via Getty Images / Feodora Chiosea The mental health crisis costs companies around the world over $1 Trillion in lost productivity and increased health care insurance premiums annually. The productivity losses are primarily caused by absenteeism, and turnover and replacement costs.
In addition, the costs attributable to the family members and loved ones of employees (employee ecosystem) cost employers approximately 250% more in lost productivity than their direct employees. According to a report from the World Health Organization (WHO), 450 million people are currently suffering from mental health disorders leading to illness and disability.
The Lancet Commission on mental health predicts that by 2030, mental illness will cost the world USD 16 trillion. If we look at the US alone, 40.3 million people are affected by the disease of addiction. Twenty percent of US deaths are attributed to addiction to tobacco, alcohol, drugs and other substances.
Stress
The National Institute for Health (NIH) defines stress as a “physiological response to challenge or demand”. There are two forms of stress: acute and chronic. Acute stress is frequently referred to as your bodyʼs fight-or-flight response.
Presenting physical signs such as muscle tension, increased heart rate, sweating, and decreased circulation to extremities. In moderate amounts stress can help an individual accomplish tasks, make changes, and reach peak performance. Chronic stress can lead to long-term health problems.
The NIH states that chronic stress can result in health conditions: such as high blood pressure, heart disease, and obesity. Along with chronic symptoms such as headaches, digestive problems, difficulty focusing, sexual problems, and chronic pain. Chronic stress can also result in emotional disturbances such as depression and anxiety. Anxiety
The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) has five major types of anxiety disorders: generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and social phobia (or social anxiety) disorder.
The diagnosis of Generalized Anxiety Disorder is characterized by excessive anxiety or worry which is difficult to control accompanied by physical symptoms such as restlessness, sleep disturbances, and muscle tension. As of 2003 the National Institute for Mental Health (NIHM) reports that 19.1% of US adults have experienced an anxiety disorder.
Addiction
The American Society of Addiction Medicine (ASAM) defines addiction as “a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations.
This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors”. This definition of addiction does not limit the scope of addictive behavior to drugs and alcohol. Addiction, as defined by the ASAM, is any behavior which one does not have control over, “negatively impacts interpersonal relationships, and is a dysfunctional emotional response”.
Depression
The DSM-V defines depression as a mood disorder characterized by low mood, loss of interest, suicidal ideation, and hopelessness. The emotional symptoms of depression can also present with physical symptoms such as weight gain or loss, lethargy, and insomnia or hypersomnia. As of 2018, the World Health Organization (WHO) estimates that approximately 300 million people worldwide suffer from depression. In 2017, the National Institute of Mental Health (NIHM) estimated that approximately 17.3 million adults in the US experience depression.
While many companies have Employee Assistance Programs in place that cover mental health issues for their employees and close family members, there is a strong reluctance amongst those covered to use the available benefits because of the stigma attached to mental health issues and the fear that the employeeʼs sensitive personal information may be accessed by the employer. Stigma is the key reason preventing many people that urgently need help from receiving it.
In addition, treatment facility capacity is another reason that people are not getting the help they need. There needs to be increased access to evidence-based treatment options for the public. The emerging field of digital therapeutics offers promising solutions.
The promise of digital therapeutics Image via Getty Images / antoniokhr
According to Wikipedia, digital therapeutics can be defined as a treatment or therapy that utilizes digital health technologies to spur changes in patient behavior. The first mention of the term in a peer-reviewed research publication was in 2015, in which Dr. Sepah et al. defined the “digital therapeutics” as “evidence-based behavioral treatments delivered online that can increase accessibility and effectiveness of health care.” (See Long- Term Outcomes of a Web-Based Diabetes Prevention Program: 2-Year Results of a Single-Arm Longitudinal Study, J Med Internet Res 2015 | vol. 17 | iss. 4 | e92.)
The methods employed by digital therapeutics can be used as a standalone therapy or in conjunction with more conventional treatments, such as pharmacological or in-person therapy. Such methods use various digital devices (e.g., smart phones, apps, sensors, computers, etc.) to help manage, monitor, and prevent illnesses in at-risk patients.
These devices are used to collect data from different sources. Such data may include personalized physiological parameters; behavior, social and geographical patterns; and even data indicative of the userʼs mood or feelings.
In the mental health area, we believe that digital therapeutic approaches can overcome three of the biggest problems with conventional therapies: lack of access, lack of affordability, and stigma. The problems with access and affordability are mainly caused by the relative scarcity of trained counselors as compared to the number of people in need of counseling.
Stigma, on the other hand, is a psychological impediment to seeking help based on a personʼs feeling of shame about his or her mental afflictions. The field of digital therapeutics offers the promise of delivering behavior therapies safely and effectively via a digital device, and thereby largely overcome the problems of access, affordability, and stigma. For this reason, we believe that now is good time to invest in the digital therapeutics space.
FDA regulatory environment: Software as a medical device Image via Getty Images / elenabs
Software has become an important part of all products, integrated widely into digital platforms that serve both medical and non-medical purposes. Software, which on its own is a medical device, called Software as a Medical Device (SaMD), is one of three types of software related to medical devices.
The other two types are software that is integral to a medical device (software in a medical device) and software used in the manufacture or maintenance of a medical device. (See also Software as a Medical Device (SAMD): Clinical Evaluation – Guidance for Industry and Food and Drug Administration Staff.)
The term Software as a Medical Device is defined by the International Medical Device Regulators Forum (IMDRF) as “software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device.” Examples of SaMD include:
Software that allows a smartphone to view images obtained from an MRI medical device for diagnostic purposes; Computer-aided detection (CAD) software that performs image post- processing to help detect breast cancer; Software with a medical purpose that operates on a general purpose computing platform, e.g., software intended for diagnosis of a condition using the tri-axial accelerometer that operates on the embedded processor on a consumer digital camera.
In addition, the FDA have recognized that artificial intelligence (AI) and machine learning (ML) technologies have the potential to transform health care by deriving important insights from the data generated during the delivery of health care. Medical device manufacturers are using these technologies to innovate their products.
The FDA is considering a total product lifecycle-based regulatory framework for these technologies that would allow for modifications to be made from real-world learning and adaptation, while still ensuring that the safety and effectiveness of the software as a medical device is maintained. Adaptive AI/ML technologies differ from other SaMD in that they have the potential to adapt and optimize device performance in real-time to continuously improve health care for patients.
Traditionally, the FDA reviews medical devices through an appropriate premarket pathway, such as premarket clearance (510(k)), De Novo classification, or premarket approval. The FDA may also review and clear modifications to medical devices, including SaMD, depending on the significance or risk posed to patients of that modification.
The FDAʼs traditional paradigm of medical device regulation was not designed for adaptive artificial intelligence and machine learning technologies. Under the FDAʼs current approach to software modifications, artificial intelligence and machine learning-driven software changes to a device may need a premarket review.
On April 2, 2019, the FDA published a discussion paper Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD) – Discussion Paper and Request for Feedback that describes the FDAʼs foundation for a potential approach to premarket review for AI- and ML-driven software modifications. Image via Getty Images / OstapenkoOlena
The ideas presented leverage practices from current premarket programs and rely on IMDRFʼs risk categorization principles. The FDA introduces a “predetermined change control plan” in premarket submissions, which would include the types of anticipated modifications—referred to as the “Software as a Medical Device Pre-Specifications”—and the associated methodology being used to implement those changes in a controlled manner that manages risks to patients —referred to as the “Algorithm Change Protocol.”
In this approach, the FDA would expect a commitment from manufacturers on transparency and real-world performance monitoring for AI and ML- based software as a medical device, as well as periodic updates to the FDA on what changes were implemented as part of the approved pre- specifications and the algorithm change protocol. The proposed regulatory framework could enable the FDA and manufacturers to evaluate and monitor a software product from its premarket development to post-market performance.
To summarize, SaMD is software used for one or more medical purposes without being part of a hardware medical device. Examples include software that allows commercially available devices to view and process images or other data for diagnostic purposes. SaMD does not include software that drives or controls a medical device, embedded software (firmware), non- medical software that just encrypts data (medical records), and software that enables clinical communication and workflow such as patient registration, scheduling visits, voice calls, and video calling.
Legislative exclusions of software (21st Century Cures Act)
The 21st Century Cures Act (Cures Act), signed into law on December 13, 2016, was designed to accelerate medical product development and bring new innovations to patients who need them faster and more efficiently. Interesting aspects of the Cures Act include:
Streamlines FDA procedures to prioritize Breakthrough Devices; Reduces or eliminates review of medical devices deemed to be low risk; and Removes five categories of software from FDA review.
Under the Cures Act, the categories of software excluded from FDA review include:
Category A: Software for administrative support of healthcare facilities, e.g., processing and maintaining financial records, claims and billing information, appointment schedules; Category B: “Healthy lifestyle” software that provides no diagnostic, prevention or treatment function; Category C: Electronic patients records, but not intended to interpret or analyze patient records; Category D: Software for transferring, storing, converting formats, or displaying test data lab tests or med device data, but not intended to interpret or analyze patient records; Category E: Clinical Decision Support Software (CDSS), i.e., software that provides recommendations based on medical information (e.g., peer-review). The software must enable independent review of the basis of the recommendations and does not include medical imaging or in vitro testing.
It should be noted that the FDA is authorized to bring Categories C, D, and E back under regulation with a showing of likelihood and severity of patient harm, the extent to which the software function is intended to support clinical judgement, a reasonable opportunity for a health care professional to review the basis of the information, and the intended user and use environment.
Mobile apps
The FDA website includes a page concerning Mobile Medical Applications, which notes that mobile apps can help people manage their own health and wellness, promote healthy living, and gain access to useful information when and where they need it. The FDA issued the Mobile Medical Applications Guidance for Industry and Food and Drug Administration Staff on September 25, 2013, which explains the agencyʼs oversight of mobile medical apps.
The FDA defines 3 broad categories that are regulated: