Mobile Software as a Medical Device (SaMD) for the Treatment of Epilepsy: Development of Digital Therapeutics Comprising Behavioral and Music-Based Interventions for Neurological Disorders

Abstract

Digital health technologies for people with epilepsy (PWE) include internet-based resources and mobile apps for seizure management. Since non-pharmacological interventions, such as listening to specific Mozart's compositions, cognitive therapy, psychosocial and educational interventions were shown to reduce epileptic seizures, these modalities can be integrated into mobile software and delivered by mobile medical apps as digital therapeutics. Herein, we describe: (1) a survey study among PWE about preferences to use mobile software for seizure control, (2) a rationale for developing digital therapies for epilepsy, (3) creation of proof-of-concept mobile software intended for use as an adjunct digital therapeutic to reduce seizures, and (4) broader applications of digital therapeutics for the treatment of epilepsy and other chronic disorders. A questionnaire was used to survey PWE with respect to preferred features in a mobile app for seizure control. Results from the survey suggested that over 90% of responders would be interested in using a mobile app to manage their seizures, while 75% were interested in listening to specific music that can reduce seizures. To define digital therapeutic for the treatment of epilepsy, we designed and created a proof-of-concept mobile software providing digital content intended to reduce seizures. The rationale for all components of such digital therapeutic is described. The resulting web-based app delivered a combination of epilepsy self-care, behavioral interventions, medication reminders and the antiseizure music, such as the Mozart's sonata K.448. To improve long-term patient engagement, integration of mobile medical app with music and multimedia streaming via smartphones, tablets and computers is also discussed. This work aims toward development and regulatory clearance of software as medical device (SaMD) for seizure control, yielding the adjunct digital therapeutic for epilepsy, and subsequently a drug-device combination product together with specific antiseizure medications. Mobile medical apps, music, therapeutic video games and their combinations with prescription medications present new opportunities to integrate pharmacological and non-pharmacological interventions for PWE, as well as those living with other chronic disorders, including depression and pain.

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

“…Positive data from clinical studies of digital technologies for the treatment of pain suggest an emergence of "digital analgesics" (11,13,14). Using digital therapeutics to deliver non-pharmacological interventions such as music and/or physical exercise creates new opportunities for combining these modalities with pharmacotherapies and clinicallyvalidated natural products (4)(5)(6). While development of digital therapeutics does not require preclinical testing (in contrast to regulatory requirements for investigational new drug (IND) enabling studies), translational implications of our study include: (1) using EE as a preclinical surrogate for testing combinations of non-pharmacological modalities for the treatment of pain and other chronic diseases, and (2) preclinical testing and FIGURE 8 | Working model of mechanisms by which musical compositions can exert their analgesic and anticonvulsant activities.…”

“…To innovate treatments for neurological disorders, we have been studying diverse strategies to integrate digital health technologies with CNS drugs (4)(5)(6). Digital health is a branch of healthcare that employs internet, digital, and mobile technologies for improving health and/or treating diseases.…”

“…Several mobile apps and video games (Table S1) received approval, or clearance, from the Food and Drug Administration (FDA) using software as a medical device (SaMD) regulatory mechanism (7,8). There are also increased interests in developing mobile apps for people living with chronic pain (9)(10)(11)(12)(13)(14)(15)(16) and epilepsy (6,(17)(18)(19).…”

Epilepsy control during an epidemic: emerging approaches and a new management framework

“…Smartphone application and remote medical care in epilepsy management Smartphone applications (APPs) and other remote medical care approaches are familiar things to patients with chronic disease. In epilepsy alone, a series of studies [32][33][34] have tested the value of Apps in management of seizures and other issues. Digital technology in the management of epilepsy features a new trend in epilepsy control.…”

Improving Self-Esteem With Motivational Quotes: Opportunities for Digital Health Technologies for People With Chronic Disorders

“…The use of wearables can further optimize digital interventions through neurobiofeedback mechanisms (Ramirez et al, 2015 ), with new biofeedback technologies, such as the FDA-cleared smartwatch Embrace (Empatica), being developed. The flexibility of digital content in mobile health technologies is further emphasized by adding music as an “active component” of therapy (Schriewer and Bulaj, 2016 ; Afra et al, 2018 ) or integrating exercise and educational empowerment into a video game designed for children with cancer (Bruggers et al, 2018 ). Integrating judiciously tailored motivational quotes into digital content as an “active ingredient” in mobile and web-based apps may offer additional means to improve patient engagement, self-esteem, and ultimately self-efficacy.…”