Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases

Abstract

Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization of adjunct DTx by the US Food and Drug Administration and draft guidelines on “prescription drug use-related software” illustrate opportunities to create drug + digital combination therapies, ultimately leading towards drug–device combination products (DTx has a status of medical devices). Digital interventions (mobile, web-based, virtual reality, and video game applications) demonstrate clinically meaningful benefits for people living with Alzheimer’s disease, dementia, rheumatoid arthritis, cancer, chronic pain, epilepsy, depression, and anxiety. In the respective animal disease models, preclinical studies on environmental enrichment and other non-pharmacological modalities (physical activity, social interactions, learning, and music) as surrogates for DTx “active ingredients” also show improved outcomes. In this narrative review, we discuss how drug + digital combination therapies can impact translational research, drug discovery and development, generic drug repurposing, and gene therapies. Market-driven incentives to create drug–device combination products are illustrated by Humira® (adalimumab) facing a “patent-cliff” competition with cheaper and more effective biosimilars seamlessly integrated with DTx. In conclusion, pharma and biotech companies, patients, and healthcare professionals will benefit from accelerating integration of digital interventions with pharmacotherapies.

Redesigning Pharmacy to Improve Public Health Outcomes: Expanding Retail Spaces for Digital Therapeutics to Replace Consumer Products That Increase Mortality and Morbidity Risks

“…Digital health technologies, including DTx, provide clinically meaningful benefits for diverse chronic medical conditions, such as low back pain, attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), diabetes, insomnia, migraine, substance use disorder, heart failure, depression, anxiety, rheumatoid arthritis, cancer, chronic obstructive pulmonary disease (COPD), irritable bowel syndrome (IBS), neurodegenerative and cardiovascular diseases (CVDs), etc. [ 27 , 31 , 32 , 33 , 34 , 35 , 36 ]. As illustrated in Table 1 , RelieVRx is an example of an FDA-authorized PDT that uses a VR system to reduce the severity of chronic low back pain (CLBP) [ 37 , 38 , 39 ].…”

“…Digital health technologies are being recognized for enhancing pharmacy care [ 88 , 89 , 90 , 91 , 92 , 93 , 94 ]. There are apparent benefits of integrating DTx with drug-based therapies, such as better therapy adherence and outcomes [ 31 , 95 , 96 , 97 , 98 , 99 ]. For example, adjunct DTx reSET-O improves cost-effectiveness and treatment outcomes of buprenorphine for opioid use disorder [ 98 , 99 , 100 , 101 ].…”

“…Mobile apps can also improve medication adherence in people with diabetes [ 105 , 106 ]. The FDA draft guidelines on “prescription drug use-related software” support the development of drug+digital combination therapies [ 31 , 107 ]. We recently reviewed how digital therapeutics can improve the effectiveness of pharmaceutical drugs and biologics using the drug–device combination product approach [ 31 ].…”

“…The FDA draft guidelines on “prescription drug use-related software” support the development of drug+digital combination therapies [ 31 , 107 ]. We recently reviewed how digital therapeutics can improve the effectiveness of pharmaceutical drugs and biologics using the drug–device combination product approach [ 31 ]. Rapid developments in applications of artificial intelligence (AI) to precision medicine support broader adoption of digital technologies for better healthcare outcomes [ 108 ].…”