Digital therapeutics from bench to bedside

Abstract

As a new therapeutic technique based on digital technology, the commercialization and clinical application of digital therapeutics (DTx) are increasing, and the demand for expansion to new clinical fields is remarkably high. However, the use of DTx as a general medical component is still ambiguous, and this ambiguity may be owing to a lack of consensus on a definition, in addition to insufficiencies in research and development, clinical trials, standardization of regulatory frameworks, and technological maturity. In this study, we conduct an in-depth investigation and analysis of definitions, clinical trials, commercial products, and the regulatory status related to DTx using published literature, ClinicalTrials.gov, and web pages of regulatory and private organizations in several countries. Subsequently, we suggest the necessity and considerations for international agreements on the definition and characteristics of DTx, focusing on the commercialization characteristics. In addition, we discuss the status and considerations of clinical research, key technology factors, and the direction of regulatory developments. In conclusion, for the successful settlement of DTx, real-world evidence-based validation should be strengthened by establishing a cooperative system between researchers, manufacturers, and governments, and there should be effective technologies and regulatory systems for overcoming engagement barriers of DTx.

Digital Health for Oncological Care

“…54,55 A somewhat related emergent technology area is digital therapeutics, which have been broadly defined as "software as a medical device that provides evidence-based therapeutic intervention to patients to prevent, manage, or treat a medical disorder or disease." 56 The bulk of such technologies queries the user via mobile app surveys and provides behavioral recommendations such as for mental health, substance use, and sleep disorders. Other use cases that may require additional input from the patient (e.g., blood glucose, physiological data) include guidance on or even direct control of medication management for diabetes, birth control, or lung disease.…”

Digital Therapeutics as a New Therapeutic Modality: A Review from the Perspective of Clinical Pharmacology

“…In the United States-where the development experiences are the most numerous-most DTx are classified as medical devices by regulatory authorities due to claims falling under the medical device jurisdiction 44 and approval/clearance for commercialization is obtained through the 510(k) or De novo pathways. 45 In addition, in the European Union, there is a general understanding that DTx solutions should be classified as medical devices. In addition, the few national reimbursement frameworks that address software suggest the need for DTx to be CE marked in order to get reimbursed (example with the DiGA reimbursement pathway in Germany 46 ).…”

“…However, we found that this is not representative of the case of studies that were used to support regulatory clearance. In fact, we have retrieved sample size information from 6 studies related to 4 US Food and Drug Administration (FDA) de novo cleared products 45 to find that the mean sample size was much larger with 230 subjects.…”

“…In the United States—where the development experiences are the most numerous—most DTx are classified as medical devices by regulatory authorities due to claims falling under the medical device jurisdiction 44 and approval/clearance for commercialization is obtained through the 510(k) or De novo pathways 45 . In addition, in the European Union, there is a general understanding that DTx solutions should be classified as medical devices.…”

Interests, Conflicts, Confluences, and Logic: A “First Principles” Perspective

“…Absent reform, we allow conflict at a grand scale while policing confluence at a lesser; and we foreclose on the many advances in standards that derive from the interactions of private sector innovation, validating research, and clinical application. In an age where quite fundamental change in prevailing practice is driven by private sector activity, such as the burgeoning array of digital therapeutics 16 -CME sanctimony that precludes education in this watershed is a threat to the standard of care.…”