Comprehensive Analysis of Clinical Studies and Regulations of Therapeutic Applications in the United States and Japan

BACKGROUND: Digital therapeutics (DTx), the provision of treatment through mobile devices such as smartphones, have attracted great interest as a new medical modality. However, the number of authorized therapeutic applications in the US and Japan is low. Understanding the obstacles in obtaining regulatory authorizations will be the key in promoting timely development of therapeutic applications. Thus, we conducted a comprehensive analysis of the clinical study designs of therapeutic applications authorized in the US and Japan. METHODS: Data on authorized therapeutic applications and the regulations involved were collated from the databases of the Food and Drug Administration (USA), Ministry of Health, Labour and Welfare (Japan), and Pharmaceuticals and Medical Devices Agency (Japan). RESULTS: Most therapeutic applications authorized targeted neuropsychiatric disorders and used cognitive behavioral therapy (CBT)-based treatments. All the involved clinical trials were randomized-controlled studies. Various types of controls—such as standard care, sham application, digital control, and therapies delivered by healthcare providers—were used. Both subjective and objective indices were acceptable as the primary endpoints. Long-term efficacy was evaluated, and all adverse events were assessed comprehensively. The setting up of controls and the need to study long-term efficacy depend heavily on the applications functionality and the target disease characteristics. CONCLUSIONS: This study reveals the points to be considered in planning clinical studies and regulatory strategies for authorizing therapeutic applications. Therapeutic applications can provide new therapy and have potential to solve unmet clinical needs. Our findings shed a light on efficient development and rapid commercialization of therapeutic applications.