Clinical Evaluation of Digital Therapeutics: Present and Future

Abstract

Objectives: Digital therapeutics (DTx) are software-based therapeutic interventions based on clinical evidence. Randomized clinical trials (RCTs) are often the source of clinical evidence, similar to conventional drugs or medical devices. However, novel approaches such as the use of real-world data or digital biomarkers are also utilized. This article aimed to review how DTx products have been clinically evaluated. Methods: DTx products approved by the US Food and Drug Administration as of 2020 were reviewed and products with sufficient published information were selected. Pivotal clinical trials were analyzed according to the elements of the Consolidated Standards of Reporting Trials (CONSORT) guideline. Case reviews were presented for other clinical evaluation strategies, considering the small number of publications. Results: Most approved DTx products used RCTs for clinical evaluations. Similar to conventional RCTs, parallel-group designs with statistical hypothesis testing were adopted. However, DTx trials were often not blinded due to practical issues and involved various comparator groups. In addition, DTx products could be readily evaluated in home-based settings and delivered through the internet. Other evaluation approaches included retrospective analyses using insurance claims data or usage data, which enabled long-term evaluations of effectiveness. Digital biomarkers obtained from real-time and continuous log data were also used to improve the objectiveness of endpoints. Conclusions: RCTs accounted for the majority of DTx evaluations. The designs of DTx trials were comparable to those of drug or device trials, but blinding and comparator elements were often different. Furthermore, the use of real-world data and digital biomarkers are also being tried.

Digital therapeutics from bench to bedside

“…However, these characteristics of DTx can cause a digital health gap due to digital disparities; therefore, a design process considering patient equity is required. Additionally, to secure the therapeutic effect of DTx, patient engagement is key 13,14 , and can be affected by sociocultural background and demographic characteristics 12,13 . The fact that DTx are influenced by demographic or sociocultural characteristics is not sufficiently empirically proven.…”

“…Among the clinical trials investigated in this study, no cases of multinational clinical trials were found, and clinical trials in Asia were also rare. In addition, DTx as software can appear in various forms compared with placebos of pharmaceuticals, and maintaining complete blind conditions is difficult 12,49 ; thus, an RCT framework considering the characteristics of DTx should be designed.…”

“…In pharmacotherapy, individual physiological characteristics are the most important influencing factors in determining drug efficacy. However, the important difference is that the efficacy of DTx can be affected not only by demographic factors but also by sociocultural and cognitive abilities 12,13 . The main disadvantages of DTx compared to pharmaceuticals are low patient accessibility from a digital barrier, need for prerequisites, and data security issues.…”

Open label randomized controlled trial of a digital therapeutics in temporomandibular disorder (TMD) patients: A preliminary study

“…The definition of Digital Therapeutics (DTx) has been recently established as "evidenced-based therapeutic interventions driven by high-quality software programs to prevent, manage, or treat a medical disorder or disease" by the Digital Therapeutics Alliance. The utilization of DTx in practice involves the presentation of therapeutic solutions for medical or psychological conditions through smartphone applications (apps) or wearable devices 39 .…”

Digital Therapeutics (DTx)

“…DTx and related concepts Regulatory bodies have held that DTx need to be clinically evaluated regarding efficacy, safety, and quality. The first aspect of clinical evaluation describes the conscientious, explicit and judicious use of currently accepted best practices to show evidence of the efficacy of a DTx (cf Sackett 1996;Huh et al 2022)…”