The Digital Therapeutics Real World Evidence Framework: An approach for guiding evidence-based DTx design, development, testing, and monitoring

Digital Therapeutics (DTx) are seen as a promising way to provide safe, effective, accessible, sustainable, scalable, and equitable approaches to advance individual, population, and public health. Developing DTx is inherently complex in that DTx may include multiple interacting components, such as tools to support activities like medication adherence, health behavior goal-setting or self-monitoring, and algorithms that adapt provision of these according to individual needs. While myriad frameworks exist for different parts of the DTx lifecycle, to date, no single unifying framework exists to guide DTx evidence production. The purpose of this paper is to fill this gap. Specifically, we propose the DTx Real-World Evidence (RWE) Framework to provide a pragmatic, iterative, milestone-driven approach for producing RWE for DTx. While it incorporates insights from multiple fields, it uses, as its starting foundation, the Obesity-Related Behavioral Intervention Trials (ORBIT) model, but with explicit adaptations established for DTx. The DTx RWE Framework has two key elements. The first is recommendations on the use of real-world data (RWD) across the DTx lifecycle to support identifying unmet needs, establish real-world benchmarks, support on-going monitoring, and, over time, enable more rapid and resource efficient development and testing based on RWD. The second is a flowchart, which maps onto the four-phase development model as delineated by ORBIT for behavioral interventions (which was adapted from the original phases used for pharmaceuticals) but includes key adaptations relevant to RWE production for DTx. The intended audiences for this are entities that develop and market DTx and thus need RWD and community-serving organizations such as healthcare organizations and public health departments that can provide RWD. We offer the DTx RWE Framework as a unified approach that integrates best practices to evidence production for DTx, which can be used now to guide the actions of DTx companies and community-serving organizations. With that said, regulators of DTx could also consider drawing on the DTx RWE Framework to improve guidance related to DTx evidence production.