Key Considerations for Designing Clinical Studies to Evaluate Digital Health Solutions

Evidence of clinical impact is critical to unlock the potential of digital health solutions (DHSs), yet many solutions are failing to deliver positive clinical results. We argue in this viewpoint that this failure is linked to current approaches to DHS evaluation design, which neglect numerous key characteristics (KCs) requiring specific scientific and design considerations. We first delineate the KCs of DHSs: (1) they are implemented at health care system and patient levels; (2) they are "complex" interventions; (3) they can drive multiple clinical outcomes indirectly through a multitude of smaller clinical benefits; (4) their mechanism of action can vary between individuals and change over time based on patient needs; and (5) they develop through short, iterative cycles-optimally within a real-world use context. Following our objective to drive better alignment between clinical evaluation design and the unique traits of DHSs, we then provide methodological suggestions that better address these KCs, including tips on mechanism-of-action mapping, alternative randomization methods, control-arm adaptations, and novel end-point selection, as well as innovative methods utilizing real-world data and platform research.