The Italian landscape of digital therapeutics in a European context.

Introduction and aim: Digital Therapeutics (DTx) are emerging as a key component of the modern healthcare landscape, offering evidence-based therapeutic interventions powered by software. Unlike wellness apps, DTx require robust clinical validation to demonstrate their efficacy in managing and treating diseases such as diabetes, anxiety, depression, and hypertension. Clinical trials evaluating DTx follow rigorous methodologies similar to traditional drug trials, including randomized controlled trials (RCTs), but also present unique challenges, such as the need for software updates and decentralized patient management. The aim of this narrative review is to examine the European landscape of clinical trials and the associated regulatory framework for DTx, followed by a focus on the current situation in Italy. Methods and results: To contextualize the development of digital therapeutics, existing literature was first reviewed to identify key therapeutic areas. A targeted analysis of clinical trials performed in Italy was conducted using ClinicalTrials.gov as the data source. Predefined keywords were applied, and retrieved records were screened based on relevance to DTx and applicability to the Italian context. Studies were included if they investigated digital interventions with therapeutic intent and were conducted in Italy. Following screening, 13 DTx-related clinical trials were identified, including 11 interventional and 2 observational studies. All interventional studies were randomized controlled trials at different stages of development. The analysis revealed heterogeneity in study design regarding control arm strategies, with approaches ranging from standard of care and active controls to no-treatment comparators and digital placebo conditions. Regulatory frameworks for DTx have evolved significantly, with the European Medical Device Regulation (MDR 2017/745) now recognizing stand-alone software as a medical device. This shift emphasizes the importance of regulatory compliance, risk classification, and continuous monitoring to ensure patient safety and therapeutic effectiveness. We also examined post-market surveillance responsibilities to provide an overview of key opportunities and considerations for stakeholders interested in commercializing a digital therapeutic. Discussion and conclusion: As DTx continue to gain traction, their integration into healthcare systems will depend on clinical evidence, regulatory adaptation, and user engagement. Future developments will likely focus on optimizing trial methodologies and enhancing digital endpoints to improve patient outcomes.