Addressing the Key Challenges of Decentralized Clinical Trials in Europe: Multistakeholder Perspective Delphi Study.

Background: Decentralized clinical trials (DCTs) represent an emerging model in clinical research, accelerated by the restrictions imposed during the COVID-19 pandemic. By leveraging digital technologies and local health care resources, DCTs aim to increase accessibility and reduce participant burden compared to traditional site-based models, which often face recruitment failures and high attrition rates. While various regulatory initiatives in Europe, such as the Accelerating Clinical Trials in the European Union program and the European Medicines Regulatory Network recommendation paper (updated in October 2025), have sought to facilitate their implementation, the widespread adoption of DCTs remains limited due to significant operational, regulatory, and technological challenges, including platform fragmentation and gaps in digital literacy. Objective: This study aimed to identify and prioritize actionable solutions to the main challenges of DCT implementation in Europe from a multistakeholder perspective, gathering insights to address specific ethical, legal, and operational barriers. Methods: Building on a preceding strengths, weaknesses, opportunities, and threats analysis, a 2-round Delphi study was conducted, involving 26 experts in clinical trials, ethics, law, regulation, and patient engagement between March and May 2023. In the first round, 309 open-ended responses were collected via REDCap (Research Electronic Data Capture; Vanderbilt University) surveys and underwent systematic inductive content analysis using ATLAS.ti (ATLAS.ti Scientific Software Development GmbH) with independent double coding. This process resulted in 244 unique proposals that were categorized according to 6 key challenges. In the second round, 39 synthesized proposals were evaluated using a 4-point Likert scale. Consensus was defined as ≥80% agreement on the appropriateness of each proposal. Results: High levels of consensus were achieved, with 32 out of the 39 proposals reaching the threshold and 14 achieving 100% unanimity. Overall, 82% of the proposals were rated as "appropriate" or "very appropriate." Key recommendations included providing support and training for health care professionals, enhancing investigational medicinal product and biological sample logistics through validated technologies, improving collaboration with local health care providers, fostering regulatory harmonization while respecting national specificities, strengthening capacity-building initiatives, and promoting accessible, user-friendly digital tools supported by hybrid trial models. Conversely, proposals such as peer-to-peer participant support and the centralization of ethics reviews at the European Union level failed to reach consensus. Conclusions: The study offers a prioritized compilation of expert-driven recommendations for overcoming current barriers to DCT implementation in Europe. The adoption of these recommendations could support the development of more inclusive, efficient, and sustainable decentralized research frameworks across diverse health care systems.