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

Clinical Snapshot

Key Findings

• Effect Size: Not applicable — qualitative Delphi consensus study; no quantitative effect size calculated

• Primary Outcome: 32 of 39 synthesised proposals reached ≥80% expert consensus as 'appropriate' or 'very appropriate' solutions to DCT implementation challenges; 14 proposals achieved 100% unanimity. Key endorsed recommendations included HCP training and support, validated IMP and biological sample logistics, improved local healthcare provider collaboration, regulatory harmonisation respecting national specificities, capacity-building initiatives, and accessible hybrid digital trial models.

• Nnt Or Sensitivity: Not applicable — consensus threshold of ≥80% agreement used as the primary decision criterion; 82% of all proposals met this threshold

Clinical Application

The recommendations are largely feasible at an institutional and system level, though implementation will require coordinated investment across regulatory bodies, healthcare systems, and technology providers. Proposals such as HCP training, hybrid trial models, and improved IMP logistics are actionable in the near term. Regulatory harmonisation across EU member states represents a longer-term structural challenge. The failure to reach consensus on EU-level centralisation of ethics review reflects real-world political and jurisdictional complexity. Australia's DCT landscape is evolving, with the TGA and NHMRC increasingly engaged with decentralised research models. The ACT EU parallels are relevant to Australia's Clinical Trials Reform agenda and the work of the Clinical Trials Taskforce. RACGP members are increasingly positioned as local investigators or referring practitioners in DCTs, making the study's recommendations on HCP training, local healthcare provider collaboration, and hybrid models directly applicable. The PBS does not currently have a specific framework for IMP logistics in DCTs, and the study's emphasis on validated supply chain solutions is pertinent to Australian sponsors navigating TGA import/export requirements. The finding that peer-to-peer participant support failed to reach consensus warrants consideration in the Australian context, where community health networks and Aboriginal and Torres Strait Islander community engagement models may require culturally adapted approaches beyond standard DCT frameworks. Clinical trial sponsors, investigators, ethics committees, regulators, digital health technology developers, and patient advocacy organisations involved in the design, conduct, or oversight of decentralised or hybrid clinical trials in Europe and comparable jurisdictions

Abstract

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.

References

1. 1.Murciano-Gamborino, C., Pérez-Breva, L., de Jong, A. J., Boeckhout, M., van Thiel, G. J. M. W., Huntley, K., Traore, H., Gardarsdottir, H., & Fons-Martinez, J. (2026). Addressing the key challenges of decentralized clinical trials in Europe: Multistakeholder perspective Delphi study. Journal of Medical Internet Research. https://doi.org/10.1111/hex.13427