Clinic for Surgery, Inflammatory Medicine and Transplantation (KIT Research), Oslo University Hospital, Oslo, Norway.
Pandemic Sciences Institute, University of Oxford, Oxford, UK.
Trials. 2024 Jan 2;25(1):3. doi: 10.1186/s13063-023-07869-x.
The new European Medicines Agency (EMA) Clinical Trials Information System (CTIS), based on the Clinical Trials Regulation (CTR EU 536/2014), came into full effect on 31 January 2022 and was intended to provide an easier, more streamlined approach to the registration of clinical trials taking place in Europe. Using the experience gained on the new regulatory framework from three multi-national European clinical research studies of outbreak-prone infectious diseases, this article describes the advantages and shortcomings of the new clinical trial submission procedure.
We report the time to approval, size of the application dossier, and number of requests for information (RFIs) for each study. We also explore the experience of each study within the regulatory framework and its use of CTIS to document the real-world, practical consequences of the system on individual studies. The study assesses the experience of three multi-country studies conducted in Europe working within the EU and non-EU regulatory environments.
While the time to regulatory and ethical approval has improved since the implementation of the new regulation, the timelines for approvals are still unacceptably slow, particularly for studies being conducted in the context of an evolving outbreak. Within the new regulatory approval procedure, there is evidence of conflicting application requirements, increased document burden, barriers to submitting important modifications, and debilitating technical hurdles.
CTIS promised to lower the administrative bar, but unfortunately this has not been achieved. There are challenges that need to be urgently confronted and addressed for international research collaborators to effectively manage health crises in the future. While the value of multi-national outbreak research is clear, the limitations and delays imposed by the system, which raise challenging ethical questions about the regulation, are prejudicial to all clinical research, especially publicly funded academic studies. This report is relevant to both regulators and clinical researchers. It is hoped that these findings can help improve pan-European clinical trials, especially for the purpose of epidemic preparedness and response.
This paper references experiences gained during management of three pan-European trials: EU-SolidAct's Bari-SolidAct (CT No. 2022-500385-99-00 - 15 March 2022) and AXL-SolidAct (CT No. 2022-500363-12-00 - 19 April 2022), and MOSAIC (CT No. 2022-501132-42-00 - 22 June 2022).
新的欧洲药品管理局（EMA）临床试验信息系统（CTIS）基于临床试验法规（CTR EU 536/2014），于 2022 年 1 月 31 日全面生效，旨在为在欧洲进行的临床试验注册提供更简便、更精简的方法。本文利用三项针对易爆发传染病的跨国欧洲临床研究在新监管框架方面获得的经验，描述了新临床试验提交程序的优点和缺点。
我们报告了每个研究的批准时间、申请文件的规模和信息请求（RFI）的数量。我们还探讨了每项研究在监管框架内的经验及其使用 CTIS 记录系统对个别研究的实际影响。该研究评估了在欧盟和非欧盟监管环境下开展的三项多国研究的经验。
虽然新法规实施后监管和伦理批准的时间有所缩短，但批准的时间仍然不可接受地缓慢，特别是对于在不断演变的疫情背景下开展的研究。在新的监管审批程序中，存在申请要求冲突、文件负担增加、提交重要变更的障碍以及技术障碍等问题。
CTIS 承诺降低行政门槛，但不幸的是，这并没有实现。国际研究合作方需要紧急应对和解决这些挑战，以便未来有效地应对卫生危机。虽然多国爆发性研究的价值是显而易见的，但该系统带来的限制和延迟对所有临床研究，特别是公共资助的学术研究，提出了具有挑战性的监管问题。本报告与监管机构和临床研究人员都相关。希望这些发现能够帮助改善泛欧临床试验，特别是为了做好疫情应对准备。
本文参考了在管理三项泛欧试验期间获得的经验：欧盟-SolidAct 的巴里-SolidAct（CT No. 2022-500385-99-00-15 年 3 月 2022 日）和 AXL-SolidAct（CT No. 2022-500363-12-00-19 年 4 月 2022 日），以及 MOSAIC（CT No. 2022-501132-42-00-22 年 6 月 22 日）。
