European regulators publish ambitious workplan to support the 10 priority areas of ACT EU
Today, the European Commission, Heads of Medicines Agencies and European Medicines Agencies released a workplan to address the ten priority areas of the Accelerating Clinical Trials in the E.U. initiative, intended to make the region a better home for multi-national clinical trials. The workplan unveils a wealth of deliverables over the next two years that aim to support efficient multi-national processes with streamlined support from regulators.
BY KIRSTEN MESSMER, PHD, RAC | AUG 30, 2022 11:11 PM EDT
ACT EU aims to address the paucity of multi-national clinical trials in the European innovative environment
- The E.U. has an extensive life science research and healthcare sector to support innovation. The E.U. has a rich pharmaceutical industry that spent EUR 39 billion on research and development alone in 2020, according to an EFPIA report on its members’ expenditures. Forty-seven percent of this research expenditure was allocated for clinical research. There were 67,656 clinical trials registered in EudraCT on July 31, 2022, of which 79% were commercial clinical trials and 20% were non-commercial.
- The clinical trial environment is challenged by small and mono-national clinical trials. According to the ACT EU Initiative statement, about 40% of clinical trials in the E.U. are conducted by academic research institutions. These are often small and mono-national due to the complex and faceted clinical trials environment in Europe. Sixty percent of clinical trials are sponsored by pharmaceutical industry, according to the statement. The EC, HMA and EMA said they recognize that greater support is needed “for Europe to flourish as a global focus for clinical trials.”
- The key challenge, according to regulators, is that a fractured set of clinical trial requirements between countries makes it difficult for some trials to run simultaneously across various member states. In particular, it can be difficult to obtain rapid trial authorizations, which can increase the cost of running a trial and slow results – a “particularly worrisome challenge” when facing a public health crisis like Covid-19. Other concerns include varying language requirements, different national applications, different processes and requirements for each national ethics committee and more.
- A focus on Covid-19: The ACT EU initiative statement notes several concerns, including a drop in the inclusion of E.U. generated clinical trial data in marketing authorization applications (MAAs) and lagging research responsiveness.
- The EC, HMA and EMA introduced the ACT EU initiative to support improvements in the clinical trial environment. The initiative provides an ambitious list of actions supported by several legislative proposals and regulatory changes. The Clinical Trial Regulation (Regulation (EU) No 536/2014), which becomes applicable on January 31, 2022, aims to support more harmonized clinical trial conduct in the E.U. ACT EU builds on the EC’s Pharmaceutical Strategy for Europe and the HMA’s European Medicines Agencies Network strategy to 2025. [Read AgencyIQ’s analysis of the Pharmaceutical Strategy and the Network Strategy Workplan.]
The ACT EU initiative includes six objectives and 10 priority actions
- The group plans to leverage a four-tier framework with goals of doing – executing, implementing, communicating; requiring through issuing guidance; influencing, through thought leadership and issuing key papers; and supporting stakeholders in their interactions.
- The initiative is broadly organized around six main objectives, through which it hopes to “deliver on these recommendations.”
- Objective 1: Optimize the E.U. clinical research environment. Specifically, this objective calls for better coordination and execution of clinical trial authorization, as well as strengthened “leadership” over the authorization process.
- Objective 2: Strengthen clinical trials that deliver “decisional evidence.” The objective aims to generate more clinical evidence supporting marketing authorization decisions within the E.U. through improved support for technology assessment bodies, academia and small businesses focused on rare diseases, and therapies for unmet medical needs.
- Objective 3: Improve impact of scientific advice to strengthen European clinical trials. “Excellent and coordinated scientific advice as a complement of clinical trial authorisation” can support optimized changes throughout the product lifecycle.
- Objectives 4, 5 and 6: Engagement, clarity and capacity: There is a need for greater engagement with stakeholders to support the delivery of “patient-oriented medicines” and strategic coordination between member states on clinical trials to create capacity “in all aspects of drug development and regulatory science,” according to the initiative.
- There are also 10 “priority actions” for ACT EU, which envisions a more streamlined and efficient network for clinical trials in the European Union.
Today, the EC, HMA and EMA released their 5-year workplan with specific deliverables for each of the 10 priority actions
- Priority Area 1: Mapping existing initiatives to develop a “governance realisation strategy” that coordinates expert and working groups. Currently, several expert groups and working parties focus on diverse areas such as providing advice, guidance and trial approval. The development of a common framework clarifying roles and responsibilities will initially focus on the Clinical Trials Coordination and Advisory Group (CTAG), Clinical Trials Coordination Group (CTCG), Commission Expert Group on Clinical Trials (CTEG) and Good Clinical Practice Inspectors Working Group (GCP IWG). A “regulatory network responsibility assignment” (RACI) matrix will be completed by end of 2022. Additionally, a RACI matrix for other groups within the European Medicines Regulatory Network (EMRN) and an ethics infrastructure are planned for the fourth quarter 2022.
- Priority Area 2 – Successful implementation of the Clinical Trials Regulation (CTR) to support conduct of large multi-national clinical trials: Regulation (EU) 536/2014 became applicable in January 2022, allowing submission of one clinical trials application through the single Clinical Trials Information System to up to 30 European countries. This priority area focuses on tracking and publishing monthly key performance indicators (KPI), providing training and addressing any issues. Deliverables for 2022 include monthly KPI publication as well as the launch of a sponsor survey to identify and then implement a process to resolve issues are planned for later this year. A scheme supporting larger multi-national trials is planned for 2023, while a “one-stop shop” supporting academics is planned for 2024. [See AgencyIQ’s analysis of the CTR/CTIS and KPI report.]
- Priority Area 3 – Development of a multistakeholder platform to enable “a more holistic discussion across the clinical trial landscape:” The regulators explain that stakeholders involved in the design, regulation and performance of clinical trials have little opportunity for regular dialogue across all E.U. levels. The multi-stakeholder platform (MSP) aims to facilitate this dialogue, and hance the “evolution of the clinical trials landscape.” Plans include a concept paper discussing the MSP in the third quarter of this year, and a kick-off and regular events starting in the second quarter next year.
- Priority Area 4 – Supporting the modernization of the ICH E6(R2) guideline on good clinical practice: The guideline discusses the application of Good Clinical Practice principles to a wide range of clinical trials and data sources. The modernization aims to implement flexibilities to facilitate use of innovative technologies in clinical trials. The ICH guideline revision process involves five steps, and this guideline is currently just at Step 1, the drafting stage. The Workplan foresees a stakeholder workshop on the ICH E6 in the first quarter of 2023, meaning we’ll likely see the draft early next year. Further deliverables include the implementation of changes (Step 3) and the development of a change management strategy for implementation of the guideline (Step 5) for the second half of 2023. [Read AgencyIQ’s analysis of the Good Clinical Practice principles.]
- Priority Area 5 – Maximize clinical trial date value through advanced analytics: The European Medicines Regulatory Network (EMRN) accumulated a wealth of clinical trial data that is “difficult to access, process and interpret” since it is contained in multiple data sources and formats, according to the workplan. The regulators plan to use advanced analytics to make the data accessible for identifying trends, with a data analytics strategy for E.U. clinical trials due for release by year’s end. A clinical trials dashboard enabling public access to the trials data will be developed starting in 2023 followed by a workshop to identify common interests.
- Priority Area 6 – Targeted communication campaign to involve all clinical trial enablers: The communication campaign focuses on sponsor needs and training available for the use of the Clinical Trial Information System as well as ACT EU events. A Clinical Trials Highlights newsletter was launched earlier this year. A dedicated ACT EU website, planned for the second quarter of 2023, will link to the MSP developed in Priority Area 2 by the first quarter of 2024.
- Priority Area 7 – Development of a consolidated clinical trials scientific advice process for efficient management with enhanced coordination: Over the next two calendar years, regulators are planning to take a hard look at the current ways in which experts provide scientific advice and interact with sponsors, with the aim of consolidating processes and enhancing how scientific advice is delivered and managed. A stakeholder survey will kick off this process, followed by the initiation of a first pilot for a consolidated scientific advice process; the pilot will be expanded through the Pharmaceutical Strategy, culminating in an optimized process by the end of 2025.
- Priority Area 8 – Provide key methodology guidance to support innovative trial designs and technologies. The use of innovative and complex trial designs such as umbrella trials and new technologies provides opportunities for efficient clinical trial conduct, but also pose methodologic challenges. Ongoing updates are rolling out: the guideline on complex clinical trials was published in June 2022, and a recommendation paper on decentralized clinical trials is planned for the end of 2022 following a workshop in September. A guidance publication roadmap should be expected by the end of 2023 followed more guideline development. [See AgencyIQ’s analysis of the question and answer document Part I and Part II.]
- Priority Area 9 – Improving clinical trial safety monitoring will initially focus on safety assessor training. Collaboration and coordinated work-sharing by Member States will aim to improve overall trial safety, surveillance, and the quality of safety data. This priority area connects to activities of the EU4Health Joint Action Safety Assessment Cooperation and Facilitated Conduct of Clinical Trials (SAFE CT). Regulators plan to launch a mentorship program and training for assessors and establish KPIs for safe clinical trials by the end of 2022. A process for safety coordination across the EMRN is planned to be defined later in 2023, followed by a assessors’ training curriculum in 2024.
- Priority Area 10 – Develop an education “ecosystem” that enables training on clinical trials through bidirectional exchange. The training curriculum aims to support better knowledge sharing particularly with universities and small-to-medium sized entities leading to high quality medicines development. The curriculum will be informed by regulatory experience. The training strategy, contracts for training content and launch of initial modules (e.g., clinical trials, data science) are planned for later this year. A training gap analysis on additional training needs (e.g., by academia) and development of additional modules for targeted audiences are planned throughout 2023.
- This first workplan lays out ambitious goals to achieve over the next 2.5 years. The EC, HMA, and EMA hit the ground running after the initiative was first announce in January this year; some deliverables on the workplan, for example guidance on complex clinical trials, have already been completed. However, the workplan contains over forty planned deliverables. Nineteen of these are planned to be completed within the next five months. Although the workplan covers 2022 – 2026, only three deliverables are currently noted for 2025.
- It should be expected that deliverables will be postponed, and a future update may add new deliverables. Delays and changes in plans should always be expected. The updates of the Big Data Workplan show that deliverables may be addressed before or after the planned timeframe. The third iteration of the Big Data Workplan has added new deliverables based on the experience gained. Similarly, it should be expected that the timings of action items change, but not the overall goals and deliverable items. [See AgencyIQ’s analysis of the Big Data Workplan.]
- Several priority areas aim to make it easier to understand “who does what” to build efficiencies into processes which would benefit all stakeholders. The current initiatives through expert and working groups are fragmented leading to inefficiencies and potential duplication of work. The mapping and responsibility assignments try to eliminate that. The multi-stakeholder platform aims to enable collaboration among all clinical trials stakeholders, which should increase trial efficiency and speed evolution of the E.U. clinical trial landscape. Improved and consolidated scientific advice processes could potentially reduce the number of scientific advice meetings sought, as well.
- Many activities specifically target smaller sponsors to increase their ability to conduct larger multi-national trials. Sponsors from academia or small-to-medium sized enterprises may not have the resources to navigate the complex clinical trial landscape to conduct multi-national trials. However, a consolidated scientific advice process would make scientific advice more accessible for these stakeholders. A targeted communication campaign and additional training material further aim to provide regulatory information allowing for better engagement of small sponsors.
- There are a few deliverable items to look out for this year and early 2023. A survey to identify sponsor issues with the implementation of the Clinical Trials Regulation is planned for the third quarter of 2022 and the initiation of a process to resolve those by end of 2022 (priority area 2). A concept paper on the multi-stakeholder platform is planned to open for consultation in the third quarter 2022 (priority area 3). The E.U. clinical trials data analytics strategy should be available by end of 2022. Further information on complex and decentralized clinical trials as well as training modules will become available through 2022 (priority areas 8 and 10). Priority area 4 deliverables suggest that the revised ICH E6 guideline will become available for consultation early in 2023.
To contact the author of this analysis, please email Kirsten Messmer.
To contact the editor of this analysis, please email Kari Oakes.
Key Documents and Dates