November 2024
Medicines and Vaccines
ICH
1. The press release from ICH Assembly Meeting, Montréal, Canada, November 2024 includes confirmation that the draft ICH E6(R3) Annex 2 Guideline on “Good Clinical Practice (GCP)” reached Step 2a/b and was endorsed by the ICH Assembly. This Annex addresses the GCP considerations that arise from the increased use of a wider range of design elements and data sources and focuses on examples of trials that incorporate decentralised elements, pragmatic elements and/or real-world data (RWD). The full press release can be accessed here.
2. ICH E6(R3) Annex 2 (draft version; endorsed on 6 Nov 2024 and currently under public consultation) addresses the GCP considerations that arise from the increased use of a wider range of design elements and data sources. Annex 2 provides additional GCP considerations, focusing on examples of trials that incorporate decentralised elements, pragmatic elements and/or real-world data (RWD). Work on Annex 2 will be progressed in parallel with work on the ICH E6(R3) Principles and Annex 1, with Annex 2 work initiated once the latter reaches ICH Step 2. Stakeholders from ICH Member countries/regions are encouraged to submit their comments to their respective Regulatory Authorities. Details of the documents are provided here. Training materials are available to download here.
CTR and CTIS
1. A reminder that the next CTIS walk-in clinic is on 20 November 2024 (16:00 Amsterdam time) and is open to all sponsor organisations, including pharmaceutical companies, contract research organisations, small and medium-sized enterprises and academic organisations. It will be a live broadcast; no registration is required for those wishing to follow the live broadcast on EMA’s website.
2. The Finnish Medicines Agency (Fimea) has defined measures for non-transferred clinical trials. If the trial cannot be transitioned, it becomes unlawful from 31 January 2025 and the authority will interrupt the trial. Fimea has provided details of the steps to be followed if eligible clinical trials have not been transitioned to the CTIS before 31 January 2025.
3. A RAPS open access article by Sharma et al, entitled “The emerging transparency paradigm for clinical trials in Europe” is available to download from here. In their article the authors address navigating the EU transparency rules within a global context.
4. The Belgian Federal Agency for Medicines and Health Products (FAMHP) has released a statement calling for the transfer of clinical trials to the CTR as soon as possible and “calls on sponsors to transfer clinical trials to Regulation 536/2014 as soon as possible.”
5. The latest CTIS newsflash was released on 19 November 2024 providing key updates on CTIS and links to useful reference materials along with details of the Winter clock stop: all timers within the evaluation of a CTA will stop on 22 December 2024 at 23:59:59 CET and resume on 8 January 2025 at 00:00:01 CET.
UK and MHRA News
1. The HRA has worked in collaboration with NHS Research Scotland, HSC Northern Ireland and Health and Care Research Wales to create a ‘carrying out research across borders’ toolkit. This toolkit is designed for use by researchers setting up and conducting research in the NHS, or health and social care settings across multiple UK nations.
2. On 12 November 2024, the International Standard Registered Clinical/Social Study Number (ISRCTN) registry announced some user interface updates to their website which means it is now more compliant with accessibility standards, resulting in several visual changes aimed at improving user experience. More information is available here.
3. The International Standard Registered Clinical/Social Study Number (ISRCTN) registry has made a few recent updates, including a refurbished transparency tracker, and a change to the 'Protocol/serial no.' field in the ISRCTN study registration form. Regarding the latter, the field is now called 'Secondary identifying number(s)' and is for any internal reference numbers given to the study by the researcher, the funder or sponsor etc. The study ID can be entered here if the study is registered in any other register apart from EudraCT/CTIS or ClinicalTrials.gov. NIHR, HTA and Wellcome Trust grant numbers should be included here.
4. On 13 November 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) published the recording of the webinar on 'Implementing the New UK Clinical Trials Regulations' held on 15 October 2024, which outlined the expected timelines for implementing the new UK Clinical Trials regulations and presented plans to share the draft guidance with stakeholders for feedback. Note: at time of preparing the CORE Reference monthly report the webinar was not available, however a blog on the subject was available from here.
5. The HRA is simplifying the process of seeking and recording consent in low risk clinical trials. To find out more and provide feedback on the proposals, please click here. Feedback will be used to help inform the future Clinical Trials regulations in the UK in 2025.
FDA Guidance and News
1. FDA and Duke-Margolis Institute for Health Policy at Duke University will hold a free Public Workshop: ‘Optimizing Use of Real-World Evidence – Looking Forward’ that will focus on recent accomplishments, ongoing opportunities and challenges, and forward-looking initiatives regarding FDA’s RWE Program. Date: Thursday 12 Dec 2024, 12:30 to 17:00 p.m. (ET); in-person participation is encouraged. Register by Fri 6 Dec 2024.
2. The National Library of Medicine has released a Report on the ClinicalTrials.gov Modernization Effort which gives an update on the Modernized ClinicalTrials.gov and PRS websites plus plans for future modernization activities.
3. The webinar recording and transcript from the 8 October 2024 webinar on the Modernized PRS is now available. The webinar highlighted features of the Modernized PRS, and showed users how to navigate the Modernized PRS.
4. The first modernised modules of the PRS results sections (Participant Flow, Limitations and Caveats and More Information) are now available on PRS Test and will soon be available in the Modernized PRS. Users are encouraged to try the available results modules in PRS Test and let CT.gov PRS know what they think. Read the latest Release Notes to learn more.
EMA Guidance and News
1. The EMA is organising a Q&A session on Improving efficiency of approval process for new medicines in the EU on 5 Dec 2024. The session will cover MAAs in the EU, the challenges companies face in meeting submission deadlines, highlight EMA’s initiatives to improve efficiency in assessment and approval processes, and share tools and recommendations to help companies better plan their submissions.
Real-World Data
1. The Fifth EMA/HMA Big Data Stakeholder Forum was held on Thursday 28 November - 09:00 - 17:30 Amsterdam time (CET). Full agenda and webinar of the meeting can be accessed here.
2. Read about the RWE policy development and the use cases in China in the article by Du and Han, entitled “Evolving Policies and Use of RWE in Regulatory Decisions in China”.
3. The UK has released Uniting the UK’s Health Data: A Huge Opportunity for Society, a review of the UK health data landscape. The report provides an extensive overview of the many sources of health-relevant data across the UK.
EMA Policy 0070 in Practice
1. Free webinar on 21 Nov 2024 entitled “Best Practices for Clinical Data Anonymsation Using the Quantitative Methodology.” The webinar will examine the quantitative anonymisation methodology and several best practices such as privacy models, anonymisation techniques, Reference Population, Risk of Re-Identification, Information Loss and Adversary Attacker Models. Register in advance here.
2. The European Medicines Agency (EMA) hosted a webinar on the next step in the resumption of the Clinical Data Publication (Policy 0070) activities on 14 November 2024. Individual presentations are available to download from here together with a video recording of the webinar.
Proposed scope of Step 2 in brief:
- All new MAAs including negative opinions, withdrawn applications, line extensions and major clinical Type II variations (extension of indications) from Q2 2025 (precise date to come; approximately April 2025 onwards)
- Exclude all biosimilars, hybrids and generics
- Continue Covid procedures and any new public health emergencies that may arise
- External Guidance - under review to publish early 2025
- Questions and answers (Q&A) document - published July 2023 – update in 2025
- Collaboration with Health Canada align processes – workshare. Pilot of single review of redaction proposal package
- EMA proposal for publication of legacy clinical data: publication upon request (access-to-documents)
Development Strategy News
1. The inaugural issue of the Global Clinical Trials Forum (GCTF) Newsletter from WHO was published in October 2024 and can be downloaded from here. The newsletter will be a source for the latest updates and insights on strengthening clinical trials (infrastructure and environment) and you can subscribe to receive the regular monthly newsletter directly here.
2. On 11 Nov 24, the 3-page Mandate of the ACT EU Steering Group was published.
3. Higgins et al, 2024 have published “Considerations for open-label randomized clinical trials: Design, conduct, and analysis.” In their paper, the authors review how best to design, conduct, and analyse open-label trials to ensure the highest level of study integrity and the reliability of the study conclusions.
4. Check out this webinar on Digital Data Flow (DDF) Solution Showcase cohosted by TransCelerate and CDISC to be held on 5 Dec 2024. This is the second webinar in this series focusing on study protocol digitalization solutions.
Artificial Intelligence/Machine Learning
The UK Department for Science, Innovation and Technology’s (DSIT) has started the public consultation on AI Management Essentials (AIME) Tool. AIME is a resource that is designed to provide clarity to organisations around practical steps for establishing a baseline of good practice for managing AI systems that they develop and/or use.
News from Asia Regulators
Hirakawa et al. published an article entitled “Planning and Implementing Master Protocol Trials in Japan: Key Considerations of the Japanese Guideline” (Note: article behind paywall).
Medical Devices
This subsection covers transparency in relation to medical devices, and the emerging intersection of the regulatory medical devices and the regulatory drugs spaces. Devices information or regulations that impact the reporting of device studies are also covered. Contextualisation is provided, where possible, to help readers understand how the information could be used.
General Updates and News
The FDA held an inaugural Digital Health Advisory Committee Meeting on November 20-21, 2024. The meeting considered premarket performance evaluation and risk management of generative AI in medical devices. A report of the meeting discussion is here. On the second day the Digital Health Advisory Committee offered the US FDA recommendations on how to think about postmarket performance evaluation of generative AI-enabled medical devices. Webcasts of the two day meeting can be accessed here.
EUDAMED News
The European Commission has released MDCG 2024-11 EUDAMED Q&A on practical aspects related to the gradual roll-out of Eudamed for MDR and IVDR, the impacts and obligations in case of interruption or discontinuation of supply, and transitional provisions for certain in vitro diagnostic medical devices. EUDAMED is the European Database on Medical Devices. One of the EUDAMED modules covers clinical investigations and performance studies of medical and in vitro diagnostic devices, respectively.
UK MHRA
The UK MHRA has launched a public consultation on Medical Devices Regulations: Routes to market and in vitro diagnostic devices. The public is invited to provide their views on proposed changes to the regulatory framework for medical devices. Consultation closes on 5 Jan 2025.