EU H2020 CORE-MD
CORE-MD will review methods for the evaluation of high-risk medical devices and give advice to EU regulators for methods to generate evidence with an appropriate balance between innovation, safety, and clinical effectiveness
CORE-MD is a European Union Horizon 2020 project, grant number 965246, that will run from April 2021 until March 2024.The consortium includes 22 partners and is led by the European Society of Cardiology. It brings together medical associations, EU regulators, national public health institutes, notified bodies universities, patients’ groups, and health technology assessment agencies. (www.CORE-MD.eu)
The Medical Device Regulation (MDR) of the European Union came into force in 2017 and has been applied since May 2021 (2017/745; MDR https://eur-lex.europa.eu/eli/reg/2017/745/oj). The MDR has increased requirements for clinical investigations for market approval of new high-risk medical devices (e. g., Annex XV of the MDR), but the regulation contains only general principles. The European Commission and the Medical Devices Coordination Group have to implement the new regulation and therefore have to provide concrete guidance on the requirements for clinical investigations for high-risk medical devices (classes IIb and III). The CORE-MD will review methodologies of clinical studies, advise on alternative designs, and develop recommendations for aggregating clinical data from registries and other real-world data sources. One important product will be a hierarchy of trial designs for high-risk medical devices.
CORE-MD consists of four work packages. Three work packages are focus on the development of recommendations on evidence generation for medical devices, and one work package addresses networking and community building to engage with stakeholders.
Overview of tasks in CORE-MD work packages 1-4
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Understanding methods used to generate clinical evidence for high-risk medical devices |
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1.1 |
Methodologies in published clinical studies of high-risk medical devices |
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1.2 |
Statistical methods for medical device studies |
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1.3 |
Regulatory utility of patient-reported outcome measures |
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1.4 |
Published regulatory guidance and expert recommendations for clinical investigations |
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New methods for generating clinical evidence |
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2.1 |
Providing evidence during the early development of high-risk medical devices |
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2.2 |
New designs for randomized clinical trials and studies of high-risk medical devices |
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2.3 |
Developing guidance for the evaluation of artificial intelligence and standalone software in medical devices |
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2.4 |
Recommendations concerning high-risk medical devices in children |
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Extracting maximal value from medical device registries and real-world evidence |
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3.1 |
Aggregating insights from registries, big data, and clinical experience |
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3.2 |
Development of a mashup for collecting clinical reports of devices from accessible trusted web sources |
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3.3 |
Study of the use of conditions for clinical evidence generation after market access |
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Networking and community building: Engaging with stakeholders |
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4.1 |
An ethics charter for medical device innovation |
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4.2 |
Evidence generation across the lifecycle of devices |
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4.3 |
Educational objectives for stakeholders |
UMIT TIROL is leading Task 1.4, which reviews already existing guidance on clinical trial design for high-risk medical devices. There are many guidance documents from regulators, but also health technology assessment bodies, academic research consortia, and medical professional associations. Some current documents cross-refer to each other, but no systematic analysis has been performed to summarize existing guidance and identify variations. The objectives of the systematic review are:
- to identify guidance on the design, conduct, analysis, and reporting of confirmatory pivotal clinical trials and other clinical investigations for high-risk medical devices, from regulators, international standardization organizations, medical professional associations, academic consortia, and HTA agencies,
- to compare their similarities and differences, and
- to identify gaps for further research on trial methodology.
The protocol for the systematic review is available under https:// osf.io/3mf7v.
Collaborating partners in Task 1.4 are the Health Products Regulatory Authority, Ireland; Bern University Hospital, Switzerland; Fundación Pública Andaluza Progreso y Salud – Andalusian Health Technology Assessment Unit, Spain; and The European Association for Medical Devices of Notified Bodies (TEAM NB).
UMIT TIROL will also contribute to Task 2.2 lead by the Uppsala clinical Research Center, Sweden. Task 2.2 investigates and develops new designs for clinical studies of high-risk medical devices in trials. For the evaluation of medicinal products, detailed guidance documents of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) already exist and are legally binding for market approval in the European Union (https://www.ich.org/). In general, many principles of trial design also apply to medical devices, but there are some characteristics of medical devices that may challenge the implementation of principles of trial design used for pharmaceuticals and, therefore guidance on trial design for high-risk medical devices should address such issues.
Medical devices are characterised by incremental development, typically by device modification having short lifecycles. Blinding of treatment arms may be prevented by the physical mechanism of action of a device. Equal recruitment and proficiency may be difficult due to provider and patient preferences. Implantable devices may have long-term effects on the health patients, for example, by late device failures and these are typically collected in registries, not during clinical trials. Furthermore, the application of implantable devices is often imbedded in highly invasive procedures, which include the risk of complications from surgery. Contextual factors such as individual and institutional learning may also have to be considered to quantify the effect of the intervention and ensure an adequate implementation of findings. New trial designs such as registry-based or adaptive trial designs or the use of objective performance criteria for long established device classes have been suggested to address some of these challenges. Such developments should be considered in recommendations for study designs. Together with the other partners in this task the University of Oxford, the European Society of Cardiology, the European Federation of National Associations of Orthopaedics and Traumatology, the European Academy of Paediatrics, Bern University Hospital, Leiden University Medical Center, and the European Patients’ Forum, UMIT TIROL will review new trial designs and all established and new designs of studies and trials for systematic collection of clinical data for high-risk medical devices will be ranked in a hierarchy according to their clinical utility and reliability.
The budget of the whole CORE-MD project is about 2,36 Mio. Euro.
