Developing EU methodological frameworks for clinical/performance evaluation and post-market clinical/performance follow-up of medical devices and in vitro diagnostic medical devices (IVDs)

ExpectedOutcome:

This topic aims at supporting activities that are enabling or contributing to one or several expected impacts of destination 6 “Maintaining an innovative, sustainable and globally competitive health industry”. To that end, proposals under this topic should aim to deliver results that are directed, tailored towards and contributing to all of the following expected outcomes:

• Patients gain faster access to innovative, safe and well-performing medical devices;
• Regulators have access to sound scientific resources for clinical/performance evaluation guidance and development of common specifications as foreseen in Article 9 of the Medical Device Regulation (MDR);
• Notified bodies, by their direct participation to the production of documents, will have a harmonised way of assessing the clinical evidence in the pre-market and post-market phases; furthermore their network^[1], will be enhanced;
• Health technology developers gain insight on the evidence needed to demonstrate that their devices meet MDR clinical requirements throughout their lifetime. They will also have more guidance on the use of real-world data for their clinical development strategies.

Scope:

The Medical Device Regulation (MDR) and in vitro diagnostic medical device Regulation (IVDR) provides a new regulatory framework where reinforcement of clinical/performance evaluation of medical devices and IVDs, and in particular high-risk medical devices, is a key element. The confirmation of conformity with the relevant general safety and performance requirements set out in the MDR and IVDR^[2] is based on clinical data and its assessment (clinical/performance evaluation), including the evaluation of the acceptability of the benefit-risk- ratio. Within this new framework, the clinical/performance evaluation should follow a defined and methodologically sound procedure based on the critical evaluation of the relevant scientific literature, a critical evaluation of the results of all available clinical investigations/performance studies, as well as consideration of currently available alternative treatment options for the device under evaluation. Clinical/performance evaluation has to be updated throughout the life cycle of the device. Hence, clinical/performance evaluation can draw on multiple types of data including data from initial clinical investigations/performance studies and data gathered by the manufacturer's post-market surveillance system. To operationalise this new requirement, research is needed to help regulators develop common methodological frameworks (including common specifications^[3]) on the clinical evidence needed to demonstrate safety, performance and clinical benefit all along the life cycle of devices taking into account the type of device and clinical intended purpose.

Such methodological frameworks and standardised approaches are particularly needed for high-risk medical devices, e.g. implantable and class III medical devices, class C and D IVDs, medical device software (including AI enabled devices and next generation sequencing) and other highly innovative devices.

In order to address the differences between evidence generation for medical devices and IVDs, the project should be tackled taking into account those differences.

Proposals should address all of the following activities:

• Development of a framework for a life-cycle approach to evidence generation and evaluation of high-risk and innovative medical devices and IVDs. This framework will provide a description of the types of evidence i) that meet safety and performance for market access, and ii) that have to be generated to fulfil post-market responsibilities. When appropriate it would be beneficial to consider to what extent the framework could be relevant to demonstrate relative effectiveness as needed for Health Technology Assessment. As regards highly innovative devices, particular attention may be paid to defining acceptable levels of uncertainty in terms of benefit-risk ratio at market entry as well as the type of post-market follow-up to be implemented to generate additional clinical evidence able to reduce this uncertainty. This could be particularly relevant for devices e.g. having no or little similarities with existing devices in terms of intended purpose, mode of action, materials or, for IVDs, with no existing reference materials.;
• For medical devices, a pilot to support development of common specifications which would set the stage for a common specification ecosystem for medical devices in the EU^[4], including the development of standardised/common endpoints and associated health outcomes measures by technology type and where relevant by clinical intended purpose;
• Development of a general methodological approach to define, determine and update the state of the art for different device technologies. The robustness of the developed approach should be evaluated on 3 different medical device types and 3 different IVD types;
• Possible use of registries and other sources of real-world data for demonstration of regulatory compliance both pre- and post-market: minimum requirements for data quality, completeness and data reliability, statistical methods for data analysis, methods for limiting biases, methods for data linkage, determination of what acceptable evidence can be drawn from registries;
• Methodology for bridging studies for devices and IVDs with iterative development: assessment of data coming from previous versions of the device and where relevant integration of that data into the device’s clinical investigation/performance study and gap assessment between the different versions of the device;
• Identification of relevant quantitative and qualitative methodologies for integrating evidence derived from various data sources in the clinical evaluation/performance evaluation;

Proposals should build on relevant completed and ongoing initiatives in the field, in particular (but not restricted to) EU-funded initiatives.^[5] Proposals should involve researchers who are specialised in the clinical/performance evaluation of medical devices/IVDs and in the use of real-world data to evaluate medical products. Proposals should involve national competent authorities, notified bodies, IVD laboratories as well as Health Technology Assessment bodies and could involve patients’ representatives where relevant.

Applicants envisaging to include clinical studies should provide details of their clinical studies in the dedicated annex using the template provided in the submission system. See definition of clinical studies in the introduction to this work programme part.

[1]Article 49 – Coordination Group of notified bodies

[2]Annex I General safety and performance

[3]Mandatory applicable “technical standards” providing to the manufacturers means of proving conformity with the safety and performance legal requirements, issued by Commission as Implementing Acts.

[4]building on previous initiatives such as PARENT, CORE-MD, JAMS

[5]e.g. PARENT (PAtient REgistries iNiTiative) Joint Action, CORE-MD (Coordinating Research and Evidence for Medical Devices) H2020 research project, JAMS (Joint Action on Market Surveillance of Medical Devices) initiative