The CORE-MD consortium organised its Final Conference on Friday, 15 March 2024, at the De Warande Club in Brussels. This event brought together representatives from regulatory authorities, notified bodies, researchers, industry, as well as patients and healthcare professionals. Notably, it provided an opportunity to share insights on the clinical evaluation of high-risk medical devices, based on the work carried out by the Consortium’s partners.
PROJECT OUTLINE AND OBJECTIVES
Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)
The CORE-MD project focuses on cardiovascular and orthopaedic devices since – together with diabetes devices – those represent the majority of high-risk medical devices. Thus the paper presenting the project’s outline and study protocol was jointly published in the European Heart Journal – Quality of Care and Clinical Outcomes and EFORT Open Reviews.
Fraser AG, Nelissen RGHH, Kjærsgaard-Andersen P, Szymański P, Melvin T, Piscoi P; CORE-MD Investigators. Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices). Eur Heart J Qual Care Clin Outcomes. 2022 May 5;8(3):249-258. https://doi.org/10.1093/ehjqcco/qcab059. PMID: 34448829.
Fraser AG, Nelissen RGHH, Kjærsgaard-Andersen P, Szymański P, Melvin T, Piscoi P; CORE–MD Investigators (see Appendix). Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices). EFORT Open Rev. 2021 Oct 19;6(10):839-849. https://doi.org/10.1302/2058-5241.6.210081. PMID: 34760284.
Final results booklet
The CORE-MD consortium organised its Final Conference on Friday, 15 March 2024, at the De Warande Club in Brussels. This event brought together representatives from regulatory authorities, notified bodies, researchers, industry, as well as patients and healthcare professionals. Notably, it provided an opportunity to share insights on the clinical evaluation of high-risk medical devices, based on the work carried out by the Consortium’s partners.
Regulatory science for high-risk medical devices, in Europe
Regulatory science for high-risk medical devices, in Europe. Fraser AG, Byrne RA, Melvin T.
[Comment, submitted by invitation in August 2025 to The Lancet, awaiting their review]
SCIENTIFIC EVIDENCE
Published results
Quality and transparency of evidence for implantable cardiovascular medical devices assessed by the CORE-MD Consortium
Siontis GC, Coles B, Häner JD, McGovern L, Bartkowiak J, Coughlan JJ, Spirito A, Galea R, Haeberlin A, Praz F, Tomii D, Melvin T, Frenk A, Byrne RA, Fraser AG, Windecker S; CORE-MD investigators. Quality and transparency of evidence for implantable cardiovascular medical devices assessed by the CORE-MD Consortium. Eur Heart J. 2024; 45: 161–77. https://doi.org/10.1093/eurheartj/ehad567 PMID: 37638967.
Accompanying editorial: Quality and transparency of clinical evidence for high-risk cardiovascular medical devices: a long way to go. Szymański P, Redberg R. Eur Heart J. 2024; 45: 178–180. https://doi.org/10.1093/eurheartj/ehad786 PMID: 38036418.
Related correspondence: Randomized controlled trials remain underutilized. Siontis GCM, Frenk A, Windecker S. European Heart J. 2024; 45: 553–4. https://doi.org/10.1093/eurheartj/ehad806
Quality and transparency of clinical evidence for high-risk cardiovascular medical devices: a long way to go
Accompanying editorial: Szymański P, Redberg R. Quality and transparency of clinical evidence for high-risk cardiovascular medical devices: a long way to go. Eur Heart J. 2024 Jan 14;45(3):178-180. https://doi.org/10.1093/eurheartj/ehad786. PMID: 38036418.
Randomized controlled trials remain underutilized
Related correspondence: Siontis GCM, Frenk A, Windecker S. Randomized controlled trials remain underutilized. Eur Heart J. 2024 Feb 16;45(7):553-554. doi: https://doi.org/10.1093/eurheartj/ehad806. PMID: 38087906.
Clinical investigations to evaluate high-risk orthopaedic devices: a systematic review of the peer-reviewed medical literature
Lübbeke A, Combescure C, Barea C, Gonzalez AI, Tucker K, Kjærsgaard-Andersen P, Melvin T, Fraser AG, Nelissen R, Smith JA. Clinical investigations to evaluate high-risk orthopaedic devices: a systematic review of the peer-reviewed medical literature. EFORT Open Reviews 2023; 8(11): 781–791. https://doi.org/10.1530/eor-23-0024. PMID: 37909694.
Download supplementary data I-III
Download supplementary data IV
Clinical evidence for high-risk CE-marked medical devices for glucose management: A systematic review and meta-analysis
Bano A, Künzler J, Wehrli F, Kastrati L, Rivero T, Llane A, Valz Gris A, Fraser AG, Stettler C, Hovorka R, Laimer M, Bally L; CORE‐MD investigators. Clinical evidence for high-risk CE-marked medical devices for glucose management: A systematic review and meta-analysis. Diabetes Obes Metab. 2024 Oct;26(10):4753-4766. http://doi.org/10.1111/dom.15849. Epub 2024 Aug 14. PMID: 39143655.
Download supplementary data
Artificial intelligence in medical device software and high-risk medical devices – a review of definitions, expert recommendations and regulatory initiatives
Fraser AG, Biasin E, Bijnens B, Bruining N, Caiani EG, Cobbaert K, Davies RH, Gilbert SH, Hovestadt L, Kamenjasevic E, Kwade Z, McGauran G, O’Connor G, Vasey B, Rademakers FE. Artificial intelligence in medical device software and high-risk medical devices – a review of definitions, expert recommendations and regulatory initiatives. Expert Rev Med Devices. 2023 Jun; 20(6): 467–491. https://doi.org/10.1080/17434440.2023.2184685. PMID: 37157833.
Evidence from clinical trials on high-risk medical devices in children: a scoping review
Guerlich K, Patro-Golab B, Dworakowski P, Fraser AG, Kammermeier M, Melvin T, Koletzko B. Evidence from clinical trials on high-risk medical devices in children: a scoping review. Pediatric Research. 2024; 95(3): 615–624. https://doi.org/10.1038/s41390-023-02819-4. PMID: 37758865.
Quality and utility of European cardiovascular and orthopaedic registries for the regulatory evaluation of medical device safety and performance across the implant lifecycle: a systematic review
Hoogervorst LA, Geurkink TH, Lübbeke A, Buccheri S, Schoones JW, Torre M, Laricchiuta P, Piscoi P, Pedersen AB, Gale CP, Smith JA, Maggioni AP, James S, Fraser AG, Nelissen RGHH, Marang-van de Mheen PJ. Quality and utility of European cardiovascular and orthopaedic registries for the regulatory evaluation of medical device safety and performance across the implant lifecycle: a systematic review. Int J Health Policy Manag. 2023; 12: 7648. https://doi.org/10.34172/ijhpm.2023.7648. PMID: 37579359.
Validating Orthopaedic Data Evaluation Panel (ODEP) Ratings Across 9 Orthopaedic Registries: Total Hip Implants with an ODEP Rating Perform Better Than Those without an ODEP Rating
Hoogervorst LA, van Tilburg MM, Lübbeke A, Wilton T, Nelissen RGHH, Marang-van de Mheen PJ. Validating Orthopaedic Data Evaluation Panel (ODEP) Ratings Across 9 Orthopaedic Registries: Total Hip Implants with an ODEP Rating Perform Better Than Those without an ODEP Rating. J Bone Joint Surg Am. 2024 Sep 4;106(17):1583-1593. https://doi.org/10.2106/jbjs.23.00793. Epub 2024 May 31. PMID: 38820172.
Safety notices and registry outlier data measure different aspects of safety and performance of total knee implants: a comparative study of safety notices and register outliers
Hoogervorst LA, Ren Y, Melvin T, Stratton-Powell AA, Lübbeke A, Geertsma RE, Fraser AG, Nelissen RGHH, Caiani EG, Marang-van de Mheen PJ. Safety notices and registry outlier data measure different aspects of safety and performance of total knee implants: a comparative study of safety notices and register outliers. Acta Orthop. 2024 Nov 25;95:667-676. https://doi.org/10.2340/17453674.2024.42361. PMID: 39584822.
Regulatory perspectives on post-market evidence generation schemes for high-risk medical devices: a systematic review
Aranda J, Dobrzynska A, Rosario-Lozano MP, Rejón-Parrilla JC, Epstein D, Blasco-Amaro JA. Regulatory perspectives on post-market evidence generation schemes for high-risk medical devices: a systematic review. Expert Rev Pharmacoecon Outcomes Res. 2024 Dec 1:1-15. https://doi.org/10.1080/14737167.2024.2431234. Epub ahead of print. PMID: 39618103.
Survey of Notified Bodies reveals very limited use of conditional certification for high-risk medical devices
Dobrzynska A, Rejon-Parrilla JC, Epstein D, Aranda-López J, Fraser AG, Blasco-Amaro JA. Survey of notified bodies reveals very limited use of conditional certification for high-risk medical devices. Frontiers in Medical Technology. 2025;7:1504294. doi: 10.3389/fmedt.2025.1504294
Perceived training needs of regulators, Notified Bodies and clinicians for successful implementation of the EU MDR: survey results
Wild C, Ettinger S. Perceived training needs of regulators, Notified Bodies and clinicians for successful implementation of the EU MDR: survey results. Journal of Medical Device Regulation 2023;20(2):45–56. https://globalregulatorypress.com/product/perceived-training-needs-of-regulators-notified-bodies-and-clinicians-for-successful-implementation-of-the-eu-mdr-survey-results/
Study protocols
Clinical evidence for high-risk medical devices in cardiology: a protocol for a systematic review and meta-epidemiological investigation
Siontis GC, Frenk A, Coles B, Bartkowiak J, McGovern L, Häner J, Tomii D, Galea R, Häberlin A, Praz F, Windecker S. Clinical evidence for high-risk medical devices in cardiology: a protocol for a systematic review and meta-epidemiological investigation. PROSPERO 2022 CRD42022308593. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308593
Clinical investigations to evaluate high-risk orthopaedic devices: systematic review and meta-analysis
Smith JA, Combescure C, Barea C, Lübbeke A. Clinical investigations to evaluate high-risk orthopaedic devices: systematic review and meta-analysis [Internet]. OSF; 2021. Available from: https://doi.org/10.17605/OSF.IO/9BJQV
Clinical evidence for high-risk medical devices used to manage diabetes: protocol for a systematic review and meta-analysis
Bano A, Laimer M, Wehrli F, Künzler J, Rivero T, Fraser AG, Stettler C, Hovorka R, Bally L. Clinical evidence for high-risk medical devices used to manage diabetes: protocol for a systematic review and meta-analysis. BMJ Open. 2023 Apr 11; 13(4): e070672. https://doi.org/10.1136/bmjopen-2022-070672 . PMID: 37041065.
An integrative systematic review of patient reported outcome measures (PROMs) used to evaluate orthopedic, cardiovascular and diabetes high risk implantable medical devices
Chaplin J, Rolfson O, Jarke H, Moons P, Norekvål T, Ingelsrud LH. An integrative systematic review of patient reported outcome measures (PROMs) used to evaluate orthopedic, cardiovascular and diabetes high risk implantable medical devices. PROSPERO 2022 CRD42022344424. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022344424
Study design recommendations in guidance documents for high-risk medical devices. A systematic review
Schnell-Inderst P, Kühne F, Rochau U, Schmid D, Siebert U. Study design recommendations in guidance documents for high-risk medical devices. A systematic review. (2022). Available from: https://osf.io/w9b5k/
Report submitted as CORE-MD deliverable:
Schnell-Inderst P, Rochau U, Kühne F, Siebert U. Study design recommendations in guidance documents for high-risk medical devices. A systematic review. (2024)
Download now
Clinical evidence for high-risk medical devices in children: A protocol for a scoping review.
Guerlich K, Patro-Golab B, Kammermeier M, Dworakowski P, Koletzko B. Clinical evidence for high-risk medical devices in children: A protocol for a scoping review. (2023). Available from: https://osf.io/uzekt
Orthopedic and cardiovascular medical device registries in Europe: a systematic review
Hoogervorst L, Geurkink T, Schoones J, Smith J, Lubbeke-Wolff A, Laricchiuta P, Torre M, Pedersen AB, James S, Fraser A, Buccheri S, Maggioni A, Gale C, Nelissen R, Marang-van de Mheen P, CORE-MD study group. Orthopedic and cardiovascular medical device registries in Europe: a systematic review. (2022). Available from: https://osf.io/5n89e
Post-approval evidence development schemes established by regulatory authorities for high-risk medical devices. A protocol for a systematic review
Hoogervorst L, Geurkink T, Schoones J, Smith J, Lubbeke-Wolff A, Laricchiuta P, Torre M, Pedersen AB, James S, Fraser A, Buccheri S, Maggioni A, Gale C, Nelissen R, Marang-van de Mheen P, CORE-MD study group. Orthopedic and cardiovascular medical device registries in Europe: a systematic review. (2022). Available from: https://osf.io/5n89e
Datasets
Clinical investigations to evaluate high-risk cardiovascular devices: a systematic review of the peer-reviewed medical literature [Data set]
Siontis, G. (2024). Clinical investigations to evaluate high-risk cardiovascular devices: a systematic review of the peer-reviewed medical literature [Data set]. Zenodo. https://doi.org/10.5281/zenodo.10617117
Clinical investigations to evaluate high-risk orthopaedic devices: a systematic review of the peer-reviewed medical literature [Data set]
Lübbeke, A. (2024). Clinical investigations to evaluate high-risk orthopaedic devices: a systematic review of the peer-reviewed medical literature [Data set]. In EFORT Open Reviews (Vol. 8, Number 11, pp. 781–791). Zenodo. https://doi.org/10.5281/zenodo.10623389
Clinical evidence for high-risk CE-marked medical devices for glucose management: a systematic review and meta-analysis (Version 1) [Data set]
Bano, A. (2024). Clinical evidence for high-risk CE-marked medical devices for glucose management: a systematic review and meta-analysis (Version 1) [Data set]. Zenodo. https://doi.org/10.5281/zenodo.10894441
Quality and Utility of European Cardiovascular and Orthopaedic Registries for the Regulatory Evaluation of Medical Device Safety and Performance Across the Implant Lifecycle: A Systematic Review [Data set]
Marang-van de Mheen, P., Nelissen, R., Geurkink, T., Lubbeke, A., Buccheri, S., Schoones, J. W., Torre, M., Laricchiuta, P., Piscoi, P., Pedersen, A., Gale, C., Smith, J., Maggioni, A., James, S., & Fraser, A. (2023). Quality and Utility of European Cardiovascular and Orthopaedic Registries for the Regulatory Evaluation of Medical Device Safety and Performance Across the Implant Lifecycle: A Systematic Review – Dataset [Data set]. https://zenodo.org/records/10812296
Secondary analyses
Inclusion and reporting by age, sex, and ethnicity in clinical trials of high-risk medical devices approved in the European Union
Coughlan JJ, Byrne RA, SiontisGCM, McGovern L, Durand R, Lübbeke A, Bano A, Fraser AG. Inclusion and reporting by age, sex, and ethnicity in clinical trials of high-risk medical devices approved in the European Union. Submitted to Eur Heart J Qual Care Clin Outcomes.
Coming soon
Cumulative risk of revision after primary total hip arthroplasty in registries internationally: Systematic review and meta-analysis of selected hip stems and cups
Combescure C, Smith JA, Barea C, Hoogervorst LA, Nelissen R, Marang-van de Mheen PJ, Lübbeke A, Arthroplasty Registry Group. Cumulative risk of revision after primary total hip arthroplasty in registries internationally: Systematic review and meta-analysis of selected hip stems and cups. Submitted to EFORT Open Reviews.
Frequency of safety signals for a random selection of hip and knee prostheses
Ren Y, Hoogervorst LA, Caiani EG, Marang-van de Mheen PJ, Smith JA, Fraser AG, Nelissen RGHH, Lubbeke A. Frequency of safety signals for a random selection of hip and knee prostheses. Submitted to Acta Orthopaedica
Coming soon
RECOMMENDATIONS
Published papers
European expert recommendations on clinical investigation and evaluation of high-risk medical devices for children
Guerlich K, Patro-Golab B, Barnacle A, Baumann U, Eicken A, Fraser AG, Gruszfeld D, Haas NA, Jonker AH, Kammermeier M, Kenny D, Kolaček S, Lapatto R, Maconochie I, Mader S, McGauran G, Melvin T, Muensterer O, Piscoi P, Romano A, Saxena AK, Schneider DT, Turner MA, Walle JV, Koletzko B; European Academy of Paediatrics. European expert recommendations on clinical investigation and evaluation of high-risk medical devices for children. Acta Paediatrica. 2023; 112: 2440–2448. https://doi.org/10.1111/apa.16919. PMID: 37485905.
CORE-MD Roadmap for Education & Training: Perceived training needs of regulators, notified bodies and clinicians for successful implementation of the EU MDR
Ettinger S, Wild C. CORE-MD Roadmap for Education & Training: Perceived training needs of regulators, notified bodies and clinicians for successful implementation of the EU MDR. AIHTA Policy Brief. (2023). Available from: https://eprints.aihta.at/1487/
Large simple randomised controlled trials – from drugs to medical devices. Lessons from recent experience
Buccheri S, James S, Mafham M, Landray M, Melvin T, Oldgren J, Bulbulia B, Bowman L, Hoogervorst LA, Marang-van de Mheen PJ, Juni P, McCulloch P, Fraser AG. Large simple randomised controlled trials – from drugs to medical devices. Lessons from recent experience. Trials 2025; 26: 24.
CORE–MD clinical risk score for regulatory evaluation of artificial intelligence-based medical device software
Rademakers FE, Biasin E, Bijnens B, Bruining N, Caiani EG, Davies RH, Gilbert SH, Kamenjasevic E, McGauran G, O’Connor G, Rouffet JB, Vasey B, Fraser AG. CORE–MD clinical risk score for regulatory evaluation of artificial intelligence-based medical device software.
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Submitted manuscripts
Consensus recommendations to assess the quality and analysis of registry data for (post)market surveillance of medical devices: which items are the minimum requirements?
Hoogervorst LA, Nelissen RGH, Melvin T, Piscoi P, Wilkinson C, Lubbeke A, Gale CP, Epstein D, Overgaard S, Walmsley P, Szymanski P, Mohaddes M, O’Connor DB, Geertsma RE, Hoebert JM, Fraser AG, Marang-van de Mheen PJ. Consensus recommendations to assess the quality and analysis of registry data for (post)market surveillance of medical devices: which items are the minimum requirements? Submitted to BMJ Surgery, Interventions, & Health Technologies
Coming soon
Open letter
Urgent action needed to secure continued access to essential medical devices for children and for patients with orphan disease
Urgent action needed to secure continued access to essential medical devices for children and for patients with orphan diseases. June (2023). https://www.eapaediatrics.eu/wp-content/uploads/2023/06/Letter-Kyriakides_Med-Devices-signed-270627.pdf
Reply from the Cabinet of President of the European Commission Ursula Von der Leyen
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Related publications
Placing patient-reported outcomes at the centre of cardiovascular clinical practice: implications for quality of care and management
Moons P, Norekvål TM, Arbelo E, Borregaard B, Casadei B, Cosyns B, Cowie MR, Fitzsimons D, Fraser AG, Jaarsma T, Kirchhof P, Mauri J, Mindham R, Sanders J, Schiele F, Torbica A, Zwisler AD. Placing patient-reported outcomes at the centre of cardiovascular clinical practice: implications for quality of care and management. Eur Heart J. 2023; 44: 3405–3422. https://doi.org/10.1093/eurheartj/ehad514. PMID: 37606064.
The Artificial Intelligence Act approved by the EU: the difficult dialogue between the black box and the cardiologist
Szymański P, Rademakers F, Fraser AG. The Artificial Intelligence Act approved by the EU: the difficult dialogue between the black box and the cardiologist. Eur Heart J. 2024;45:2686–2688. https://doi.org/10.1093/eurheartj/ehae281. PMID: 38848102
Orphan Medical Devices and Pediatric Cardiology - What Interventionists in Europe Need to Know, and What Needs to be Done
Melvin T, Kenny D, Gewillig M, Fraser AG. Orphan Medical Devices and Pediatric Cardiology – What Interventionists in Europe Need to Know, and What Needs to be Done. Pediatr Cardiol. 2023 Feb;44(2):271-279. https://doi.org/10.1007/s00246-022-03029-1. Epub 2022 Oct 18. PMID: 36258097
Orphan and paediatric medical devices in Europe: recommendations to support their availability for on-label and off-label clinical indications
Melvin T, Dooms MM, Koletzko B, Turner MA, Kenny D, Fraser AG, Gewillig M, Jonker AH. Orphan and paediatric medical devices in Europe: recommendations to support their availability for on-label and off-label clinical indications. Expert Rev Med Devices. 2024 Oct;21(10):893-901. https://doi.org/10.1080/17434440.2024.2404257. Epub 2024 Sep 20. PMID: 39302881.
TOOLS
Published papers
Validation of CORE-MD PMS support tool: a novel strategy for aggregating information from notices of failures to support medical devices' post-market surveillance
Ren Y, Bertoldi M, Fraser AG, Caiani EG. Validation of CORE-MD PMS support tool: a novel strategy for aggregating information from notices of failures to support medical devices’ post-market surveillance. Ther Innov Regul Sci. 2023 May;57(3):589-602. https://doi.org/10.1007/s43441-022-00493-y. PMID: 36652105.
Leveraging natural language processing to aggregate field safety notices of medical devices across the EU
Ren Y, Caiani EG. Leveraging natural language processing to aggregate field safety notices of medical devices across the EU. NPJ Digit Med. 2024 Dec 4;7(1):352. https://doi.org/10.1038/s41746-024-01337-9. PMID: 39632973.
Development of a framework dealing with partial data unavailability and unstructuredness to support post-market surveillance
Ren Y, Caiani EG. Development of a framework dealing with partial data unavailability and unstructuredness to support post-market surveillance. 2023 IEEE EMBS International Conference on Biomedical and Health Informatics (BHI), Pittsburgh, PA, USA: IEEE, Oct. 2023, pp. 1–4. doi: 10.1109/BHI58575.2023.10313402. https://bhiconference.github.io/BHI2023/2023/pdfs/1570918894.pdf
Datasets
Dataset - CORE-MD Post-Market Surveillance Tool (Version 1.0.0)
Ren, Y., & Caiani, E. G. (2024). Dataset – CORE-MD Post-Market Surveillance Tool (Version 1.0.0) [Data set]. Zenodo. https://doi.org/10.5281/zenodo.10864069
Software
CORE-MD Risk Calculator: source code and dataset (1.0)
van Egeraat, J., Steyerberg, E., & de Vries, B. P. (2024). CORE-MD Risk Calculator: source code and dataset (1.0). Zenodo. https://doi.org/10.5281/zenodo.11366097
PhD Thesis
Safety and performance of high-risk medical devices: the role of real-world data
Lotje Anna Hoogervorst, Leiden University [awarded November 2025].
Natural language processing for regulatory science: aggregating field safety notices to support post-market surveillance of medical devices
Yijun Ren, Politecnico di Milano [awarded March 2025].
Master's theses
Use of patient-reported outcome measures in clinical trials of closed-loop insulin systems – a systematic review
Ivan Gibanica, University of Gothenburg, 2023.
Development of a mapping tool between EMDN and GMDN nomenclatures to support post-market surveillance of medical devices
Riccardo Gibelli, Politecnico di Milano, 2023.
Development of an IT tool for assisting medical devices post-market surveillance: application to the Italian scenario
Michele Bertoldi, Politecnico di Milano, 2022.
Innovative use for safety signal detection of aggregated medical device safety alert data: A preliminary study
Elena Zattoni, 2024.