Advances in medical device technology have been dramatic in recent years resulting in both an increased number of medical devices and an increase in the invasiveness and critical function which devices perform. Two new regulations entered into force in Europe in May 2017, the Medical Device Regulation (MDR) and the In Vitro Diagnostic Device Regulation (IVDR). These regulations will replace the current directives over the coming years. These regulations, for the first time introduce requirements relating to registries.
Medical device manufacturers are required to have systematic methods for examining their devices once available on the market, by systematically gathering, recording and analysing data on safety and performance.
Registries can assist public health protection in very practical ways, for example, to help urgently identify patients or devices. Registries can also be powerful tools for collecting and appraising real-world clinical evidence concerning medical devices. Clinical investigations are limited in terms of the sample size and the duration of follow-up which can reasonably be expected. Registries may also be the only available tool to examine rare adverse effects, sub-populations or for time durations which it is not possible or feasible to study in a clinical investigation. By ensuring that a core dataset is collected which can be compared to other registries or trial data, it is possible to pool data to better examine outcomes. There are a range of excellent initiatives which have aimed at ensuring the appropriate regulatory application of registry data.
Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180061
On behalf of the CORE–MD Investigators (see Appendix)
On behalf of the CORE–MD Investigators (see Appendix)Alan Fraser, Piotr Szymański, Chris Gale, Aldo Maggioni, Elisabetta Zanon, Christina Dimopoulou, Cinzia Ceccarelli, Polyxeni Vairami, Anett Ruszanov, Per Kjærsgaard-Andersen, Rob Nelissen, Adrian Ott, Elizabeth Macintyre, Loredana Simulescu, Marieke Meijer, Berthold Koletzko, Sarah Wieczorek, Adamos Hadjipanayis, Stefano Del Torso, Perla Marang-van de Mheen, Lotje Hoogervorst, Ewout W. Steyerberg, Bas Penning De Vries, Peter McCulloch, Martin Landray, Daniel Prieto Alhambra, James Smith, Anne Lubbeke-Wolf, Stefan James, Sergio Buccheri, Robert Byrne, Laurna McGovern, Stephan Windecker, Andre Frenk, Georgios Siontis, Christoph Stettler, Arjola Bano, Lia Bally, Frank E. Rademakers, Jan D‘hooge, Anton Vedder, Elisabetta Biasin, Erik Kamenjasevic, Petra Schnell-Inderst, Felicitas Kühne, Ola Rolfson, Joel Jakobsson, Amanda Tornsö, Enrico G. Caiani, Lorenzo Gianquintieri, Cinzia Cappiello, Maristella Matera, Tom Melvin, Niall MacAleenan, Ria Mahon, Michèle Meagher, Gearóid McGauran, Thomas Wejs Møller, Ann-Sofie Sonne Holm-Schou, Jan Szulc, Robert E. Geertsma, Jantine W.P.M. van Baal, Joëlle M. Hoebert, Susana L.F. Cabaço, Paola Laricchiuta, Marina Torre, Filippo Boniforti, Eugenio Carrani, Stefania Ceccarelli, Claudia Wild, Sabine Ettinger, Juan Antonio Blasco Amaro, Juan Carlos Rejón Parrilla, Agnieszka Dobrzynska, David Epstein, Valentina Strammiello, Hannes Jarke, Kaisa Immonen, Françoise Schlemmer, Sabina Hoekstra, Marianna Mastroroberto, Christoph Ziskoven, Michael Hahn, Erman Melikyan, Richard Holborow, Suzanne Halliday, Alexey Shiryaev, Gero Viola, Harry van Vugt
Search for other papers by On behalf of the CORE–MD Investigators (see Appendix) in Google Scholar PubMedClose
In the European Union (EU), the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, while authorising the placing on the market of medical devices is decentralised to independent ‘conformity assessment’ organisations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the Medical Device Directive, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details – which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE–MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024. Here, we describe how it may contribute to the development of regulatory science in Europe.
Cite this article: EFORT Open Rev 2021;6:839-849. DOI: 10.1302/2058-5241.6.210081
Anne LübbekeDivision of Orthopaedic Surgery & Traumatology, Geneva University Hospitals and University of Geneva, Switzerland Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK
James A SmithCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK National Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
The objective of this systematic review was to give an overview of clinical investigations regarding hip and knee arthroplasty implants published in peer-reviewed scientific medical journals before entry into force of the EU Medical Device Regulation in May 2021.
We systematically reviewed the medical literature for a random selection of hip and knee implants to identify all peer-reviewed clinical investigations published within 10 years before and up to 20 years after regulatory approval. We report study characteristics, methodologies, outcomes, measures to prevent bias, and timing of clinical investigations of 30 current implants. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
We identified 2912 publications and finally included 151 papers published between 1995 and 2021 (63 on hip stems, 34 on hip cups, and 54 on knee systems). We identified no clinical studies published before Conformité Européene (CE)-marking for any selected device, and no studies even up to 20 years after CE-marking in one-quarter of devices. There were very few randomized controlled trials, and registry-based studies generally had larger sample sizes and better methodology.
The peer-reviewed literature alone is insufficient as a source of clinical investigations of these high-risk devices intended for life-long use. A more systematic, efficient, and faster way to evaluate safety and performance is necessary. Using a phased introduction approach, nesting comparative studies of observational and experimental design in existing registries, increasing the use of benefit measures, and accelerating surrogate outcomes research will help to minimize risks and maximize benefits.