The origins of device regulation in Europe are unusual, and arguably the root of many current problems. In the United States, legislation controlling pharmaceutical safety followed deaths from sulfanilamide syrup in 1937, and the first European Economic Community directive on medicines was a direct response to the thalidomide disaster of 1957 to 1962. American device legislation likewise grew out of a 1970 expert report chaired by Theodore Cooper, which attacked an unquestioning acceptance of safety claims unsupported by scientific fact. Europe’s device rules, by contrast, were not precipitated by any scandal and were not designed after objective analysis. They emerged from requests to the European Commission by manufacturers’ trade associations, and when the first Medical Device Directive was drafted in the late 1980s, policymakers applied the so-called New Approach adopted by the Council of Ministers in 1985, a framework intended to harmonise standards for industrial products across the common market, not to safeguard patients.

Under that New Approach, the evaluation of evidence demonstrating that a device conformed with requirements was outsourced to independent, private inspection companies known as notified bodies. Those organisations remain central to the system today: manufacturers must submit technical documentation, quality management systems and clinical evaluation reports to a notified body for all medium-risk Class II and high-risk Class III devices, and for nearly all in vitro diagnostics, before receiving the certificates of conformity required for CE-marking and market access. With hindsight, the authors argue, applying an industrial harmonisation model to high-risk medical devices was a poor decision. Notified bodies effectively act as quasi-regulators, deciding whether devices are approved, yet as private companies operating in a competitive marketplace they are not bound by European requirements for public access to documents. Their dual role also limits the advice they can give to the very companies whose products they assess, because of inherent conflicts of interest, and oversight by national authorities has often been inadequate.

The original directive’s rules were deliberately written in rather abstract terms, leaving manufacturers to decide for themselves what clinical studies were needed. Concerns accumulated over decades: standards varied between notified bodies, some devices reached patients with insufficient evidence, and serious complications and deaths were reported from high-risk implantables approved on claims of equivalence to existing devices without any new clinical investigation. A public consultation launched by the Commission in 2008 eventually produced the Medical Device Regulation, which came into force in 2021, alongside the In Vitro Diagnostic Medical Devices Regulation. The MDR aimed to raise standards of evidence for high-risk devices, but its central requirement remained vague, asking only for clinical data providing sufficient clinical evidence. Common specifications, which would have set mandatory scientific standards for particular device types, were never realised, apparently due to limited regulatory capacity. Instead, guidance documents issued by the Medical Device Coordination Group are voluntary, interpretation varies between member states, and the type of clinical evidence required for new high-risk devices, whether observational or experimental, is still not defined.

The MDR also created unintended consequences for patients. Massive recertification requirements and unpredictable, protracted conformity assessments drove up costs, and manufacturers withdrew some essential products from the market, including well-established technologies and devices designed for children. A perception spread that Europe had become hostile to device innovation, and the Austrian National Public Health Institute is now monitoring device availability on behalf of the Commission. The scheduled five-year review of the legislation was brought forward after intense lobbying from industry and other stakeholders, culminating in the December 2025 draft regulation. At a High-Level Conference on Medical Devices: Innovation and Patient Safety held in Brussels in March 2026, European Commissioner for Health Olivér Várhelyi declared that a major overhaul was absolutely necessary, but insisted it must come without compromising on patient safety. How to reconcile those goals is the central question of the reform.

One project has supplied much of the evidence base for answering it. CORE–MD, Coordinating Research and Evidence for Medical Devices, was funded by the EU Horizon Europe programme from 2021 to 2024 and led by the European Society of Cardiology together with the European Federation of National Associations of Orthopaedics and Traumatology, with support from the Biomedical Alliance in Europe. Every stakeholder group, including national regulatory agencies and notified bodies, contributed to an extensive review of the system. The consortium confirmed deficiencies in the evidence available for high-risk devices, a dearth of randomised trials and a high risk of bias in many published studies. It proposed a progressive framework matching observational studies and controlled trials to each stage of a device’s life-cycle, and separately described alternative methodologies under the banner of large simple trials, including registry trials and pragmatic studies, which could make rigorous randomised evidence feasible at realistic cost.

The contrast with medicines regulation is instructive. The US Food and Drug Administration and the European Medicines Agency both implement scientific approaches to support regulatory decision-making, whereas for devices the EU has emphasised interpretation of legal rules applied by a patchwork of independent organisations. The authors argue that reform should set explicit standards for demonstrating clinical efficacy where needed for high-risk therapeutic implants, while retaining simpler safety and performance requirements for low-risk devices. Clinical evidence should represent women as well as men, and safe, effective technologies should be equitably accessible to all patients, including children and those with rare conditions. The in vitro diagnostics regulation needs its own tailored policies rather than a copy of the device framework: the authors call for relaxed restrictions on sharing laboratory-developed tests between health institutions, and for the abolition of IVDR Article 5.5 d, which forbids use of an in-house test if an equivalent CE-marked product exists, a rule they say stifles diagnostic innovation in favour of market monopolies.

The European Medicines Agency is set to play a much larger role. The MDR already established Expert Panels of independent clinicians and scientists who provide non-binding opinions on notified bodies’ clinical evaluations of selected high-risk devices. The Screening Panel has judged that roughly ten per cent of high-risk submissions require a full scientific opinion; sixteen have been published, most identifying deficiencies in clinical evidence, yet every reviewed device was still granted market access, prompting calls for transparency about how notified bodies act on expert recommendations. A recent analysis of thirty-four opinions found that nearly half of expert comments concerned the sufficiency of clinical evidence supporting benefit–risk determinations. Under the draft regulation, the panels’ remit will expand to advising the Commission, member states, notified bodies and manufacturers, contributing to guidance and common specifications, and designating breakthrough and orphan status for promising devices. The authors welcome this but warn that delivery is impossible without major investment: the Commission unit coordinating the regulations has only one medically qualified officer, while notified bodies employed 4,099 full-time staff in conformity assessment in 2025.

The deeper prescription is cultural as much as legislative. The authors endorse a definition of regulatory science as the use of scientific approaches to determine which policies and standards best assure safety and efficacy, so that approved technologies improve individual outcomes and public health without disproportionate over-regulation. They want regulatory science to become a recognised subspecialty for clinicians, laboratory scientists, epidemiologists, statisticians and engineers, supporting the EMA and notified bodies alike, with medical associations supplying high-quality evidence from comprehensive device registries. CORE–MD insights already shaped consensus recommendations submitted to the Commission by the Biomedical Alliance on behalf of thirty-five professional associations. Among their warnings: easing conditions for establishing equivalence would repeat a mistake that caused major problems under the old directive, and deleting the standard of sufficient clinical evidence risks more subjectivity rather than consistency. A new high-risk implantable, they argue, should not enter an existing class without a randomised trial against an active comparator or evidence from objective performance criteria. With equivalent standards promoted globally through the International Medical Device Regulators Forum, Europe has a chance to break free from recurrent legislative revisions, if it commits to funding regulatory science as a public good.

Subject of Research: Reform of the European Union regulatory framework for medical devices and in vitro diagnostics

Article Title: Empowering regulatory science for medical devices in Europe

Article References: Empowering regulatory science for medical devices in Europe. (n.d.). https://doi.org/10.1016/j.lanepe.2026.101876

Image Credits: AI Generated

DOI: 10.1016/j.lanepe.2026.101876

Keywords: medical devices, EU regulation, MDR, IVDR, notified bodies, European Medicines Agency, regulatory science, CORE-MD, clinical evidence, in vitro diagnostics, CE-marking, patient safety

The study, published in The Lancet Regional Health – Europe by a team of researchers affiliated with the European Medicines Agency and national regulatory authorities, is the first to stitch together data from the EU’s two clinical trial registries into a single harmonised dataset. The authors extracted records from the legacy EudraCT database, which operated under the Clinical Trials Directive from 2004 until 2022, and from the Clinical Trials Information System, or CTIS, the centralised portal launched under the successor Clinical Trials Regulation. After applying strict eligibility criteria to 55,052 retrieved records, the final analytical dataset comprised 25,320 authorised trials initiated between 1 January 2013 and 31 December 2025.

The technical challenge of merging the two systems was considerable. Under the old Directive, public disclosure was limited to a subset of information on authorised trials, and adult phase I trials were entirely invisible unless they involved children or formed part of a paediatric investigation plan. The new regulation swept those restrictions away, mandating publication of every assessed trial with legally binding timelines. To make the two periods comparable, the researchers excluded adult phase I trials not linked to paediatric plans, removed trials conducted exclusively in the United Kingdom following Brexit, and carefully deduplicated transitioned studies that had migrated from EudraCT into CTIS, assigning them their original authorisation dates to avoid double counting.

The headline numbers tell a story of stability, disruption and contraction. Between 2013 and 2019, the EU/EEA authorised a steady average of around 1,989 trials per year. Activity then surged during the pandemic, peaking at 2,364 trials in 2021 as researchers raced to test vaccines and therapeutics and as delayed non-COVID studies resumed. From 2022 onwards, however, annual counts settled at an average of just 1,721 trials. The authors caution that part of this decline may represent a correction after exceptional pandemic conditions and adjustments to the new regulatory framework, but they note that the persistence of lower volumes through 2025 suggests deeper structural forces are at work, including the global redistribution of clinical research toward Asia and the post-pandemic contraction in biopharmaceutical investment.

The composition of European research is changing as much as its volume. Phase IV trials, which monitor medicines after market approval, shrank from about 20.5 percent of all authorisations to 13.7 percent between the two periods, while multi-phase trials combining stages such as phase I–II or II–III nearly doubled their share from 8.9 percent to 16.5 percent. Phase II trials remained the most common category at roughly 37 percent of authorisations, followed by phase III trials at 32 percent. The authors suggest that the rise of multi-phase designs may reflect more integrated development programmes using adaptive designs, in which a single application covers multiple research objectives, potentially reducing the count of distinct registered trials even as scientific output continues.

Perhaps the most troubling finding concerns who is sponsoring European trials. Before the pandemic, commercial and non-commercial sponsors were almost evenly matched, averaging 1,024 and 956 trials per year respectively. After 2022, commercial activity fell modestly to 941 trials per year, a reduction of 8.1 percent, while non-commercial activity plummeted to 778 trials per year, an 18.6 percent drop. Academic sponsors, the analysis shows, remain overwhelmingly mononational, with only about 9 percent of their trials spanning multiple countries, whereas commercial sponsors now run more than three-quarters of their trials across several European states. This asymmetry points to well-documented structural barriers facing academic researchers, including fragmented funding, heavy regulatory compliance burdens, limited operational infrastructure and difficulties in procuring and manufacturing investigational products for multinational studies.

Therapeutic priorities have shifted markedly over the thirteen-year window. Cancer remains the dominant research area, accounting for 25.2 percent of all authorised trials, followed by nervous system diseases at 7.5 percent and cardiovascular diseases at 6.5 percent. But trials targeting immune system diseases nearly tripled their share, from 3.3 percent in 2013 to 9.4 percent in 2025, making them the second most researched area since 2024. Viral disease research spiked dramatically during the pandemic, reaching 14.5 percent of trials in 2020 before falling back to baseline. Meanwhile, research into rare diseases intensified, rising from 17.1 percent of trials in the earlier period to 20.3 percent after 2022, and the proportion of trials including elderly participants climbed steadily from 68.7 percent in 2013 to a peak of 81.4 percent in 2025.

The molecular character of European research is also evolving. Trials involving biologic medicines, produced from or containing biological substances, rose from 35.1 percent of authorisations in 2013 to 49.1 percent in 2025, approaching half of all European clinical research. Advanced therapy medicinal products, which include gene therapies, somatic cell therapies and tissue-engineered products, grew from 3.2 percent to 4.0 percent of trials, with gene therapy emerging as the fastest-growing modality within the category. Intriguingly, the analysis also reveals that Europe occupies a distinctive position in the global landscape: phase I trials make up only about 18 percent of authorised EU/EEA trials, compared with roughly 40 percent of global trial starts in 2024, while nearly half of European trials are multinational, spanning an average of six Member States, in contrast to a worldwide trend toward single-country studies.

European regulators are not standing still. The Accelerating Clinical Trials in the EU initiative has established two quantitative performance targets: authorising an additional 500 multinational trials over the next five years and ensuring that at least two-thirds of trials recruit their first patient within 200 days of application. In January 2026, the Heads of Medicines Agencies launched FAST-EU, a coordinated fast-track approach designed to bring greater predictability and speed to multinational trial authorisations. The study’s authors argue, however, that these ambitions may fall short without targeted support for the academic sector, whose predominantly national footprint stands in stark contrast to the multinational goals. They point to complementary initiatives, including the revision of the EU’s pharmaceutical legislation, the recently proposed EU Biotech Act, and funding programmes such as Horizon Europe and ERA4Health, as vehicles for building the operational capacity academic sponsors need.

The study is not without limitations, which the authors address candidly. The exclusion of adult phase I trials, though necessary for comparability, means the reported figures understate total trial activity, although an unpublished analysis including non-public phase I data corroborated the observed decline. A small number of authorised CTIS trials were temporarily hidden from the public portal under confidentiality rules, requiring internal EMA data to complete the picture. Classification of therapeutic areas relied on MeSH codes, which may fragment some conditions across categories, and structural differences between the two registries demanded custom mapping of definitions, particularly for biologic therapies. Still, the analysis establishes something the European research community has lacked: a reproducible, transparent framework for monitoring clinical trial activity across regulatory eras, built entirely on public data. As Europe fights to retain its place in a global research order increasingly shaped by China-headquartered sponsors and shifting investment flows, that foundation may prove as valuable as the findings themselves.

Subject of Research: Longitudinal trends in clinical trials of medicinal products in the EU/EEA from 2013 to 2025 based on harmonised EudraCT and CTIS registry data

Article Title: Clinical trials on medicinal products in the EU/EEA, 2013–2025: a cross-sectional analysis of CTIS and EudraCT data

Article References: Machado, T., Capone, G., den Rooijen, I., Bindt, F., Marcelino, M., van Wyk, J., Zanoletty Perez, A., Pioppo, L., Santos Ivo, R., & Arlett, P. (2026). Clinical trials on medicinal products in the EU/EEA, 2013–2025: a cross-sectional analysis of CTIS and EudraCT data. The Lancet Regional Health – Europe, 71, Article 101884. https://doi.org/10.1016/j.lanepe.2026.101884

Image Credits: AI Generated

DOI: 10.1016/j.lanepe.2026.101884

Keywords: clinical trials, EU/EEA, CTIS, EudraCT, Clinical Trials Regulation, European Medicines Agency, non-commercial sponsors, multinational trials, biologic medicines, advanced therapy medicinal products, rare diseases, pharmaceutical policy