Transparency for medical devices under the EU Medical Device Regulation
Device approval in Europe was decentralised, its data stayed with national authorities, and far less public information existed on devices than on medicines. The EU Medical Device Regulation was expected to make much more of it public through a rebuilt European database and to make devices traceable through a unique identifier. Device investigations drew press criticism for their funding and for results that go unpublished, and device documents could come into public view as medicines documents had, with medical writers providing clear documents for the general public.
Device approval and the public record
Transparency had become an objective for medicines, culminating in the European Medicines Agency's decision to release full clinical study reports into the public domain, while medical devices had largely stayed outside the push for transparency.
Unlike the approval of medicinal products in the United States and Europe, and of devices in the United States, device approval in Europe is not centrally regulated. Until 2010, data on device approvals were held at a national level, even though CE-marked devices can be marketed throughout the EU. So a device approved by a notified body and the competent authority in one member state could be marketed in any other without that state's competent authority having automatic, easy access to regulatory information about it.
Little information was publicly available about which device CE marks had been received, denied or withdrawn, whereas the same information was readily available for medicines. For example, the European Medicines Agency's 2015 annual report recorded 93 medicines recommended for marketing authorisation, including 39 new active medicines, and no comparable information was publicly available for devices at a pan-European level.
Eudamed, the European database for medical devices, was the first web-based repository to address the lack of communication between notified bodies and member states. It started in 1997 as a European-funded project managed by the German Institute of Medical Documentation and Information, and the European Commission then took it over, updating it in 2009 and mandating in 2010 that all competent authorities use it. By 2017 it served as a central repository to which national competent authorities submitted information on manufacturers, certificates, clinical investigations and vigilance for the Commission. A 2012 Commission survey found that competent authorities mostly used Eudamed to monitor the activity of notified bodies, while most member states were not using it for market surveillance or clinical investigation decisions, arguing that the datasets were insufficient.
The registration of device trials was a gap in Europe: they fall outside the mandate of the EudraCT registry, although some sponsors register them there voluntarily.
What the Regulation was expected to make public
The Medical Device Regulation (MDR) closes the gap in the registration of device trials. Like the Clinical Trial Regulation, it requires increased transparency of clinical data, with selected documents made available to the public. The February 2017 draft of the MDR states on transparency:
- (4) Key elements of the existing regulatory approach, such as the supervision of notified bodies, conformity assessment procedures, clinical investigations and clinical evaluation, vigilance and market surveillance, should be significantly reinforced, whilst provisions ensuring transparency and traceability regarding medical devices should be introduced, to improve health and safety.
- (43) Transparency and adequate access to information, appropriately presented for the intended user, are essential in the public interest, to protect public health, to empower patients and healthcare professionals and to enable them to make informed decisions, to provide a sound basis for regulatory decision-making and to build confidence in the regulatory system.
- (48) For implantable devices and for class III devices, manufacturers should summarise the main safety and performance aspects of the device and the outcome of the clinical evaluation in a document that should be publicly available.
Eudamed was to be completely overhauled into a public-facing searchable database, with different levels of access for competent authorities, notified bodies, manufacturers and the public. It was to collect more information, including the results of clinical investigations under Article 77.5 of the MDR and post-marketing vigilance data. Through it the public was to be able to access:
- lists of devices on the market, the relevant economic operators and certificates
- ongoing recalls and other field safety corrective actions
- a list of devices withdrawn from the market, or restricted
- a database of registered clinical investigations
- clinical investigation reports and lay summaries of these reports
Under the MDR, the sponsor of a clinical investigation has to upload to Eudamed the final report of the investigation and a summary of that report that is readily understandable to the public, and the summary is to be available to the public. Clinical study reports are to be made available to the public together with a lay summary, so that patients and other interested parties can learn the results of the clinical studies that led to CE certification.
Manufacturers of class III and implantable devices have to upload summaries of safety and clinical performance to Eudamed. The lay summaries and the summary of safety and clinical performance, a new, device-specific document, are both for public viewing, and they may need to be published in the local language.
Patients were often not told in the past when something went wrong with a device, as press reporting on implants claimed, and the MDR intends to fix this by centralising the relevant information about a device in Eudamed. Information about device certification, clinical studies and their lay summaries, clinical study reports, and the summary of safety and performance of implantable class III devices is to be accessible there (Article 33).
The MDR leaves a gap for clinical investigations done outside Europe: their data do not have to be entered into Eudamed and their results do not have to be made public, although the manufacturer can still rely on the data to demonstrate compliance. One regulatory consultant expects relying on such studies to become more common, as European hospitals are expected to be flooded with requests for device studies.
Unique device identification and nomenclature
Devices are difficult to trace in a market of more than 28 member states with many different local regulations, and the MDR's unique device identifier (UDI) should improve their traceability. The UDI is a numeric or alphanumeric code for each device, made of two parts: a device identifier and a production identifier. Proper labelling should contribute to market transparency, help during recalls and discourage counterfeiting. The UDI will also make it easier for patients to report incidents involving a device to the competent authorities themselves.
Pharmaceutical writers are used to generic drug names, but the device industry had no standard generic terms. A device nomenclature and the UDI were expected to supply them, with both planned to be harmonised with those the FDA uses, and once they are in place writers have to take them into account in the documents they write.
Building the new Eudamed
Eudamed was to be accessible to manufacturers, notified bodies, competent authorities and the European Commission, and to organise data on devices placed on the market, manufacturers, certificates, clinical investigations, UDIs, vigilance cases and post-market surveillance, the notified bodies, and device nomenclature. Each of those parties has to input its own part of the information, so implementing the database requires a coordinated effort. Nobody expected Eudamed to be running when the MDR was approved, and many believed it would take a long time before it was fully functional and could reduce administrative work and regulatory compliance costs.
The database was at first planned to go live in 2020, with clinical study results accessible through it from then on. In 2020 its launch was moved to May 2022, when the MDR and the IVDR would already apply, to allow more time to ensure that the platform was fully functional. The new Eudamed is an update of Eudamed2, which only the competent authorities and the European Commission could access, and it is built to be accessible to all stakeholders, including the public, as a multi-purpose registration, collaboration, notification and dissemination system. Its large scope and six main modules, which no other medical registration system then implemented, made developing and implementing it challenging in many ways. The Medical Device Coordination Group's decisions on the database include decisions on legacy devices and on the nomenclature to be implemented in it. Every stakeholder needs to review the relevant guidance documents to understand the database's functionality and its requirements for uploading data.
The modules were to be released in stages until the database was fully functional in 2022. Although the MDR's date of application had been postponed by a year, the first module was still to be released at the end of 2020, and by May 2021 at the latest, in time for that date. The large data submissions, whether through web-based forms, bulk uploads or machine-to-machine inputs, call for extensive, early preparation and an understanding of the requirements. For medical writers, the system's potential will not be fully realised if data and documents do not meet its requirements in time for digital submission.
Funding and independence of device investigations
Press reporting on implants claimed that device studies are barely independent: their authors frequently have financial relations with the manufacturer, and most studies are funded by industry. Many clinical investigators may indeed have a financial relationship with the manufacturer of the device, but in one experienced writer's account that relationship is controlled:
- It must be declared in medical society presentations and publications as a conflict of interest statement.
- In clinical investigations, investigators have to disclose any conflict of interest, for example on a financial disclosure form, which is commonly submitted to the ethics committees and competent authorities with the investigators' other professional details. A declared interest has to be justified as not influencing the investigator's participation in the study.
- Financial contracts for clinical studies are commonly negotiated with the institution, since paying investigators directly is not allowed in most European countries.
- Only the work performed may be reimbursed, and the payments have to reflect fair market value.
- In most European countries, financial contracts for clinical studies are supervised at a national or local institutional level. In France, for example, the Conseil National de l'Ordre des Médecins (CNOM, the French Medical Council) has to review and approve each contract between industry, investigators and all other involved health care professionals before the study starts at the investigation site. In most European countries, relevant parts of the contract, such as payment details, also have to be submitted to the competent authority with the study application.
- In relevant clinical studies leading to CE certification, separate contracts are often made with independent data safety monitoring boards, clinical event review committees and core laboratories, adding another level of independence. These committees are paid by the sponsor for their services, but in the writer's experience they are well aware of their responsibility.
That most studies are funded by industry is true, but for premarket and mandated post-market studies this is not voluntary. The same writer imagines that companies, particularly small start-ups that depend on external funding, would welcome someone else paying for their premarket trials, which generally cost several million euros. National registries are already common for post-market data, such as the FRANCE registry, the TVT registry in the US and the GARY registry in Germany for transcatheter implantation, and the Scandinavian SCAAR registry for stent placement.
Publication of device investigations
Fewer clinical investigations are needed to approve a device than a new drug, and many of them are published in articles. One regulatory consultant warns against comparing publication rates for devices and drugs directly: on average, more new devices enter the European market in a single day than new medicinal substances in a year, and numbers on that scale require a different approach.
The results of device clinical investigations are not always published, yet manufacturers rely on the scientific literature to prepare the clinical evaluation report when they apply for the CE mark.
Press reporting on implants also quoted physicians saying that negative studies disappear. One experienced writer disagrees from experience: to be published in peer-reviewed journals, device clinical trials must be posted on platforms such as ClinicalTrials.gov, and both positive and negative outcomes have to be published. Discussion that only around half of studies were reported turned out to rest on an analysis algorithm that counted a study as reported only when its ClinicalTrials.gov number appeared in the abstract or methods section, and many more studies had in fact been reported. In the same writer's experience, a trial that found no difference between its groups, a negative result for its sponsor, needed submissions to at least five journals and more than two years to be published.
What the change asked of medical writers
The regulations that govern drugs and devices were slowly but surely being aligned, and EudraCT already listed many current clinical trials that involve devices. The exact implementation of the MDR's provisions was still unclear. If its transparency requirements closely follow those of the Clinical Trial Regulation, its implementation guidelines may resemble the European Medicines Agency's Policy 0070. In that case many of the device clinical documents medical writers routinely write, from the clinical investigation report to the clinical evaluation report, may have to be posted for public access.
How Eudamed would be linked to the EU portal being developed under the Clinical Trial Regulation was unclear, though both rest on the same principle. Posting protocols and results through Eudamed could be expected to work as it does through that portal, and whether clinical study reports would also have to be disclosed through it was still to be determined. Registration and potential disclosure through the database bring data protection into play, so posting protocols and results means thinking about redaction and anonymisation.
The final adoption of the MDR by the European Parliament in April 2017 triggered a three-year countdown to its implementation. Within that time, Eudamed would be under pressure to complete, test and deploy its plans to improve its transparency. Medical writers had the same time to expand their knowledge and capabilities in medical devices, so as to help the push towards a more transparent system by providing clear, well-written documents for the general public.