High-Risk Medical Device Approval Process in Europe Inches Towards Transparency


But further steps are needed, one expert argues. “It’s impossible to practice evidence-based medicine without access to the evidence.”

The European Union (EU) is moving ahead with plans to provide better access to data surrounding the approval of implantable and high-risk medical devices, but a group of experts suggest that full transparency with respect to clinical and preclinical data, among other things, is the best path forward.

In 2017, a new EU law was introduced that will eventually require manufacturers to provide a summary of the safety and clinical performance (SSCP) of high-risk medical devices. Prior to the regulation, the details of which are still being ironed out, the information that led to the approval of implantable, high-risk medical devices—drug-eluting stents, prosthetic heart valves, pacemakers, and the like—was confidential. Indeed, the first news a physician might hear about a new device was that it had been approved for use.

While the new approach to public disclosure, which is governed by EU regulation 2017/745, is designed to ensure adequate access to all available data, experts are urging those finalizing the details of the legislation to completely pull back the curtain.

“It’s impossible to practice evidence-based medicine without access to the evidence,” said Alan Fraser, MBChB (University Hospital of Wales, Cardiff), the lead author of a new perspective published July 19, 2018, in the Lancet. “It seems strange to have to state that,” he told TCTMD, “but if we want to find the range of devices within any class and review the evidence for each of the options, and then make a judgement as to which appears most effective for our patients, then we need access to the information.”

Contradictory and Incompatible

Fraser, the chairman of the European Society of Cardiology committee on EU regulatory affairs, said that accessing the available information for implantable and high-risk medical devices is no different than being able to review the data when a new drug is approved. In fact, the Declaration of Helsinki states that every study involving human subjects, whether it’s positive, negative, or inconclusive, must be registered in a publicly accessible database.

While European medical device directives, which are now known as regulations, stated that clinical studies must be carried out in accordance with the Helsinki Declaration, the EU had given device manufacturers an escape clause by stating that companies and reviewing bodies are bound to observe confidentiality when assessing clinical data. Fraser said these provisions “were contradictory and mutually incompatible.”

“Until the new [2017] medical device regulations, there has been no information available about the regulatory review of high-risk medical devices,” said Fraser. “All that one ever hears is an announcement that a device has been approved and received a CE Mark.”

The 2017/745 regulation on medical devices states that healthcare professionals should have adequate access to essential information needed to make informed decisions. The regulation—which will be in place by 2020—requires the manufacturer to provide a summary of the safety and efficacy data for all implantable and high-risk medical devices and to make this information publicly available on an EU database for medical devices (Eudamed). The laws passed in 2017 allow for additional legislation, which enables regulators to shape the details of the SSCP that will be posted on Eudamed.

The EU regulation outlines the minimum requirements of the SSCP for high-risk medical devices, including the approved clinical indications, contraindications, and target populations, and a task force has proposed several other requirements that have not yet been finalized. In their perspective, however, Fraser and colleagues are pushing for making all available clinical and preclinical data available to physicians and interested patients.     

This would include posting, publicly, basic information about the manufacturer, date of approval, and name and contact details of the independent body who reviewed and recommended approval. It would also include the names, contact details, and expertise of the notified body, which is the independent panel who reviewed the available evidence and made the recommendation for approval.

More importantly, however, their proposed regulations would ensure that all clinical evidence available to date is published, including but not limited to biocompatibility studies, bench testing, basic science experiments, first-in-human studies, observational studies and randomized trials, and data on device performance. The trial that formed the basis of approval should include number, average age, and gender distribution of study participants, as well as cumulative exposure to therapy.

The SSCP should also detail any unanswered questions and highlight the approved program for postmarket clinical follow-up. Any reports of complications or unexpected device failure should be noted, as should field safety notices, alerts, or recalls.

Is All That Data Completely Necessary?

Ori Ben-Yehuda, MD (Cardiovascular Research Foundation, New York, NY), who spoke to TCTMD about the European regulation, is not certain that all that information is useful to practicing physicians, particularly the early, preclinical data. He said data relevant for clinical use are widely disseminated and are already available in the device label and instructions for use.

“Preclinical testing can involve volumes and volumes of material,” he said. “It’s usually not very clinically relevant. Findings in animal models don’t always translate to humans, for example. The important thing is the clinical data—that’s what’s important. So, of course, the clinical trial data should be completely transparent, but it already is. It’s presented at meetings, it’s published in journals.”

The proposed inclusion of preclinical evidence as part of Eudamed, including computer simulations, in-vitro bench testing or in-vivo studies with cells, tissues, or animal models, will also require more paperwork and increase costs, said Ben-Yehuda. “Will people actually use it is the question,” he said. He doesn’t believe the inclusion of these data will hinder development, but it’s another hurdle that might not be completely necessary.

Fraser, for his part, said the information they would like to see included in the SSCP published on Eudamed is not unlike what it is already included in the US Food and Drug Administration (FDA)’s Summary of Safety and Effectiveness Data (SSED). Since companies already must provide the information to the FDA, it shouldn’t be an issue to provide the same data to the European regulatory authorities.

“If you look at the FDA website, it does provide most of this information,” said Fraser, referring to their full list of data demands. “For example, the FDA does give you the results of preclinical testing of new high-risk/implantable devices. Biocompatibility data, animal studies, materials and durability testing—the FDA website will give you that information.” At present, though, such information is not currently part of the proposed SSCP, but Fraser believes it should be. There is no evidence that such a policy will hinder innovation by industry, he added.

Old, Opaque Way of Doing Things

Under the European system, a review of the clinical evidence is performed on behalf of regulators by one of the independent notified bodies who are approved by a member states’ regulatory authority. In the United Kingdom, for example, the Medicine and Healthcare Regulatory Agency (MHRA) designates the notified bodies to evaluate the clinical evidence, but notified bodies are independent organizations and historically have not been bound by freedom of information legislation within the EU.

“We have had this very strange situation where it’s an official [review] process, but we don’t have access to the information,” said Fraser. “More than that, if clinicians in the past ask why a notified body approved a device—what was the evidence presented, what was the opinion of the reviewers, or on what basis was a change approved—the notified bodies would refuse to give that information. They only give information to the competent authorities, and the competent authorities don’t disclose what the notified bodies tell them. We have had a system that has operated in secrecy and yet this is a public service evaluating high-risk devices. It’s important for clinicians and patients to have access to the evidence.”

In contrast to the independent notifying bodies, the European Medicines Agency (EMA), which is an agency of the EU and is responsible for evaluating, supervising, and monitoring pharmaceuticals in Europe, is legally bound to provide access to all clinical data. Trials are registered in EU Clinical Trials Database (EudraCT) and all data is published on the EMA website, among other requirements. 

“It’s not logical clinically,” said Fraser, referring to the different approval and disclosure processes for drugs and medical devices.

A second major draft of the SSCP has been completed, but it is expected to undergo revisions in the next month. If it is approved after resubmission, it will be available to device manufacturers and the independent notified bodies next year and full compliance in place by 2020, said Fraser.



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