Higher risk of safety issues with medical devices first approved in EU

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Thomas J Hwang (Harvard University, Cambridge, USA, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA) and others report in the British Medical Journal that medical devices that are approved in the European Union (EU) prior to being approved in the USA have a higher rate of postmarketing safety alerts and recalls than those that are approved in the USA first.

Hwang et al state that the approval and regulation of medical devices are handled differently in the EU from how they are handled in the USA. They explain that devices can be marketed in the EU if they perform “as intended” and are likely to be safe with clinical testing only required for some high-risk devices. But in the USA, high-risk devices must demonstrate reasonable safety and effectiveness in clinical trials before they can be used by patients. As a result, many high-risk devices are approved faster in the EU than in the USA. This has led to controversy over device safety and calls for regulatory reforms in both the EU and the USA.

In the study, Hwang et al identified high profile new medical devices approved in the EU between 2005 and 2010 and evaluated safety issues related to these devices and subsequent approvals in the USA. They focused on cardiovascular, neurologic and orthopaedic devices, which account for the majority of high risk devices used in clinical practice.

Using data from public and commercial databases, the authors identified a total of 309 devices (245 cardiovascular, 36 orthopaedic, and 28 neurologic devices). Nearly a quarter (75 of 309, 24%) were classified as major innovations. While the majority (206 of 309) of the devices were ultimately approved in both the EU and the USA, 63% of these (129 of 206) were approved first in the EU. Hwang et al note that “patients in the USA may not have access for up to three years later than patients in the EU.” They add: “Supporters of the current EU system argue these delays have public health implications if some patient populations can benefit from earlier treatment, although a device’s true benefits might only be known in retrospect after the trials needed for FDA approval are conducted.”

Overall, nearly a quarter (24%; 73 devices) of devices were associated with safety issues after they became commercially available (as of 31 January 2016). In a multivariable analysis, devices approved first in the EU were associated with a 2.9-fold greater rate of safety alerts and recalls and a 4.6-fold greater rate of recalls than devices approved first in the USA. Furthermore, among the 75 devices classified as major innovations, pivotal trial results were published for 37 (49%), with an overall publication rate of 37% five years after approval.

Hwang et al comment that their study “provides an important empirical measure of the trade-offs associated with the USA and the EU frameworks for regulating medical devices.” “Patients and clinicians need access to, and balanced presentation of, the available evidence of the safety and effectiveness of novel devices, as well as clear communication about the evidentiary gaps,” they add.

According to the authors, patients in the EU have “substantially less and lower quality information” on the potential benefits and harms of new devices compared with the USA, which raises ethical concerns because CE marking may be “misinterpreted as signifying that devices are safe and clinically effective.” For this reason, they note, associations like the European Society of Cardiology and others have called for a “centralised system” for evaluating high risk devices; stronger and more transparent clinical data requirements that incorporate expert medical advice and public education on the limitations of CE marking.

“Our findings suggest that products introduced earlier in their development cycle are also more likely to increase the risk of harms, underscoring the urgent need for transparency to make truly informed decisions,” Hwang et al conclude.

The study was published shortly after the EU agreed new rules for approving medical devices and in vitro diagnostic medical devices. The Netherlands’ presidency of the European Council and representatives of the European Parliament have reached a political agreement on two draft regulations for medical devices. The new regulations are aimed at ensuring that medical devices and in vitro diagnostic medical devices are safe while allowing patients to benefit of innovative health care solutions in a timely manner. However, the agreement is subject to the approval by the Council’s Permanent Representatives Committee and of the Parliament’s ENVI committee.