Medical devices available in the EU before the USA are at higher risk for emergence of safety issues

Aaron S Kesselheim
Aaron S Kesselheim

A cohort study has found that medical devices approved first in the European Union (EU) are associated with a greater rate of post-marketing safety alerts and recalls compared with devices approved first in the USA.

First author Thomas J Hwang (Harvard University, Cambridge, USA Brigham and Women’s Hospital and Harvard Medical School, Boston, USA) and colleagues note in the study, recently published in the BMJ, that clinical trial results for many new medical devices that could guide treatment decisions also remain unpublished or unavailable up to five years after approval.

As such, the researchers call for greater regulatory transparency to enable patients and clinicians to make informed decisions about treatment.

Hwang et al point out that medical devices play an important role in patient care, but their approval and regulation are handled differently in the EU and the USA. In the EU, devices can be marketed if they perform “as intended” and are likely to be safe, but clinical testing may only be required for some high-risk devices. In the USA, however, 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 their 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.

They identified in public and commercial databases a total of 309 devices (245 cardiovascular, 36 orthopedic, and 28 neurologic devices). Nearly a quarter (75 of 309, 24%) were classified as major innovations.

The majority (206 of 309) of devices identified were approved in both the USA and the EU, of which 63% (129 of 206) were approved first in the EU.

Overall, roughly a quarter (24%, 73 devices) of the devices were associated with safety issues after they reached the market as of 31 January 2016. The unadjusted rate of safety alerts and recalls in devices approved first in the EU (including CE marked devices not yet approved in the USA) was 27% compared with 14% for devices approved first in the USA (risk ratio 2.1, 95% confidence interval 1.0 to 3.4; p=0.04).

In multivariable Cox regression modelling, 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.

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.

The authors point to some study limitations, but say this study “provides an important empirical measure of the trade-offs associated with the USA and the EU frameworks for regulating medical devices.” They note that although most devices, including the majority of those identified as major innovations, are ultimately approved in both the USA and the EU, “patients in the USA may not have access for up to three years later than patients in the EU.”

They continue, “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.”

The researchers note that “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 argue that 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 that reason, associations like the European Society of Cardiology and others, Hwang et al comment, 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,” they conclude.

Aaron S Kesselheim (Brigham and Women’s Hospital and Harvard Medical School, Boston, USA) is the senior author of the study.