The majority of cardiovascular devices that have been subject to Class I recalls by the US Food and Drug Administration (FDA) were brought to market without adequate premarket clinical testing, according to a new analysis published in the Annals of Internal Medicine. The study highlights potential weaknesses in the device approval process and raises concerns about patient safety.
Kushal T. Kadakia, MSc (Harvard Medical School, Boston, MA), the senior investigator, noted that cardiology devices experiencing safety issues shortly after authorization often lacked robust premarket evidence or postmarket evidence requirements.
Device Approval Pathways and Recalls
Over a 10-year period, from 2013 to 2022, there were 137 Class I recalls affecting 157 unique cardiovascular devices. Class I recalls are the most serious, indicating a potential for injury or death. Automated external defibrillators, intra-aortic balloon pumps, and implantable cardioverter defibrillators (ICDs) were among the most frequently recalled devices. A significant 71.3% of these devices were approved via the FDA’s 510(k) pathway, while the remaining 28.7% were approved under the Premarket Approval (PMA) process.
The 510(k) pathway is intended for moderate-risk class II devices that are similar to already-approved devices. It allows for a swifter approval process without requiring new premarket clinical testing. However, this pathway has faced criticism for not being rigorous enough. Steven Nissen, MD (Cleveland Clinic, OH), stated that the regulation of medical devices is not rigorous, leading to mistakes that ultimately harm patients.
Higher-risk class III devices, such as pacemakers, ICDs, stents, and bioprosthetic valves, are approved under the PMA pathway, which requires clinical evidence demonstrating safety and effectiveness. However, even under the PMA pathway, new indications or labeling changes can be approved via a supplement process that doesn’t require supporting clinical evidence.
Quality of Premarket Clinical Testing
Of the recalled devices, only a small fraction had undergone premarket clinical testing. Even when testing was conducted, the studies were often of lower quality, typically nonrandomized, unblinded clinical trials using surrogate endpoints without active control groups. The median follow-up in these studies was only 6 months.
Kadakia emphasized the need for robust evidence requirements, stating that when studies are performed in the premarket setting, they are often not the best quality, lacking randomization, control groups, and having short follow-up periods.
Postmarket Surveillance Deficiencies
The study also revealed deficiencies in postmarket surveillance. Only 22 of the recalled devices were required to complete postmarket approval studies, and nearly half of the devices approved as a PMA had postapproval study requirements. Alarmingly, 20 devices with mandates for postapproval studies experienced a Class I recall before the studies were completed.
Kadakia stressed that if the 510(k) pathway is intended to allow for iterative innovation, it is crucial to understand what is happening with the devices in the real world once they are approved. He suggested that if regulators are providing manufacturers with flexibility in premarket evidence requirements, there need to be robust requirements in the postmarket setting.
Proposed Changes and Future Directions
The FDA has proposed changes to the 510(k) pathway, including new draft guidance on evidence expectations for devices, recommendations for the use of clinical data, and best practices for choosing an appropriate predicate device. These changes, if adopted, are expected to tighten evidence requirements for 510(k) submissions.
Nissen suggested that an approval pathway falling between the 510(k) and PMA pathways could be beneficial, requiring at least some safety and efficacy data for devices that are similar to previous ones.
Kadakia concluded that while devices are essential in cardiology care, it is necessary to strengthen the evidence-generation apparatus to ensure sufficient evidence across the device life cycle regarding both the benefits and potential risks.
