October 16, 2024 – Before the FDA puts prescribed drugs in the marketplace, drug manufacturers must prove they're secure and effective. What is less known is that almost all medical devices – including those implanted into the human body – don't have to fulfill the identical rigorous standards with the intention to be sold and used.
This causes avoidable harm to patients, say critics of the device testing process. And some were injured or died.
“They want things to be reviewed and tested and to remember in the FDA mandate that safety comes before effectiveness,” said Richard Kovacs, MD, a professor at Indiana University School of Medicine and chief medical officer of the American College of Cardiology. “The Swiss cheese has numerous holes [regulatory approach]. We need more science in the FDA approval process.”
Putting the highlight on the issue is a new study in the Annals of Internal Medicine Examining recalls of cardiac devices – similar to pacemakers, stents and defibrillators – from 2013 to 2022, 157 cardiac devices were found with Class I recalls, essentially the most urgent type.
Only a fifth of the recalled devices underwent clinical testing. Most of them – 71% – were delivered to market after their manufacturers demonstrated that they were much like approved devices already available. The FDA believes that devices approved through this 501(k) pathway pose a moderate risk.
The other 29%, considered high-risk patients, followed a special path that required clinical trials. However, these studies don't meet the standards required for testing latest drugs. The studies for 30 of the recalled devices weren't randomized and 18 didn't include a control group. “Surrogate measures” similar to laboratory results or radiological images quite than patient results were often used as endpoints.
The follow-up period of those clinical trials lasted a median of six months, which might not be long enough to “capture the medium- and longer-term safety risks,” the authors write. In a study of a Medtronic stent graft system, the first endpoint was not determined until 30 days after implantation. In 2021, greater than 33,000 units were recalled because some broke or leaked in patients' bodies.
“Medical devices that were later recalled for safety reasons often had little clinical evidence supporting their initial approval,” the authors concluded.
An FDA spokesperson responded to our request for comment: “FDA's mission is to protect and promote the public health, including ensuring that devices are safe and effective.” That stays our top priority and should be the main focus of each medical device review.”
How we came
Public pressure on the FDA to hurry up approvals – which has increased because the HIV/AIDS epidemic within the Nineteen Eighties – may account for the shortage of clinical evidence in most Class I recalls, in line with a comment that got here with the brand new study.
“Public and political pressures have tended to emphasize the need for more innovation, faster review, and earlier access to medical interventions,” wrote the commentary's writer, Ezekiel Emanuel, MD, PhD, vice provost for global initiatives and co-director of the Department of Health Transformation Institute the University of Pennsylvania. The result: regulatory pathways aimed toward expediting the “review of new drugs, biologics and devices.”
According to the commentary, greater than one million patients received high-risk cardiac devices subject to a category I remember. These include 600,000 coronary stents, 200,000 implantable pacemakers, roughly 200,000 heart valves, 1000's of venous stents and other prostheses.
Similar concerns exist with other medical devices, similar to metal-on-metal hip replacements. These devices have four times as much of revision procedures in comparison with all hip prostheses inside five years.
This will not be the primary time that the problem has attracted public attention.
In 2011, the Institute of Medicine (IOM) reviewed the FDA's 510(k) approval process for medical devices and concluded that it ought to be eliminated since it was not relevant to patient safety. The FDA rejected the IOM's position, even though it has since modified a few of its policies and procedures, similar to clarifying clinical testing requirements and expectations for implanted devices.
But cardiologist Rita Redberg, MD, a member of the 2011 IOM task force, said the FDA device review process doesn't appear to guard patient safety any higher today than it did back then.
In fact, she said, the method is in some ways even worse: The FDA has expanded the 510(k) pathway to incorporate a “de novo” approach to obtaining approval. This is meant for brand new devices with out a “predicate” or for existing authorized devices against which the product may be compared. The FDA may approve these devices with little or no clinical data in the event that they are deemed sufficiently low risk.
“The problem is that without evidence it is very difficult to assess the risk of a device,” said Redberg, a professor of medication on the University of California, San Francisco.
Most de novo requests involve clinical data that “scale to what the FDA deems necessary to mitigate risk and demonstrate benefit,” the FDA spokesperson said.
It's also value noting that the label for a brand new device generally is a recalled device, said study co-author Kushal Kadakia, a third-year Harvard medical student who studies medical device regulation and worked for the FDA has. Using a recalled device as a predicate “leads to a six times greater risk of a recall of the new product,” he said. In 2023, the FDA updated theirs Guide to identifying predicate devicesand requires device manufacturers to contemplate any reported questions of safety or recalls.
Some devices proceed for use even after a recall. For example, some patients are still receiving implantable cardioverter-defibrillators (ICDs), which I recall are subject to a category, “even though the underlying problem is not completely resolved,” said a Report in New England Journal of Medicine.
According to the FDA spokesperson, some recalled devices won't be faraway from the market if alternative treatments are limited and the issue that led to the recall “can be thoroughly corrected by correcting the device or its labeling.”
Abbott's MitraClip cardiac device was recalled in 2016, but implantation continued after Abbott revised the instructions to be used and required doctors who implant the chip in leaky heart valves to undergo training. A Getinge intra-aortic balloon pump – a tool used as a bridge to a heart transplant or for recovery from heart failure – suffered eight Class I recalls from December 2022 to July 2023. The FDA allowed doctors to proceed using the pump Because alternative treatment options were limited, the implant was eventually withdrawn from the market after 15 patients died.
Doctors say more tests are needed
The doctors we spoke to agreed that medical devices ought to be tested in additional rigorous clinical trials before approval.
The pressure to do this can not come from device manufacturers, and never simply because they need to bring their products to market more quickly, said Redberg. A U.S. Supreme Court decision protects them from lawsuits if the FDA approves their devices after premarket testing, she said.
Most device recalls are based on antagonistic event reporting, however the FDA's antagonistic event reporting and postmarketing surveillance are underfunded, she said.
“Much of the funding for the device division comes from the Medical Device User Fee and Modernization Act,” or MDUFA, Redberg said. Under this law, medical device manufacturers pay fees to the FDA for regulatory services, giving them influence over the method, Redberg said. “The [device] Companies are mandating that the FDA spend all of the MDUFA money on getting devices to market more quickly, which generally means lowering standards or eliminating any evidence standards.”
Device manufacturers are required to report problems with their devices within 30 days of becoming aware of it. But these reports are often delayed. And many doctors don't report device problems to the FDA, in part because they don't know how, Kovacs said.
“When I talk over with other physicians, I ask, 'How a lot of you've ever filed a MedWatch report a couple of device or a side effect of a medicine?'” Kovacs said. “Very few hands are raised in the audience. First, no one knows there is a MedWatch program, and doctors are not taught that it is their responsibility to report these problems.”
What patients should know and ask their doctor
Before a medical device is implanted, patients should understand the potential risks.
“I let them know that these devices are machines,” Kovacs said. “Machines break down, cables break, and so there is a real risk of a medical device failing. It’s a small chance, but it’s real and should be discussed.”
When Kovacs learns of a device recall, he arranges a visit with patients who have the device to discuss their options and weigh the potential benefits of device replacement against the potential harms of further surgery.
Kenneth Kubitschek, MD, a retired internist in Asheville, North Carolina, remembers his conversations with patients about the artificial metal-on-metal hips. “The query was: Do you replace them with significant morbidity and even mortality, or do you allow them alone?” he said. “That was a really difficult question to answer.”
Jeffrey Kagan, MD, an internist in Newington, Connecticut, has seen patients with implanted devices recalled. “Some were in a rush to alter it, but some said, 'I'm not going through that again,'” he said.