Oct. 16, 2024 — Before the FDA allows prescription medicines on the market, drugmakers must prove they’re safe and effective. What’s less widely known is that most medical devices — including those implanted in the human body — don’t have to meet the same rigorous standards to be sold and used.
As a result, patients are being exposed to avoidable harm, critics of the device review process say. And some have been injured or died.
“You want things to be vetted and tested, and to remember that safe comes before effective in the FDA mandate,” said Richard Kovacs, MD, a professor at Indiana University School of Medicine and chief medical officer of the American College of Cardiology. “There are numerous holes in the Swiss cheese of this [regulatory approach]. We need more science in the FDA approval process.”
Spotlighting the issue is a new study in the Annals of Internal Medicine looking at recalls of heart devices -- like pacemakers, stents, and defibrillators -- from 2013 to 2022. It found 157 heart devices with class I recalls, the most urgent kind.
Only a fifth of the recalled devices had been subjected to clinical testing. Most of them -- 71% -- had been allowed on the market after their manufacturers showed they were similar to already-available authorized devices. The FDA considers devices approved through this “501(k) pathway” to be moderate risk.
The other 29%, seen as high-risk, followed a different pathway requiring clinical trials. But these studies fall short of the standards required for testing new drugs. Trials for 30 of the recalled devices were not randomized, and 18 did not include a control group. Often, “surrogate” measures like lab results or radiology images were used as endpoints, rather than patient outcomes.
The follow-up period for these clinical trials lasted an average of six months, which may not be long enough to “capture the medium- and longer-term safety risks,” the authors wrote. In a study of a Medtronic stent graft system, the primary endpoint was assessed only 30 days after implantation. In 2021, more than 33,000 units were recalled because some fractured or leaked in patients’ bodies.
“Medical devices later recalled due to safety issues often had little clinical evidence supporting their original authorization,” the authors concluded.
An FDA spokesperson responded to our request for a comment with the following: “The mission of the FDA is to protect and promote public health, including helping to ensure that devices are safe and effective. That remains our highest priority and must be at the heart of every medical device review.”
How We Got Here
Public pressure on the FDA to speed approvals — which has been growing since the HIV/AIDs epidemic of the 1980s — may be to blame for the lack of clinical evidence in most class I recalls, according to a commentary that came with the new study.
“Public and political pressure has tended to emphasize the need for more innovation, faster review, and earlier access to medical interventions,” wrote the commentary’s author, Ezekiel Emanuel, MD, PhD, vice provost for global initiatives and co-director of the Health Transformation Institute at the University of Pennsylvania. The result: regulatory pathways aimed at expediting the “review of new drugs, biologics, and devices.”
More than a million patients have received high-risk heart devices that have been subject to a class I recall, according to the commentary. These include 600,000 coronary stents, 200,000 implantable pacemakers, about 200,000 heart valves, thousands of venous stents, and other prosthetics.
Similar concerns have cropped up with other medical devices, such as metal-on-metal hip replacements. These devices have four times the rate of revision surgery compared with all hip replacement prostheses within five years.
This isn’t the first time the issue has drawn public interest.
In 2011, the Institute of Medicine (IOM) reviewed the FDA’s 510(k) clearance process for medical devices, saying it should be scrapped because it lacked relevance for patient safety. The FDA rejected the IOM position, though it has since changed some of its policies and procedures, such as clarifying clinical testing requirements and expectations for implanted devices.
But cardiologist Rita Redberg, MD, a member of that 2011 IOM task force, said the FDA device review process does not appear to be protecting patient safety any better now than it did back then.
In fact, she said, the process is worse in a way: The FDA has expanded the 510(k) pathway to include a “de novo” method of gaining approval. This is designed for new devices with no “predicate,” or existing authorized device the product can be compared to. The FDA can approve these devices with little or no clinical data if they are considered low enough risk.
“The problem is that, without evidence, it’s very hard to know the risk of any device,” said Redberg, a professor of medicine at the University of California San Francisco.
Most de novo requests do include clinical data, which “scales to what the FDA determines is needed to mitigate risk and demonstrate benefit,” the FDA spokesperson said.
It’s also worth noting that the predicate for a new device can be a recalled device, said study co-author Kushal Kadakia, a third-year Harvard medical student who is researching medical device regulation and has worked for the FDA. Using a recalled device as a predicate “leads to a six times higher risk of recall of the new product,” he said. In 2023, the FDA updated its guidance on identifying predicate devices, urging device makers to consider any reported safety issues or recalls.
Some devices continue to be used even after being recalled. For example, some patients are still receiving implantable cardioverter defibrillators (ICDs) that have been subject to a class I recall, “although the underlying issue is not fully corrected,” said a report in the New England Journal of Medicine.
According to the FDA spokesperson, some recalled devices are not removed from the market if alternative treatments are limited and if the issue leading to the recall can be “addressed thoroughly with a correction to the device or its labelling.”
Abbott’s MitraClip cardiac device was recalled in 2016, but it continued to be implanted after Abbott revised instructions for its use and required doctors who implant the chip for leaky heart valves to undergo training. A Getinge intra-aortic balloon pump — a device used as a bridge to a heart transplant or recovery from heart failure — saw eight class I recalls from December 2022 to July 2023. The FDA allowed doctors to continue implanting it because alternative treatments were limited but finally removed it from the market after 15 patients died.
More Testing Is Needed, Doctors Say
The doctors we spoke to agreed medical devices should be tested in more rigorous clinical studies before approval.
Pressure to do so won’t come from device manufacturers, and not just because they want to get their products to market faster, Redberg said. A U.S. Supreme Court decision protects them against lawsuits if the FDA approved their devices after premarket testing, she said.
Most device recalls are based on reporting of adverse events, but the FDA’s adverse event reporting and postmarket surveillance is underfunded, she said.
“A lot of funding for the device division comes from the Medical Device User Fee and Modernization Act,” or MDUFA, Redberg said. Under this law, medical device companies pay fees to the FDA for regulatory services, which gives them influence over the process, Redberg said. “The [device] companies dictate that the FDA spend all of the MDUFA money on getting devices to market faster, which generally means lowering the standards or eliminating any standard for evidence.”
Device makers are required to report problems with their devices within 30 days of being made aware of them. But these reports are often delayed. And many doctors don’t report device issues to the FDA, in part because they don’t know how, Kovacs said.
“When I speak to other physicians, I’ll ask, ‘How many of you have ever filed a MedWatch report for a device or the side effect of a drug?’” said Kovacs. “Very few hands go up in the audience. First of all, no one knows there’s a MedWatch program, and physicians are not taught it’s their responsibility to report these problems.”
What Patients Should Know and Ask Their Doctor
Before having a medical device implanted, patients should understand the potential risks.
“I inform them that these devices are machines,” Kovacs said. “Machines break, wires break, and so the chance that a medical device will fail is real. It’s a small chance, but it’s real and should be discussed.”
When Kovacs hears about a device recall, he schedules a visit with patients who have that device to talk about their options, weighing the potential benefits of replacing the device against the potential harms of another operation.
Kenneth Kubitschek, MD, a retired internist in Asheville, North Carolina, recalls his discussions with patients about the metal-on-metal artificial hips. “The question became, do you replace it with considerable morbidity and even mortality, or do you leave it alone?” he said. “That was a really hard question to answer.”
Jeffrey Kagan, MD, an internist in Newington, Connecticut, has seen patients with implanted devices that had been recalled. “Some were in a big rush to have it changed, but some of them said, ‘I’m not going through that again,’” he said.
