Do All Those Postmarket Device Modifications Add Up to Patient Harm?

The more modifications allowed to high-risk medical devices on the market, the more there are subsequent device recalls, according to a study shining a light on premarket approval (PMA) supplements and patient safety.

An FDA database showed that every additional device supplement per year increased the risk of any recall by nearly 30% (HR 1.28, 95% CI 1.15-1.44). Class I recalls in particular, the most serious kind, were predicted both by increased number of postapproval supplements (HR 1.32, 95% CI 1.06-1.64) and cardiovascular devices (HR 3.51, 95% CI 1.15-10.72).

Indeed, cardiovascular devices accounted for 45.4% of recalled devices and 57.5% of all recalls, reported researchers led by Jonathan Dubin, MD, an orthopedic surgeon at the University of Missouri-Kansas City, in JAMA Network Open.

"The primary findings of this analysis indicate that postapproval modifications to high-risk medical devices approved through PMA are associated with the risk of recall," the authors wrote. "An estimated 10% of U.S. residents will have medical devices implanted during their lifetime, and physicians should be aware of this association because many devices undergo extensive postapproval modifications."

One famous example is the Riata/Riata ST. These cardiac defibrillator leads were recalled in 2011 for deadly lead failures that sparked numerous lawsuits. Notably, the wires had been cleared for 78 device modifications to an original PMA from 1996.

This was possible because the FDA allows several types of PMA supplements to be stacked to modify an original PMA of a high-risk (or class III) medical device. Only the rare panel track supplement (PTS) requires scrutiny of clinical data for applications seeking approval of expanding indications and major design changes.

In the present report, PTS represented just 1.2% of all supplements; much more frequent were 30-day supplements (67.3%), 180-day supplements (16.7%), and real-time supplements (11.5%). Unlike other supplements, PTS were not associated with the risk of recall or class I recall, suggesting that the clinical data may provide some protective effect.

Even so, recalls likely underestimate the true nature of device-related complications, study authors warned. They also acknowledged that their retrospective, observational study cannot prove that PMA supplements cause patient harm.

"Our results should not be misconstrued to imply that the regulatory process is intrinsically flawed. The supplement process is critical in expediting delivery of incremental device changes with potentially greater safety and effectiveness profiles," Dubin and colleagues noted. "Rather, we believe physicians should be aware of the risks associated with modified devices for their practices."

"Physician awareness, improved preapproval testing, and postmarket surveillance strategies should be used to mitigate risks to patient safety and public health," they stressed.

Unfortunately, the postmarket surveillance aspect is currently limited and the clinical impact of PMA supplements unclear -- partly because medical devices cannot be reliably identified in health records, commented cardiology fellow Hope Caughron, MD, and cardiologist Sanket Dhruva, MD, MHS, both of the University of California San Francisco School of Medicine.

In an accompanying editorial, they cited a proposal to include the device identifier portion of each device's unique device identifier on administrative forms.

"Surveillance of all medical devices, including those modified through PMA supplements, would become feasible, enabling safety concerns to be prospectively identified. More timely notification could also be provided to patients who had been treated with a recalled device, thereby mitigating harm," Caughron and Dhruva suggested.

For the study, Dubin's group probed an FDA database and identified 373 original devices approved via PMA from January 2008 through December 2019. While these devices ran the gamut from cardiac pacemakers to breast and cochlear implants, cardiovascular devices constituted 37.0% of original devices and microbiology devices constituted 12.1%; no other specialty contributed more than 10%.

During this time period, 10,776 supplements to these PMA devices were approved, with a median of 2.5 supplements per device approved annually. The most common reason for supplement submission was manufacturing process changes (67.7%).

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