Post-marketing studies on CV devices are still lacking in the United States


The 21st Century Cures Act did not inspire more companies to conduct continued research after FDA approval.

Recent efforts by regulators in the United States to speed up the approval of new devices without sacrificing safety are based on the idea that post-marketing studies will provide reassurance as the products are used in the real world. But figures from US Food and Drug Administration databases show that such studies are no more common than before and often lack rigour.

The 21st Century Cures Act, passed in 2016, states that “the FDA shall” consider the role of postmarketing information in determining the least burdensome means “for approval,” researchers point out in a JAMA internal medicine search letter. Post-marketing studies can help reinforce, retroactively, the efficacy data needed to bring a device to market.

Even before the advent of the law on cures, there were worries that FDA approval of cardiovascular devices is often is based on early evidence.

Lead author Rita F. Redberg, MD (University of California, San Francisco), told TCTMD that upon entering their new study, she felt optimistic that the legislation had spurred change. “There’s definitely been a lot of buzz about the total product lifecycle and how post-marketing is going to play a really robust role, so we were hoping we’d see that,” Redberg said.

“Post-marketing has always been important, because device testing is usually very limited before market in size and scope. And so we’ve always relied on post-marketing. [studies] for devices,” she continued. But the passage of ‘the Cures Act – and the idea that we can shorten the pre-market because we’re going to have a robust post-market, and the whole ‘least constraining’ philosophy – made it very important to see if things had changed since we watched 10 years ago.”

There are positive trends toward a higher prevalence of studied devices after FDA approval, she acknowledged. However, progress so far has been slow.

The fact that we continue to accept and use devices based on incomplete data limits our ability to take the best care of our patients. Rita F. Redberg

Redberg, with co-authors Danelle Hidano, MD (University of Washington, Seattle), and Sanket S. Dhruva, MD (University of California, San Francisco), identified 71 high-risk (Class III) cardiovascular devices approved by the FDA between 2015 and 2019. Twenty-seven of these approvals occurred before January 1, 2017, and 44 after. They then cross-checked information from the agency Post-Approval Studies (PAS) Database for more details on post-marketing research.

A total of 68 post-approval studies were commissioned for 49 of the devices. Devices approved after the Cures Act were statistically no more likely than those before it to be followed up with a post-marketing study (75% vs. 59%; P = 0.16).

Most (71%) were prospective, unblinded cohort studies, while 18% were randomized clinical trials and 12% involved active surveillance. Only 7% involved blinding, and only RCTs had active control groups. For 37 studies (55%), the primary outcomes included surrogate measures, such as primary patency based on Doppler velocities. The remaining 31 studies (46%) used a clinical outcome, such as claudication.

About a third of studies (38%) were completed after a median follow-up of 4 years, with 44% ongoing and 18% delayed, revised or completed. Twenty-five of the 26 completed studies (95%) listed the results in the PAS database, compared to 33% of the ongoing studies.

“To improve the timeliness, quality, and availability of postmarketing evidence, the FDA should consider requiring postmarketing randomized clinical trials that use clinical endpoints,” the authors advise. “The FDA should also consider implementing time-limited device approvals, with continued commercialization contingent on the timely generation and reporting of clinically meaningful post-approval data.”

A way forward might not rest with the FDA, Redberg suggested. Rather, it could fall to the Centers for Medicare & Medicaid Services (CMS), which could require participation in a clinical trial as a prerequisite not only for reimbursement, but also for access to approved treatment. This is currently being considered for the Alzheimer’s drug aducanumab (Aduhelm; Biogen), she pointed out. “You could do the same for a device. . . . You allow people to get it, but you still collect data on [its safety and effectiveness].”

A similar model was tried years ago with the standby device (Boston Scientific) for closure of the left atrial appendage, she observed. But in this case, there was a loophole: Patients could still get the device outside of a trial setting, it just wouldn’t be paid for by CMS, Redberg explained. “These post-marketing RCTs only work if that’s the only way to get the device, because otherwise the implanters say, ‘Why should I randomize when I could get paid to put it in everybody? ‘”

Redberg urged cardiologists who use medical devices to take an active role in demanding that the FDA provide solid data: “If the FDA heard the message that doctors really want more than a small study with a surrogate marker that doesn’t is not meaningful for patients and very unclear safety data, I think it could make a difference. The fact that we continue to accept and use devices based on incomplete data limits our ability to take the best care of our patients.


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