Five years after the US Food and Drug Administration (FDA) began the “Breakthrough Devices Program” program, an investigation from Stat News finds that the program has led to breakthrough profits for device-makers, but not commensurate benefits for patients.
What is a “Breakthrough” device?
The Breakthrough Device Program allows for a sped-up approval process for devices that “provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.” Manufacturers of devices under this pathway get to connect with FDA experts throughout the process to help it go more smoothly, and their submission gets priority for FDA review.
This “preferred” designation is the device equivalent of the FDA’s “Breakthrough Therapy” designation for drugs, which expedites FDA review of drugs that “may demonstrate substantial improvement over available therapy.” Like the FDA’s “Accelerated Approval” pathway*, many of these drugs designated as breakthrough therapies have been approved on the basis of poor-quality evidence. A 2018 study of 46 breakthrough therapies found that only 59% of trials used to approve these drugs were randomized, only 54% had a control group, and the vast majority were based on surrogate outcomes, rather than meaningful clinical outcomes.
*The difference between these two programs is that breakthrough designation asks the sponsor to demonstrate a benefit over existing drugs, whereas accelerated approval is meant for drugs “fitting an unmet need.” A drug that has received a breakthrough therapy designation can also be eligible for the accelerated approval pathway.
Where’s the evidence?
The same issue of low evidence of benefit appears to be the case with the FDA’s breakthrough designation for devices. Although the term “breakthrough” would lead one to believe that a device with that designation has shown to be exceedingly effective, it’s actually the opposite — the FDA does not actually require clinical evidence that the new device is more effective than an existing one, just that the devicemaker “demonstrates a reasonable expectation that the device could provide for more effective treatment” than existing devices on the market.
“A complete set of clinical data is not required for designation. Instead, a sponsor should demonstrate a reasonable expectation that the device could provide for more effective treatment or diagnosis of the disease or condition.”
FDA Guidance, 2018
The StatNews investigation cites devices that were approved based on trials that did not show statistically significant improvements in the primary outcome, or that required “statistical gymnastics” to look effective. These devices ended up getting approved mainly because there weren’t other good options for those conditions on the market.
“There’s a lot of [breakthrough] products that come to market with negligible evidence…that it provides any value whatsoever,” said Joseph Ross, physician and health policy researcher at the Yale School of Medicine, in Stat.
Safety of patients at stake
The safety of these devices is an issue as well as efficacy. According to Stat, two breakthrough devices have been recalled for failures that could lead to serious injury or death. These safety issues around devices are not new. A 2018 report from the International Consortium of Investigative Journalists found that that medical devices were linked to more than 1.7 million injuries and nearly 83,000 deaths from 2008-2017.
Many of these breakthrough devices end up getting cleared through the 510(k) pathway (about 25% according to Stat‘s database of breakthrough devices). This pathway clears devices for market if they are “substantially equivalent” to an existing device on the market, rather than based on it safety and efficacy. This has created a sort of pyramid-scheme of device clearances, in which untested devices are approved based on existing devices, which themselves were untested, leading to numerous safety issues.
(Aside from the safety issues, I found it curious that so many “breakthrough” medical devices, which are approved on the basis of being potentially better than existing devices, were being cleared through the 510(k) pathway, which by definition says that this device is basically the same as an existing one. Are these devices better than the ones on the market, or the same — which is it?)
Potential for profits
The breakthrough device program was not being used extensively by device manufacturers until a CMS rule was proposed in 2019 to automatically grant device makers four years of reimbursement for authorized breakthrough devices. Although the proposed rule was scrapped recently, device makers were already off to the races — from 2019-2020, applications for breakthrough devices rose by 60%.
With the breakthrough designation, the standard for evidence behind these devices has lessened while the financial benefits increased, which is a dangerous combination.
Beyond the financial appeal of instant Medicare coverage, device makers have used the breakthrough designation to show investors that the device is a good bet. Some have used the designation to promote their devices, saying that their device has the potential to be more effective. Obviously, the lenient requirement of this pathway aren’t mentioned in these promotions.
The breakthrough device designation is another example of how the FDA has made it easier for drugs and devices to enter the market. With the breakthrough designation, the standard for evidence behind these devices has lessened while the financial benefits increased, which is a dangerous combination. As political pressure grows for CMS to cover these devices more quickly, it’s especially important that clinicians, patients and the public keep an eye on these approvals.