Dive Brief:

• A significant minority of devices brought to market via the De Novo pathway lack positive primary endpoint data from a pivotal trial, according to a research letter published in JAMA Internal Medicine.

• The paper, which went live Monday, describes an analysis of 63 FDA De Novo authorizations of moderate-risk therapeutic devices between 2011 and 2019. One-fifth of the devices were not evaluated in pivotal studies, and one-third failed to meet at least one primary effectiveness endpoint in those studies.

• Only one device was found subject to an FDA-mandated postmarket study. The Yale and University of California, San Francisco researchers who wrote the paper discussed the value of requiring devices to meet pre-specified endpoints and undergo postmarket studies.

Dive Insight:

A low- to moderate-risk technology authorized via the De Novo pathway establishes a new classification category that can then open a floodgate for comparable devices to enter the market via 510(k) clearance.

The agency is working to finalize a rule on the De Novo process to "make it more transparent and predictable for manufacturers." Even without it, use of the De Novo pathway has increased in recent years. FDA cleared 65 devices via the pathway from 1997, the year it was established, to 2012. From 2013 to 2019, FDA cleared 187 devices via the pathway. The authorization rate for 2020 is slightly outpacing last year.

It's notable that De Novo-cleared devices can serve as predicates for products that come to market via the 510(k) route, which has been criticized by the Institute of Medicine and others as having a low bar for clinical evidence and oversight. As such, the regulatory standards for the De Novo pathway have implications for products beyond the 252 that came to market via the De Novo route between 1997 and 2019.

To assess the evidence needed to get De Novo medical devices to market, researchers scrutinized the moderate-risk therapeutic devices cleared via the pathway from 2011 to 2019. The search found 65 devices that met the criteria.

Twelve of the devices came to market without being evaluated in pivotal studies. Of the 60 studies run to assess premarket effectiveness, 17 missed at least one primary efficacy endpoint. The number of medical devices cleared without pivotal data, coupled to the prevalence of failed studies, shows many products came to market without positive results from a late-phase clinical trial.

Postmarket studies give regulators a way to confirm the safety and effectiveness of medical devices that have mixed or limited clinical data without delaying patient access by requiring more premarket work. FDA made limited use of postmarket studies in the analyzed dataset. The researchers found one device, a powered exoskeleton, that was subject to a FDA-required postmarket study. That authors acknowledged they didn't look at non–FDA-required postmarket studies, "and may therefore underestimate the strength of evidence supporting device safety and effectiveness."

The combination of clearances based on mixed or limited data and little postmarket activity informed the discussion of next steps.

“The FDA could require that devices cleared through the De Novo pathway meet prespecified effectiveness end points for clearance and that postmarket studies include larger patient populations. Such studies could be particularly informative for devices cleared without pivotal studies and those that failed to meet effectiveness end points,” the authors wrote.

None of the assessed products were the subject of Class I recalls during the analyzed period. Half of the devices served as a predicate for products subsequently cleared via the 510(k) pathway.