Nearly 1 in 10 FDA-authorized therapeutic breakthrough devices enter the market without premarket clinical testing, according to a recent study.
Researchers conducted a cross-sectional study to evaluate the clinical and regulatory characteristics of therapeutic devices that were authorized by the U.S. Food and Drug Administration (FDA) under the Breakthrough Devices Program from 2016 to 2024. The findings were published in JAMA Internal Medicine.
Using publicly available FDA data through September 30, 2024, investigators—led by Kushal T. Kadakia, MD, of Harvard Medical School in Boston, Massachusetts—assessed all therapeutic breakthrough-designated devices that received FDA authorization. The primary outcomes included technological novelty, review timelines, and characteristics of both premarket and post-market evidence. Among 1,041 devices granted breakthrough designation, 127 were authorized (12.2%), including 75 therapeutic devices (59.1%).
Of the 75 authorized therapeutic devices, 34 (45.3%) were categorized as high-risk and reviewed under the Premarket Approval (PMA) pathway. Within this high-risk group, 23 devices (67.6%) were identified as first of a kind, and 14 (41.1%) were first commercialized in the U.S. The mean FDA review time was 225.8 (107.6) days for all therapeutic devices and 243.3 (98.4) days for high-risk devices. Among 30 PMA devices with established h Medical Device User Fee Authorization targets, 22 (73.3%) were reviewed within statutory timeframes.
Premarket clinical testing was conducted for 67 of the 75 therapeutic devices (89.3%). This testing supported 75 pivotal studies that evaluated 81 primary effectiveness end points. Of these, 40 end points (49.4%) used surrogate measures, and 27 (33.3%) were composite outcomes. Only 66 end points (81.5%) were statistically tested; 54 (81.8%) met effectiveness criteria, 43 (65.2%) were assessed for superiority, and 6 (9.1%) were assessed for noninferiority. Median patient enrollment in pivotal studies was 134.5 (interquartile range [IQR] = 65.3–223.5), and the median follow-up duration for implantable devices was 6 months (IQR = 3.8–12 months).
Post-market studies were mandated for 30 devices (40%), totaling 46 studies. These studies had a median planned enrollment of 299 patients (IQR = 150–580) and a median follow-up of 5 years (IQR = 3–5 years). Notably, 60% of end points in post-market studies were surrogate based. Nine devices (12%) were subject to FDA recalls, including one class I recall. The FDA did not require post-market studies for any of the 8 devices that lacked premarket clinical data and required such studies for only 4 of 11 devices (36.4%) that failed to meet pivotal end points.
The researchers concluded that while most therapeutic breakthrough-designated devices were novel and reviewed within mandated timeframes, the limited use of robust clinical evidence—both premarket and post-market—raises concerns about the program’s consistency in advancing public health benefits.
Full disclosures can be found in the published study.
Source: JAMA Internal Medicine
