Clinical Evidence Supporting FDA Clearance of First-of-a-Kind Therapeutic Devices via the De Novo Pathway Between 2011 and 2019: A Retrospective Cross-Sectional Analysis

ABSTRACT Importance In recent years, the US Food and Drug Administration (FDA) and manufacturers have increasingly sought to expedite patient access to first-of-a-kind devices via the De Novo premarket review pathway. Understanding the strength of clinical evidence supporting FDA clearance through this pathway can help guide clinical adoption of novel devices and ongoing regulatory development of the postmarket surveillance infrastructure. Objective Our primary objective was to characterize the strength of clinical evidence supporting FDA clearance of therapeutic De Novo devices. Key secondary objectives were 1) characterization of FDA post-marketing requirements for De Novo devices and 2) study of the use of these devices as the basis for devices subsequently cleared via the 510(k) process. Design Retrospective cross-sectional analysis Setting Publicly available online FDA databases, including the De Novo database, the 510(k) clearance database, the 522 Post Market Surveillance database, and the Recalls of Medical Devices database Participants All moderate-risk therapeutic devices cleared via the De Novo pathway between January 1, 2011, and December 31, 2019. Main Outcome Measures (1) proportion of De Novo devices cleared based on evidence from a pivotal clinical study, (2) proportion of pivotal study primary effectiveness endpoints that were met, (3) proportion of De Novo devices subject to FDA-required postmarket studies, and (4) proportion of De Novo devices serving as the basis for at least one subsequently cleared 510(k) device (i.e., new models or competitor products). Results There were 63 (of 65; 96.9%) moderate-risk therapeutic devices cleared by FDA via the De Novo pathway between 2011 and 2019 for which decision summary documentation was publicly available. Of the 63 devices, 51 (81.0%) were supported by pivotal clinical studies (n=54 studies); the remainder (n= 12; 19.0%) were not supported by a pivotal clinical study. The majority of pivotal studies were randomized (57.4%), multi-armed (61.1%), and used an active (25.9%) or sham (35.2%) comparator arm; 17 (31.5%) failed to meet at least one primary effectiveness endpoint. Among the 63 devices cleared via the De Novo pathway, one (1.6%) was subject to an FDA-required posttmarket study and 32 (47.8%) served as a predicate device for new models or competitor devices subsequently cleared through the 510(k) process. Conclusions Between 2011 and 2019, the FDA cleared the majority of first-of-a-kind moderate-risk therapeutic devices via the De Novo pathway based on premarket evidence from pivotal clinical studies. However, 43% of devices were cleared without clinical evidence from pivotal studies or based on pivotal studies that failed to meet at least one primary effectiveness endpoint. The FDA rarely required postmarket studies of these devices, which often served as the basis for new models and competitor products subsequently cleared via the 510(k) process. KEY POINTS Question What is the strength of premarket clinical evidence supporting FDA clearance of first-of-a-kind therapeutic devices via the De Novo review pathway? Findings In this retrospective cross-sectional analysis of 63 devices, 43% were cleared without supporting premarket pivotal studies or based on pivotal studies that failed to meet at least one primary effectiveness endpoint. The FDA rarely required postmarket studies of therapeutic De Novo devices, which often served as the basis for new models and competitor products subsequently cleared via the 510(k) process. Meaning The FDA often clears first-of-a-kind therapeutic devices via the De Novo pathway despite limited clinical evidence of effectiveness.