US Food and Drug Administration Sentinel Initiative and Postmarket Drug Safety Surveillance: A Review.

Abstract

The US Food and Drug Administration (FDA) Sentinel Initiative's Active Risk Identification and Analysis (ARIA) system enables medical product safety surveillance using a large, national distributed network of administrative claims and electronic health record data. As FDA increasingly emphasizes evaluating medical products across their life cycle, the ARIA system's role in supporting postmarket safety surveillance has grown. To evaluate ARIA system use and characterize challenges related to transparency, accessibility, and consistency amid ongoing plans to modernize the Sentinel Initiative through the forthcoming Prescription Drug User Fee Act (PDUFA) reauthorization. Publicly available information from the Sentinel Initiative website was reviewed as of September 30, 2025, including 2 FDA reports covering ARIA system assessments from 2016 to 2024. When FDA identifies safety concerns for medical products, they undergo a sufficiency determination to assess whether the concerns can be addressed using the ARIA system. For concerns deemed sufficient, FDA initiates a drug study-a structured investigation of 1 or more related safety concerns. Across the 2 FDA reports covering ARIA system assessments from 2016 to 2024, 548 safety concerns and 119 drug studies were publicly disclosed, along with 31 redacted safety concerns and 23 redacted drug studies. Due primarily to limitations of claims-based data, the ARIA system was often deemed insufficient to evaluate safety concerns (333 of 579 [57.5%] publicly disclosed and redacted concerns from 2016-2024), particularly those identified during premarket medical product review (165 of 187 [88.2%] concerns from 2016-2021; not reported for 2022-2024). For safety concerns deemed sufficient, 87 (73.1%) of the 119 publicly disclosed drug studies were reported as completed, which most commonly provided reassurance that no further regulatory action was needed (27 [31.0%]), informed label changes (10 [11.5%]), or supported monitoring for new safety signals (7 [8.0%]). While the Sentinel Initiative website and FDA reports provide valuable information, challenges were identified related to information transparency, accessibility, and consistency. In particular, there is no centralized database of all safety concerns, the ARIA system information is often incomplete, and there is a lack of standardized terminology across documentation of the Sentinel Initiative. This review observed that as FDA considers modernizing the Sentinel Initiative as part of forthcoming PDUFA reauthorization, opportunities exist to strengthen the use and impact of the ARIA system by creating a publicly available, centralized, and regularly updated database of safety concerns, establishing a complete record of ARIA system information, adopting standardized terminology, and further expanding data linkages beyond claims data.