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Drug Studies

The Office of Surveillance and Epidemiology in the Center for Drug Evaluation and Research (CDER) leads the Sentinel System. Sentinel was created to meet the mandate described in Section 905 of the Food and Drug Administration Amendments Act 2007 (FDAAA) to create an active postmarket drug safety surveillance system. CDER uses Sentinel to proactively assess the safety of FDA approved drugs under real-world conditions.


The Active Risk Identification and Analysis (ARIA) system is the largest and most developed component of Sentinel. ARIA uses state-of-the-art analysis tools and a distributed database of standardized claims and claims linked with electronic health records (EHR) data to monitor the safety of medications. The data undergo continuous quality checks and refreshes. With ARIA, safety analyses are conducted more efficiently compared to studies with fully customized analytics—often in a matter of months, rather than several years. 

How Drug Safety Studies Inform FDA’s Regulatory Process

FDA conducts safety studies in Sentinel for the following purposes, as described in Section 505(o)(3)(B) of FDAAA:

  • Assess a known serious risk related to the use of the drug
  • Assess signals of serious risk related to the use of the drug
  • Identify an unexpected serious risk

Sentinel drug safety studies can contribute to FDA’s regulatory process in a variety of ways. This includes:

  • Providing reassuring data to address new concerns about the safety of a medical product
  • Contributing evidence to support an FDA Drug Safety Communication or Label Change
  • Responding to a citizen's petition
  • Informing FDA’s risk management strategy for a drug
  • Becoming part of an Advisory Committee deliberation
  • Providing evidence that alleviates a drug safety concern

To learn more about how the FDA has used the Sentinel and ARIA Systems, please see the following assessment report. This assessment covers fiscal years 2018 through 2022, the period aligning with the Prescription Drug and User Fee Act (PDUFA) VI.

 

An Assessment of the Sentinel System: Focus on the Active Risk Identification and Analysis (ARIA) System

  • Signal Identification: analyses used to detect new and unsuspected potential safety concerns.
  • Level 1: analyses used to describe and characterize patterns of medication use or rates of health outcomes of interest. The Sentinel Query Builder application represents a subset of Level 1 functionality. Query Builder analyses are typically run on Merative™ MarketScan® Research Databases but some are also run on Sentinel's distributed database. 
  • Levels 2 and 3: analyses used to study whether a potential adverse health outcome is related to the use of drug and estimates the size of that risk.
     

Levels of ARIA Analyses

The graph below captures the total number of analyses conducted by the FDA since 2016 throughout the Sentinel System, including the Sentinel Distributed Database (SDD), IBM Watson Health, IBM Explorys, TriNetX, HCA Healthcare, PCORnet, and Veradigm. 

Sentinel’s ARIA system is complemented by EHR data systems, enabling the selection of a data source that best fits a drug safety question of interest. There are 3 categories of EHR data sources:

  • Data Aggregators: Compiles EHR data from multiple, discrete healthcare organizations in a single platform.
  • Data Warehouse: Stores extracted, standardized data from transactional systems in a central repository.
  • Network: An integrated partnership of standardized EHR data among multiple data partners.

 

All drug safety studies conducted in Sentinel are included below. The table is organized by the drug or population of interest and the health outcome(s) under study. When available, links are provided to the analytic code (package), results, communications and the study’s regulatory outcome.

Sentinel Study Status

Sentinel Study Purpose

FDA Sentinel Drug Studies: from ARIA and other Sentinel Data Sources