Active Risk Identification and Analysis (ARIA) System

The largest and most developed component of the Sentinel System.

Funder: United States Food and Drug Administration

Leadership: Sengwee Darren Toh

Year Initiated: 2021

Project Summary

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 the Sentinel System. 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.

ARIA greatly enhances the efficiency of safety analyses.

FDA conducts safety studies in ARIA for the following purposes* 

  • 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

Drug safety studies can contribute to FDA's regulatory process by

  • 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
  • Providing evidence that alleviates a drug safety concern 

*as described in Section 505(o)(3)(B) of FDAAA

The following analyses are available: 

  • 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. These are descriptive analyses and can provide unadjusted rates.
  • Level 2: Analyses used to study whether a potential adverse health outcome is related to the use of drug and estimates the size of that risk. These are adjusted analyses with sophisticated confounding control.
  • Level 3: Analyses used to monitor whether a potential adverse health outcome is related to the use of a drug and estimates the size of that risk. These are sequential adjusted analyses with sophisticated confounding control.

Drug safety studies can contribute to FDA's regulatory process by

  • 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
  • Providing evidence that alleviates a drug safety concern 

*as described in Section 505(o)(3)(B) of FDAAA

Visit the Sentinel website for and overview of Key Database Statistics describing the data available within the ARIA system, as well as to get more detail on the analytic designs available within ARIA’s Routine Querying Tools.

The ARIA system has contributed to multiple FDA Safety Communications and Labeling Changes and has contributed data to Advisory Committees.

The FDA also uses the ARIA System to monitor the safety of medications. During the drug approval process, potential safety concerns are sometimes found that require further study after FDA approval. Before requiring the drug's manufacturer to conduct a post-approval safety study, FDA must determine whether it is feasible to answer the safety question in ARIA.
 

Explore the ARIA System

Learn more about the different types of analyses performed using ARIA, along with the regulatory impacts.

Visit the Sentinel System

Six Years of FDA's Postmarket Active Risk Identification and Analysis System (ARIA) in the Sentinel Initiative: Implications for Real World Evidence Generation

Featured Key Publication

Six Years of FDA's Postmarket Active Risk Identification and Analysis System (ARIA) in the Sentinel Initiative

Congress mandated the creation of a postmarket active risk identification and analysis (ARIA) system containing data on 100 million individuals for monitoring risks associated with drug and biologic products using data from disparate sources to complement the US Food and Drug Administration's (FDA's) existing postmarket capabilities. 

We report on the first six years of ARIA utilization in the Sentinel System (2016 -2021). The FDA has used the ARIA system to evaluate 133 safety concerns; 54 of these evaluations have closed with regulatory determinations, while the rest remain in progress.