Sentinel System expands capacity, data linkages, report indicates
The US Food and Drug Administration’s Sentinel System, which monitors the safety of approved medical products, has expanded its capacity to support regulatory decisions and become an established resource for real-world data (RWD), according to a new assessment.The assessment, which was conducted by a third-party advisor, is required as part of the agency’s commitments under the Prescription Drug User Fee Act (PDUFA) VI. It spells out the Sentinel System’s progress in expanding its data infrastructure and data analysis capability, as well as its contribution to real-world evidence generation. This is the third assessment of the Sentinel System since it was created by FDA in 2008 (RELATED: Sentinel: FDA Outcomes Five-Year Roadmap, Regulatory Focus 09 January 2019).
“Sentinel has made substantial progress in developing methods and data linkages, testing, and incorporating novel technologies for more efficient performance, enhancing the use of RWD for evaluating medical product safety, and disseminating knowledge to advance regulatory science,” according to the assessment. “Sentinel continues to deliver value both within and beyond its mandated mission.”
Data infrastructure expansion
As of 2021, Sentinel can access claims-based data that covers 341 million unique patient identifiers, exceeding the requirement for the system to access data on 100 million patient lives. Additionally, Sentinel can also access data from integrated delivery systems covering 22.8 million patient identifiers, which provide claims data that is enhanced with select clinical data, typically from electronic health records (EHRs).
Through the Sentinel Distributed Database (SDD), the agency can gain real-world evidence for regulatory decisions by running specific queries through data partners, who return summary level data. Sentinel can also request access to de-identified patient-level medical chart data for more than 180 million enrollment records in the SDD. “This capacity for de-identified medical chart data to be shared with the [Sentinel Operation Center] can be leveraged when FDA requires information only available in medical charts, for example to confirm health outcomes of interest identified in claims data, to support FDA decisions,” according to the assessment.
Sentinel has also created a mother-infant linkage (MIL) table in the Sentinel Common Data Model that allows FDA to assess safety concerns related to medical product use in pregnancy, which previously could not be evaluated. The number of linked mother-infant pairs in the SDD rose from 4.9 million deliveries in 2019 to 5.7 in 2021, an increase of 16.3%. Sentinel has also increased the patient identifiers included in the laboratory results table and the vital signs table. However, the number of patient identifiers in the cause of death table decreased 16.7% from 2017-2021, due to increased state restrictions.
The assessment noted that Sentinel users are seeking increased laboratory and vital sign information, as well as expanded access to EHR linkage with claims data, health risk factors, clinical health outcomes data, expanded linked mother-infant pairs, and socio-demographic information.
The assessment of Sentinel also notes that the Sentinel Common Data Model has “proven scalable and extensible.” Sentinel added prescribing, facility, and provider tables in 2020, expanded the capture of laboratory results and COVID-19 diagnostic test results in 2020, and added a mother-infant linkage table in 2018. However, Sentinel can also be inflexible, with a lengthy process for changing the Sentinel Common Data Model and performing quality assurance to validate that data partners have updated their versions of the data model, according to the assessment.
New data sources
Under the Sentinel Five-Year Strategy, the agency has expanded the data sources from outside the SDD used in studies to include the National Patient-Centered Clinical Research Network, TriNetX, the claims-based Merative (previously IBM) MarketScan database, and HCA Healthcare.
“Increasing the richness of available data and the types of questions Sentinel can answer will enhance Sentinel's value,” according to the assessment. “These data sources include additional information not in claims, such as non-prescription and inpatient medications as well as lifestyle factors such as smoking status, and the possibility of using unstructured data, such as medical record chart notes.”
COVID-19 response
Sentinel was also adapted to assist in the FDA’s response to the COVID-19 pandemic. The Rapid COVID-19 SDD is a database with six data partners that allows more timely access to data. Data is refreshed between monthly and every eight weeks. In fiscal years 2020 and 2021, there were 17 studies – resulting from 48 queries – related to COVID-19. Some of these studies are still ongoing. The Rapid COVID-19 SDD provided critical insights including, information on the use of products authorized under an emergency use authorization, informed understanding of racial/ethnic disparities in COVID-19 testing and mortality and helped describe the natural history of hospitalized patients with COVID-19.
Sentinel System assessment