Successful Comparison of US Food and Drug Administration Sentinel Analysis Tools to Traditional Approaches in Quantifying a Known Drug‐Adverse Event Association

Abstract

The US Food and Drug Administration's Sentinel system has developed the capability to conduct active safety surveillance of marketed medical products in a large network of electronic healthcare databases. We assessed the extent to which the newly developed, semiautomated Sentinel Propensity Score Matching (PSM) tool could produce the same results as a customized protocol-driven assessment, which found an adjusted hazard ratio (HR) of 3.04 (95% confidence interval [CI], 2.81-3.27) comparing angioedema in patients initiating angiotensin-converting enzyme (ACE) inhibitors vs. beta-blockers. Using data from 13 Data Partners between 1 January 2008, and 30 September 2013, the PSM tool identified 2,211,215 eligible ACE inhibitor and 1,673,682 eligible beta-blocker initiators. The tool produced an HR of 3.14 (95% CI, 2.86-3.44). This comparison provides initial evidence that Sentinel analytic tools can produce findings similar to those produced by a highly customized protocol-driven assessment.

Safety assessment of niacin in the US Food and Drug Administration's mini‐sentinel system

“…We used the Mini‐Sentinel Cohort Identification and Descriptive Analysis and Propensity Score Matching (PSM) tools to conduct a parallel group, active‐comparator, propensity score‐matched new user cohort study comparing rates of major gastrointestinal bleeding and intracranial hemorrhage among initiators of extended‐release niacin and initiators of fenofibrate. These programs have recently been shown to produce estimates of effect consistent with prior observational studies for several well‐known associations between drugs and adverse health outcomes …”

A Query Workflow Design to Perform Automatable Distributed Regression Analysis in Large Distributed Data Networks

“…The tool also can create a de-identified patient-level analytic dataset to be stored locally at each data partner site. The dataset can then serve as an input file for other re-usable Sentinel tools (e.g., propensity score analysis tool, and the DRA algorithm) for inferential analysis [2627]. …”

Precision drug dosing: A major opportunity for patients and pharmacists

“…Because patient variable names (eg, weight, age, and lab values) have been standardized, and hospitals are adding genetic testing results to the clinical record, it is now feasible to aggregate very large patient numbers (eg, 100 000 to greater than 1 million) between hospitals and clinics to study pharmacogenomics and important public health questions. The FDA uses this new electronic environment to detect serious adverse events more rapidly and with greater certainty (eg, the Sentinel network) …”