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

Clin Pharmacol Ther. 2016 Nov;100(5):558-564. doi: 10.1002/cpt.429. Epub 2016 Aug 22.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects*
  • Angioedema / chemically induced*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Databases, Factual
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Models, Statistical
  • Product Surveillance, Postmarketing / statistics & numerical data*
  • United States
  • United States Food and Drug Administration


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors