Early steps in the development of a claims-based targeted healthcare safety monitoring system and application to three empirical examples

Drug Saf. 2012 May 1;35(5):407-16. doi: 10.2165/11594770-000000000-00000.

Abstract

Background: Several efforts are under way to develop and test methods for prospective drug safety monitoring using large, electronic claims databases. Prospective monitoring systems must incorporate signalling algorithms and techniques to mitigate confounding in order to minimize false positive and false negative signals due to chance and bias.

Objective: The aim of the study was to describe a prototypical targeted active safety monitoring system and apply the framework to three empirical examples.

Methods: We performed sequential, targeted safety monitoring in three known drug/adverse event (AE) pairs: (i) paroxetine/upper gastrointestinal (UGI) bleed; (ii) lisinopril/angioedema; (iii) ciprofloxacin/Achilles tendon rupture (ATR). Data on new users of the drugs of interest were extracted from the HealthCore Integrated Research Database. New users were matched by propensity score to new users of comparator drugs in each example. Analyses were conducted sequentially to emulate prospective monitoring. Two signalling rules--a maximum sequential probability ratio test and an effect estimate-based approach--were applied to sequential, matched cohorts to identify signals within the system.

Results: Signals were identified for all three examples: paroxetine/UGI bleed in the seventh monitoring cycle, within 2 calendar years of sequential data; lisinopril/angioedema in the second cycle, within the first monitoring year; ciprofloxacin/ATR in the tenth cycle, within the fifth year.

Conclusion: In this proof of concept, our targeted, active monitoring system provides an alternative to systems currently in the literature. Our system employs a sequential, propensity score-matched framework and signalling rules for prospective drug safety monitoring and identified signals for all three adverse drug reactions evaluated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Achilles Tendon / injuries
  • Adverse Drug Reaction Reporting Systems / standards*
  • Algorithms
  • Angioedema / chemically induced
  • Anti-Infective Agents / adverse effects
  • Antihypertensive Agents / adverse effects
  • Ciprofloxacin / adverse effects*
  • Databases, Factual
  • Drug Monitoring / methods*
  • Electronic Health Records
  • Gastrointestinal Hemorrhage / chemically induced
  • Humans
  • Lisinopril / adverse effects*
  • Paroxetine / adverse effects*
  • Pilot Projects
  • Prospective Studies
  • Rupture
  • Serotonin Uptake Inhibitors / adverse effects
  • Time Factors

Substances

  • Anti-Infective Agents
  • Antihypertensive Agents
  • Serotonin Uptake Inhibitors
  • Paroxetine
  • Ciprofloxacin
  • Lisinopril