A comparison of the empirical performance of methods for a risk identification system

Drug Saf. 2013 Oct;36 Suppl 1:S143-58. doi: 10.1007/s40264-013-0108-9.


Background: Observational healthcare data offer the potential to enable identification of risks of medical products, and the medical literature is replete with analyses that aim to accomplish this objective. A number of established analytic methods dominate the literature but their operating characteristics in real-world settings remain unknown.

Objectives: To compare the performance of seven methods (new user cohort, case control, self-controlled case series, self-controlled cohort, disproportionality analysis, temporal pattern discovery, and longitudinal gamma poisson shrinker) as tools for risk identification in observational healthcare data.

Research design: The experiment applied each method to 399 drug-outcome scenarios (165 positive controls and 234 negative controls across 4 health outcomes of interest) in 5 real observational databases (4 administrative claims and 1 electronic health record).

Measures: Method performance was evaluated through Area Under the receiver operator characteristics Curve (AUC), bias, mean square error, and confidence interval coverage probability.

Results: Multiple methods offer strong predictive accuracy, with AUC > 0.70 achievable for all outcomes and databases with more than one analytical approach. Self-controlled methods (self-controlled case series, temporal pattern discovery, self-controlled cohort) had higher predictive accuracy than cohort and case-control methods across all databases and outcomes. Methods differed in the expected value and variance of the error distribution. All methods had lower coverage probability than the expected nominal properties.

Conclusions: Observational healthcare data can inform risk identification of medical product effects on acute liver injury, acute myocardial infarction, acute renal failure and gastrointestinal bleeding. However, effect estimates from all methods require calibration to address inconsistency in method operating characteristics. Further empirical evaluation is required to gauge the generalizability of these findings to other databases and outcomes.

Publication types

  • Comparative Study

MeSH terms

  • Area Under Curve
  • Databases, Factual
  • Drug-Related Side Effects and Adverse Reactions / diagnosis*
  • Humans
  • Research Design*
  • Risk Assessment / methods*