Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics

Pharmacoepidemiol Drug Saf. 2006 May;15(5):291-303. doi: 10.1002/pds.1200.

Abstract

Background: Large health care utilization databases are frequently used to analyze unintended effects of prescription drugs and biologics. Confounders that require detailed information on clinical parameters, lifestyle, or over-the-counter medications are often not measured in such datasets, causing residual confounding bias.

Objective: This paper provides a systematic approach to sensitivity analyses to investigate the impact of residual confounding in pharmacoepidemiologic studies that use health care utilization databases.

Methods: Four basic approaches to sensitivity analysis were identified: (1) sensitivity analyses based on an array of informed assumptions; (2) analyses to identify the strength of residual confounding that would be necessary to explain an observed drug-outcome association; (3) external adjustment of a drug-outcome association given additional information on single binary confounders from survey data using algebraic solutions; (4) external adjustment considering the joint distribution of multiple confounders of any distribution from external sources of information using propensity score calibration.

Conclusion: Sensitivity analyses and external adjustments can improve our understanding of the effects of drugs and biologics in epidemiologic database studies. With the availability of easy-to-apply techniques, sensitivity analyses should be used more frequently, substituting qualitative discussions of residual confounding.

Publication types

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

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Databases as Topic
  • Humans
  • Pharmacoepidemiology / statistics & numerical data*
  • Risk
  • Sensitivity and Specificity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors