Use of case-time-control design in pharmacovigilance applications: exploration with high-risk medications and unplanned hospital admissions in the Western Australian elderly

Pharmacoepidemiol Drug Saf. 2013 Nov;22(11):1159-70. doi: 10.1002/pds.3469. Epub 2013 Jun 25.


Purpose: To use a case-time-control design to derive preliminary estimates of unplanned hospitalisations attributable to suspected high-risk medications in elderly Western Australians.

Methods: Using pharmaceutical claims linked to inpatient and other health records, the study applied a case-time-control design and conditional logistic regression to estimate odds ratios (ORs) for unplanned hospital admissions associated with anticoagulants, antirheumatics, opioids, corticosteroids and four major groups of cardiovascular drugs. Attributable fractions (AFs) were derived from the ORs to estimate the number and proportion of admissions associated with drug exposure. Results were compared with those obtained from a more conventional method using International Classification of Diseases (ICD) external cause codes to identify admissions related to adverse drug events.

Results: The study involved 1 899 699 index hospital admissions. Six of the eight drug groups were associated with an increased risk of unplanned hospitalisation, opioids (adjusted OR = 1.81, 95%CI 1.75-1.88; AF = 44.9%) and corticosteroids (1.48, 1.42-1.54; 32.2%) linked with the highest risks. For all six, the estimated number of hospitalisations attributed to the medication in the exposed was higher (two to 31-fold) when derived from the case-time-control design compared with identification from ICD codes.

Conclusions: This study provides an alternative approach for identifying potentially harmful medications and suggests that the use of ICD external causes may underestimate adverse drug events. It takes drug exposure into account, can be applied to individual medications and may overcome under-reporting issues associated with conventional methods. The approach shows great potential as part of a post-marketing pharmacovigilance monitoring system in Australia and elsewhere.

Keywords: adverse drug events; australian elderly; case-time-control design; data linkage; hospitalisation; pharmaceutical claims; pharmacoepidemiology; pharmacovigilance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Epidemiologic Research Design
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • International Classification of Diseases
  • Logistic Models
  • Male
  • Odds Ratio
  • Patient Admission / statistics & numerical data
  • Pharmacoepidemiology / methods*
  • Pharmacovigilance*
  • Research Design*
  • Risk Factors
  • Time Factors
  • Western Australia / epidemiology