Behavior of the exposure odds ratio in a case-control study when the hazard function is not constant over time

J Clin Epidemiol. 1989;42(12):1179-84. doi: 10.1016/0895-4356(89)90116-9.


In case-control studies of adverse drug effects there is rarely much evidence to support the assumption that the hazard function among users is constant during therapy. Nonetheless, this assumption is often implicitly made. We will use both clinical reasoning and a simple model to show how non-constancy of the hazard function affects odds ratio interpretation. When the hazard function is non-constant and there is more than one temporal pattern of drug usage, the odds ratio will estimate a weighted mean of incidence ratios with weights dependent on the corresponding fractions of person-time. If the duration-specific incidence ratios differ widely, the odds ratio will depend not only on the drug but also on its usage pattern in the study population. This may explain some of the large regional odds ratio variation for dipyrone-related agranulocytosis in the International Agranulocytosis and Aplastic Anemia Study (JAMA 1986; 256: 1749-1757.

MeSH terms

  • Agranulocytosis / chemically induced
  • Agranulocytosis / epidemiology
  • Case-Control Studies*
  • Dipyrone / adverse effects
  • Drug-Related Side Effects and Adverse Reactions*
  • Epidemiologic Methods
  • Humans
  • Models, Theoretical
  • Probability


  • Dipyrone