The case-crossover design: a method for studying transient effects on the risk of acute events

Am J Epidemiol. 1991 Jan 15;133(2):144-53. doi: 10.1093/oxfordjournals.aje.a115853.


A case-control design involving only cases may be used when brief exposure causes a transient change in risk of a rare acute-onset disease. The design resembles a retrospective nonrandomized crossover study but differs in having only a sample of the base population-time. The average incidence rate ratio for a hypothesized effect period following the exposure is estimable using the Mantel-Haenszel estimator. The duration of the effect period is assumed to be that which maximizes the rate ratio estimate. Self-matching of cases eliminates the threat of control-selection bias and increases efficiency. Pilot data from a study of myocardial infarction onset illustrate the control of within-individual confounding due to temporal association of exposures.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bias*
  • Case-Control Studies*
  • Confounding Factors, Epidemiologic
  • Humans
  • Research Design*
  • Retrospective Studies
  • Risk Factors
  • Time Factors