The Case-Crossover Design: A Method for Studying Transient Effects on the Risk of Acute Events

Abstract

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 nonrandomlzed 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. Am J Epidemiol 1991:133:144-53.