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

1991/01/15 by Malcolm Maclure · 2,326 citations
Economics, Econometrics and Finance · Mathematics · Medicine · #Advanced Causal Inference Techniques #Confidence interval #Confounding #Crossover study #Environmental health #Estimator #Health Systems, Economic Evaluations, Quality of Life #Incidence (geometry) #Internal medicine #Matching (statistics) #Mathematics #Medicine #Population #Rate ratio #Sample size determination #Selection bias #Statistical Methods and Inference #Statistics

paper · doi:10.1093/oxfordjournals.aje.a115853

published in American Journal of Epidemiology 133(2), 144-153 (Oxford University Press)

openalex publication_date 1991/01/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05

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 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.

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