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 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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The case-crossover study design permits the assessment of change in the risk of an event during a brief hazard period during and after exposure to a transient risk factor.
“The casecrossover study design permits the assessment of change in the risk of an event during a brief”
From Triggering of Sudden Death from Cardiac Causes by Vigorous Exertion (2000) · cites this paper as [13]
The case-crossover design with self-matching eliminates confounding by traditional risk factors for myocardial infarction that differ among patients.
“this study eliminated the effect of confounding by factors that differed among patients.”
From Triggering of Acute Myocardial Infarction by Heavy Physical Exertion -- Protection against Triggering by Regular Exertion (1993) · cites this paper as [11]
The case-crossover study design was developed in the 1990s to study triggers of acute myocardial infarction and has subsequently been applied to several other acute conditions.
“The case-crossover study design was developed in the 1990s to study triggers of acute myocardial infarction and has subsequently been applied to several other acute conditions24,25.”
From Triggers of Spontaneous Preterm Delivery – Why Today? (2014) · cites this paper as [24]
Self-matching in a case-crossover design eliminates confounding by risk factors that are constant within individuals over the sampling period but often differ between study subjects.
“Because control information for each subject is based on his or her own past exposure experience, self-matching eliminates confounding by risk factors that are constant within individuals over the sampling period but often differ between study subjects.”
From Coffee and acute ischemic stroke onset: The Stroke Onset Study (2010) · cites this paper as [11]
The case-crossover design uses subjects as their own controls, so there is no variability in traditional risk factors for stroke.
“Since the casecrossover design uses subjects as their own controls, there is no variability in traditional risk factors for stroke.11”
From Coffee and acute ischemic stroke onset: The Stroke Onset Study (2010) · cites this paper as [11]
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- Authors
- Maclure, M.
- Affiliations
- Harvard University (US)
- Corresponding author
- Maclure, Malcolm
- ORCID
- Maclure, Malcolm
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 1991-01-15
- Volume
- 133
- Issue
- 2
- Pages
- 144-153
- ISSN
- 0002-9262 (ISSN-L)
- 1476-6256
- OpenAlex
- W2136527705
- Cited by
- 2,327
- References
- 12
- Citations by year
- 2026: 76 · 2025: 75 · 2024: 124 · 2023: 93 · 2022: 139 · 2021: 121 · 2020: 113 · 2019: 118 · 2018: 113 · 2017: 100 · 2016: 112 · 2015: 115 · 2014: 118 · 2013: 113 · 2012: 94
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL41016, R01HL041016)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Keywords
- case-crossover design, incidence rate ratio, Mantel-Haenszel estimator, control selection bias, myocardial infarction, exposure duration
- MeSH terms
- Humans, Research Design, Retrospective Studies, Risk Factors, Time Factors, Bias, Confounding Factors, Epidemiologic, Case-Control Studies
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