Abstract

Case-crossover designs have become widespread in biomedical investigations of transient associations. However, the most popular reference-selection strategy - the time-stratified scheme - may not be an optimum solution to control systematic bias in case-crossover studies. To prove this, we conducted a time series decomposition for daily ozone records and examined the capability of the time-stratified scheme to control for yearly, monthly, and weekly time trends; and observed its failure on the control for the weekly time trend. To solve this issue, we proposed a new logistic regression approach in which we suggest the adjustment for the weekly time trend. We compared the performance of the proposed with that of the traditional method by simulation. We further conducted an empirical study to explore the performance of the new logistic regression approach in examining potential associations between ambient air pollutants and acute myocardial infarction hospitalizations. The time-stratified scheme provides effective control for yearly and monthly time trends but not of the weekly time trend. Uncontrolled weekly time trends could be the dominant source of systematic bias in time-stratified case-crossover studies. In contrast, the proposed logistic regression approach can effectively minimize systematic bias in a case-crossover study.

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