Bias in case‐crossover studies of medications due to persistent use: A simulation study

Purpose The case‐crossover design is increasingly used to evaluate the effects of chronic medications; however, as traditionally implemented in pharmacoepidemiology, with referent period preceding the outcome, it may lead to bias in the presence of persistent exposures. We aimed to evaluate the extent and magnitude of bias in case‐crossover analyses of chronic and persistent exposures, using simulations. Methods We simulated cohorts with either...