Case-crossover and case-time-control studies: concepts, design, and analysis

Case-crossover studies are the case-control version of crossover studies. In these studies, cases and controls are the same subjects. The term crossover is applied for designs that all subjects pass through both treatment (exposure) and placebo (non-exposure) phases. In fact they are crossover of subjects between periods of exposure and non-exposure. This design is most suitable for outcomes, which their induction time is short. Whatever the onset of outcome is more abrupt, it is more amenable to be studied in case-crossover studies. Case-crossover design can be implemented in a number of ways. In this article some common terms in the literature of case- crossover studies, major concerns in selection of controls, different ways for designing case- crossover studies, some examples for analyzing these data according to different sampling designs and also design and analysis of case-time-control designs with practical examples are being explored.