Introduction to Self-controlled Study Design

Abstract

Self-controlled study designs, also known as case-only designs or Self-controlled Crossover Observational PharmacoEpidemiologic (SCOPE) studies, include case-crossover (CCO) and self-controlled case series (SCCS). These designs compare different time windows (i.e., lengths of time) within the same person. An SCCS compares the occurrence of an outcome (event) during periods with and without exposure in the same person, whereas a CCO compares periods with and without the outcome for exposure. The main strength of self-controlled study designs is that they can ignore confounding factors that do not change over time (e.g., sex, genetics, habitual healthy or unhealthy behaviors). The effect of these factors are canceled out through statistical analyses, even if they are unknown or unmeasured. However, self-controlled study designs cannot be used for all research questions. Assumptions specific to each study design are needed. In CCO, there should be no substantial changes in exposure trends during the study period, the exposure should be transient (intermittent), and the outcome should be abrupt (sudden). In SCCS, event rates should be constant within each defined period and events must be independently recurrent or rare. In addition, the occurrence of an event should not affect subsequent exposures. Self-controlled study designs may be particularly useful in studies using electronic health records, in which some (time-invariant) confounding factors may not have been recorded, provided that the research question meets the assumptions required for each study design.