The methodology of self-controlled case series studies

Abstract

The self-controlled case series method is increasingly being used in pharmacoepidemiology, particularly in vaccine safety studies. This method is typically used to evaluate the association between a transient exposure and an acute event, using only cases. We present both parametric and semiparametric models using a motivating example on MMR vaccine and bleeding disorders. We briefly describe approaches for censoring events and a sequential version of the method for prospective surveillance of drug safety. The efficiency of the self-controlled case series method is compared to the that of cohort and case control studies. Some further extensions, to long or indefinite exposures and to bivariate counts, are described.

Risk of ischemic stroke during the initiation period of α-blocker therapy among older men

“…10,13,14,17,18 The key advantage of a self-controlled case series design is that time-invariant confounders, such as sex, location, genetics and underlying state of health, are controlled for implicitly. 14 In the conditional Poisson regression model, we adjusted only for age at the index date and development of atrial flutter or fibrillation (ICD-9-CM code 427.3), which was included as a time-varying term.…”

Safety of sulfadoxine/pyrimethamine for intermittent preventive treatment of malaria in infants: evidence from large-scale operational research in southern Tanzania

“…A novel approach to the generation of safety signals is the use of self-controlled case series analysis. 28 This method compares the incidence of signs, symptoms, abnormal laboratory values or diagnoses in periods before and after administration of an intervention in individuals who are reliably identified at each contact with the health system. This approach has the advantage of not requiring a clinician to consider the possibility of an adverse event and to fill in a form, and can generate signals of adverse reactions not previously recognised as associated with the intervention, occurring a considerable time after the intervention or arising after multiple doses of the treatment.…”

The international generalisability of evidence for health policy: A cross country comparison of medication adherence following policy change

“…The study design was advantageous in that it eliminated confounding by time-invariant variables such as socio-economic status. [30] …”