Evaluation strategies for case series: is Cox regression an alternative to the self controlled case series method for terminal events?

In this paper, we deal with the analysis of case series. The self-controlled case series method (SCCS) was developed to analyse the temporal association between time-varying exposure and an outcome event. We apply the SCCS method to the vaccination data of the German Examination Survey for Children and Adolescents (KiGGS). We illustrate that the standard SCCS method cannot be applied to terminal events such as death. In this situation, an extension of SCCS adjusted for terminal events gives unbiased point estimators. The key question of this paper is whether the general Cox regression model for time-dependent covariates may be an alternative to the adjusted SCCS method for terminal events. In contrast to the SCCS method, Cox regression is included in most software packages (SPSS, SAS, STATA, R, …) and it is easy to use. We can show that Cox regression is applicable to test the null hypothesis. In our KiGGS example without censored data, the Cox regression and the adjusted SCCS method yield point estimates almost identical to the standard SCCS method. We have conducted several simulation studies to complete the comparison of the two methods. The Cox regression shows a tendency to underestimate the true effect with prolonged risk periods and strong effects (Relative Incidence >2). If risk of the event is strongly affected by the age, the adjusted SCCS method slightly overestimates the predefined exposure effect. Cox regression has the same efficiency as the adjusted SCCS method in the simulation. Copyright Springer-Verlag 2012