On Incremental Incidence Rates in Long-Term Cohort Safety Studies

In long-term single cohort safety studies, the incremental incidence rate is a useful concept in evaluating risks related to adverse events of medical interest ( EMI). We propose estimates for the incremental (say annual) incidence rates in the presence of independent random right censoring and describe their statistical properties. More importantly, we propose tests for the null hypothesisthat the incremental incidence rates remain constant during the study against various alternative hypotheses, such as rates changing over the years or having a specific trend, say monotonic increasing or decreasing. In contrast with the existing methods that test constant hazard rates, the proposed method allows nonconstant hazard within each year; therefore, it is especially useful for EMIsthat have a seasonal occurrence pattern. This article explores and characterizes properties of these tests under various alternatives via theory and simulations. A numerical example based on a real long-term single cohort safety stu...