Time-dependent Prognostic Score Matching for Recurrent Event Analysis to Evaluate a Treatment Assigned During Follow-up

Abstract

Recurrent events often serve as the outcome in epidemiologic studies. In some observational studies, the goal is to estimate the effect of a new or "experimental" (i.e., less established) treatment of interest on the recurrent event rate. The incentive for accepting the new treatment may be that it is more available than the standard treatment. Given that the patient can choose between the experimental treatment and conventional therapy, it is of clinical importance to compare the treatment of interest versus the setting where the experimental treatment did not exist, in which case patients could only receive no treatment or the standard treatment. Many methods exist for the analysis of recurrent events and for the evaluation of treatment effects. However, methodology for the intersection of these two areas is sparse. Moreover, care must be taken in setting up the comparison groups in our setting; use of existing methods featuring time-dependent treatment indicators will generally lead to a biased treatment effect since the comparison group construction will not properly account for the timing of treatment initiation. We propose a sequential stratification method featuring time-dependent prognostic score matching to estimate the effect of a time-dependent treatment on the recurrent event rate. The performance of the method in moderate-sized samples is assessed through simulation. The proposed methods are applied to a prospective clinical study in order to evaluate the effect of living donor liver transplantation on hospitalization rates; in this setting, conventional therapy involves remaining on the wait list or receiving a deceased donor transplant.