Comparing Modeling Approaches for Discrete Event Simulations With Competing Risks Based on Censored Individual Patient Data: A Simulation Study and Illustration in Colorectal Cancer

Abstract

Objectives: This study aimed to provide detailed guidance on modeling approaches for implementing competing events in discrete event simulations based on censored individual patient data (IPD).

Methods: The event-specific distributions (ESDs) approach sampled times from event-specific time-to-event distributions and simulated the first event to occur. The unimodal distribution and regression approach sampled a time from a combined unimodal time-to-event distribution, representing all events, and used a (multinomial) logistic regression model to select the event to be simulated. A simulation study assessed performance in terms of relative absolute event incidence difference and relative entropy of time-to-event distributions for different types and levels of right censoring, numbers of events, distribution overlap, and sample sizes. Differences in cost-effectiveness estimates were illustrated in a colorectal cancer case study.

Results: Increased levels of censoring negatively affected the modeling approaches' performance. A lower number of competing events and higher overlap of distributions improved performance. When IPD were censored at random times, ESD performed best. When censoring occurred owing to a maximum follow-up time for 2 events, ESD performed better for a low level of censoring (ie, 10%). For 3 or 4 competing events, ESD better represented the probabilities of events, whereas unimodal distribution and regression better represented the time to events. Differences in cost-effectiveness estimates, both compared with no censoring and between approaches, increased with increasing censoring levels.

Conclusions: Modelers should be aware of the different modeling approaches available and that selection between approaches may be informed by data characteristics. Performing and reporting extensive validation efforts remains essential to ensure IPD are appropriately represented.

Keywords: censoring; competing events; competing risks; discrete event simulation; modeling; survival analysis.