Considerations for analysis of time-to-event outcomes subject to competing risks in veterinary clinical studies

In veterinary medicine, prospective clinical trials are increasingly utilized to address questions regarding effectiveness of therapies and patient prognosis. A large number of these trials involve time-to-event (TTE) endpoints, which require special methods of analysis to handle data in which not all subjects are observed to have the event of interest. Analyses and interpretation of the results can be further complicated when an endpoint of interest is not observed in some patients because they incur a competing risk, such as death from an unrelated cause. Competing risks have been the source of confusion in many epidemiologic analyses leading to the potential for misinterpretation. In this article, we review key considerations for the TTE analysis in the setting of competing risks. We briefly review standard TTE tools, namely Kaplan-Meier survival curves and Cox regression. In the setting of outcomes with competing risks, we provide guidance on the appropriate analysis techniques, such as cumulative incidence curves, to estimate the risk of an event of interest. We also describe a common pitfall of treating competing risks as censoring in Kaplan-Meier survival curve analysis, which can overestimate the event rate of interest. We describe two common regression methods that examine associated risk factors in the presence of competing risks and highlight the different research questions these methods address. This article provides an introductory overview and illustrates concepts with examples from veterinary trials and with example data sets.