Practical methods for competing risks data: a review

Abstract

Competing risks data arise naturally in medical research, when subjects under study are at risk of more than one mutually exclusive event such as death from different causes. The competing risks framework also includes settings where different possible events are not mutually exclusive but the interest lies on the first occurring event. For example, in HIV studies where seropositive subjects are receiving highly active antiretroviral therapy (HAART), treatment interruption and switching to a new HAART regimen act as competing risks for the first major change in HAART. This article introduces competing risks data and critically reviews the widely used statistical methods for estimation and modelling of the basic (estimable) quantities of interest. We discuss the increasingly popular Fine and Gray model for subdistribution hazard of interest, which can be readily fitted using standard software under the assumption of administrative censoring. We present a simulation study, which explores the robustness of inference for the subdistribution hazard to the assumption of administrative censoring. This shows a range of scenarios within which the strictly incorrect assumption of administrative censoring has a relatively small effect on parameter estimates and confidence interval coverage. The methods are illustrated using data from HIV-1 seropositive patients from the collaborative multicentre study CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe).