On the relation between the cause‐specific hazard and the subdistribution rate for competing risks data: The Fine–Gray model revisited

Biometrical Journal, vol. 62, pp. 790–807

Abstract

The Fine-Gray proportional subdistribution hazards model has been puzzling many people since its introduction. The main reason for the uneasy feeling is that the approach considers individuals still at risk for an event of cause 1 after they fell victim to the competing risk of cause 2. The subdistribution hazard and the extended risk sets, where subjects who failed of the competing risk remain in the risk set, are generally perceived as unnatural . One could say it is somewhat of a riddle why the Fine-Gray approach yields valid inference. To take away these uneasy feelings, we explore the link between the Fine-Gray and cause-specific approaches in more detail. We introduce the reduction factor as representing the proportion of subjects in the Fine-Gray risk set that has not yet experienced a competing event. In the presence of covariates, the dependence of the reduction factor on a covariate gives information on how the effect of the covariate on the cause-specific hazard and the subdistribution hazard relate. We discuss estimation and modeling of the reduction factor, and show how they can be used in various ways to estimate cumulative incidences, given the covariates. Methods are illustrated on data of the European Society for Blood and Marrow Transplantation.

Authors 3

1. Hein Putter corresponding Aachen Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands Department of Biomedical Data Sciences

   Leiden University Medical Center

   Affiliation as printed

   Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands

   Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands

2. Martin Christian Schumacher

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Institute for Medical Biometry and Statistics Faculty of Medicine and Medical Center University of Freiburg Freiburg im Breisgau Germany

   Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany

3. Hans C. van Houwelingen Aachen Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands Department of Biomedical Data Sciences

   Leiden University Medical Center

   Affiliation as printed

   Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands

   Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands