A robust hazard ratio for general modeling of survival-times

Int J Biostat. 2021 Aug 23;18(2):537-551. doi: 10.1515/ijb-2021-0003. eCollection 2022 Nov 1.


Hazard ratios (HR) associated with the well-known proportional hazard Cox regression models are routinely used for measuring the impact of one factor of interest on a time-to-event outcome. However, if the underlying real model does not fit with the theoretical requirements, the interpretation of those HRs is not clear. We propose a new index, gHR, which generalizes the HR beyond the underlying survival model. We consider the case in which the study factor is a binary variable and we are interested in both the unadjusted and adjusted effect of this factor on a time-to-event variable, potentially, observed in a right-censored scenario. We propose non-parametric estimations for unadjusted gHR and semi-parametric regression-induced techniques for the adjusted case. The behavior of those estimators is studied in both large and finite sample situations. Monte Carlo simulations reveal that both estimators provide good approximations of their respective inferential targets. Data from the Health and Lifestyle Study are used for studying the relationship of the tobacco use and the age of death and illustrate the practical application of the proposed technique. gHR is a promising index which can help facilitate better understanding of the association of one study factor on a time-dependent outcome.

Keywords: Cox regression model; hazard ratio; mis-specified model; omitted covariate; robust procedure.

MeSH terms

  • Computer Simulation*
  • Monte Carlo Method
  • Proportional Hazards Models
  • Regression Analysis