Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis
View Presentation View Presentation
*Lee-Jen Wei, Harvard School of Public Health 

Keywords: survival analysis, hazard ratio, proportional hazards

In a longitudinal clinical study to compare two groups, often the primary endpoint is the time to a specific event (e.g., disease progression, death). The hazard ratio estimate is routinely used to empirically quantify the between-group difference under the assumption that the ratio of the two hazard functions is approximately constant over time. When this assumption is plausible, such a ratio estimate may capture the relative difference between two survival curves. However, the clinical meaning of such a ratio estimate is difficult, if not impossible, to interpret when the underlying proportional hazards (PH) assumption is violated (i.e., the hazard ratio is not constant over time). Although this issue has been studied extensively, and various alternatives to the hazard ratio estimator have been discussed in the statistical literature, such crucial information does not seem to have reached the broader community of health science researchers. In this paper, we summarize several critical concerns regarding this conventional practice and discuss various well-known alternatives for quantifying the underlying differences between groups with respect to a time-to-event endpoint. The data from three recent cancer clinical trials, which reflect a variety of scenarios, are utilized throughout for illustration of our discussions. When there is not sufficient information about the profile of the between-group difference at the design stage of the study, we encourage practitioners to consider a pre-specified, clinically meaningful, model-free measure for quantifying the difference and to utilize robust estimation procedures to draw primary inferences.