We read with interest the article by Mauro and colleagues proposing a framework to handle non-proportional hazards (NPH) in pivotal phase III trials in hepatocellular carcinoma (HCC), including recommendations for interim analyses (IA) and use of alternative estimands/tests such as MaxCombo and restricted mean survival time (RMST) [1]. The topic is clinically relevant. Nonetheless, several methodological aspects warrant clarification; possible solution strategies are summarised in Table 1.
We read with interest the article by Mauro and colleagues proposing a framework to handle non-proportional hazards (NPH) in pivotal phase III trials in hepatocellular carcinoma (HCC), including recommendations for interim analyses (IA) and use of alternative estimands/tests such as MaxCombo and restricted mean survival time (RMST) [1]. The topic is clinically relevant. Nonetheless, several methodological aspects warrant clarification; possible solution strategies are summarised in Table 1.