Stratified modestly weighted log-rank tests in settings with an anticipated delayed separation of survival curves

Delayed separation of survival curves is a common occurrence in confirmatory studies in immuno-oncology. Many novel statistical methods that aim to efficiently capture potential long-term survival improvements have been proposed in recent years. However, the vast majority do not consider stratification, which is a major limitation considering that most large confirmatory studies currently employ a stratified primary analysis. In this article, we combine recently proposed weighted log-rank tests that have been designed to work well under a delayed separation of survival curves, with stratification by a baseline variable. The aim is to increase the efficiency of the test when the stratifying variable is highly prognostic for survival. As there are many potential ways to combine the two techniques, we compare several possibilities in an extensive simulation study. We also apply the techniques retrospectively to two recent randomized clinical trials.