Group sequential designs using average hazard with survival weight for clinical trials

Music City Center 

The limitations of the traditional log-rank/hazard-ratio test/estimation approach for comparing time-to-event outcomes between groups have been widely discussed. While theories supports that this traditional approach offers the most powerful test when the proportional hazards assumption is correct, it loses this advantage when the assumption is incorrect. Also, interpreting hazard ratios under non-proportional hazards conditions becomes challenging, as they deviate from their foundational definition within this assumption. Methods to derive hazard ratios under non-proportional hazards conditions often involve weighted averages of time-specific hazard ratios, where weights may lack intuitive meaning or depend on study-specific censoring time distributions. To address these limitations, alternative approaches have been proposed. One such approach is using average hazard with survival weight (AHSW), which offers a robust alternative recently proposed. However, the use of AHSW with group sequential designs remain underexplored. This talk examines the implementation of AHSW-based analysis in group sequential designs, focusing on methodology and practical considerations.