All Times EDT
Keywords: Cancer Immunotherapy; Immuno-oncology (IO) trials; Study design; Sample size and power calculations;
A typical challenge facing the design and analysis of immuno-oncology (IO) trials is the prevalence of nonproportional hazards (NPH) patterns manifested in Kaplan-Meier curves under time-to-event endpoints. The NPH patterns would violate the proportional hazards assumption, and yet conventional design and analysis strategies often ignore such a violation, resulting in underpowered or even falsely negative IO studies. In this article, we explore, both empirically and analytically, the fundamental causes for the occurrence of various NPH patterns and then present novel design and analysis strategies to properly address such issue. Empirical studies demonstrate that the proposed strategies can ensure adequate study power, whereas the conventional alternative leads to a severe power loss. More importantly, the proposed strategies pinpoint a solution to enhance the study efficiency, alleviate the NPH patterns and outline a path towards precision immunotherapy design.