Statistical considerations in long-term efficacy evaluation of anti-cancer therapies

Abstract

Anti-cancer therapy has been a significant focus of research. Developing and marketing various types and mechanisms of anti-cancer therapies benefit a variety of patients significantly. The long-term benefit to patients in evaluating the risk-benefit ratio of anti-cancer therapy has become a significant concern. This paper discusses the evaluation of long-term efficacy within the estimand framework and summarizes the various strategies for addressing potential intercurrent events. Non-proportional hazards of survival data may arise with novel anti-cancer therapies, leading to potential bias in conventional evaluation methods. This paper reviews statistical methods for addressing this issue, including novel endpoints, hypothesis testing, and efficacy estimation methods. We also discuss the influences of treatment switching. Although advanced methods have been developed to address the non-proportional hazard, they still have limitations that require continued collaborative efforts to resolve issues.

Keywords: anti-cancer therapy; estimand; long-term efficacy evaluation; non-proportional hazard assumption; patient-reported outcomes; treatment switching.