当生物标志物实际上是生存的预后因素时，为什么对纵向生物标志物的有益治疗效果不能转化为对生存的总体治疗益处？在最近的肿瘤学探索性数据分析中，我们面临着这个看似矛盾的结果。为了解决这个问题，我们应用了一种称为动态路径分析的理论原理方法，它使我们能够利用纵向中介变量和生存结果进行中介分析。分析的目的是将总治疗效果分解为直接治疗效果和通过精心构建的中介路径介导的间接治疗效果。基础方法的动态本质使我们能够描述这些影响如何随时间演变，这可以增加对基础过程的机械理解。在本文中，我们详细描述了动态路径分析框架，并使用模拟和真实数据说明了其在生存中介分析中的应用。用例分析明确了感兴趣的具体探索性问题，而该方法则推广到药物开发中的广泛应用，其中事件发生时间是感兴趣的主要临床结果。© 2024 John Wiley

Why does a beneficial treatment effect on a longitudinal biomarker not translate into overall treatment benefit on survival, when the biomarker is in fact a prognostic factor of survival? In a recent exploratory data analysis in oncology, we were faced with this seemingly paradoxical result. To address this problem, we applied a theoretically principled methodology called dynamic path analysis, which allows us to perform mediation analysis with a longitudinal mediator and survival outcome. The aim of the analysis is to decompose the total treatment effect into a direct treatment effect and an indirect treatment effect mediated through a carefully constructed mediation path. The dynamic nature of the underlying methodology enables us to describe how these effects evolve over time, which can add to the mechanistic understanding of the underlying processes. In this paper, we present a detailed description of the dynamic path analysis framework and illustrate its application to survival mediation analysis using simulated and real data. The use case analysis provides clarity on the specific exploratory question of interest while the methodology generalizes to a wide range of applications in drug development where time-to-event is the primary clinical outcome of interest.© 2024 John Wiley & Sons Ltd.