In medical research, the development of mediation analysis with a survival outcome has facilitated investigation into causal mechanisms. However, studies have not discussed the death-truncation problem for mediators, the problem being that conventional mediation parameters cannot be well defined in the presence of a truncated mediator. In the present study, we systematically defined the completeness of causal effects to uncover the gap, in conventional causal definitions, between the survival and nonsurvival settings. We propose a novel approach to redefining natural direct and indirect effects, which are generalized forms of conventional causal effects for survival outcomes. Furthermore, we developed three statistical methods for the binary outcome of survival status and formulated a Cox model for survival time. We performed simulations to demonstrate that the proposed methods are unbiased and robust. We also applied the proposed method to explore the effect of hepatitis C virus infection on mortality, as mediated through hepatitis B viral load.

中文翻译：

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死亡截断中介的生存中介分析：生存中介参数的完整性

在医学研究中，具有生存结果的中介分析的发展促进了对因果机制的调查。然而，研究尚未讨论中介体的死亡截断问题，问题是在截断中介体存在的情况下无法很好地定义常规中介参数。在本研究中，我们系统地定义了因果效应的完整性，以揭示传统因果定义中生存和非生存环境之间的差距。我们提出了一种重新定义自然直接和间接效应的新方法，这些效应是生存结果的常规因果效应的广义形式。此外，我们为生存状态的二元结果开发了三种统计方法，并为生存时间制定了 Cox 模型。我们进行了模拟以证明所提出的方法是无偏和稳健的。我们还应用所提出的方法来探索丙型肝炎病毒感染对死亡率的影响，这是通过乙型肝炎病毒载量介导的。