Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven and Universiteit Hasselt, Kapucijnenvoer 35, Block D, bus 7001, B3000 Leuven, Belgium.
Stat Med. 2010 Jul 20;29(16):1724-34. doi: 10.1002/sim.3918.
Progression-related endpoints (such as time to progression or progression-free survival) and time to death are common endpoints in cancer clinical trials. It is of interest to study the link between progression-related endpoints and time to death (e.g. to evaluate the degree of surrogacy). However, current methods ignore some aspects of the definitions of progression-related endpoints. We review those definitions and investigate their impact on modeling the joint distribution. Further, we propose a multi-state model in which the association between the endpoints is modeled through a frailty term. We also argue that interval-censoring needs to be taken into account to more closely match the latent disease evolution. The joint distribution and an expression for Kendall's tau are derived. The model is applied to data from a clinical trial in advanced metastatic ovarian cancer.
与疾病进展相关的终点（如进展时间或无进展生存期）和死亡时间是癌症临床试验中的常见终点。研究与疾病进展相关的终点和死亡时间之间的关联（例如，评估替代程度）很有意义。然而，目前的方法忽略了与疾病进展相关的终点定义的某些方面。我们回顾了这些定义，并研究了它们对联合分布建模的影响。此外，我们提出了一种多状态模型，其中通过脆弱性项来模拟终点之间的关联。我们还认为，需要考虑区间删失，以更紧密地匹配潜在疾病的演变。推导了联合分布和肯德尔 tau 的表达式。该模型应用于晚期转移性卵巢癌临床试验的数据。
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