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使用生存数据和 PFS 数据联合建模的普通微分方程模型估算进展时间和进展后生存。

Estimation of time to progression and post progression survival using joint modeling of summary level OS and PFS data with an ordinary differential equation model.

机构信息

Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA.

出版信息

J Pharmacokinet Pharmacodyn. 2022 Aug;49(4):455-469. doi: 10.1007/s10928-022-09816-w. Epub 2022 Jul 23.

DOI:10.1007/s10928-022-09816-w
PMID:35870059
Abstract

measures such as progression-free survival (PFS) and overall survival (OS) are commonly reported in literature for oncology trials, while time to progression (TTP) and post progression survival (PPS) are not usually reported. A time-variant transition hazard model was developed using an ordinary differential equation (ODE) model to estimate TTP and PPS from summary level PFS and OS. The model was applied to published data from immune checkpoint inhibitor trials for non-small cell lung cancer (NSCLC) in a meta-analysis framework. This model-based method was able to robustly estimate TTP and PPS from summary level OS and PFS data, provided a quantitative approach for understanding the patterns of disease progression across different treatments through the time-variant disease progression rate function, and provided a summary of how different treatments affect TTP and PPS. The proposed method can be generalized to characterize and quantify multiple time-to-event endpoints jointly in oncology trials and improve our understanding of disease prognostics for different treatments.

摘要

在肿瘤学试验中,文献中通常报告无进展生存期(PFS)和总生存期(OS)等措施,而进展时间(TTP)和进展后生存期(PPS)通常不报告。使用常微分方程(ODE)模型开发了一个时变转移风险模型,以从汇总水平的 PFS 和 OS 估算 TTP 和 PPS。该模型应用于免疫检查点抑制剂治疗非小细胞肺癌(NSCLC)的荟萃分析框架中的已发表数据。该基于模型的方法能够从汇总水平的 OS 和 PFS 数据中稳健地估算 TTP 和 PPS,通过时变疾病进展率函数提供了一种定量方法来了解不同治疗方法的疾病进展模式,并总结了不同治疗方法如何影响 TTP 和 PPS。该方法可以推广到肿瘤学试验中联合描述和量化多个时间事件终点,并提高我们对不同治疗方法疾病预后的理解。

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