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比较离散事件模拟中竞争风险建模策略:结直肠癌中的模拟研究和实例

Comparing Strategies for Modeling Competing Risks in Discrete-Event Simulations: A Simulation Study and Illustration in Colorectal Cancer.

机构信息

Health Technology and Services Research Department, Technical Medical Centre, University of Twente, Enschede, The Netherlands.

Department of Medical Oncology, University Medical Centre, Utrecht University, Utrecht, The Netherlands.

出版信息

Med Decis Making. 2019 Jan;39(1):57-73. doi: 10.1177/0272989X18814770.

Abstract

BACKGROUND

Different strategies toward implementing competing risks in discrete-event simulation (DES) models are available. This study aims to provide recommendations regarding modeling approaches that can be defined based on these strategies by performing a quantitative comparison of alternative modeling approaches.

METHODS

Four modeling approaches were defined: 1) event-specific distribution (ESD), 2) event-specific probability and distribution (ESPD), 3) unimodal joint distribution and regression model (UDR), and 4) multimodal joint distribution and regression model (MDR). Each modeling approach was applied to uncensored individual patient data in a simulation study and a case study in colorectal cancer. Their performance was assessed in terms of relative event incidence difference, relative absolute event incidence difference, and relative entropy of time-to-event distributions. Differences in health economic outcomes were also illustrated for the case study.

RESULTS

In the simulation study, the ESPD and MDR approaches outperformed the ESD and UDR approaches, in terms of both event incidence differences and relative entropy. Disease pathway and data characteristics, such as the number of competing risks and overlap between competing time-to-event distributions, substantially affected the approaches' performance. Although no considerable differences in health economic outcomes were observed, the case study showed that the ESPD approach was most sensitive to low event rates, which negatively affected performance.

CONCLUSIONS

Based on overall performance, the recommended modeling approach for implementing competing risks in DES models is the MDR approach, which is defined according to the general strategy of selecting the time-to-event first and the corresponding event second. The ESPD approach is a less complex and equally performing alternative if sufficient observations are available for each competing event (i.e., the internal validity shows appropriate data representation).

摘要

背景

离散事件模拟(DES)模型中实施竞争风险的策略有多种。本研究旨在通过对替代建模方法进行定量比较,根据这些策略为建模方法提供建议。

方法

定义了四种建模方法:1)事件特定分布(ESD),2)事件特定概率和分布(ESPD),3)单峰联合分布和回归模型(UDR),4)多峰联合分布和回归模型(MDR)。每种建模方法都应用于模拟研究和结直肠癌病例研究中的未删失个体患者数据。根据相对事件发生率差异、相对绝对事件发生率差异和时间至事件分布的相对熵来评估它们的性能。还为病例研究说明了健康经济结果的差异。

结果

在模拟研究中,ESP D 和 MDR 方法在事件发生率差异和相对熵方面均优于 ESD 和 UDR 方法。疾病途径和数据特征,如竞争风险的数量和竞争时间至事件分布之间的重叠,极大地影响了方法的性能。尽管在健康经济结果方面没有观察到明显差异,但病例研究表明,ESP D 方法对低事件发生率最敏感,这会对性能产生负面影响。

结论

根据整体性能,推荐在 DES 模型中实施竞争风险的建模方法是 MDR 方法,该方法根据选择时间至事件优先和相应事件第二的一般策略进行定义。如果每个竞争事件都有足够的观察值(即内部有效性显示出适当的数据表示),则 ESP D 方法是一种更简单但表现相当的替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/6311678/6bdd0b8513be/10.1177_0272989X18814770-fig1.jpg

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