Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Comput Methods Programs Biomed. 2010 Sep;99(3):261-74. doi: 10.1016/j.cmpb.2010.01.001. Epub 2010 Mar 15.
In recent years, multi-state models have been studied widely in survival analysis. Despite their clear advantages, their use in biomedical and other applications has been rather limited so far. An important reason for this is the lack of flexible and user-friendly software for multi-state models. This paper introduces a package in R, called 'mstate', for each of the steps of the analysis of multi-state models. It can be applied to non- and semi-parametric models. The package contains functions to facilitate data preparation and flexible estimation of different types of covariate effects in the context of Cox regression models, functions to estimate patient-specific transition intensities, dynamic prediction probabilities and their associated standard errors (both Greenwood and Aalen-type). Competing risks models can also be analyzed by means of mstate, as they are a special type of multi-state models. The package is available from the R homepage http://cran.r-project.org. We give a self-contained account of the underlying mathematical theory, including a new asymptotic result for the cumulative hazard function and new recursive formulas for the calculation of the estimated standard errors of the estimated transition probabilities, and we illustrate the use of the key functions of the mstate package by the analysis of a reversible multi-state model describing survival of liver cirrhosis patients.
近年来，多状态模型在生存分析中得到了广泛的研究。尽管它们具有明显的优势，但迄今为止，它们在生物医学和其他应用中的应用相当有限。造成这种情况的一个重要原因是缺乏灵活和用户友好的多状态模型软件。本文介绍了一个在 R 中的包，称为“mstate”，用于多状态模型分析的各个步骤。它可应用于非参数和半参数模型。该包包含了一些函数，用于在 Cox 回归模型的背景下方便数据准备和灵活估计不同类型的协变量效应，以及用于估计患者特定转移强度、动态预测概率及其相关标准误差（Greenwood 和 Aalen 类型）的函数。通过 mstate 也可以分析竞争风险模型，因为它们是多状态模型的一种特殊类型。该包可从 R 主页 http://cran.r-project.org 获得。我们给出了底层数学理论的一个自包含的说明，包括累积风险函数的一个新的渐近结果和计算估计转移概率的估计标准误差的新递归公式，并通过分析一个描述肝硬化患者生存的可逆多状态模型来说明 mstate 包的关键函数的用法。
