A threshold regression mixture model for assessing treatment efficacy in a multiple myeloma clinical trial.
A threshold regression mixture model for assessing treatment efficacy in a multiple myeloma clinical trial.
复制标题
用于评估多发性骨髓瘤临床试验中治疗效果的阈值回归混合模型。
DOI：
10.1080/10543400802398524
复制
发表时间：
2008
影响因子：
1.1
通讯作者：
Whitmore,GA
中科院分区：
文献类型：
--
作者：
Lee,Mei-LingTing;Chang,Mark;Whitmore,GA
首次命中时间（FHT）生存模型假设患者的健康状态过程逐渐下降，直到患者在水平首次达到临界阈值时死亡。阈值回归（TR）是一种新的回归方法，它结合了协变量对该FHT模型的阈值和过程参数的影响。在这项研究中，我们使用TR来分析来自多发性骨髓瘤治疗的随机临床试验的数据。该试验比较了万珂和大剂量地塞米松，前者是一种新的治疗方法，后者是一种已确立的治疗方法。根据患者的反应，患者在两种药物之间转换。这项工作的新贡献是使用TR模型的混合物对该临床试验设计进行建模。具体来说，我们提出了一个混合FHT模型来拟合生存分布。该模型包括一个复合时间尺度，区分转换前后的疾病进展率。分析显示，万珂初始治疗具有显著获益。与相同数据的考克斯比例风险回归分析进行比较。
A first-hitting-time (FHT) survival model postulates a health status process for a patient that gradually declines until the patient dies when the level first reaches a critical threshold. Threshold regression (TR) is a new regression methodology that incorporates the effects of covariates on the threshold and process parameters of this FHT model. In this study, we use TR to analyze data from a randomized clinical trial of treatment for multiple myeloma. The trial compares VELCADE and high-dose Dexamethasone, the former a new therapy and the latter an established therapy for this disease. Patients are switched between the two drugs based on patient response. The novel contribution of this work is the modeling of this clinical trial design using a mixture of TR models. Specifically, we propose a mixture FHT model to fit the survival distribution. The model includes a composite time scale that differentiates the rate of disease progression before and after switching. The analysis shows significant benefit from initial treatment by VELCADE. A comparison is made with a Cox proportional hazards regression analysis of the same data.