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序贯治疗的转移性人表皮生长因子受体2阳性乳腺癌患者疾病进展模拟模型的参数化

Parameterization of a disease progression simulation model for sequentially treated metastatic human epidermal growth factor receptor 2 positive breast cancer patients.

作者信息

Diaby Vakaramoko, Ali Askal A, Adunlin Georges, Kohn Christine G, Montero Alberto J

机构信息

a College of Pharmacy and Pharmaceutical Sciences, Florida A&M University , Tallahassee , FL , USA ;

b Virginia Commonwealth University School of Medicine , Richmond , VA , USA ;

出版信息

Curr Med Res Opin. 2016 Jun;32(6):991-6. doi: 10.1185/03007995.2016.1149056. Epub 2016 Mar 2.

Abstract

UNLABELLED

Background The objective of this study is twofold: 1) to propose a simulation model for HER2+ metastatic breast cancer (mBC) which could further be used to assess the overall cost-effectiveness of the treatment sequences that would maximize survival of patients, and 2) to estimate transitional probabilities between treatment lines required to parameterize the simulation model, in the absence of individual patient data (IPD). Methods Individual patient data (IPD) were reconstructed for treatment lines composing four treatment sequences. Parametric models were tested to select the model that best fits the IPD. The transitional probability equations, used for disease progression modeling, were obtained by substituting the parameters of the general equation for transitional probabilities by the parameters estimated from fitted distributions. Results The log-logistic model best fitted the reconstructed data for progression-free and overall survival curves for each line of treatment. The shapes and scales of the log-logistic models were used to develop the transitional probability equations for the HER2+ mBC simulation model.

KEY LIMITATIONS

The estimation of the transitional probabilities depends heavily on the accuracy of the IPD reconstruction. Nonetheless, analytical and graphical tests can be performed to check the face validity of the reconstructed data. Additionally, sensitivity analyses can be conducted to test the impact of uncertainty surrounding the estimated parameters defining equations for transitional probabilities. Conclusion The results of this study can be used as input in model-based economic evaluations of sequential therapy for HER2+ mBC.

摘要

未标注

背景 本研究有两个目标:1)提出一种用于HER2阳性转移性乳腺癌(mBC)的模拟模型,该模型可进一步用于评估能使患者生存最大化的治疗方案的总体成本效益;2)在缺乏个体患者数据(IPD)的情况下,估计参数化模拟模型所需的治疗线之间的转移概率。方法 针对构成四个治疗方案的治疗线重建个体患者数据(IPD)。测试参数模型以选择最适合IPD的模型。通过用从拟合分布估计的参数替换转移概率通用方程的参数,获得用于疾病进展建模的转移概率方程。结果 对数逻辑模型最适合每条治疗线的无进展生存曲线和总生存曲线的重建数据。对数逻辑模型的形状和尺度用于开发HER2阳性mBC模拟模型的转移概率方程。

关键限制

转移概率的估计在很大程度上取决于IPD重建的准确性。尽管如此,可以进行分析和图形测试以检查重建数据的表面有效性。此外,可以进行敏感性分析以测试围绕定义转移概率方程的估计参数的不确定性的影响。结论 本研究结果可作为基于模型的HER2阳性mBC序贯治疗经济评估的输入。

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