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Adaptive Two-Stage Optimal Designs for Estimating Multiple EDps Under the 4-Parameter Logistic Model

机译:四参数Logistic模型下估计多个EDps的自适应两阶段优化设计

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摘要

In dose-finding studies, c-optimal designs provide the most efficient design to study an interesting target dose. However, there is no guarantee that a c-optimal design that works best for estimating one specific target dose still performs well for estimating other target doses. Considering the demand in estimating multiple target dose levels, the robustness of the optimal design becomes important. In this study, the 4-parameter logistic model is adopted to describe dose-response curves. Under nonlinear models, optimal design truly depends on the pre-specified nominal parameter values. If the pre-specified values of the parameters are not close to the true values, optimal designs become far from optimum. In this research, I study an optimal design that works well for estimating multiple EDps and for unknown parameter values. To address this parameter uncertainty, a two-stage design technique is adopted using two different approaches. One approach is to utilize a design augmentation at the second stage, the other one is to apply a Bayesian paradigm to find the optimal design at the second stage. For the Bayesian approach, one challenging task is that it requires heavy computation in the numerical calculation when searching for the Bayesian optimal design. To overcome this problem, a clustering method can be applied. These two-stage design strategies are applied to construct a robust optimal design for estimating multiple EDps. Through a simulation study, the proposed two-stage optimal designs are compared with the traditional uniform design and the enhanced uniform design to see how well they perform in estimating multiple ED ps when the parameter values are mis-specified.
机译:在剂量寻找研究中,c最优设计提供了研究有趣目标剂量的最有效设计。但是,不能保证对估计一个特定目标剂量最有效的c最佳设计在估计其他目标剂量时仍然表现良好。考虑到估计多个目标剂量水平的需求,最佳设计的鲁棒性变得很重要。在这项研究中,采用四参数逻辑模型来描述剂量反应曲线。在非线性模型下,最佳设计确实取决于预先指定的名义参数值。如果参数的预定值不接近真实值,则最佳设计将远非最佳。在这项研究中,我研究了一种最佳设计,该设计非常适合估算多个EDps和未知参数值。为了解决该参数不确定性,采用了两种不同方法的两阶段设计技术。一种方法是在第二阶段利用设计扩充,另一种方法是应用贝叶斯范式在第二阶段找到最佳设计。对于贝叶斯方法,一项艰巨的任务是,在寻找贝叶斯最优设计时,在数值计算中需要大量计算。为了克服这个问题,可以应用聚类方法。这两个阶段的设计策略适用于构建用于估计多个EDps的稳健的最佳设计。通过仿真研究,将拟议的两阶段最优设计与传统的统一设计和增强的统一设计进行比较,以了解当参数值指定不正确时,它们在估计多个ED ps方面的性能如何。

著录项

  • 作者

    Zhang, Anqing.;

  • 作者单位

    North Dakota State University.;

  • 授予单位 North Dakota State University.;
  • 学科 Statistics.
  • 学位 Ph.D.
  • 年度 2018
  • 页码 73 p.
  • 总页数 73
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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