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Nonparametric Statistical Approaches for Benchmark Dose Estimation in Quantitative Risk Assessment.

机译:定量风险评估中基准剂量估计的非参数统计方法。

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摘要

A major component of quantitative risk assessment involves dose-response modeling. Therein, an appropriate statistical model that approximately quantifies the relationship between exposure level (dose) and response (adverse endpoint) is fit to experimental data. The objective of this dissertation is to estimate adverse risks encountered in settings when the statistical model is formally defined and developed. From this, statistical inferences on the risk are conducted.;First introduced are eight parametric models. The advantage of parametric models is they can produce consistent result when the selected model fits the dose-response curve very well. The simplicity of knowing the expression of these models allows for the construction of a variety of lower confidence limits, based on the Wald approach.;However, if the true dose-response curve deviates significantly from a posited parametric model, the result may perform poorly. Non-parametric methods are then needed. The percentile bootstrap method from linear splines with Pool Adjacent Violator is first introduced. The method appeals to an asymptotic approximation, hence there is interest in assessing the small-sample coverage properties of this method. These are addressed via Monte Carlo computer simulations. We find that this method with four doses operates reasonably well at large sample sizes except for the concave increasing dose-response curve. In practice, small sample sizes are more common, therefore we turn to increasing the number of doses. We do see that, in general, the coverage becomes better as the doses number increases.;To study the most common four dose design, the biased-corrected and accelerated bootstrap method from linear spline with Pool Adjacent Violator and discrete delta approach are also introduced. Simulation results show that the coverage are similar from these methods and have no improvement over the concave increasing dose-response curve.;A final quadratic spline is then considered. For four doses design, this is repeated at four different points, to find an averaged extra risk function. In order to understand the operating characteristics of the method, another Monte Carlo simulation study is undertaken. This study produces similar results to those found using the percentile bootstrap method from linear splines.
机译:定量风险评估的主要组成部分涉及剂量反应模型。其中,合适的统计模型可以近似地量化暴露水平(剂量)与反应(不良终点)之间的关系,适合于实验数据。本文的目的是估计统计模型正式定义和开发时在环境中遇到的不利风险。据此,对风险进行统计推断。首先介绍了八个参数模型。参数模型的优势在于,当所选模型非常符合剂量反应曲线时,它们可以产生一致的结果。基于Wald方法,了解这些模型的表达式的简单性可以构建各种较低的置信度限制;但是,如果真实的剂量反应曲线与设定的参数模型有显着差异,则结果可能会表现不佳。然后需要非参数方法。首先介绍了使用池相邻违反器的线性样条的百分比自举方法。该方法吸引人的是渐近逼近,因此有兴趣评估此方法的小样本覆盖率特性。这些可以通过蒙特卡洛计算机仿真解决。我们发现,除了凹入式剂量响应曲线不断增加外,这种采用四剂的方法在大样本量下也能很好地运行。实际上,较小的样本量更为常见,因此我们转向增加剂量数量。我们确实看到,总的来说,随着剂量数量的增加,覆盖范围会变好。;为了研究最常见的四剂量设计,还引入了线性样条的偏差校正和加速自举方法以及Pool Violator和离散delta方法。 。仿真结果表明,这些方法的覆盖率相似,并且对增加的凹形剂量反应曲线没有改善。然后考虑了最终的二次样条。对于四剂设计,在四个不同点重复此操作,以求出平均额外风险函数。为了理解该方法的操作特性,进行了另一次蒙特卡洛模拟研究。这项研究产生的结果与使用线性样条线的百分比引导法发现的结果相似。

著录项

  • 作者

    Xiong, Hui.;

  • 作者单位

    The University of Arizona.;

  • 授予单位 The University of Arizona.;
  • 学科 Applied Mathematics.;Health Sciences Pharmacology.;Statistics.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 123 p.
  • 总页数 123
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:44:33

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