Biostatistical Assessment of Mutagenicity Studies: A Stepwise Confidence Procedure

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2019-04-14 DOI:10.1155/2019/3249097

Michael J. Adjabui, Nathaniel K. Howard, M. Akamba

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引用次数: 3

Abstract

The paper addresses the issue of identifying the maximum safe dose in the context of noninferiority trials where several doses of toxicological compounds exist. Statistical methodology for identifying the maximum safe dose is available for three-arm noninferiority designs with only one experimental drug treatment. Extension of this methodology for several experimental groups exists but with multiplicity adjustment. However, if the experimental or the treatment groups can be ordered a priori according to their treatment effect, then multiplicity adjustment is unneeded. Assuming homogeneity of variances across dose group in normality settings, we employed the generalized Fieller’s confidence interval method in a multiple comparison stepwise procedure by incorporating the partitioning principle in order to control the familywise error rate (FWER). Simulation results revealed that the procedure properly controlled the FWER in strong sense. Also, the power of our procedure increases with increasing sample size and the ratio of mean differences. We illustrate our procedure with mutagenicity dataset from a clinical study.

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致突变性研究的生物统计学评估:逐步置信度程序

本文讨论了在存在几种剂量毒理学化合物的非劣效性试验中确定最大安全剂量的问题。确定最大安全剂量的统计方法可用于只有一种实验药物治疗的三组非劣效性设计。该方法已扩展到几个实验组，但进行了多重性调整。然而，如果实验组或治疗组可以根据其治疗效果进行先验排序，则不需要进行多重性调整。假设在正态性设置中，剂量组之间的方差是均匀的，我们在多重比较逐步过程中采用了广义Fieller置信区间方法，结合了划分原理，以控制家庭误差率（FWER）。仿真结果表明，该程序在很强的意义上正确地控制了FWER。此外，我们的程序的能力随着样本量和平均差异比率的增加而增加。我们用一项临床研究的致突变性数据集来说明我们的程序。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.