León Novelo Luis G, Womack Andrew, Zhu Hongxiao, Wu Xiaowei
Department of Biostatistics, The University of Texas Health Science Center at Houston-School of Public Health, 1200 Pressler St, RAS E805, Houston, 77030, TX, U.S.A.
Department of Statistics, Indiana University, 309 N. Park Ave, Bloomington, 47408, IN, U.S.A.
Stat Med. 2017 May 30;36(12):1907-1923. doi: 10.1002/sim.7218. Epub 2017 Jan 20.
This paper addresses model-based Bayesian inference in the analysis of data arising from bioassay experiments. In such experiments, increasing doses of a chemical substance are given to treatment groups (usually rats or mice) for a fixed period of time (usually 2 years). The goal of such an experiment is to determine whether an increased dosage of the chemical is associated with increased probability of an adverse effect (usually presence of adenoma or carcinoma). The data consists of dosage, survival time, and the occurrence of the adverse event for each unit in the study. To determine whether such relationship exists, this paper proposes using Bayes factors to compare two probit models, the model that assumes increasing dose effects and the model that assumes no dose effect. These models account for the survival time of each unit through a Poly-k type correction. In order to increase statistical power, the proposed approach allows the incorporation of information from control groups from previous studies. The proposed method is able to handle data with very few occurrences of the adverse event. The proposed method is compared with a variation of the Peddada test via simulation and is shown to have higher power. We demonstrate the method by applying it to the two bioassay experiment datasets previously analyzed by other authors. Copyright © 2017 John Wiley & Sons, Ltd.
本文探讨了在生物测定实验数据分析中基于模型的贝叶斯推断。在这类实验中,将不断增加剂量的化学物质给予各个治疗组(通常是大鼠或小鼠),持续一段固定时间(通常为2年)。此类实验的目的是确定化学物质剂量的增加是否与不良反应(通常是腺瘤或癌的出现)概率的增加相关。数据包括研究中每个单位的剂量、存活时间以及不良事件的发生情况。为了确定这种关系是否存在,本文提出使用贝叶斯因子来比较两个概率单位模型,即假设剂量效应增加的模型和假设无剂量效应的模型。这些模型通过Poly - k类型校正来考虑每个单位的存活时间。为了提高统计功效,所提出的方法允许纳入来自先前研究对照组的信息。所提出的方法能够处理不良事件发生次数极少的数据。通过模拟将所提出的方法与Peddada检验的一种变体进行比较,结果表明该方法具有更高的功效。我们通过将其应用于先前其他作者分析过的两个生物测定实验数据集来展示该方法。版权所有© 2017约翰威立父子有限公司。