Revisiting Cohen et al. 2015, Cohen et al. 2014 and Waalkes et al. 2014: a bayesian re-analysis of tumor incidences
Revisiting Cohen et al. 2015, Cohen et al. 2014 and Waalkes et al. 2014: a bayesian re-analysis of tumor incidences
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回顾科恩等人。
DOI：
10.1007/s00204-016-1749-0
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发表时间：
2016
影响因子：
6.1
通讯作者：
L. Burgoon
中科院分区：
文献类型：
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作者：
Ingrid L. Druwe;L. Burgoon
2011年Tokar等报道的对照动物肿瘤发病率与Waalkes等2014年发表的同组研究报告并无差异。我们的完整分析可以在Burgoon和Druwe（2015）中找到；然而，我们在这里简要地讨论方法和结果。为了检验零假设，我们使用了贝叶斯方法。最初，我们在没有使用Waalkes实验室中肿瘤发病率的任何先验知识的情况下检查了是否存在差异；因此，我们使用平坦先验分布。我们将Tokar 2011和Waalkes研究中的对照肿瘤发生率建模为伯努利分布。计算后验分布，并在Burgoon和Druwe（2015）中显示。这两个分布的均值相差约13%。然而，这一事实本身并不意味着发病率来自不同的分布。事实上，我们可以观察到的情况是，每项研究的发病率取自同一分布的不同侧面。因此，为了检验假设，我们从后验分布中抽取样本并计算差值以获得差值的分布。如果两项研究中的发病率来自相同的分布，我们会期望0或接近0的差异是可信的值。为了实现这一点，我们使用了一种方法，在差分布的零差和95%最高密度区间（HDI）周围设置了一个实际等效区域（ROPE）。ROPE在零差附近划定了一个区域，该区域在功能上等同于无差。一般来说，如果95% HDI的任何部分在ROPE内，那么我们接受零假设，即研究中的对照肿瘤发病率是相同的。否则，我们拒绝零假设。我们的决策规则的完整解释可以在Burgoon和Druwe（2015）中找到。在过去的一年里，该杂志以Waalkes等人与Cohen等人的致编辑信的形式，就Waalkes等人2014年发表在该杂志上的一篇题为“人体相关剂量的‘终身’无机砷暴露诱导小鼠肺部肿瘤”的文章进行了热烈的讨论。对于Tokar et al.（2011）和Waalkes et al.（2014）发表的砷暴露研究中对照动物肿瘤发病率的可重复性，Cohen等人提出了一系列深思熟虑的问题。此外，Cohen等人质疑小鼠肺部肿瘤的发展是否与研究所用小鼠的遗传背景有关，而不是与砷暴露有关。Cohen和他的同事们提出的许多问题都集中在他们认为在两项研究中使用的对照动物中肿瘤发病率的不确定性，以及Tokar和Waalkes进行的研究的质量。如果Cohen等人的断言被证明是正确的，风险评估者将无法使用Waalkes等人（2014）的研究来评估无机砷的危害和剂量反应。因此，我们执行了所要求的分析
The control animal tumor incidences reported by Tokar et al. in 2011 are not different from the study reported by the same group in the Waalkes et al. 2014 publication. Our full analysis can be found in Burgoon and Druwe (2015); however, we briefly discuss the approach and results here. To test the null hypothesis, we used a Bayesian approach. Initially, we examined whether or not a difference existed without using any prior knowledge of what the tumor incidence in Waalkes’ laboratory was; therefore, we used a flat prior distribution. We modeled the control tumor incidences from the Tokar 2011 and Waalkes studies as Bernoulli distributions. The posterior distributions were calculated and are shown in Burgoon and Druwe (2015). There is a difference of about 13% between the means of these two distributions. However, that fact alone does not mean that the incidences are from different distributions. In fact, what we could be observing is a case where the incidences for each study were taken from different sides of the same distribution. Thus, to test the hypothesis, we took samples from the posterior distributions and calculated the difference to obtain a distribution of the differences. If the incidences in both studies were from the same distribution, we would expect a difference of 0, or close to 0, to be a credible value. In order to accomplish this, we used an approach that sets a region of practical equivalence (ROPE) around the zero difference, and the 95% highest density interval (HDI) of the difference distribution. The ROPE demarcates a region around zero difference that is functionally equivalent to no difference. In general, if any part of the 95% HDI is within the ROPE, then we accept the null hypothesis that the control tumor incidences from the studies are the same. Else, we reject the null hypothesis. A complete explanation of our decision rules can be found in Burgoon and Druwe (2015).Over the past year, this journal has published a lively discussion in the form of letters to the editor between Waalkes et al. and Cohen et al. regarding an article published in this journal titled “Lung Tumors in Mice induced by ‘whole Life’inorganic arsenic exposure at human relevant doses” by Waalkes et al. in 2014. Cohen et al. raised a series of thoughtful questions with respect to the reproducibility of the control animal tumor incidences in the arsenic exposure studies published by Tokar et al.(2011) and Waalkes et al.(2014). In addition, Cohen et al. brought into question whether the development of lung tumors in the mice was related to the genetic background of the mice used in the study rather than arsenic exposure. Many of the questions raised by Cohen and colleagues centered around what they deemed to be uncertainty in the tumor incidences in the control animals used in both studies, and by extension, the quality of the studies performed by Tokar and Waalkes. If the assertions made by Cohen et al. proved true, risk assessors would be unable to use Waalkes et al.’s (2014) study in hazard and dose–response assessments of inorganic arsenic. Thus, we performed the analysis requested