Scholze Martin, Kortenkamp Andreas
The School of Pharmacy, University of London, London, United Kingdom.
Environ Health Perspect. 2007 Dec;115 Suppl 1(Suppl 1):84-90. doi: 10.1289/ehp.9364.
The endocrine disruptor field has been vexed by difficulties in reproducing various claims of effects at unusually low doses. In previous analyses, variations in control responses from experiment to experiment and problems with observing effects in positive controls have been identified as possible explanations of the resulting impasse.
In this article, we argue that both of these viewpoints fail to take sufficient account of the problems that exist in estimating low effects and low-effect doses. We have carried out post hoc power analyses on selected published data to illustrate that claims of low-dose effects (or their absence) are often compromised by insufficient statistical power of the chosen experimental design.
We demonstrate that low-dose estimates such as the no observed adverse effect levels derived from statistical hypothesis-testing procedures are dependent on the specific experimental conditions used for testing. Thus, below the statistical detection limit of the experiment, the presence of effects can neither be proven nor ruled out. Common practice is to attempt to establish "doses without effect." However, low-dose estimations in the endocrine-disruptor field could be improved if decisions regarding the toxicologic effect size of relevance formed the starting point of testing procedures. Statistical power considerations could then reveal the resources necessary to demonstrate effect magnitudes of concern.
内分泌干扰物领域一直因难以重现各种关于极低剂量效应的说法而困扰。在以往的分析中，实验间对照反应的差异以及在阳性对照中观察效应的问题已被确定为导致僵局的可能解释。
在本文中，我们认为这两种观点都没有充分考虑在估计低效应和低效应剂量时存在的问题。我们对选定的已发表数据进行了事后功效分析，以说明低剂量效应（或其不存在）的说法往往因所选实验设计的统计功效不足而受到影响。
我们证明，诸如从统计假设检验程序得出的未观察到不良反应水平等低剂量估计值取决于用于测试的具体实验条件。因此，在实验的统计检测限以下，效应的存在既无法证明也无法排除。常见的做法是试图确定“无效应剂量”。然而，如果将关于相关毒理学效应大小的决策作为测试程序的起点，内分泌干扰物领域的低剂量估计可能会得到改善。然后，统计功效的考虑可以揭示证明关注效应大小所需的资源。
