Department of Mathematics and Statistics, Youngstown State University, Youngstown, OH, USA.
Biom J. 2021 Apr;63(4):825-840. doi: 10.1002/bimj.202000073. Epub 2021 Jan 6.
Relative potency is widely used in toxicological and pharmacological studies to characterize potency of chemicals. The relative potency of a test chemical compared to a standard chemical is defined as the ratio of equally effective doses (standard divided by test). This classical concept relies on the assumption that the two chemicals are toxicologically similar-that is, they have parallel dose-response curves on log-dose scale-and thus have constant relative potency. Nevertheless, investigators are often faced with situations where the similarity assumption is deemed unreasonable, and hence the classical idea of constant relative potency fails to hold; in such cases, simply reporting a single constant value for relative potency can produce misleading conclusions. Relative potency functions, describing relative potency as a function of the mean response (or other quantities), is seen as a useful tool for handling nonconstant relative potency in the absence of similarity. Often, investigators are interested in assessing nonconstant relative potency at a finite set of some specific response levels for various regulatory concerns, rather than the entire relative potency function; this simultaneous assessment gives rise to multiplicity, which calls for efficient statistical inference procedures with multiplicity adjusted methods. In this paper, we discuss the estimation of relative potency at multiple response levels using the relative potency function, under the log-logistic dose-response model. We further propose and evaluate three approaches to calculating multiplicity-adjusted confidence limits as statistical inference procedures for assessing nonconstant relative potency. Monte Carlo simulations are conducted to evaluate the characteristics of the simultaneous limits.
相对效力在毒理学和药理学研究中被广泛用于描述化学物质的效力。测试化学物质与标准化学物质的相对效力定义为等效剂量的比值（标准除以测试）。这个经典概念基于这样的假设，即两种化学物质在毒理学上是相似的，也就是说，它们在对数剂量尺度上具有平行的剂量反应曲线，因此具有恒定的相对效力。然而，研究人员经常面临这样的情况，即相似性假设被认为是不合理的，因此恒定相对效力的经典概念不再适用；在这种情况下，简单地报告一个单一的恒定相对效力值可能会产生误导性的结论。相对效力函数将相对效力描述为平均响应（或其他数量）的函数，被视为在缺乏相似性的情况下处理非恒定相对效力的有用工具。通常，研究人员有兴趣在各种监管关注的特定响应水平的有限集合中评估非恒定相对效力，而不是整个相对效力函数；这种同时评估会产生多重性，这需要使用具有多重调整方法的有效统计推断程序。在本文中，我们讨论了在对数逻辑剂量反应模型下，使用相对效力函数在多个响应水平上估计相对效力的问题。我们进一步提出并评估了三种方法，作为评估非恒定相对效力的统计推断程序，用于计算多重调整置信限。通过蒙特卡罗模拟来评估同时限的特征。
