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Understanding synergy

机译：了解协同作用

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Analysis of the interactive effects of combinations of hormones or other manipulations with qualitatively similar individual effects is an important topic in basic and clinical endocrinology as well as other branches of basic and clinical research related to integrative physiology. Functional, as opposed to mechanistic, analyses of interactions rely on the concept of synergy, which can be defined qualitatively as a cooperative action or quantitatively as a supra-additive effect according to some metric for the addition of different dose-effect curves. Unfortunately, dose-effect curve addition is far from straightforward; rather, it requires the development of an axiomatic mathematical theory. I review the mathematical soundness, face validity, and utility of the most frequently used approaches to supra-additive synergy. These criteria highlight serious problems in the two most common synergy approaches, response additivity and Loewe additivity, which is the basis of the isobole and related response surface approaches. I conclude that there is no adequate, generally applicable, supra-additive synergy metric appropriate for endocrinology or any other field of basic and clinical integrative physiology. I recommend that these metrics be abandoned in favor of the simpler definition of synergy as a cooperative, i.e., nonantagonistic, effect. This simple definition avoids mathematical difficulties, is easily applicable, meets regulatory requirements for combination therapy development, and suffices to advance phenomenological basic research to mechanistic studies of interactions and clinical combination therapy research.
机译：在本质和临床内分泌学以及与综合生理学有关的基础和临床研究的其他分支中，对激素组合或其他操作与定性相似的个体作用的相互作用影响进行分析是一个重要的主题。相互作用的功能分析（与机理分析相反）依赖于协同作用的概念，可以根据添加不同剂量效应曲线的某种指标，将其定性定义为协同作用，或定量地定义为超加和效应。不幸的是，添加剂量效应曲线远非一帆风顺。相反，它需要发展公理数学理论。我回顾了最常用的超加合协同方法的数学稳定性，面部有效性和实用性。这些标准突出了两种最常见的协同方法（响应可加性和Loewe可加性）中的严重问题，这是等心线和相关响应面方法的基础。我得出的结论是，没有足够的，普遍适用的，适用于内分泌学或其他任何基础和临床整合生理学领域的超加合协同指标。我建议放弃这些指标，而更简单地将协同效应定义为合作效应，即非对抗效应。这个简单的定义避免了数学上的困难，易于应用，满足了联合疗法开发的法规要求，并且足以将现象学基础研究推进到相互作用的机理研究和临床联合疗法研究中。

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