Department of Statistics, GlaxoSmithKline, NC, U.S.A.
Stat Med. 2013 Dec 20;32(29):5145-55. doi: 10.1002/sim.5905. Epub 2013 Aug 1.
A method for detecting deviations from the Loewe additive drug combination reference model for in vitro drug combination experimentation is described. It is often difficult to fit a response surface model to drug combination data, especially in situations where the experimental design contains a sparse set of combinations. The literature does contain good response surface modeling approaches, but they tend to be complex and can be difficult to execute. It is especially difficult to check model quality when fitting to more than two combined agents. A simple method based on sound statistical principles is proposed that examines the mean response deviation of each combination from the predicted response under Loewe additivity. The method can readily handle any number of combined agents, does not require sophisticated modeling, and can even be programmed into Microsoft Excel without the use of macros. Several potential extensions to the method are discussed in detail. Computer-generated simulations demonstrate the statistical capabilities of the approach, and a real-data example is given to illustrate the method.
描述了一种用于检测体外药物组合实验中偏离 Loewe 加性药物组合参考模型的方法。拟合药物组合数据的响应曲面模型通常很困难，特别是在实验设计包含稀疏组合集的情况下。文献中确实包含了很好的响应曲面建模方法，但它们往往很复杂，难以执行。当拟合超过两种组合药物时，检查模型质量尤其困难。本文提出了一种基于合理统计原理的简单方法，该方法检查了每个组合相对于 Loewe 加性预测响应的平均响应偏差。该方法可以轻松处理任意数量的组合药物，不需要复杂的建模，甚至可以在不使用宏的情况下在 Microsoft Excel 中编程。详细讨论了该方法的几个潜在扩展。计算机生成的模拟演示了该方法的统计能力，并给出了一个真实数据示例来说明该方法。
