Summarizing EC50 estimates from multiple dose- response experiments: A comparison of a meta- analysis strategy to a mixed- effects model approach
Summarizing EC50 estimates from multiple dose- response experiments: A comparison of a meta- analysis strategy to a mixed- effects model approach
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DOI：
10.1002/bimj.201300123
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发表时间：
2014-05-01
影响因子：
1.7
通讯作者：
Kopp-Schneider, Annette
中科院分区：
文献类型：
--
作者：
Jiang, Xiaoqi;Kopp-Schneider, Annette
进行剂量反应研究以研究化合物的效力。EC50是产生半数最大反应的化合物浓度。剂量反应数据通常通过使用对数逻辑模型进行评估，该模型包括EC50作为模型参数之一。通常，进行一个以上的实验来确定化合物的EC50值，需要从一系列实验中总结EC50估计值。在这种情况下，混合效应模型被设计为通过同时考虑实验内和实验间的变异性来估计所有实验中EC50值的平均行为。然而，拟合非线性混合效应模型比线性情况下更复杂，并且经常遇到收敛问题。另一种策略是应用荟萃分析方法，该方法结合了从单独的对数逻辑模型拟合获得的EC50估计值。这两个建议的策略，总结EC50估计从多个实验进行了比较，在模拟研究和真实的数据的例子。我们得出结论，荟萃分析策略是一种简单而稳健的方法，可以从多个实验中总结EC50估计值，特别适合于少量实验的情况。
Dose-response studies are performed to investigate the potency of a compound. EC50 is the concentration of the compound that gives half-maximal response. Dose-response data are typically evaluated by using a log-logistic model that includes EC50 as one of the model parameters. Often, more than one experiment is carried out to determine the EC50 value for a compound, requiring summarization of EC50 estimates from a series of experiments. In this context, mixed-effects models are designed to estimate the average behavior of EC50 values over all experiments by considering the variabilities within and among experiments simultaneously. However, fitting nonlinear mixed-effects models is more complicated than in a linear situation, and convergence problems are often encountered. An alternative strategy is the application of a meta-analysis approach, which combines EC50 estimates obtained from separate log-logistic model fitting. These two proposed strategies to summarize EC50 estimates from multiple experiments are compared in a simulation study and real data example. We conclude that the meta-analysis strategy is a simple and robust method to summarize EC50 estimates from multiple experiments, especially suited in the case of a small number of experiments.