Comparing Statistical Methods for Quantifying Drug Sensitivity Based on In Vitro Dose-Response Assays
Comparing Statistical Methods for Quantifying Drug Sensitivity Based on In Vitro Dose-Response Assays
复制标题
比较基于体外剂量反应测定的药物敏感性量化统计方法
DOI：
10.1089/adt.2011.0388
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发表时间：
2012-02-01
影响因子：
1.8
通讯作者：
Pang, Lei
中科院分区：
文献类型：
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作者：
Huang, Shuguang;Pang, Lei
体外药敏试验对于评估化疗药物对癌细胞的作用是非常有价值的。然而，这些分析产生的剂量-反应曲线，通常由四参数Logistic(4PL)模型近似，往往难以解释，没有明确的指示应该使用哪个指标来比较它们。在模拟和实际场景中，比较了五个常用的指标，即绝对和相对半最大抑制浓度(IC50)、基于梯形规则和参数方法的剂量-效应曲线下的面积(AUC)以及最大浓度下的影响(E-max)，以评估它们在4PL曲线中的应用。尽管IC50是分析剂量-反应曲线最广泛使用的指标，但这项研究表明，它不是所测试的指标中最可靠的。拟合AUC在模拟和现实场景中都显示出最好的整体性能；梯形AUC在大多数情况下表现出与拟合AUC相似的性能。
In vitro chemosensitivity assays are invaluable for assessing chemotherapeutic agents effects on cancer cells. Yet the dose-response curves generated by those assays, usually approximated by four-parameter logistic (4PL) models, are oftentimes difficult to interpret, with no clear indication of which metric should be used to compare them. Here, five commonly used metrics, absolute and relative half-maximal inhibitory concentration (IC50), area under the dose-response curve (AUC) based on trapezoidal rule and a parametric approach, and the effect at the maximal concentrations (E-max), were compared in both simulations and real-life scenarios to evaluate their use with 4PL curves. Despite the fact that IC50 is the most widely used metric to analyze dose-response curves, this study demonstrated that it was not the most reliable of the metrics tested. Fitted AUC showed the best overall performance in both the simulation and real-life scenarios; trapezoidal AUC showed similar performance to fitted AUC in most cases.