Guidelines for accurate EC50/IC50 estimation

Guidelines for accurate EC50/IC50 estimation
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DOI:
10.1002/pst.426
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发表时间:
2011-03-01
影响因子:
1.5
通讯作者:
Sebaugh, J. L.
Sebaugh, J. L.
中科院分区:
医学4区
文献类型:
--
作者:
Sebaugh, J. L.

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本文提供了对EC50/IC50估计的准确性有信心的最低要求。考虑EC50/IC50的两种定义:相对定义和绝对定义。相对EC_(50)/IC_(50)是四参数Logistic模型中的参数c,是对应于高原上下两个估计值之间的响应的浓度。绝对EC50/IC50是对应于50%对照(0%和100%测定对照的平均值)的反应。指南首先描述了如何决定是使用相对EC50/IC50还是绝对EC50/IC50。没有稳定的100%对照的分析必须使用相对的EC50/IC50。具有稳定的100%对照但其50%对照平均值的估计误差可能超过5%的分析应使用相对EC50/IC50。通过使用绝对EC50/IC50,可以证明能够产生准确和稳定的100%对照并且50%控制平均值的估计误差小于5%的分析方法可以获得效率和准确性。接下来,指南提供了决定EC50/IC50估计何时可以报告的规则。只有当至少有两种测定浓度超过上、下弯曲线点时,才应使用相对EC50/IC50。只有在至少有两个测定浓度的预测响应小于50%和两个的预测响应大于50%的情况下,才应使用绝对EC50/IC50。在制定指南时,考虑了各种典型的分析条件。版权所有(C)2010 John Wiley&Sons,Ltd.
This article provides minimum requirements for having confidence in the accuracy of EC50/IC50 estimates. Two definitions of EC50/IC50s are considered: relative and absolute. The relative EC50/IC50 is the parameter c in the 4-parameter logistic model and is the concentration corresponding to a response midway between the estimates of the lower and upper plateaus. The absolute EC50/IC50 is the response corresponding to the 50% control (the mean of the 0% and 100% assay controls). The guidelines first describe how to decide whether to use the relative EC50/IC50 or the absolute EC50/IC50. Assays for which there is no stable 100% control must use the relative EC50/IC50. Assays having a stable 100% control but for which there may be more than 5% error in the estimate of the 50% control mean should use the relative EC50/IC50. Assays that can be demonstrated to produce an accurate and stable 100% control and less than 5% error in the estimate of the 50% control mean may gain efficiency as well as accuracy by using the absolute EC50/IC50. Next, the guidelines provide rules for deciding when the EC50/IC50 estimates are reportable. The relative EC50/IC50 should only be used if there are at least two assay concentrations beyond the lower and upper bend points. The absolute EC50/IC50 should only be used if there are at least two assay concentrations whose predicted response is less than 50% and two whose predicted response is greater than 50%. A wide range of typical assay conditions are considered in the development of the guidelines. Copyright (C) 2010 John Wiley & Sons, Ltd.