CALCULATION OF BENCHMARK DOSES FROM CONTINUOUS DATA
CALCULATION OF BENCHMARK DOSES FROM CONTINUOUS DATA
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DOI：
10.1111/j.1539-6924.1995.tb00095.x
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发表时间：
1995-02-01
期刊：
影响因子：
3.8
通讯作者：
CRUMP, KS
中科院分区：
文献类型：
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作者：
CRUMP, KS
基准剂量(BMD)是与健康影响的反应(称为基准反应或BMR)的规定增加相对应的物质的剂量。在设定可接受的人体暴露水平时，建议使用基准剂量的统计下限(BMDL)来替代未观察到的不良反应水平(NOAEL)。本文提出了一种从连续数据计算BMDS和BMDL的方法，该方法与由定量数据计算的方法一致。该方法包括直接通过指定将连续响应分为正常和异常类别的截止x(0)来定义异常响应，或者间接地通过指定在未暴露的受试者中预期的异常响应的比例P-0来定义异常响应。该方法实际上不涉及将个体连续反应分成定量反应，并且在某些情况下可以应用于汇总形式的连续数据(例如，离散剂量组中受试者的连续反应的平均值和标准差)。除了指定BMR和x(0)或P-0外，该方法还要求指定连续反应的分布，包括指定用于衡量中心趋势的剂量-反应θ(D)。图示了一种方法，用于选择theta(D)以使异常反应的概率成为任何所需的剂量-反应函数。这实现了相同的剂量-反应模型(威布尔模型、对数逻辑模型等)。用于异常响应的概率，而不管基础数据是连续的还是定量的。当连续反应以标准差西格玛为正态分布时(与剂量无关)，该方法相当于将骨密度定义为与平均反应相对于西格玛的规定变化相对应的剂量。
A benchmark dose (BMD) is the dose of a substance that corresponds to a prescribed increase in the response (called the benchmark response or BMR) of a health effect. A statistical lower bound on the benchmark dose (BMDL) has been proposed as a replacement for the no-observed-adverse-effect-level (NOAEL) in setting acceptable human exposure levels. A method is developed in this paper for calculating BMDs and BMDLs from continuous data in a manner that is consistent with those calculated from quantal data. The method involves defining an abnormal response, either directly by specifying a cutoff x(0) that separates continuous responses into normal and abnormal categories, or indirectly by specifying the proportion P-0 of abnormal responses expected among unexposed subjects. The method does not involve actually dichotomizing individual continuous responses into quantal responses, and in certain cases can be applied to continuous data in summarized form (e.g., means and standard deviations of continuous responses among subjects in discrete dose groups). In addition to specifying the BMR and either x(0) or P-0, the method requires specification of the distribution of continuous responses, including specification of the dose-response theta(d) for a measure of central tendency. A method is illustrated for selecting theta(d) to make the probability of an abnormal response any desired dose-response function. This enables the same dose-response model (Weibull, log-logistic, etc.) to be used for the probability of an abnormal response, regardless of whether the underlying data are continuous or quantal. Whenever the continuous responses are normally distributed with standard deviation sigma (independent of dose), the method is equivalent to defining the BMD as the dose corresponding to a prescribed change in the mean response relative to sigma.