Benigni R
Istituto Superiore di Sanità, Laboratory of Comparative Toxicology and Ecotoxicology, Rome, Italy.
J Toxicol Environ Health. 1991 Sep;34(1):27-37. doi: 10.1080/15287399109531546.
This paper presents a new procedure aimed at quantifying the ability of short-term tests (STT) to discriminate between carcinogens and noncarcinogens. While the sensitivity, specificity, and accuracy indices provide an estimate that is not biased by the relative proportion of carcinogens and noncarcinogens of the different databases, the new index, called Relative Operating Characteristics (ROC), goes a step further, and overcomes the problem of the decision criterion bias. In fact, if the threshold--that is, minimum increase over the control above which an STT result is positive--is varied, sensitivity and other factors are also consequently affected. A similar problem occurs when the STTs are assembled in batteries: the performance of the battery in discriminating between carcinogens and noncarcinogens depends on the preliminary decision of how many and which assays should be positive for considering a chemical as positive in the battery. The ROC analysis produces a single value, which places the performance of different systems on a common, easily interpreted scale (instead of using several different indices such as sensitivity, etc.). Most importantly, this index is independent of the decision criterion bias; consequently it is the best measure of the true ability of STTs to discriminate between carcinogens and noncarcinogens. To illustrate the approach, the ROC analysis is applied to a battery composed of the four in vitro assays studied by the U.S. National Toxicology Program: the analysis confirmed the previous results, pointing to the limited ability of this battery to discriminate between carcinogens and noncarcinogens.
本文提出了一种新方法,旨在量化短期试验(STT)区分致癌物和非致癌物的能力。虽然灵敏度、特异性和准确性指数提供了一种不受不同数据库中致癌物和非致癌物相对比例影响的估计,但新的指数,即相对操作特征(ROC)更进一步,克服了决策标准偏差的问题。事实上,如果阈值(即超过对照的最小增加量,超过该增加量STT结果为阳性)发生变化,灵敏度和其他因素也会相应受到影响。当将STT组合成试验组时也会出现类似问题:试验组在区分致癌物和非致癌物方面的性能取决于初步决定多少种以及哪些检测应为阳性,才能将一种化学物质视为试验组中的阳性物质。ROC分析产生一个单一值,该值将不同系统的性能置于一个共同的、易于解释的尺度上(而不是使用诸如灵敏度等几个不同的指数)。最重要的是,该指数与决策标准偏差无关;因此,它是衡量STT区分致癌物和非致癌物真实能力的最佳指标。为了说明该方法,将ROC分析应用于由美国国家毒理学计划研究的四种体外试验组成的试验组:分析证实了先前的结果,表明该试验组区分致癌物和非致癌物的能力有限。