Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies.
Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies.
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DOI：
10.1289/ehp.8458385
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发表时间：
1984-12
影响因子：
10.4
通讯作者：
Haseman JK
中科院分区：
文献类型：
--
作者：
Haseman JK
讨论了动物致癌性研究设计、分析和解释中的统计学问题。在实验设计领域，必须考虑的问题包括动物随机化、样本量考虑、剂量选择和动物实验组分配以及潜在混杂因素的控制。在分析肿瘤发病率数据时，应考虑组间生存差异。重要的是要努力区分导致动物死亡的肿瘤和尸检时发现的死于无关原因的动物中的“偶然”肿瘤。生命表分析（适用于致死性肿瘤）和偶然的肿瘤试验（适用于非致死性肿瘤）进行了描述，并讨论了这些程序的使用由国家毒理学计划。尽管过去对致癌性数据的解释往往侧重于一般的成对比较，特别是高剂量效应，但不应忽视趋势检验的重要性，因为这些程序对检测致癌效应比成对比较更敏感。在解释致癌性数据时，不应采用严格的统计“决策规则”。虽然观察到的肿瘤增加的统计学意义可能是评估过程中使用的最重要的证据，但还必须考虑许多生物学因素。还讨论了历史对照数据的使用、假阳性问题和对阴性趋势的解释。
Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies are discussed. In the area of experimental design, issues that must be considered include randomization of animals, sample size considerations, dose selection and allocation of animals to experimental groups, and control of potentially confounding factors. In the analysis of tumor incidence data, survival differences among groups should be taken into account. It is important to try to distinguish between tumors that contribute to the death of the animal and "incidental" tumors discovered at autopsy in an animal dying of an unrelated cause. Life table analyses (appropriate for lethal tumors) and incidental tumor tests (appropriate for nonfatal tumors) are described, and the utilization of these procedures by the National Toxicology Program is discussed. Despite the fact that past interpretations of carcinogenicity data have tended to focus on pairwise comparisons in general and high-dose effects in particular, the importance of trend tests should not be overlooked, since these procedures are more sensitive than pairwise comparisons to the detection of carcinogenic effects. No rigid statistical "decision rule" should be employed in the interpretation of carcinogenicity data. Although the statistical significance of an observed tumor increase is perhaps the single most important piece of evidence used in the evaluation process, a number of biological factors must also be taken into account. The use of historical control data, the false-positive issue and the interpretation of negative trends are also discussed.