Finkelstein D M, Schoenfeld D A
Department of Biostatistics, Harvard School of Public Health, Massachusetts General Hospital, Boston.
Biometrics. 1989 Mar;45(1):219-30.
Rodent tumorigenicity experiments are conducted to determine the safety of substances for human exposure. The carcinogenicity of a substance is generally determined by statistical tests that compare the effects of treatment on the rate of tumor development at several body sites. The statistical analysis of such studies often includes hypothesis testing of the dose effect at each of the sites. However, the multiplicity of the significance tests may cause an excess overall false positive rate. In consideration of this problem, recent interest has focused on developing methods to test simultaneously for the treatment effect at multiple sites. In this paper, we propose a test that is based on the count of tumor-bearing sites. The test is appropriate regardless of tumor lethality or of treatment-related differences in the underlying mortality. Simulations are given which compare the performance of the proposed test to several other tests including a Bonferroni adjustment of site-specific tests, and the test is illustrated using the data from the large ED01 experiment.
进行啮齿动物致癌性实验以确定物质对人类暴露的安全性。一种物质的致癌性通常通过统计检验来确定，这些检验比较了处理对多个身体部位肿瘤发生率的影响。此类研究的统计分析通常包括对每个部位剂量效应的假设检验。然而，显著性检验的多重性可能导致总体假阳性率过高。考虑到这个问题，最近的研究兴趣集中在开发同时检验多个部位处理效应的方法上。在本文中，我们提出了一种基于荷瘤部位计数的检验方法。无论肿瘤致死性或潜在死亡率中与处理相关的差异如何，该检验都是合适的。给出了模拟结果，将所提出检验的性能与其他几种检验进行了比较，包括对部位特异性检验的Bonferroni校正，并使用大型ED01实验的数据对该检验进行了说明。
