Wahrendorf J, Zentgraf R, Brown C C
Biometrics. 1981 Mar;37(1):45-54.
In this paper we consider the design of animal experiments conducted to test for interaction between two carcinogens or other toxicants. We examine 2 x 2 designs which contain an untreated control group, two groups treated with a single dose of each toxic agent alone, and one group treated with both agents together. Optimal rules for allocating animals to the experimental groups are derived on the basis of expected response rates for acute toxicity studies and these rules are then extended to long-term carcinogenesis studies by considering times-to-tumor under an assumption of proportional hazards. Unbalanced designs with more animals in the combination group than in the control group are shown to provide a gain in efficacy of about 20% over balanced designs.
在本文中，我们考虑为测试两种致癌物或其他毒物之间的相互作用而进行的动物实验设计。我们研究了2×2设计，其中包括一个未处理的对照组、分别用单剂量每种毒物处理的两个组，以及同时用两种毒物处理的一个组。基于急性毒性研究的预期反应率得出了将动物分配到实验组的最优规则，然后通过在比例风险假设下考虑肿瘤发生时间，将这些规则扩展到长期致癌研究。结果表明，组合组动物数量多于对照组的非平衡设计比平衡设计在功效上提高约20%。
