Feder P I, Olson C T, Hobson D W, Matthews M C, Joiner R L
Battelle, Columbus, OH 43201-2693.
Neurosci Biobehav Rev. 1991 Spring;15(1):129-33. doi: 10.1016/s0149-7634(05)80104-6.
The use of stagewise, group sequential experimental designs with dichotomous responses in toxicity or drug screening programs is discussed. Such designs represent a compromise between the standard, fixed sample size designs and fully sequential designs. Stagewise group sequential designs place specified numbers of animals on test at each stage, up to a maximum number of stages. The greatest increases in sample size efficiency occur with small numbers of stages, particularly when going from one stage to two. Two-stage designs can result in a 15 to 20 percent reduction in average sample size. Five-stage designs can result in a 30 to 40 percent reduction in average sample size, with no appreciable decrease in Type 1 error or power. Examples of the efficiencies that arose in actual screening programs are given. This paper demonstrates that the routine use of stagewise, group sequential designs in standardized screening protocols can result in substantial savings in animal use with virtually no sacrifice of statistical sensitivity.
本文讨论了在毒性或药物筛选项目中使用具有二分反应的分阶段、成组序贯实验设计。此类设计代表了标准的固定样本量设计与完全序贯设计之间的一种折衷。分阶段成组序贯设计在每个阶段安排特定数量的动物进行测试，直至最大阶段数。样本量效率的最大提升出现在阶段数较少时，尤其是从一个阶段增加到两个阶段时。两阶段设计可使平均样本量减少15%至20%。五阶段设计可使平均样本量减少30%至40%，且第一类错误或检验效能没有明显降低。文中给出了实际筛选项目中所产生的效率示例。本文表明，在标准化筛选方案中常规使用分阶段、成组序贯设计可大幅节省动物使用量，而几乎不牺牲统计灵敏度。
