Design and statistical methods in studies using animal models of development
Design and statistical methods in studies using animal models of development
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DOI：
10.1093/ilar.47.1.5
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发表时间：
2006-01-01
期刊：
影响因子：
2.5
通讯作者：
Festing, MFW
中科院分区：
文献类型：
--
作者：
Festing, MFW
涉及新生儿的实验应遵循与大多数其他实验相同的基本原则。它们应该是无偏的，有力的，有很好的适用范围，不过于复杂，并且可以进行统计分析，以显示结论中的不确定性范围。然而，研究新生经产动物的生长和发育提出了与“实验单位”的选择和窝间差异相关的特殊问题：“窝效应”。描述了两种主要类型的实验，并对其设计和统计分析提出了建议：第一，当雌性或整个窝被分配到一个处理组时，使用“窝间设计”。在这种情况下，窝而不是窝中的个体是实验单位，应该是统计分析的单位。需要在每窝中合并对单个新生动物进行的测量。将每个新生儿作为单独的观察结果进行计数可能会导致错误的结论。各结局的观察次数（“n”）基于给药雌性或整窝的数量。当窝仔数不同时，可能需要使用加权统计分析，因为基于更多观察结果的平均值比基于少数观察结果的平均值更可靠。其次，当新生儿可以单独分配到治疗组时，使用更强大的“窝内设计”，以便一窝内的个体可以接受不同的治疗。在这种情况下，个体新生儿是实验单位，并且“n”基于个体幼仔的数量，而不是基于整个窝的数量。然而，窝仔数的变化意味着可能难以在每窝内每个处理组中使用相同数量的动物进行平衡实验。这增加了统计分析的复杂性。附录中提供了使用一般线性模型方差分析的数值示例。应将同基因菌株的使用视为新生儿疾病研究。这些菌株就像基因相同个体的不朽克隆（即，它们是均匀的、稳定的和可重复的），并且它们的使用应该导致更强大的实验。与不同近交品系的雄性交配的近交雌性将产生F1杂交后代，其将是均匀的、健壮的和遗传上相同的。不同的菌株可能以不同的速度发展，并对实验治疗作出不同的反应。
Experiments involving neonates should follow the same basic principles as most other experiments. They should be unbiased, be powerful, have a good range of applicability, not be excessively complex, and be statistically analyzable to show the range Of uncertainty in the Conclusions. However, investigation of growth and development in neonatal multiparous animals poses special problems associated with the choice of "experimental unit" and differences between litters: the "litter effect." Two main types of experiments are described, with recommendations regarding their design and statistical analysis: First, the "between litter design" is used when females or whole litters are assigned to a treatment group. In this case the litter, rather than the individuals within a litter, is the experimental unit and should be the unit for the statistical analysis. Measurements made on individual neonatal animals need to be combined within each litter. Counting each neonate as a separate observation may lead to incorrect conclusions. The number of observations for each outcome ("n") is based oil the number of treated females or whole litters. Where litter sizes vary, it may be necessary to use a weighted statistical analysis because means based on more observations are more reliable than those based on a few observations. Second, the more powerful "within-litter design" is used when neonates can be individually assigned to treatment groups so that individuals within a litter can have different treatments. In this case, the individual neonate is the experimental unit, and "n" is based on the number of individual pups, not on the number of whole litters. However, variation in litter size means that it may be difficult to perform balanced experiments with equal numbers of animals in each treatment group within each litter. This increases the complexity of the statistical analysis. A numerical example using a general linear model analysis of variance is provided in the Appendix. The use of isogenic strains should be considered ill neonatal research. These strains are like immortal clones of genetically identical individuals (i.e., they are uniform, stable, and repeatable), and their use should result in more powerful experiments. Inbred females mated to males of a different inbred strain will produce F1 hybrid offspring that will be uniform, vigorous, and genetically identical. Different strains may develop at different rates and respond differently to experimental treatments.