A comparison of methods for testing homogeneity of proportions in teratologic studies

We consider teratologic studies in which the aim is to compare the survival rate of animals in a treatment group to the corresponding rate in a control group. The design of such studies often involves the allocation of intact litters of animals to treatment, invalidating the application of standard statistical methods. We review the strengths and weaknesses of several approaches for dealing with this problem including methodology recently developed for the analysis of clustered binary data. A simulation study is conducted in which litter sizes are generated from a distribution having specified mean and degree of imbalance. It is recommended on the basis of this study and on theoretical considerations that the choice of method should depend on whether the comparison of interest is experimental or observational. For experimental comparisons, involving the random assignment of litters to different treatment groups, methods based on the adjustment of standard chi-square statistics are recommended unless the number of litters in each group is very large.