Trend tests for proportional responses in developmental toxicity experiments

The data from developmental toxicity experiments usually are very difficult to analyze statistically because of the lack of independence among littermates and the random nature of the litter size. Only a few of the models that have been proposed in the literature have accounted for both of these features. One of the models proposed by Van Ryzin is invoked to construct a test of trend (dose response). The construction is achieved via a statistical technique called isotonic regression, which is applied to the moment estimators derived by Van Ryzin. The trend test based on isotonic regression is relatively straightforward to calculate, and when the number of dose groups (including control) is four or less, the significance of the observed results is easily determined. An example, in which fetolethality is the end point of interest, demonstrates the test.