Analysis of trinomial responses from reproductive and developmental toxicity experiments.
This paper presents a Dirichlet-trinomial distribution for modelling data obtained from reproductive and developmental studies. The common endpoints for the evaluation of reproductive and developmental toxic effects are the number of dead fetuses, the number of malformed fetuses, and the number of normal fetuses for each litter. With current statistical methods for the evaluation of reproductive and developmental effects, the effect on the number of deaths and the effect on the number of malformations are analyzed separately. The Dirichlet-trinomial model provides a procedure for the analysis of multiple endpoints simultaneously. This proposed Dirichlet-trinomial model is a generalization of the beta-binomial model that has been used for handling the litter effect in reproductive and developmental experiments. Likelihood ratio tests for differences in the number of deaths, the number of malformations, and the number of normals among dosed and control groups are derived. The proposed test procedure based on the Dirichlet-trinomial model is compared with that based on the beta-binomial model with an application to a real data set.
Chen
J J
JJ
National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079.
Kodell
R L
RL
Howe
R B
RB
Gaylor
D W
DW
D000014:Abnormalities, Drug-Induced; D000818:Animals; D005260:Female; D005327:Fetal Resorption; D005333:Fetus / Q000187:drug effects; D008433:Mathematics; D015233:Models, Statistical; D011247:Pregnancy; D012098:Reproduction / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens