title: Cluster sampling techniques in quantal response teratology and developmental toxicity studies.
abstract: This paper presents a model-free approach for evaluating teratology and developmental toxicity data involving clustered binary responses. In teratology studies, a major statistical problem arises from the effect of intralitter correlation, or the potential for littermates to respond similarly. Some statistical methods impose strict distributional assumptions to account for extra-binomial variation, while others rely on nonparametric resampling and empirical variance estimation techniques. Quasi-likelihood methods and generalized estimating equations (GEE), which model the marginal mean/variance relationship, also avoid strict distributional assumptions. The proposed approach, often used to analyze complex sample survey data, is based on a first-order Taylor series approximation and a between-cluster variance estimation procedure, yielding consistent variance estimates for binomial-based proportions and regression coefficients from dose-response models. The cluster sample technique, presented here in the context of a logistic dose-response model, incorporates many of the advantages of quasi-likelihood methods, are valid for any underlying nested correlation structure, and are adaptable to a variety of analytical settings. The results of a simulation study show the cluster sample technique to be a viable competitor to GEE methods currently receiving attention.
authors.affiliation: Research Triangle Institute, Research Triangle Park, North Carolina 27709-2194, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Bieler
authors.forename: R L
authors.initials: RL
authors.lastname: Williams
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D016000:Cluster Analysis; D005260:Female; D005313:Fetal Death; D008098:Litter Size; D015233:Models, Statistical; D011247:Pregnancy; D011336:Probability; D011897:Random Allocation; D012044:Regression Analysis; D013723:Teratogens / Q000633:toxicity*; D018600:Teratology / Q000379:methods; D014116:Toxicology / Q000379:methods*
chemical_list: D013723:Teratogens