 Optimal Designs for Estimating the Effective Dose in Developmental Toxicity ExperimentsDaniel Krewski, Robert Smythe and Karen Y. Fung Risk Analysis, 2002, vol. 22, issue 6, 1195-1205 Abstract: Recent advances in risk assessment have led to the development of joint dose‐response models to describe prenatal death and fetal malformation rates in developmental toxicity experiments. These models can be used to estimate the effective dose corresponding to a 5% excess risk for both these toxicological endpoints, as well as for overall toxicity. In this article, we develop optimal experimental designs for the estimation of the effective dose for developmental toxicity using joint Weibull dose‐response models for prenatal death and fetal malformation. Based on an extended series of developmental studies, near‐optimal designs for prenatal death, malformation, and overall toxicity were found to involve three dose groups: an unexposed control group, a high dose equal to the maximum tolerated dose, and a low dose above or comparable to the effective dose. The effect on the optimal designs of changing the number of implants and the degree of intra‐litter correlation is also investigated. Although the optimal design has only three dose groups in most cases, practical considerations involving model lack of fit and estimation of the shape of the dose‐response curve suggest that, in practice, suboptimal designs with more than three doses will often be preferred. Date: 2002 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:wly:riskan:v:22:y:2002:i:6:p:1195-1205 Access Statistics for this article More articles in Risk Analysis from John Wiley & Sons |
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