Optimal designs for dose-finding experiments in toxicity studies

Dette, H., Pepelyshev, Andrey ORCID: https://orcid.org/0000-0001-5634-5559 and Wong, W. K. 2009. Optimal designs for dose-finding experiments in toxicity studies. Bernoulli 15 (1) , pp. 124-145. 10.3150/08-BEJ152

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Abstract

We construct optimal designs for estimating fetal malformation rate, prenatal death rate and an overall toxicity index in a toxicology study under a broad range of model assumptions. We use Weibull distributions to model these rates and assume that the number of implants depend on the dose level. We study properties of the optimal designs when the intra-litter correlation coefficient depends on the dose levels in different ways. Locally optimal designs are found, along with robustified versions of the designs that are less sensitive to misspecification in the initial values of the model parameters. We also report efficiencies of commonly used designs in toxicological experiments and efficiencies of the proposed optimal designs when the true rates have non-Weibull distributions. Optimal design strategies for finding multiple-objective designs in toxicology studies are outlined as well.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Mathematics
Subjects:	Q Science > QA Mathematics
Uncontrolled Keywords:	dose-finding experiment; locally c-optimal design; multiple-objective design; robust optimal design; Weibull model
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/1350-7265/ (accessed 25/02/2014)
Publisher:	Bernoulli Society for Mathematical Statistics and Probability
ISSN:	1350-7265
Date of First Compliant Deposit:	30 March 2016
Last Modified:	14 May 2023 11:03
URI:	https://orca.cardiff.ac.uk/id/eprint/49059

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