Optimal experimental design strategies for detecting hormesis
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Date
2010-06-15
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Abstract
Hormesis is a widely observed phenomenon in many branches of life sciences
ranging from toxicology studies to agronomy with obvious public health and risk
assessment implications. We address optimal experimental design strategies for
determining presence of hormesis in a controlled environment using the recently
proposed Hunt-Bowman model. We propose alternative models that have an implicit
hormetic threshold, discuss their advantages over current models, construct
and study properties of optimal designs for (i) estimating model parameters, (ii)
estimating the threshold dose, and (iii) testing for the presence of hormesis.
We also determine maximin optimal designs that maximize the minimum of the
design efficiencies when we have multiple design criteria or there is model uncertainty
where we have a few plausible models of interest. We apply our optimal
design strategies to a teratology study and show our proposed designs outperform
the implemented design by a very wide margin for many situations.
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Keywords
Continuous design, Dose-response, Hunt-Bowman model, Logistic model, Maximin design, Quadratic-logistic model, Weibull model