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Cost-cautious designs for confirmatory bioassay
Authors:Alexander N Donev  Randy Tobias  Farinaz Monadjemi
Institution:1. School of Mathematics, University of Manchester, Manchester, M13 9PL, UK;2. Linear Models R&D, SAS Institute Inc., Cary, NC 27513, USA;3. Department of Probability and Statistics, University of Sheffield, Sheffield, S3 7RH, UK
Abstract:Confirmatory bioassay experiments take place in late stages of the drug discovery process when a small number of compounds have to be compared with respect to their properties. As the cost of the observations may differ considerably, the design problem is well specified by the cost of compound used rather than by the number of observations. We show that cost-efficient designs can be constructed using useful properties of the minimum support designs. These designs are particularly suited for studies where the parameters of the model to be estimated are known with high accuracy prior to the experiment, although they prove to be robust against typical inaccuracies of these values. When the parameters of the model can only be specified with ranges of values or by a probability distribution, we use a Bayesian criterion of optimality to construct the required designs. Typically, the number of their support points depends on the prior knowledge for the model parameters. In all cases we recommend identifying a set of designs with good statistical properties but different potential costs to choose from.
Keywords:Bayesian experimental design  Bioassay  DD- and Ggif" overflow="scroll">D- and GG-optimality" target="_blank">gif" overflow="scroll">G-optimality  Cost-cautious designs  General Equivalence Theorem  Nonlinear models
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