Robustness of design in dose–response studies

Authors


Douglas P. Wiens, Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, Alberta, T6G 2G1, Canada.
E-mail: doug.wiens@ualberta.ca

Abstract

Summary.  We construct experimental designs for dose–response studies. The designs are robust against possibly misspecified link functions; for this they minimize the maximum mean-squared error of the estimated dose required to attain a response in 100p% of the target population. Here p might be one particular value—p=0.5 corresponds to ED50-estimation—or it might range over an interval of values of interest. The maximum of the mean-squared error is evaluated over a Kolmogorov neighbourhood of the fitted link. Both the maximum and the minimum must be evaluated numerically; the former is carried out by quadratic programming and the latter by simulated annealing.

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