Robustness of design in dose-response studies

Abstract

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. © 2011 Royal Statistical Society.