Optimum designs for non-linear mixed effects models in the presence of covariates.

In this article, we present a new method for optimizing designs of experiments for non-linear mixed effects models, where a categorical factor with covariate information is a design variable combined with another design factor. The work is motivated by the need to efficiently design preclinical experiments in enzyme kinetics for a set of Human Liver Microsomes. However, the results are general and can be applied to other experimental situations where the variation in the response due to a categorical factor can be partially accounted for by a covariate. The covariate included in the model explains some systematic variability in a random model parameter. This approach allows better understanding of the population variation as well as estimation of the model parameters with higher precision.