Recycled Two-Stage Estimation in Nonlinear Mixed Effects Regression Models

Abstract

We consider a re-sampling scheme for estimation of the population parameters in the mixed effects nonlinear regression models of the type use for example in clinical pharmacokinetics, say. We provide an estimation procedure which {\it recycles}, via random weighting, the relevant two-stage parameters estimates to construct consistent estimates of the sampling distribution of the various estimates. We establish the asymptotic consistency and asymptotic normality of the resampled estimates and demonstrate the applicability of the {\it recycling} approach in a small simulation study and via example.