We consider a re-sampling scheme for estimation of the population parameters in the mixed-effects nonlinear regression models of the type used, for example, in clinical pharmacokinetics. We provide a two-stage estimation procedure which resamples (or recycles), via random weightings, the various parameter's estimates to construct consistent estimates of their respective sampling distributions. In particular, we establish under rather general distribution-free assumptions, the asymptotic normality and consistency of the standard two-stage estimates and of their resampled version and demonstrate the applicability of our proposed resampling methodology in a small simulation study. A detailed example based on real clinical pharmacokinetic data is also provided.

我们考虑重新采样方案，用于估计混合效应非线性回归模型中使用的类型（例如，临床药代动力学）中的群体参数。我们提供了一个两阶段的估计程序，它通过随机加权重新采样（或回收）各种参数的估计值，以构建其各自采样分布的一致估计值。特别是，我们在相当普遍的无分布假设下建立了标准两阶段估计及其重采样版本的渐近正态性和一致性，并证明了我们提出的重采样方法在小型模拟研究中的适用性。还提供了基于真实临床药代动力学数据的详细示例。