Fitting correlated residual error structures in nonlinear mixed-effects models using SAS PROC NLMIXED

Nonlinear mixed-effects (NLME) models remain popular among practitioners for analyzing continuous repeated measures data taken on each of a number of individuals when interest centers on characterizing individual-specific change. Within this framework, variation and correlation among the repeated measurements may be partitioned into interindividual variation and intraindividual variation components. The covariance structure of the residuals are, in many applications, consigned to be independent with homogeneous variances, σ2Ini$$ {\sigma}^2{\mathbf{I}}_{n_i} $$, not because it is believed that intraindividual variation adheres to this structure, but because many software programs that estimate parameters of such models are not well-equipped to handle other, possibly more realistic, patterns. In this article, we describe how the programmatic environment within SAS may be utilized to model residual structures for serial correlation and variance heterogeneity. An empirical example is used to illustrate the capabilities of the module.