Maximum likelihood estimation of nonlinear mixed-effects models with crossed random effects by combining first-order conditional linearization and sequential quadratic programming

Nonlinear mixed-eirects (NLME) modek have become popular in various disciplines over the past several decades.However,the existing methods for parameter estimation imple-mented in standard statistical packages such as SAS and R/S-Plus are generally limited k) single-or multi-level NLME models that only allow nested random effects and are unable to cope with crossed random effects within the framework of NLME modeling.In t his study,wc propose a general formulation of NLME models that can accommodate both nested and crassed random effects,and then develop a computational algorit hm for parameter estimation based on normal assumptions.The maximum likelihood estimation is carried out using the first-order conditional expansion (FOCE) for NLME model linearization and sequential quadratic programming (SCJP) for computational optimization while ensuring positive-definiteness of the estimated variance-covariance matrices of both random effects and error terms.The FOCE-SQP algorithm is evaluated using the height and diameter data measured on trees from Korean larch (L.olgeiisis var,Chang-paienA.b) experimental plots aa well as simulation studies.We show that the FOCE-SQP method converges fast with high accuracy.Applications of the general formulation of NLME models are illustrated with an analysis of the Korean larch data.