Software
Data modeling and simulation were performed primarily in software NONMEM (ICON, Ellicott City, Maryland, version 7.3) in conjunction with a gfortran (64-bit) compiler using Pirana (version 2.9.7)16 as an interface. The Laplace integral approximation with -2 times log-likelihood option was used throughout the analyses. The R environment17 for statistical computing version 3.6.2 was used for simulation and plotting.