A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models

A method is presented for automated preparation of bootstrap data samples a nd their presentation to NONMEM for use in the validation of population pha rmacokinetic or pharmacodynamic models, which have been developed with rela tively small numbers of subjects. The bootstrap sampling procedure involves the use of an MS-DOS batch file and a script file for use with the public- domain text processing program, AWK, which is a single EXE file (48k in siz e for the version used in this report). A UNIX version of AWK is also avail able and UNIX users can adapt the process to their needs. Its use obviates the need for expensive, high-end statistical packages and associated script files written using in-built programming languages. The method can easily be adapted to bootstrap sampling requirements in other biomedical modelling applications. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.