Achieving target goals most precisely using nonparametric compartmental models and "multiple model" design of dosage regimens

Multiple model (MM) design and stochastic control of dosage regimens permit essentially full use of all the information contained in either a Bayesian prior nonparametric EM (NPEM) population pharmacokinetic model or in an MM Bayesian posterior updated parameter set, to achieve and maintain selected therapeutic goals with optimal precision (least predicted weighted squared error). The regimens are visibly more precise in the achievement of desired target goals than are current methods using mean or median population parameter values. Bayesian feedback has now also been incorporated into the MM software. An evaluation of MM dos:age design using an NPEM population model versus dosage design based on conventional mean population parameter values is presented, using a population model of vancomycin. Further feedback control was also evaluated, incorporating realistic simulated uncertainties in the clinical environment such as those in the preparation and administration of doses.