부산대학교 도서관

Nonlinear mixed effects models (NLMEM) are used in pharmacokinetics to analyse concentrations of patients during drug development, particularly for pediatric studies. Approaches based on the Fisher information matrix can be used to optimize their design. Local design needs some a priori parameter values which might be difficult to guess. Therefore, two-stage adaptive designs are useful to provide some flexibility. We implemented in the R function PFIM the Fisher matrix for two-stage designs in NLMEM. We evaluated, with simulations, the impact of one-stage and two-stage designs on the precision of parameter estimation when the true and a priori parameters are different. [ABSTRACT FROM PUBLISHER]