Interpretation of Simulation Studies for Efficient Estimation of Population Pharmacokinetic Parameters

OBJECTIVE:To develop new approaches for evaluating results obtained from simulation studies used to determine sampling strategies for efficient estimation of population pharmacokinetic parameters.METHODS:One-compartment kinetics with intravenous bolus injection was assumed and the simulated data (one observation made on each experimental unit [human subject or animal]), were analyzed using NONMEM. Several approaches were used to judge the efficiency of parameter estimation. These included: (1) individual and joint confidence intervals (CIs) coverage for parameter estimates that were computed in a manner that would reveal the influence of bias and standard error (SE) on interval estimates; (2) percent prediction error (%PE) approach; (3) the incidence of high pair-wise correlations; and (4) a design number approach. The design number (Φ) is a new statistic that provides a composite measure of accuracy and precision (using SE).RESULTS:The %PE approach is useful only in examining the efficiency of estimation...