Bootstrap approach for constructing confidence intervals for population pharmacokinetic parameters. II: A bootstrap modification of standard two-stage (STS) method for phase I trial.
For population pharmacokinetics in phase I trials, the standard two-stage (STS) method is quite appealing, especially to non-statisticians, because the method is theoretically and computationally simple. The method, however, does not take into account the uncertainty in estimating individual-specific parameters and gives biased estimates for population variances of pharmacokinetic parameters. This is one of the main reasons why the STS method is not generally recommended. This paper proposes a simple bootstrap modification of the STS method for estimating confidence intervals of population means and standard deviations of pharmacokinetic parameters in phase I trials. The proposed approach adopts a bootstrap bias correction in estimating population variances of pharmacokinetic parameters. Applications are given to a simulated data set and an actual phase I trial to show how the proposed approach works in practice.
Yafune
A
A
Department of Clinical Pharmacology, Kitasato Institute, Tokyo, Japan.
Ishiguro
M
M
D017321:Clinical Trials, Phase I as Topic / Q000379:methods / Q000706:statistics & numerical data*; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D003710:Demography; D006801:Humans; D015233:Models, Statistical; D010599:Pharmacokinetics