Bootstrap approach for constructing confidence intervals for population pharmacokinetic parameters. II: a bootstrap modification of standard two-stage (STS) method for phase I trial

✍ Scribed by Akifumi Yafune; Makio Ishiguro

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 133 KB
• Volume: 18
• Category: Article
• ISSN: 0277-6715
• DOI: 10.1002/(sici)1097-0258(19990315)18:5<601::aid-sim48>3.0.co;2-l

✦ Synopsis

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.