Modification of pharmacokinetic sampling schedules in clinical phase I trials: a use of Kullback-Leibler information.
In clinical phase I trials, pharmacokinetic sampling schedules often have to be modified while the trials proceed. The modifications are based on the observations from a limited number of subjects or only one subject in extreme cases. This paper describes a Kullback-Leibler information approach for modifying pharmacokinetic sampling schedules in clinical phase I trials. The proposed approach presupposes that the pharmacokinetic profile for each subject is specified by an appropriate pharmacokinetic model and the subject-specific parameters. The best modification plan is selected from arbitrarily chosen candidates based on the Kullback-Leibler information. Applications are given to a simulation study and an actual phase I trial of an anti-cancer drug.
Yafune
A
A
Division of Biostatistics, Center for Clinical Pharmacy and Clinical Sciences, Kitasato University Graduate School, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Ishiguro
M
M
D017321:Clinical Trials, Phase I as Topic / Q000706:statistics & numerical data*; D016001:Confidence Intervals; D016903:Drug Monitoring / Q000706:statistics & numerical data*; D006801:Humans; D008432:Mathematical Computing; D015233:Models, Statistical; D010599:Pharmacokinetics