Article

A simulation-based confidence band for drug concentrations in blood: an application to a clinical phase I trial.

Clinic Sendagaya, 1-29-3 Sendagaya, Shibuya-ku, Tokyo 151-0051, Japan.
Statistics in Medicine (impact factor: 1.88). 11/2003; 22(19):3045-53. DOI:10.1002/sim.1543 pp.3045-53
Source: PubMed

ABSTRACT Since drug concentrations in blood are usually related to the effectiveness and toxicity, a confidence band for the drug concentrations gives useful information for the treatment. This paper proposes a simulation-based approach for constructing confidence bands for drug concentrations in blood. The confidence band covers the whole profile of the drug concentrations with a specified probability. The proposed approach presupposes that actual concentrations of a subject fluctuate randomly around a curve specified by an appropriate pharmacokinetic model and the subject-specific pharmacokinetic parameters. The confidence band is constructed by taking into account both the random fluctuations of the actual concentrations and the statistical uncertainty of the parameter estimates. The proposed approach is applied to a simulation study and an actual phase I trial.

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Keywords

actual concentrations
 
actual phase
 
appropriate pharmacokinetic model
 
confidence band
 
confidence bands
 
drug concentrations
 
proposed approach
 
proposed approach presupposes
 
random fluctuations
 
randomly
 
simulation study
 
simulation-based approach
 
specified probability
 
statistical uncertainty
 
subject-specific pharmacokinetic parameters
 
toxicity
 
whole profile
 

Akifumi Yafune