Confidence intervals for ratios of AUCs in the case of serial sampling: a comparison of seven methods

• Published in: Pharmaceutical statistics : the journal of the pharmaceutical industry Vol. 8; no. 1; pp. 12 - 24
• Main Authors: Jaki, Thomas, Wolfsegger, Martin J., Ploner, Meinhard
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2009
• Subjects: Area Under Curve; AUC; bioequivalence; bootstrap; Confidence Intervals; Data Interpretation, Statistical; Humans; Pharmacokinetics; Research Design; Sample Size; serial sacrifice design; serial sampling design; sparse sampling; Therapeutic Equivalency
• ISSN: 1539-1604; 1539-1612; 1539-1612
• DOI: 10.1002/pst.321

Pharmacokinetic studies are commonly performed using the two‐stage approach. The first stage involves estimation of pharmacokinetic parameters such as the area under the concentration versus time curve (AUC) for each analysis subject separately, and the second stage uses the individual parameter estimates for statistical inference. This two‐stage approach is not applicable in sparse sampling situations where only one sample is available per analysis subject similar to that in non‐clinical in vivo studies. In a serial sampling design, only one sample is taken from each analysis subject. A simulation study was carried out to assess coverage, power and type I error of seven methods to construct two‐sided 90% confidence intervals for ratios of two AUCs assessed in a serial sampling design, which can be used to assess bioequivalence in this parameter. Copyright © 2008 John Wiley & Sons, Ltd.