Statistical considerations in bioequivalence of two area under the concentration–time curves obtained from serial sampling data

Steven Hua, D. Hawkins and Jihao Zhou

Journal of Applied Statistics, 2013, vol. 40, issue 5, 1140-1154

Abstract: In this paper, we study the bioequivalence (BE) inference problem motivated by pharmacokinetic data that were collected using the serial sampling technique. In serial sampling designs, subjects are independently assigned to one of the two drugs; each subject can be sampled only once, and data are collected at K distinct timepoints from multiple subjects. We consider design and hypothesis testing for the parameter of interest: the area under the concentration–time curve (AUC). Decision rules in demonstrating BE were established using an equivalence test for either the ratio or logarithmic difference of two AUCs. The proposed t-test can deal with cases where two AUCs have unequal variances. To control for the type I error rate, the involved degrees-of-freedom were adjusted using Satterthwaite's approximation. A power formula was derived to allow the determination of necessary sample sizes. Simulation results show that, when the two AUCs have unequal variances, the type I error rate is better controlled by the proposed method compared with a method that only handles equal variances. We also propose an unequal subject allocation method that improves the power relative to that of the equal and symmetric allocation. The methods are illustrated using practical examples.

Date: 2013
References: Add references at CitEc
Citations:

Downloads: (external link)
http://hdl.handle.net/10.1080/02664763.2013.780234 (text/html)
Access to full text is restricted to subscribers.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:taf:japsta:v:40:y:2013:i:5:p:1140-1154

Ordering information: This journal article can be ordered from
http://www.tandfonline.com/pricing/journal/CJAS20

DOI: 10.1080/02664763.2013.780234

Access Statistics for this article

Journal of Applied Statistics is currently edited by Robert Aykroyd

More articles in Journal of Applied Statistics from Taylor & Francis Journals
Bibliographic data for series maintained by Chris Longhurst ().