A Study on Statistical Evaluation of In Vitro Bioequivalence with Consideration of Variance Components
Date Issued
2009
Date
2009
Author(s)
Tsai, Pei-Ying
Abstract
For some locally acting products such as nasal aerosols and nasal sprays that are not intended to be absorbed into the bloodstream, the in vitro bioavailability / bioequivalence studies based on machinery experiments are used to measure that whether the two drug products provide the same therapeutic effect. According to the U.S. Food and Drug Administration (FDA) draft guidance (2003b), the evaluation of the in vitro bioequivalence (BE) between two drug products would be determined by comparing the upper 95% confidence limit of with zero. This method was first proposed by Hyslop, Hsuan and Holder (2000) based on a linearized bioequivalence criterion. However, their method does not consider the variations due to different sources. Hence, we apply the method of modified large-sample (MLS) for the variance components under the 2-stage nested random-effects model for construction of the upper 95% confidence limit. The total variance of the 95% upper limit considers the variance components due to lot, life stage and sample which are obtained through the MLS method. The results of empirical size and empirical power from simulation under different sample size and variance combinations are provided to investigate the performance of the extended MLS method. A numerical example illustrates the proposed method.
Subjects
Nasal Aerosols
Nasal Sprays
In Vitro Bioequivalence and Bioavailability
Upper 95% Confidence Limit
MLS
Variance Components
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-98-R96621203-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):4bee91b8bb8e17137ac13dac95ad26f9