IVPT Data Challenges in the Real World: Outliers, Anomalous and Aberrant Data: Examples.

Abstract

Background: The in vitro permeation test (IVPT) is a sensitive and robust model system that has been vital in elucidating the fundamental parameters surrounding the absorption of both therapeutic agents and industrial chemicals through skin. Unlike most clinical bioequivalence study designs, the IVPT method allows for the evaluation of multiple replicates (skin sections) from the same donor ("subject") at the same time. Though this should provide an advantage for a better characterization of the topical permeation kinetics within a donor, it also comes with the likelihood that any given skin replicate within the same donor, may demonstrate an unusual or anomalous absorption profile. These are often described as 'outliers', those sections demonstrating a substantial difference in percutaneous absorption kinetics to the other replicates.

Methods: A retrospective analysis of data from the authors' archives has been screened with the objective of finding and addressing a number of questions regarding skin section and donor data outliers, anomalous data, missing data and the establishment of a representative J_max.

Conclusion: When the IVPT method has been properly designed and performed, outliers reflect anomalies in the donor's skin and donor population rather than as an artifact of the IVPT method. Identification and statistical confirmation approaches help to differentiate anomalous data from the core data set. In addition, missing data, and determining a representative J_max, confound the accurate determination of BE for topical formulations.