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

Area of Science:

• Dermatology
• Pharmacokinetics
• Toxicology

Background:

• The in vitro permeation test (IVPT) is a key method for studying skin absorption of chemicals and drugs.
• IVPT allows multiple skin replicates from a single donor, offering detailed kinetic analysis.
• Anomalous absorption profiles ('outliers') can occur within replicates from the same donor.

Purpose of the Study:

• To investigate the nature and implications of data outliers in IVPT.
• To address issues of anomalous data, missing data, and representative Jmax determination in IVPT.
• To differentiate true biological variability from methodological artifacts in skin permeation studies.

Main Methods:

• Retrospective analysis of data from the authors' archives.
• Screening for and evaluating skin section and donor data outliers.
• Assessing anomalous and missing data points.
• Investigating methods for establishing a representative maximum flux (Jmax).

Main Results:

• Outliers in IVPT typically reflect genuine anomalies in donor skin or population, not the test method itself.
• Statistical approaches are effective in distinguishing anomalous data from the main dataset.
• Missing data and challenges in determining a representative Jmax can hinder accurate bioequivalence (BE) assessment.

Conclusions:

• When properly conducted, IVPT outliers are informative about biological variability.
• Identifying and statistically validating outliers is essential for robust IVPT data interpretation.
• Accurate determination of bioequivalence for topical products relies on addressing data anomalies and missing values.