Adaptive designs for IVPT data with mixed scaled average bioequivalence.

Area of Science:

• Pharmacokinetics and Drug Delivery
• Biostatistics
• Dermatological Drug Development

Background:

• In vitro permeation tests (IVPT) are crucial for developing topical dermatological products.
• The FDA proposes a new experimental design for assessing bioequivalence of generic acyclovir 5% cream using IVPT.
• Mixed scaled average bioequivalence (MSABE) is the hypothesis testing method for this design.

Purpose of the Study:

• To examine the statistical properties of the MSABE method for IVPT bioequivalence studies.
• To develop and evaluate adaptive designs incorporating MSABE for enhanced efficiency and power.
• To explore modifications for adaptive designs in IVPT bioequivalence trials.

Main Methods:

• Incorporation of MSABE into an adaptive design combining group sequential design and sample size re-estimation.
• Conducting simulation studies to assess passing rates of proposed adaptive methods.
• Considering modifications such as Bonferroni's adjustment and conditional power function.

Main Results:

• Simulation studies evaluated the performance of adaptive designs under various scenarios.
• The proposed adaptive designs demonstrated potential for earlier decisions and resource savings.
• Modifications like Bonferroni's adjustment and conditional power were considered for improved control.

Conclusions:

• Adaptive designs integrating MSABE offer a promising approach for efficient IVPT bioequivalence trials.
• These methods can optimize resource allocation while maintaining statistical rigor.
• A case study confirmed the practical advantages of adaptive methods in real-world data analysis.