Modifications of sequential designs in bioequivalence trials.

Area of Science:

• Pharmacokinetics and Drug Development
• Biostatistics
• Regulatory Science

Background:

• Bioequivalence (BE) studies are critical in drug development to confirm therapeutic equivalence between formulations.
• Uncertainty in formulation variability and performance necessitates adaptive study designs.
• Existing sequential designs for BE studies can be complex and lack transparency.

Purpose of the Study:

• To propose a modified sequential design for bioequivalence studies (MSDBE).
• To improve upon existing methods by simplifying multiplicity adjustment and futility stopping rules.
• To enhance the transparency and applicability of sequential designs in BE studies.

Main Methods:

• Development of the Modified Sequential Design for Bioequivalence studies (MSDBE).
• Focus on simplified multiplicity adjustment and futility stopping criteria.
• Performance evaluation through simulation studies comparing MSDBE with existing methods.

Main Results:

• MSDBE demonstrates comparable performance to original published sequential methods.
• The proposed method offers increased transparency in the study design and analysis.
• MSDBE shows improved applicability for practical use in drug development.

Conclusions:

• The MSDBE method provides a viable and improved approach for sequential bioequivalence studies.
• MSDBE facilitates more informed decision-making during study design and interim analyses.
• The availability of the R package MSDBE enhances its accessibility and adoption in pharmaceutical research.