Sample Size Determination and Study Design Impact on Dose-Scale Pharmacodynamic Bioequivalence: a Case Study Using...

Area of Science:

• Pharmacometrics
• Drug Bioequivalence
• Pharmacodynamics

Background:

• Dose-scale pharmacodynamic bioequivalence is crucial for locally acting drugs.
• Orlistat serves as a model drug for evaluating formulation consistency.

Purpose of the Study:

• Investigate sample size determination for dose-scale pharmacodynamic bioequivalence.
• Assess the impact of different study designs on bioequivalence evaluation.

Main Methods:

• Developed a population pharmacodynamic model for orlistat using NONMEM.
• Simulated three study designs (2x1 and 2x2 crossovers) with varying test/reference ratios.
• Determined sample sizes using a stochastic simulation and estimation approach.

Main Results:

• Study Design 3 (2x2 crossover) required the minimum sample size for bioequivalence.
• Study Design 2 was the least efficient in sample size determination.
• Asymmetric sample size requirements were observed based on the test/reference ratio, varying by study design.

Conclusions:

• Study Design 3 is the most effective for minimizing sample size in orlistat bioequivalence studies.
• The choice of study design significantly impacts sample size determination.
• Test/reference ratio influences sample size requirements asymmetrically across designs.