A note on sample size determination for bioequivalence studies with high-order crossover designs

Area of Science:

• Pharmacokinetics and Drug Development
• Biostatistics
• Clinical Trial Design

Background:

• Bioequivalence studies are crucial for comparing drug formulations.
• Accurate sample size determination is essential for the statistical power of bioequivalence assessments.
• Higher-order crossover designs are increasingly used in pharmaceutical development.

Purpose of the Study:

• To derive approximate formulas for sample size determination in bioequivalence studies.
• To apply these formulas to various higher-order crossover designs.
• To facilitate sample size calculations for comparing two drug formulations.

Main Methods:

• Utilized Schuirmann's two one-sided tests procedure.
• Derived formulas for additive and multiplicative models.
• Applied methods to Balaam's design, two-sequence dual design, and two four-period designs.
• Tabulated required sample sizes for selected powers and parameter values.

Main Results:

• Developed simple, pocket-calculator-friendly formulas for sample size determination.
• Provided tabulated sample sizes for four common higher-order crossover designs.
• Formulas are applicable to both additive and multiplicative bioequivalence models.

Conclusions:

• The derived formulas offer a practical approach to sample size calculation in bioequivalence studies.
• The study simplifies the process for researchers using higher-order crossover designs.
• Results support efficient planning of clinical trials for drug formulation comparison.