Sample size determination in bioequivalence studies under 2x2 crossover design

Approximate formulas for sample size determination are derived based on Schuirmann's (1987) two one-sided tests (TOST) in bioequivalence studies. For bioequivalence studies, the additive and the multiplicative models are used. The most popular design is 2x2 crossover design, which contains two sequences, two periods and two treatments. In clinical trials, crossover trials are experiments in which patients/volunteer are allocated a series of treatments with the objective of comparing the different treatments or different doses of the same treatment. This design attracts clinicians because it eliminates between subjects variability.Sample size calculation plays an important role in bioequivalence trials. In practice, a bioequivalence study is usually conducted under a crossover design or a parallel design with raw data or log-transformed data. The purpose of this work is to determine the number of subjects/sample size required to conduct a clinical trial in order to compare the efficacy or futility of a new produced drug/treatment with that of the reference drug in case of heterogeneous variability. A simulation study was carried out to construct two-one sided (1-2alpha)x100 percent confidence intervals for ratios of the test and reference formulations of a drug product to assess whether the test and the reference drug products are bioequivalence or not. Finally, the simulation is performed through R 2.14.0 statistical software.