All Times EDT
Keywords: Bioequivalence study, Parallel design
Bioequivalence study is designed to compare bioavailabilities of different formulations of the same drug or different drug products. Bioavailability is the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of drug action, and is usually measured with Cmax (maximum drug concentration) and AUC (area under the drug concentration versus time curve). In general, bioequivalence is concluded if confidence intervals for test-to-reference ratios are within (80%, 125%) for both Cmax and AUC. Common bioequivalence study often uses two-sequence, two-period crossover design. Based on this design, Potvin, et al. compared four methods for sample size re-estimation based on the variance estimated from the first stage to minimize the increase in type I error rate. In oncology studies, due to the nature of the diseases and treatment, a crossover design is usually not ethical, and parallel study is commonly used. However, few studies have extended these methods to two-stage parallel study design. In our study, we extend Potvin’s methods to the two-stage parallel study design with more than two treatment arms, and to study with unbalanced sample sizes between treatment groups in stage 1, stage 2 or both.