Group Sequential Design and Analysis of Bioequivalence Study for Non-systematic Drug Product

I. INTRODUCTION When the drug can be absorbed by the blood system, the bioequivalence of a generic drug is evaluated with a crossover design based on pharmacokinetic endpoints. However, for treatment of non-systemic symptoms, bioequivalence evaluation is regularly designed as a randomized clinical trial with three parallel treatment groups – T, the test treatment group, R, the reference treatment (the innovative drug product) group and P, the placebo group. The study endpoint is often the therapeutic outcome. The objective of the study is to assess whether the test treatment is effective and whether it is equivalent to the referenced innovative product with the pre-specified equivalence limit. Hence the analysis involves testing of the following hypotheses [1]