Pilot trial for the assessment of relative bioavailability in generic drug product development: statistical power

In developing generic drug products, pilot trials are used for identifying successful test formulations to enter pivotal trials. In this study, we derive the power function based on the log-normal distribution and evaluate the effects of potential influential factors-the true test-reference ratio, intrasubject variability, and sample sizes-on the statistical power of a pilot trial to identify successful test formulations, defined as the probability that the test-reference ratio estimate from a pilot trial falls within a predetermined acceptance range when the true ratio is acceptable. Of these influential factors, the test-reference ratio exhibits the largest impact on the statistical power of a pilot trial, followed by intrasubject variability, sample sizes of pivotal trials, and sample sizes of pilot trials. The sample sizes that are used in pilot trials (8-12 subjects) may be sufficient for test products with low intrasubject variability and true ratio close to 1 and may fall short otherwise.