PHARMACOMETRICS A Comparison of the Two One-Sided Tests Procedure and the Power Approach for Assessing the Equivalence of Average Bioavailability

The statistical test o f the hypothesis o f no difference between the average bioavailabilities o f two drug formulations, usually supplemented by an assessment of what the power of the statistical test would have been i f the true averages had been inequivatent, continues to be used in the statistical analysis of bioavailability/bioequivalence studies. In the present article, this Power Approach (which in practice usually consists o f testing the hypothesis o f no difference at level 0.05 and requiring an estimated power o f 0.80) is compared to another statistical approach, the Two One-Sided Tests Procedure, which leads to the same conclusion as the approach proposed by Westlake (2) based on the usual (shortest) 1 2 a confidence interval for the true average difference. It is found that for the specific choice of a = 0.05 as the nominal level of the one-sided tests, the two one-sided tests procedure has uniformly superior properties to the power approach in most cases. The only cases where the power approach has superior plvperties when the true averages are equivalent correspond to cases where the chance of concluding equivalence with the power approach when the true averages are not equivalent exceeds 0.05. With appropriate choice of the nominal level of significance o f the one-sided tests, the two one-sided tests procedure always has uniformly superior properties to the power approach. The two one-sided tests procedure is compared to the procedure proposed by Hauck and Anderson (1).