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Assessment of Bioequivalence and Biosimilarity (306696)

Keywords: Bioequivalence, similarity, bootstrap calibration, overlap coefficient, fiducial, quadratic form.

A common bioequivalence criterion is the average bioequivalence (ABE), testing if the difference of appropriate mean responses is within a predefined limit. A popular ABE test is the two one-sided t-test (TOST). The TOST is conservative as the variability increases. While this may not always be a practical concern, we noticed that this conservatism can be fixed by applying a bootstrap calibration, making the type I error closer to the nominal level and significant gain in power.

For assessing equivalence, an evaluation of the similarity between the distributions of the responses can be used as an alternative criterion. We propose the use of the overlap coefficient (OC), which is the area of overlap between two probability distributions, as a measure of similarity between distributions. Using a fiducial approach, we have explored the computation of confidence limits for the OC value.

For assessing multivariate bioequivalence, we explore a test due to Munk and Pfluger (1999), when the hypothesis is stated in terms of a quadratic form, and the test is derived by inverting Hotelling’s T^2. We have characterized the test somewhat explicitly using results from Dong and Mathew (2015).