Abstract
Average biosimilarity is investigated under a three-arm parallel design: one arm corresponds to the test drug T, and the other two arms correspond to two versions of the reference drug, say R1 and R2. The hypothesis of interest is the equivalence of the population average response for T with the mean of the population average responses for R1 and R2. The parameter of interest is formulated as the absolute difference of the above two averages, scaled by the absolute difference between the population means corresponding to R1 and R2. A difference parameter is also proposed. For the ratio parameter, a test can be derived using the asymptotic normality of an appropriate test statistic; however, the test is not satisfactory in terms of type I error probabilities. Improved tests are derived by applying a bootstrap calibration, and by using the idea of a generalized pivotal quantity (gpq). The tests are developed under equal variance and unequal variance scenarios. Sample size determination is also addressed. For the difference parameter, a satisfactory test is developed using the gpq idea. The proposed methods result in tests that are satisfactory in terms of type I error performance
Highlights
Biosimilar drugs are highly similar products or imitations of already approved biological drugs
We developed a test using the concept of a generalized pivotal quantity
In order to assess the performance of the delta method based test proposed by Kang and Chow [7] along with the improvement resulting from bootstrap calibration, and to compared with the gpq based test, we shall report some simulation results
Summary
Biosimilar drugs are highly similar products or imitations of already approved biological drugs. For the approval of generic drug products, the commonly used method is to assess average bioequivalence (ABE) regarding drug absorption through the conduct of bioequivalence studies. Such a criterion alone may not be appropriate for concluding biosimilarity; the equivalence of averages should be a minimum requirement. We refer to the U.S FDA guidance document [6] and the book by Chow [2] for further background information on biosimilars. Chow’s book provides a thorough discussion, including a discussion of the various statistical criteria that can be used for establishing biosimilarity
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