To develop a biosimilar product, it is necessary to demonstrate\nbiosimilarity between the proposed biosimilar product and the\nreference product in terms of the purity, potency, efficacy, and\nsafety. In this paper, clinical efficacy data required for establishing\nbiosimilarity are considered. Non-inferiority (NI) and equivalence\nmethods are commonly used for analyzing clinical trials to meet\nthis requirement. The equivalence approach often requires large,\ncostly, and lengthy clinical trials. The non-inferiority approach\nwhile requiring somewhat smaller trials are not accepted by all as\nadequately addressing the similarity issue between the proposed\nbiosimilar product and the reference product as they do not rule out\nthe prospect that the biosimilar product has increased activity which\nmight be associated with more adverse effects. To address some\nof the challenges faced by the use of non-inferiority or equivalence\nmethods, a constrained non-inferiority (cNI) approach is proposed\nto address both the clinical efficacy of the biosimilar product and\nthe similarity to the reference product. The performance of the\nproposed constrained non-inferiority approach for analyzing a\nbiosimilar trial is demonstrated through simulation and examples.
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