A Constrained Noninferiority Approach for Assessing Clinical Efficacy to Establish Biosimilarity

• Activity Number: 145
• Type: Contributed
• Date/Time: Monday, August 10, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Jason Liao*
• Companies: Novartis Pharmaceuticals
• Keywords: Biosimilarity ; Constrained non-inferiority ; Effect preservation ; Equivalence ; Power ; Type I error

Abstract

To develop a biosimilar product, it is necessary to demonstrate biosimilarity between the proposed biosimilar product and the reference product in terms of the purity, potency, efficacy, and safety. In this paper, clinical efficacy data required for establishing biosimilarity are considered. Non-inferiority (NI) and equivalence methods are commonly used for analyzing clinical trials to meet this requirement. The equivalence approach often requires large, costly, and lengthy clinical trials. The non-inferiority approach while requiring somewhat smaller trials are not accepted by all as adequately addressing the similarity issue between the proposed biosimilar product and the reference product as they do not rule out the prospect that the biosimilar product has increased activity which might be associated with more adverse effects. To address some of the challenges faced by the use of non-inferiority or equivalence methods, a constrained non-inferiority (cNI) approach is proposed to address both the clinical efficacy of the biosimilar product and the similarity to the reference product. The performance of the proposed constrained non-inferiority approach for analyzing a biosimilar