On the Asymmetrical Margins Approach to Biosimilarity Clinical Trials with Efficacy Endpoints

• Activity Number: 343
• Type: Contributed
• Date/Time: Tuesday, July 31, 2012 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Yulan Li*+ and Qing Liu
• Companies: Novartis and Johnson & Johnson
• Keywords: Bioequivalence trials ; Immunogenicity ; Lower Predictive Bound ; Non-inferiority Trials ; Retention of effect

Abstract

Development of biosimilars to innovative therapeutic biologics promises reduction of health care cost, and therefore, provide patients world wide more access to effective treatments. Because of the differences in the raw materials or manufacturing processes, "equivalence" of bioavailability between a biosimilar and the reference biologic is generally insufficient, and clinical trials providing efficacy and safety data are often required by regulatory agencies. Motivated by the World Health Organization (WHO) guideline (2009)and FDA draft guidance (2012), we propose a biosimilarity trial design for evaluating clinical efficacy. The design employs a non-inferiority margin and an asymmetrical non-superiority margin for statistical inference. The choice of both margins provides the scientific foundation for drawing clinical efficacy conclusions while maintaining the logical consistency of the inference. The design also has a higher statistical power than a naive equivalence trial design.