Novel Adaptive Design for Integrated Development of Therapies with Competitive Challenge

• Activity Number: 36
• Type: Contributed
• Date/Time: Sunday, July 29, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Yijie Zhou*+ and Ziliang Li and Amarjot Kaur
• Companies: Merck and Merck and Merck Research Laboratories
• Keywords: adaptive design ; combination therapy ; additivity

Abstract

Drug development is a complex process and becomes more challenging when a large number of therapies already exist. The development goal in the presence of available competing therapies also includes to investigate whether the new therapy is additive to existing therapies and provides enhanced efficacy. A trial to test additivity, i.e., to compare the combination therapy with its individual components, typically requires larger sample size than a trial to test monotherapy efficacy, due to the reduced effect size on top of an already efficacious therapy. Thus there is a need to utilize novel trial designs when developing such drugs to address the competitive environment. This presentation will discuss the novel trial designs with an integrated adaptive strategy across a monotherapy dose-ranging study and a combination therapy crossover study with series of planned interim analyses to minimize upfront cost. The primary objective of the planned interim analyses is to inform the conduct (or not) of an affirmative and more costly assessment of combination therapy. The operating characteristics of such designs along with challenges of decision making will also be discussed.