A Dose-Finding Method in Joint Modeling of Efficacy and Safety: An Extension of the MCP-Mod Method

• Activity Number: 514
• Type: Contributed
• Date/Time: Wednesday, August 4, 2010 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Aiyang Tao*+ and Yong Lin and Jose Carlos Pinheiro and Weichung J. Shih
• Companies: Novartis and University of Medicine and Dentistry of New Jersey and Johnson & Johnson and University of Medicine and Dentistry of New Jersey
• Keywords: Dose Finding ; Joint Modeling ; Efficacy and Safety ; MCP-Mod ; risk benefit

Abstract

Determination of appropriate dose(s) to advance into Phase III is one of the most challenging and important decisions made during drug development. Selecting a dose too high may result in unacceptable safety problems, while a too low dose may lead to ineffective drugs. Proper estimation of such dose-response profiles for relevant safety and efficacy endpoints allows the reliable evaluation of the risk benefit profile of a drug at the end of Phase II, as well as the selection of appropriate doses to be brought into confirmatory Phase III trials. This paper will address how to select dose(s) in Phase II trials by combining information about the efficacy and safety in a joint model setting. The methods we present in the paper may play a key role in drug development program and are often the gate-keeper for large confirmatory Phase III trials with greater chance for success of approval.