Response-Adaptive Dose Finding Combing Multiple Comparison and Modeling Approaches

• Activity Number: 177
• Type: Topic Contributed
• Date/Time: Monday, August 4, 2008 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Frank Bretz*+ and Jose Pinheiro and Bjoern Bornkamp
• Companies: Novartis Pharmaceuticals and Novartis Pharmaceuticals and University of Dortmund
• Keywords: dose-response ; dose-finding ; contrast ; multiple testing ; non-linear regression ; adaptation

Abstract

Adaptive dose-ranging studies form an innovative class of designs aimed at striking the desired balance between needed dose response information and increased costs and timelines. In these designs, the number of doses and/or proportion of patients allocated to doses are allowed to change as safety and efficacy information is accrued and analyzed. This presentation will describe an adaptive dose-ranging approach based on a hybrid methodology combining multiple comparison procedures (MCP) and modeling, the so-called MCP-Mod method. In the response-adaptive version of MCP-Mod, dose allocation ratios are recalculated at each interim analysis, based on the accumulated information, according to a Bayesian optimality criterion which accounts for model uncertainty. The methodology will be compared to alternative dose ranging strategies via simulation.