Overcoming Challenges with Implementing CRM Designs

• Activity Number: 197
• Type: Roundtables
• Date/Time: Monday, August 5, 2013 : 12:30 PM to 1:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Aileen Murphy*+ and Alan Hartford
• Companies: Seattle Genetics, Inc. and Agensys, Inc
• Keywords: CRM ; oncology ; simulations

Abstract

Although the first paper defining the Continual Reassessment Method (CRM) was published in 1990, the method has seen surprisingly limited uptake in first-in-human oncology trials. Initial challenges with the CRM of exposing an undesirable number of patients to doses above an MTD have been overcome with the use of a hybrid approach combining the CRM with rule-based bounds such as limiting dose escalation to a single dose step. Simulation studies show that the MTD is more accurately estimated with use of a CRM when compared to the 3+3 design, and yet the CRM design is often not used. Although some larger companies now solely employ variations of CRM for their oncology dose-escalation studies, many still rely on the 3+3 design. This roundtable will allow participants to discuss the obstacles to using CRM in their organization and share their successes with implementing it. In addition, issues to consider (e.g., IRB review, drug supply) when employing a CRM-based trial will be discussed.