Extending the TITE CRM to Multiple Outcomes

• Activity Number: 618
• Type: Contributed
• Date/Time: Thursday, August 2, 2012 : 8:30 AM to 10:20 AM
• Sponsor: ENAR
• Author(s): Joseph S Koopmeiners*+
• Companies: University of Minnesota

Abstract

In traditional phase 1 oncology trials, the safety of a new chemotherapeutic agent is tested in a dose escalation study to identify the MTD, which is defined as the highest dose with acceptable toxicity. An alternate approach is to jointly model toxicity and efficacy and allow dose finding to be directed by a tradeoff between efficacy and toxicity. With this goal in mind, several phase 1 designs have been proposed to jointly model toxicity and efficacy in phase 1 oncology trials. A factor limiting the use of these designs is that toxicity and efficacy must be observed in a timely manner. This is particularly problematic for the efficacy outcome, which is often measured over a longer timeframe than the toxicity outcome. One approach to overcoming this problem is to model toxicity and efficacy as time-to-event outcomes. We propose a phase 1 clinical trial that jointly models toxicity and efficacy as time-to-event outcomes by extending the TITE CRM to accommodate multiple outcomes. The operating characteristics of our design are evaluated by simulation and compared to the operating characteristics for existing phase 1 designs that consider toxicity and efficacy as binary outcomes.