An Efficiency Ratio for Criteria Selection in Futility Assessment of Clinical Trials

• Activity Number: 513
• Type: Contributed
• Date/Time: Wednesday, August 1, 2012 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Jianliang Zhang*+
• Companies: MedImmune
• Keywords: futility Assessment ; futility criteria ; efficiency ratio

Abstract

In some clinical development scenarios, where large trials are commenced for an agent whose true efficacy is uncertain due to insufficient existing clinical data, there is an increased risk of failure. Thus, futility analyses are desirable for ethical reasons and cost saving considerations. There exist various statistical methodology and criteria for evaluating interim analysis outcomes for futility decision-making, e.g., conditional power and predictive power. While the methods are broadly used in clinical trials practice, the futility criteria (cutoffs) are adopted quite arbitrarily. We discuss the interchangeability of futility criteria across statistical methods and the possibility of establishing a uniform futility assessment criterion. We propose a futility efficiency ratio of the chance for intended trial termination if the agent is truly ineffective versus the power loss incurred from the futility assessment. This efficiency ratio is a function of the futility method and cutoff and, thus, could be used for cutoff selection across various futility methods to achieve a desirable balance between futility termination and power loss.