Enrichment Design for Targeted Therapy

• Activity Number: 62
• Type: Topic Contributed
• Date/Time: Sunday, August 9, 2015 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Bo Yang* and Yijie Zhou and Lanju Zhang and Lu Cui
• Companies: AbbVie Pharmaceutical Research & Development and AbbVie and AbbVie and AbbVie
• Keywords: Type-1 error control ; enrichment trial ; all-comer trial ; weighted test statistic

Abstract

Targeted therapy or immunotherapy has become important area in drug development. Often times, success of such therapy depends on the biomarker identification and validation and development of companion diagnostic. The treatment approach provides an opportunity to identify patient sub-populations that may be more responsive to a treatment. In this talk, we consider an enrichment trial design where efficacy in the enriched population and further extended patient population can be evaluated. Specifically, a new weighted test statistic is derived to assess the treatment effect in an extended patient population under an enriched trial setting, coupled with noval design based on screening information for weight determination. The proposed design and analysis method control the overall type-1 error and enhance the probability of success compared to an all-comer population. It allows a generalization of the enrichment trial result to an all-comer population despite the fact that the enriched population is disproportionally distributed in the study. Sample size determination and data collection are discussed along with examples and simulations.