A Counterfactual P-Value Approach for Benefit-Risk Assessment in Clinical Trials

• Activity Number: 37
• Type: Contributed
• Date/Time: Sunday, July 29, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Donglin Zeng*+ and Guanghui Wei and Joseph Ibrahim and Ming-Hui Chen and Beiying Ding and Chunlei Ke and Qi Jiang
• Companies: The University of North Carolina at Chapel Hill and Amgen, Inc. and The University of North Carolina at Chapel Hill and University of Connecticut and Amgen, Inc. and Amgen, Inc. and Amgen, Inc.
• Keywords: Benefit-Risk ; Counterfactual P-value ; Weight ; Drug Development

Abstract

Clinical trials generally allow various efficacy and safety outcomes to be collected. Benefit-risk assessment is an important issue when evaluating a new drug. Currently, there is a lack of standardized benefit-risk assessment approaches in drug development. To quantify efficacy and adverse drug reactions, we propose a counterfactual p-value approach, which evaluates the extreme probabilities of observing a weighted benefit-risk value in one treatment plan as if patients were treated in the other treatment plan. The proposed approach is applicable to single benefit and single risk outcome as well as multiple benefit and risk outcomes assessment. In addition, the prior information in weight schemes relevant to the importance of outcomes can be incorporated in the approach. The proposed counterfactual p-values plot is intuitive with visualized weight pattern. The average area of p-values over time is used for overall treatment comparison and bootstrap approach is applied for statistical inference. We assess an experimental drug versus placebo according to progression free survival and overall survival as well as several safety outcomes using proposed approach and simulated data.