Go/No Go Criteria Based on a Joint Evaluation of Efficacy and Safety Using a Clinical Utility Index

• Activity Number: 113
• Type: Topic Contributed
• Date/Time: Monday, August 4, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Theresa Ashton*+ and Ohad Amit and Kert Viele
• Companies: GlaxoSmithKline and GlaxoSmithKline and Berry Consultants
• Keywords: adaptive design ; utility function ; go/no go ; Bayesian methods

Abstract

Traditional go/no go criteria in phase 2 have been based on the evaluation of a drug's efficacy. As there are many different domains involved in the evaluation of patient safety, specifying quantitative go/no go criteria based on safety/tolerability endpoints has been challenging. We propose a set of go/no go criteria based on the joint evaluation of a safety and efficacy endpoint. The evaluation is based on a clinical utility function which assigns different utilities based on different efficacy and safety outcomes. A clinically significant utility is pre-specified and therapies are evaluated against that utility using Bayesian methods. An example of a recently designed adaptive trial is provided to demonstrate the incorporation of go/no go criteria based on the clinical utility index.