Predictive Power to Assist Phase III Go/No-Go Decision

• Activity Number: 473
• Type: Contributed
• Date/Time: Wednesday, August 3, 2011 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Shengyan Hong*+ and Li Shi
• Companies: MedImmune, Inc. and MedImmune, Inc.
• Keywords: Predictive power ; phase 3 go/no go decision ; hazard ratio ; progression-free survival ; overall survival

Abstract

One of the most critical decision points during drug development is to make a phase 3 go/no go decision after a phase 2 proof of concept (POC) trial is conducted. It is particularly challenging in oncology drug development where oftentimes the primary endpoint for phase 3 trial is overall survival (OS) but the phase 2 POC trial is powered only for an early endpoint, typically progression-free survival (PFS), whose relationship to OS is often unclear. We propose the use of predictive power to assist the phase 3 go/no go decision by evaluating the strength of actual observed phase 2 efficacy outcomes in terms of how likely it will predict the chance of OS success in subsequent phase 3 trial. The formula is provided for calculation of predictive power based on either observed PFS outcome only, or observed OS outcome only, or both. An example is provided to compare these three predictive powers. It shows that when there is little prior information about OS and PFS, the observed PFS outcome has low predictability itself and also has limited added value to the predictability based on the observed OS outcome only.