A Proposed Study Design for QT Assessment Using Exposure-Response Modeling

• Activity Number: 191
• Type: Contributed
• Date/Time: Monday, August 10, 2015 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Fang Liu* and Devan Mehrotra and Deborah Panebianco and Kuenhi Tsai
• Companies: Merck and Merck and Merck and Merck
• Keywords: QTC Study ; TQT Study ; Exposure-Response method ; PK QTC modeling ; exposure-QTc modeling

Abstract

Thorough QT (TQT) studies are generally quite expensive and the corresponding statistical analysis methodology based on the ICH E14 guidance used has been criticized by some as being too conservative. As a result, some researchers have proposed replacing the TQT study by using exposure-response (ER) modeling to assess a potential QT effect. Darpo et al (2014) showed that the ER method is a robust QT assessment approach with acceptable false positive and false negative properties if the design and analysis are done correctly. In this presentation, we will propose a new QTc study design motivated by a real example. The new QTC study design uses ER modeling as the primary analysis method; power consideration based on ER analysis will be discussed. Similar to a traditional TQT study, this new study design includes moxifloxacin as the positive control to test assay sensitivity, while requiring a notably smaller sample size compared to a traditional TQT study.