Statistical Considerations on Validating Microarray Platform in Clinical Development

• Activity Number: 256
• Type: Contributed
• Date/Time: Monday, August 2, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Guang (Gary) Chen*+ and Christopher Ramsborg and Yue Wang and Miho Kibukawa and Joel A. Klappenbach
• Companies: Merck & Co., Inc. and Merck & Co., Inc. and Merck & Co., Inc. and Merck & Co., Inc. and Merck & Co., Inc.
• Keywords: Design of Experiment (DOE) ; Microarray ; Pharmacogenomic (PGx) ; Biomarker

Abstract

Pharmacogenomic (PGx) has identified biomarkers as potentially power tools to help usher in the era of personalized medicine. The broad applications make them useful both during drug development and the regulatory approval process. A PGx biomarker should undergo an appropriate level of analytical validation, following the Fit-for-Purpose principle, prior to being utilized as a decision making tool in clinical development. The design and execution of experiments to characterize a high-throughput platform are logistically demanding as well as resource and time intensive. Fractional factorial and mixed-level design principles are adopted to evaluate sources of variance in the end-to-end microarray process. In this presentation, we described our experience with the peripheral whole blood as the tissue of interest. The statistical strategy and approach can be applied in general.