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BioMed Research International
Volume 2013, Article ID 891391, 9 pages
Research Article

Practical Guidance for Implementing Predictive Biomarkers into Early Phase Clinical Studies

Merck Research Laboratories, Clinical Biomarkers and Diagnostics Laboratory, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA

Received 28 June 2013; Accepted 11 September 2013

Academic Editor: Sudhish Mishra

Copyright © 2013 Matthew J. Marton and Russell Weiner. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The recent U.S. Food and Drug Administration (FDA) coapprovals of several therapeutic compounds and their companion diagnostic devices (FDA News Release, 2011, 2013) to identify patients who would benefit from treatment have led to considerable interest in incorporating predictive biomarkers in clinical studies. Yet, the translation of predictive biomarkers poses unique technical, logistic, and regulatory challenges that need to be addressed by a multidisciplinary team including discovery scientists, clinicians, biomarker experts, regulatory personnel, and assay developers. These issues can be placed into four broad categories: sample collection, assay validation, sample analysis, and regulatory requirements. In this paper, we provide a primer for drug development teams who are eager to implement a predictive patient segmentation marker into an early clinical trial in a way that facilitates subsequent development of a companion diagnostic. Using examples of nucleic acid-based assays, we briefly review common issues encountered when translating a biomarker to the clinic but focus primarily on key practical issues that should be considered by clinical teams when planning to use a biomarker to balance arms of a study or to determine eligibility for a clinical study.