Affiliations: Department of Clinical Pharmacology, Merck Research
Laboratories, Rahway, NJ, USA
Note: [] Address for correspondence: John A. Wagner, MD, PhD, Department
of Clinical Pharmacology, Merck Research Laboratories, PO Box 2000, RY34-A548,
126 East Lincoln Avenue, Rahway, NJ 07065, USA. Tel.: +1 732 594 0274; Fax: +1
732 594 5405; E-mail: wagner@merck.com
Abstract: There are numerous factors that recommend the use of biomarkers in
drug development including the ability to provide a rational basis for
selection of lead compounds, as an aid in determining or refining mechanism of
action or pathophysiology, and the ability to work towards qualification and
use of a biomarker as a surrogate endpoint. Examples of biomarkers come from
many different means of clinical and laboratory measurement. Total cholesterol
is an example of a clinically useful biomarker that was successfully qualified
for use as a surrogate endpoint. Biomarkers require validation in most
circumstances. Validation of biomarker assays is a necessary component to
delivery of high-quality research data necessary for effective use of
biomarkers. Qualification is necessary for use of a biomarker as a surrogate
endpoint. Putative biomarkers are typically identified because of a
relationship to known or hypothetical steps in a pathophysiologic cascade.
Biomarker discovery can also be effected by expression profiling experiment
using a variety of array technologies and related methods. For example,
expression profiling experiments enabled the discovery of adipocyte related
complement protein of 30 kD (Acrp30 or adiponectin) as a biomarker for {\it in
vivo} activation of peroxisome proliferator-activated receptors (PPAR)
γactivity.
