Biomarkers

The use of biomarkers in basic and clinical research as well as in clinical practice has become so commonplace that their presence as primary endpoints in clinical trials is now accepted almost without question. In the case of specific biomarkers that have been well characterized and repeatedly shown to correctly predict relevant clinical outcomes across a variety of treatments and populations, this use is entirely justified and appropriate. In many cases, however, the “validity” of biomarkers is assumed where, in fact, it should continue to be evaluated and reevaluated. This article will consider the current conceptual status of biomarkers as clinical and diagnostic tools and as surrogate endpoints in clinical research with the goal of providing context for interpreting studies that rely heavily on such biological measures.The term “biomarker”, a portmanteau of “biological marker”, refers to a broad subcategory of medical signs – that is, objective indications of medical state observed from outside the patient – which can be measured accurately and reproducibly. Medical signs stand in contrast to medical symptoms, which are limited to those indications of health or illness perceived by patients themselves. There are several more precise definitions of biomarkers in the literature, and they fortunately overlap considerably. In 1998, the National Institutes of Health Biomarkers Definitions Working Group defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”  A joint venture on chemical safety, the International Programme on Chemical Safety, led by the World Health Organization (WHO) and in coordination with the United Nations and the International Labor Organization, has defined a biomarker as “any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease”