Evolution of Biomarkers

During the last 50 years, the definition of biomarker has been modified according to scientific and clinical progress. The term “biomarker” was used for the first time in 1973 to indicate the presence or absence of biological material. However, the concept is older, referenced as a “biochemical marker” in 1949 and “biological marker” in 1957. 

In 2000, the Biomarker Definition Working Group, supported by the U.S. National Institute of Health (NIH), defined a biomarker as “a characteristic that is objectively measured and evaluated as an indication of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention”. This definition has two major limitations. The first one lies in the fact that sometimes a biomarker is measured by subjective parameters. The second one is the fact that additional processes or responses beyond those covered by the definition are excluded. 

In 2016, Fitzgerald and colleagues redefined the concept of biomarker as “a functional variant or quantitative index of a biological process that predicts or reflects the evolution of or predisposition to a disease or a response to a therapy”. Nevertheless, this description lacks the consideration of structural variants and qualitative index as potential biomarkers. 

In order to harmonize the term of biomarker, the Food and Drug Administration (FDA) in collaboration with the NIH Joint Leadership Council convened the FDA-NIH Biomarker Working Group in 2016. This group simplified the biomarker definition being considered as “a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes or responses to an exposure or intervention”. This definition, clearer and more concise, defines a biomarker specifying its principal applications without any unnecessary complexity or contradictory information. Besides, to ensure its clinical use, a good biomarker should be measured with high reproducibility, present a sizeable signal-to-noise ratio and, more importantly, meet the condition of being modified in a dynamic and reliable way as the clinical condition progress. In addition, a biomarker should be accessible for its detection and measurement, as would be the case of a plasmatic parameter or a genetic marker, or being detected by histological or image/neuroimaging techniques.

[More to come ...]