Table 1 Biomarkers: a basic glossary (derived from NIH working group) [11]

Biological marker (biomarker):

A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.

Type 0 biomarker:

A marker of the natural history of a disease and correlates longitudinally with known clinical indices.

Type I biomarker:

A marker that captures the effects of a therapeutic intervention in accordance with its mechanism of action.

Surrogate endpoint (type 2 biomarker):

A marker that is intended to substitute for a clinical endpoint; a surrogate endpoint is expected to predict clinical benefit (or harm or lack of benefit or harm) on the basis of epidemiological, therapeutic, pathophysiological, or other scientific evidence.

Risk factor:

A risk factor is associated with a disease because it is in the causal pathway leading to the disease.

Risk marker:

A risk marker is associated with the disease (statistically) but need not be causally linked; it may be a measure of the disease process itself.

Clinical endpoint:

A characteristic or variable that reflects how a patient feels, functions, or survives.

Intermediate (non-ultimate) endpoint:

A true clinical endpoint (a symptom or measure of function, such as symptoms of angina frequency or exercise tolerance) but not the ultimate endpoint of the disease, such as survival or the rate of other serious and irreversible morbid events.

Validation of a biomarker (assay or method validation):

A process for assessing performance characteristics (i.e., sensitivity, specificity, and reproducibility) of a biomarker measurement or an assay technique.

Qualification of a biomarker (clinical validation):

The evidentiary process linking a biomarker to disease biology or clinical outcome.

Evaluation of a biomarker:

A process of linking biomarkers to outcomes, often with a view to establish surrogate status.