A biomarker, or biological marker, is a defined, measurable characteristic that indicates normal biological activity, a disease process, or a response to an exposure or intervention. In medicine, biomarkers support disease detection, monitoring, treatment research, and assessment of treatment effects. They include molecular measurements, tissue characteristics, imaging findings, and physiological measurements. Unlike direct assessments of symptoms, functioning, or survival, biomarkers provide evidence about biological processes rather than directly measuring how a person feels or fares. (fda.gov)
Forms and measurement
Biomarkers are not restricted to individual molecules. Blood glucose, blood pressure, and tumor size illustrate biochemical, physiological, and imaging-based measurements, respectively. A biomarker may consist of one characteristic or a panel of several measurements. Its full description specifies the characteristic being measured, the specimen or other source, and the analytical method; naming a substance alone does not completely define its measurement or intended interpretation. (fda.gov)
In cancer, biomarkers include alterations in genes, levels of proteins, and other characteristics of tumor cells. Tests may examine a single marker, several markers, or large portions of the tumor’s DNA. Molecular testing can distinguish tumors that arise in the same organ but differ in biologically relevant features. Samples may come from a tissue biopsy or, for certain tests, from blood or other fluids. A blood-based test for tumor-derived material is commonly called a liquid biopsy. (cancer.gov)
Categories of use
The joint US Food and Drug Administration–National Institutes of Health BEST terminology distinguishes seven categories according to intended use. These categories describe what a measurement is used to establish, rather than separate classes of substances. (fda.gov)
- Susceptibility/risk biomarkers indicate the potential to develop a disease or condition.
- Diagnostic biomarkers detect or confirm a disease, or identify a disease subtype, supporting diagnosis.
- Monitoring biomarkers are measured repeatedly to assess disease status, exposure, or an intervention’s effects.
- Prognostic biomarkers indicate the likelihood of a clinical event, recurrence, or progression in someone who already has the relevant condition.
- Predictive biomarkers identify individuals more likely to experience a particular effect from an intervention.
- Pharmacodynamic/response biomarkers show that a biological response to an exposure or intervention has occurred; that response does not necessarily establish clinical benefit.
- Safety biomarkers indicate the possibility or presence of toxicity associated with an exposure or intervention. (ncbi.nlm.nih.gov)
A single measurement can serve several purposes, provided evidence supports each interpretation. For example, a safety marker measured repeatedly can also function as a monitoring marker. Serial measurements may describe disease progression, response to treatment, drug exposure, or toxicity; the relevant information may be the measured level, its rate of change, or its relationship to other patient characteristics. (ncbi.nlm.nih.gov)
Validation and clinical usefulness
A biomarker’s biological plausibility is distinct from evidence that its test performs adequately. Analytical validation establishes that the test measures what it is intended to measure. Clinical validation establishes that the biomarker, as measured by that test, can detect, measure, or predict the relevant clinical concept. Reliable measurement and reproducibility are therefore necessary, but do not by themselves establish every proposed medical use. (ncbi.nlm.nih.gov)
Clinical usefulness also depends on the decision the result is intended to inform. A marker that distinguishes disease groups in research is not automatically suitable for screening, treatment selection, or predicting treatment benefit. The evaluation of biomarkers consequently includes assessment of the evidence linking the measurement to biological processes and clinical outcomes, together with assessment of its proposed application. (ncbi.nlm.nih.gov)
For early cancer detection, the National Cancer Institute’s Early Detection Research Network uses a five-phase framework: discovery, clinical assay development and validation, retrospective longitudinal studies, prospective screening, and cancer-control studies. Its approach to study design includes prospective specimen collection followed by retrospective blinded evaluation, intended to reduce bias during discovery and validation. (edrn.cancer.gov)
Biomarkers and surrogate endpoints
A biomarker used as a surrogate endpoint substitutes for a direct measure of clinical benefit in a clinical trial. This is a more demanding role than showing that an intervention affects a biological process. A change in the marker must be supported as a predictor of the clinical benefit of interest, rather than merely as evidence of biological activity. (fda.gov)
FDA terminology distinguishes candidate, reasonably likely, and validated surrogate endpoints. Candidate endpoints remain under evaluation. Validated endpoints have a mechanistic rationale and clinical evidence strongly supporting the relationship between an intervention’s effect on the endpoint and a specific clinical benefit. The interpretation is context-dependent; evidence supporting one disease or treatment setting does not establish universal applicability. Reduction in glycated hemoglobin, or HbA1c, is an established example used in certain diabetes mellitus trials. (fda.gov)
Treatment selection and regulatory qualification
Biomarker testing contributes to precision medicine by identifying characteristics relevant to treatment selection. Certain EGFR gene alterations, for example, identify cancers for which corresponding EGFR-targeted treatments may be applicable. Tests can also identify alterations associated with lack of response. However, a matching biomarker does not guarantee effectiveness: tumors may contain different cell populations, and their biomarker patterns can change over time. (cancer.gov)
Regulatory qualification is separate from validation of a particular test. In the FDA’s biomarker qualification program, qualification establishes that a biomarker can be relied upon for a specified interpretation within a defined context of use in drug development. That context determines the evidence required. Qualification permits use across development programs within the qualified context; it does not constitute unrestricted endorsement of every application or approval of every measurement method. (fda.gov)