Understand Translational Research Tools


What are Biomarkers and Why Are They Important?
This 2 minute video from the Food and Drug Administration (FDA) explains how developing biomarkers for rare diseases can improve the success rate and efficiency of therapy development. An audio transcript is available. 


Biological markers (biomarkers) are characteristics that can be objectively measured and used as an indicator of normal biological processes, disease processes, or pharmacologic responses to a therapy. Biomarkers are important for the development of drugs, biologics, and certain medical devices.

  • Biomarkers are a subcategory of medical signs and can be detected through different tests and procedures. Examples of biomarkers include:
    • Blood pressure and body temperature (physiological biomarkers).
    • LDL cholesterol level and red blood cell count (molecular biomarkers).
    • Tumor detected by contrast MRI or bone fracture detected by X-ray (imaging biomarkers).
  • Biomarkers can also be categorized by what they measure. The biomarkers that are important to the therapy development process include:
    • Susceptibility/risk biomarkers
      • Associated with an  increased or decreased chance of developing a disease or medical condition.
      • Identifies patients who do not yet clinically have the disease, which is important when the treatment will be most effective prior to development of symptoms.
    • Diagnostic biomarkers
      • Confirms or establishes diagnosis.
      • Selects patient population for clinical trials.
    • Monitoring biomarker
      • Detects the change in degree or extent of disease.
      • Indicates toxicity or assesses safety.
      • Provides evidence of exposure.
    • Prognostic biomarker
      • Identifies the likelihood of a clinical event, disease recurrence, or progression in patients diagnosed with the disease.
      • Enriches clinical trials with patients who have a higher likelihood of experiencing an event and therefore increase statistical power.
    • Predictive biomarker
      • Indicates the likely benefit to the patient from the treatment, compared with their condition at baseline. 
      • Classifies patients into responders and non-responders for the therapeutic agent using companion diagnostics (a test or assay that detects a predictive biomarker).
      • Enriches later phases of clinical trials with patients more likely to respond to the therapeutic agent.
      • Is usually specific to a therapeutic agent.
      • Does not guarantee benefit, but rather excludes patients who are most likely not to benefit.
    • Pharmacodynamic (response) biomarker
      • Shows biological response related to a therapy or environmental exposure.
      • May act as a surrogate clinical endpoint (also known as efficacy response biomarker) in a clinical trial when validated. For a biomarker to be validated, it: 
        • Must be solid scientific evidence that a biomarker consistently and accurately predicts a clinical outcome, either a benefit or harm.
        • Is important if survival or recurrence is the clinical outcome endpoint.
      • Validated surrogate clinical endpoint biomarkers may
        • Provide early evidence about the safety and efficacy of a therapy.
        • Reduce the risk of harm to subjects; the early data provided by biomarkers can allow researchers the opportunity to stop administration of a therapy potentially harmful to subjects before the associated clinical data would be available.
        • Provide useful information for patient management, for example, whether to continue treatment or to adjust dose.
        • Allow researchers to design smaller, more efficient studies, reducing the number of subjects exposed to a given experimental therapy.
        • Speed the overall therapy development process, allowing effective treatments to reach their target patient populations sooner.
      • Until validated, a biomarker can still be considered by the U.S. Food and Drug Administration (FDA) in the marketing review process of the potential therapy as “reasonably likely surrogate endpoint” or “candidate surrogate endpoint.”
    • Safety biomarker
      • Monitors adverse effects of the therapy.
  • CDER Biomarker Qualification Program (2018) provides more information about biomarkers and their use in clinical trials, as well as steps to have a biomarker qualified by the FDA. 
    • Qualification means the biomarker has undergone a formal regulatory process to ensure that the FDA can rely on it to have a specific interpretation and application in therapy development and marketing review process, within the stated context of use.
  • Other resources include:
    • BEST (Biomarkers, EndpointS, and other Tools) Resource (2018) is a glossary that clarifies definitions of different types of biomarkers and clinical assessments. This glossary describes the roles of biomarkers in research and therapy development and was developed by the FDA-NIH Biomarker Working Group
    • Developing and Validating Biomarkers (2016) is a video presentation from a Global Genes Rare Advocacy Summit that outlines the role of patient advocacy organizations in the development of biomarkers. The 1 hour presentation:
      • Defines biomarkers and different types.
      • Discusses how they can be used in research.
      • Includes specific examples of the use of biomarkers in accelerating diagnosis and treatment of rare diseases.


Assay Guidance Manual National Center for Advancing Translational Sciences (NCATS) (link)
CDER Biomarker Qualification Program U. S. Food and Drug Administration (FDA) (link)
Cell and Animal Models
Animal Model Qualification Program U. S. Food and Drug Administration (FDA) (link)
NCI Best Practices for Biospecimen Resources National Cancer Institute (NCI) (link)