• The broader context of biomarker and surrogate endpoint evaluation by the FDA, including the legal and regulatory basis for claims made on CFSAN-regulated products

Examples are included on blood pressure as a surrogate endpoint, HIV/AIDS drug development, arrhythmia suppression interventions, exercise tolerance in congestive heart failure, and kidney toxicity biomarkers.


Biomarkers have a wide array of uses in a variety of fields. These fields include medicine, oral health, mental health, nutrition, environmental health, toxicology, developmental biology, and basic scientific research. They are used to study the safety and efficacy of interventions, develop understanding of the mechanisms of disease, make good decisions in clinical care, and guide the policies that impact public health. Table 2-1 gives a list of several categories of biomarker use.

For the uses in Table 2-1, any biomarker would need to be evaluated to ensure that data supporting the biomarker’s association with the disease or condition of interest and the analytical validation of the test are adequate for the proposed use. In situations, however, where biomarker data will not or is not yet anticipated to be submitted to the FDA for a regulatory purpose or used by professional societies or other groups for clinical practice guidelines or other decision-making processes impacting public health or the practice of medicine, this may be an informal process. Ideally, evaluations are already done by clinicians, product developers, government regulators, professional societies, and scientists; this report’s contribution is to propose a systematic process for biomarker evaluation.

Use of Biomarkers and Surrogate Endpoints for Clinical Efficacy Studies and Formation of Clinical Practice Guidelines

Surrogate endpoints were defined in Chapter 1 and can be found in several locations in Table 2-1. First, they have been used in approvals of products or claims for drugs, biologics, devices, foods, and supplements. This will be discussed further in several subsections of this chapter’s section on evolution of regulatory perspectives on surrogate endpoints and in Chapter 5. Second, they have been used in the formulation of clinical practice guidelines. As defined by an Institute of Medicine (IOM) committee in 1990, “practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care

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