Develop tools and methods that can help identify, evaluate, and qualify predictive or prognostic clinical and non-clinical biomarkers and surrogate endpoints
A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes, or biological responses to therapeutic intervention. A biomarker can be a physiologic, pathologic, or anatomic characteristic or measurement that is thought to relate to some aspect of normal or abnormal biological function or process.39 Research in this area is expanding rapidly. Nevertheless, more research is needed to identify biomarkers for assessing medical product safety and efficacy in women throughout a product’s life cycle, including facilitating predictions in preclinical development that can be used during product development as well as in monitoring safety after marketing (e.g., during postapproval testing and surveillance).
A biomarker can be used as a surrogate endpoint, that is, as a substitute for a clinical endpoint. A surrogate endpoint would be expected to predict clinical benefit (or harm or lack of benefit or harm) based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence. Surrogate endpoints are a subset of biomarkers and have been used to establish therapeutic efficacy in pivotal studies or confirmatory studies used to grant accelerated marketing approval for certain therapeutics.
Biomarkers can be used to help ensure that safety issues specific to women can be identified early in medical product development and that women enrolled in clinical trials can avoid ineffective or unsafe treatments. Additionally, biomarkers may be able to identify differences in response to an FDA-regulated product resulting from other factors, like age, sex, and ethnicity, and drug interactions.
Research in this area should help FDA identify and qualify biomarkers that can better measure and predict toxicity or the safety and efficacy of FDA-regulated products in women in non- or preclinical studies and during clinical trials. Important considerations in biomarker development include, for example, pre-analytical considerations such as sample collection, storage, and transport to ensure analyte/sample stability; the use of analytically validated (i.e., with adequate sensitivity, specificity, accuracy, reproducibility) assays to ensure reliable biomarker data; and reproducibility using a learn and confirm paradigm (i.e., use of datasets to test and confirm). For biomarker qualification, additional considerations include context of use (COU) of the biomarker in drug development; biological rationale for use of the biomarker; and characterization of the relationships among the biomarker, the clinical outcomes, and the treatment (where applicable) required for the proposed COU.
Public health in general will benefit from research in this area. For example, sex-specific biomarkers could be used to identify how men and women respond differently to medical products, improving the availability of safe and effective medical products for all Americans. More specific biomarkers could also help increase the efficiency of clinical trials and accelerate the movement of beneficial medical products to the market.
4.1 Identify, develop, and evaluate biomarkers to be used in the assessment of products related to conditions that affect women and in the identification of sex differences in the performance of medical products for other conditions.
- Assess the sensitivity, specificity, accuracy, reproducibility of biomarkers
- Document the evidence supporting the correlation of identified biomarkers as indicators of health or disease processes, or therapeutic response
39 There are various types of biomarkers. Examples include diagnostic biomarkers to identify the presence or absence of a specific physiological or pathophysiological state or disease; prognostic biomarkers to help identify and categorize patients by degree of risk for disease occurrence or progression or to inform about the natural history of a disorder in a particular patient in the absence of a therapeutic intervention; and predictive biomarkers to help identify and categorize patients by their likelihood of response to a particular treatment and to help identify a subpopulation likely to respond to a treatment intervention in a particular way. For more on biomarkers, see draft guidance FDA Guidance for Industry and FDA Staff, Qualification Process for Drug Development Tools. See also Biomarkers Definitions Working Group (2001). Clinical Pharmacology and Therapeutics ,69, p. 89–95. Accessed July 2015.