Skip to main content

Currently Skimming:

Summary
Pages 1-16

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 1...
... During its deliberations, the committee identified a need for the FDA to evaluate biomarker use with the same degree of scientific rigor across the product categories regulated by the agency, including drugs, biologics, devices, foods, and supplements. The committee has also recommended strategies for implementing the evaluation framework, supporting the use of evidence-based regulation and the protection and promotion of public health.
From page 2...
... Cholesterol and blood sugar levels are biomarkers, as are blood pressure, enzyme levels, measurements of tumor size from MRI or CT, and the biochemical and genetic variations observed in age-related macular degeneration. Emerging technologies have also enabled the use of simul
From page 3...
... These signatures can also be combinations of several of these types of measure ments; ideally, each component of a signature is identified. Biomarkers are used to describe risk, exposures, intermediate effects of treatment, and biologic mechanisms; as surrogate endpoints, biomarkers are used to predict health outcomes.
From page 4...
... At one end are endpoints defined by biomarkers alone that have less relationship to patient or consumer experience; in the middle are clinical events that depend on biomarkers as part of the definition; further along the spectrum are endpoints that are more closely related to events that affect patients' and consumers' lives; and at the other end of the spectrum are the clearest clinical endpoints, such as death. 1 In this report, the term food is inclusive of foods consumed as part of meals and snacks, dietary supplements, and components contained in them (nutrients, other bioactive substances)
From page 5...
... Biomarker Evaluation Process The committee concluded that it was important to address several challenges revealed by previous biomarker evaluation efforts. First, preanalytical and analytical validation of biomarker tests has often been underemphasized in that it has not been considered an integral component of biomarker qualification.
From page 6...
... The committee also recognizes that some biomarker evaluation steps may occur concurrently. The evaluation framework is intended to be applicable across a wide range of biomarker uses, from exploratory uses for which less evidence is required to surrogate endpoint uses for which strong evidence is required.
From page 7...
... In addition, the circle in the center signifies ongoing processes that should continually inform1, editable biomarker evaluation process. Figure each step in the and training are needed to conduct the evaluation reviews, focusing on the utilization step, because case-by-case analyses are the only way to ensure proper use of biomarkers given the state of the science.
From page 8...
... value cutoff concentration, and the total imprecision at the cutoff concentration. Depending on the use, biomarker tests need to be reliable, need to be reproducible across multiple laboratories and clinical settings, and possess adequate sensitiv ity and specificity for the biomarker being measured before data based on their use can be relevant in the subsequent biomarker evaluation steps.
From page 9...
... Given that biomarkers are "indicators" -- in that they are not necessarily causal -- and that an abnormal value or a gradient in level over time is not necessarily informative or predictive depending on the clinical situation, the committee instead used these criteria as a structure for assessing the prognostic value, or degree of association between the biomarker and the clinical outcomes of interest absent any interventions. For a surrogate endpoint, or a biomarker deemed useful as a substitute for a defined, disease-relevant clinical end point, prognostic value is a necessary -- but not sufficient -- criterion for
From page 10...
... Strong evidence and a compelling context are needed for the utilization of a biomarker as a surrogate endpoint in situations with regulatory impact. In the case of chronic disease, where there are multiple pathogenetic pathways leading to development of clinical outcomes and multiple manifestations of disease, the probabilistic nature of predictions made using biomarker data means that no biomarker can give absolute certainty of an event's future occurrence nor absolute certainty of the timing of
From page 11...
... The committee does not intend to imply that selection of endpoints for clinical trials would be simple or risk free if investigators were simply to avoid surrogate endpoints. Clinical and surrogate endpoints have been defined in a way that may imply a clear distinction between the two, in that clinical endpoints typically reflect patient or consumer experience and surrogate endpoints do not.
From page 12...
... These potential harms emphasize the need to weigh a biomarker's potential context of use in the utilization step. The committee's biomarker evaluation framework is intended to accomplish the goal of consistent evaluation of biomarkers across different types of products and contexts of use.
From page 13...
... Ancillary Recommendations Effective implementation of the committee's biomarker evaluation framework process across all contexts of use will benefit from coordination within the FDA and with other government agencies. Useful compo nents of this coordination include the systematic collection of data, build ing and supporting needed information technology infrastructure, and strengthening the surveillance systems required for linking biomarker and clinical outcome data.
From page 14...
... In other words, a surrogate endpoint may not be on the causal pathway of the disease process and a substance or intervention may have mechanisms of action independent of the disease process. Dotted lines indicate possible pathways.
From page 15...
... 2002. Overview of biomarkers and surrogate endpoints in drug development.


This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More information on Chapter Skim is available.