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Institute of Medicine (US) Forum on Neuroscience and Nervous System Disorders. Neuroscience Biomarkers and Biosignatures: Converging Technologies, Emerging Partnerships, Workshop Summary. Washington (DC): National Academies Press (US); 2008.

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Neuroscience Biomarkers and Biosignatures: Converging Technologies, Emerging Partnerships, Workshop Summary.

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The number of innovative medical therapies that have reached the market has been disappointing, given escalating research investment. One major reason for the slowdown has been the paucity of suitable biomarkers that might streamline the clinical testing of putative therapies. Biomarkers are quantitative biological measurements of many types that provide information about a disease state or a response to treatment, in addition to other disease characterizations.

One common category of biomarkers is used to identify people at risk for a disease; others are used to diagnose disease, assess its progression, or predict disease outcome. In the therapeutic setting, biomarkers can reveal information about whether a drug is adequately engaging its intended target or what therapeutic side effects or efficacy to expect. Of considerable interest to the pharmaceutical industry is the category of biomarkers known as “surrogate”1 biomarkers, which are qualified indicators that can substitute for clinically meaningful endpoints in clinical trials (U.S. Department of Health and Human Services, 2006). Surrogate markers are sometimes used to substitute for clinical endpoints. Often they are used to reduce the time or study size needed to determine the response to a candidate treatment, thus shortening the path to use in a clinical setting. A biomarker of any type may be used individually; if a biomarker is used in combination with another biomarker, the two (or more) are sometimes referred to as a “biosignature.” An example of a biosignature would be a composite measure of imaging and genomics that offered improved diagnostic sensitivity and specificity compared to that of either measure alone.

The expected value of biomarkers to the pharmaceutical industry is to increase the efficiency of drug development, thereby permitting more drug candidates to be brought forward and perhaps increasing the information gleaned from the trials performed. The expected value to public health and to individual patients is to hasten access to safe and effective therapies. For these reasons, all potential partners have a stake in and stand to benefit from biomarker development.

There is a great need for new biomarkers for nervous system disorders, observed Dr. Dennis Choi, executive director of Strategic Neuro-sciences Initiative and Director of the Comprehensive Neuroscience Center in the Woodruff Health Sciences Center at Emory University and chairman of the planning committee for this workshop. Advances in basic neuroscience have identified a growing number of plausible therapeutic targets, but the gap between animal models of brain disorders and humans is profound. Estimating the potential of a putative new treatment is often impossible without clinical testing, which in many psychiatric, neurological, or retinal disorders has remained difficult and expensive and has been plagued by factors such as patient heterogeneity, lengthy trial durations, subjective readouts, and placebo responses. As a result, some potentially important experimental therapeutics are never explored. The availability of suitable biomarkers would likely significantly enhance the availability of needed treatments.

What has impeded the development of biomarkers for nervous system disorders? Certainly the complexity of the brain, limited access to brain tissue, and the blood-brain barrier are factors. But another key reason lies with incentives. Academic and government researchers already have provided a good scientific foundation for the preliminary identification of many biomarkers, several of which are described in this summary. But the industrial heavy lifting necessary to develop these candidate biomarkers into practical, reliable, and well-characterized tools ready for clinical use is usually not within the purview of academic researchers; it is too applied, process oriented, and resource intensive. Conversely, development is usually too remote from competitive-edge and commercial payoff to be justified within the research budgets of individual pharmaceutical companies. In other words, biomarker development may sometimes fall between the cracks of academic, government, and industry research programs. Some candidate biomarkers are likely to emerge only from large-scale molecular profiling efforts, whose assembly can require a daunting combination of resources, technology, and access to human subjects, often beyond the capabilities of individual organizations.


A logical path forward is the formation of public-private research partnerships that bring together academic, government, and industry researchers. The partnerships would be tasked with developing nervous system biomarkers in the precompetitive space, which describes the ability of organizations, including companies, sponsors, and developers, to work together on research and development without jeopardizing their intellectual property. The precompetitive space does not confer a competitive advantage to any individual pharmaceutical company. Bringing such biomarkers forward would broadly aid therapeutic development in given disease arenas, making it easier for any company to develop a successful treatment and giving no individual company a competitive advantage over another. An example of a public-private partnership in the neurosciences that has been extremely successful is the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a partnership launched several years ago by the National Institute on Aging (Table I-1).

TABLE I-1. Sponsors of the ADNI Initiative.


Sponsors of the ADNI Initiative.

This initiative, and the promise it holds for biomarker development, served as an impetus for a coordinated and focused process in biomarker development across multiple therapeutic areas (see agenda for further details). It led to the formation of the Biomarkers Consortium, launched in 2006 by the Foundation for the National Institutes of Health (FNIH), the National Institutes of Health, the FDA, and the Pharmaceutical Research and Manufacturers of America (Foundation for the National Institutes of Health, 2007).

The IOM Forum on Neuroscience and Nervous System Disorders (the Forum) was expressly created by the IOM in 2005 to bring together the public and private sectors, among other key stakeholders, to discuss issues of mutual interest and concern on topics of common and critical importance, particularly ones that stimulate partnerships to accelerate understanding and treatment of nervous system disorders. The Forum is a venue for convening stakeholders, sponsoring workshops, and producing workshop summaries intended to inform both the Forum membership and the general public.

In light of the aforementioned considerations, the time seemed right for the Forum to convene leaders from academic and industry organizations to assess the state of biomarker development and to consider strategies to galvanize public-private partnerships for nervous system diseases. For this purpose, the Forum sponsored a workshop, “Neuroscience Biomarkers and Biosignatures: Converging Technologies, Emerging Partnerships.”

The organization of this summary essentially follows that of the sessions in the agenda (Appendix B). The first session describes the underlying goals of the workshop and includes an introduction to the FNIH and ADNI. Next, participants presented information on the potential tools for biomarker and biosignature development, including discussion of the parameters that should be considered when developing a high-impact biomarker for neurological or psychiatric disorders. The next two sessions focused specifically on biomarkers for psychiatric diseases and drug addition, and then neurological and eye diseases. The workshop concluded with a roundtable discussion on directions for the future.

This summary provides a synthesis of the workshop held on February 26 and 27, 2007, and presents insights made by participants at the workshop, but, in accordance with IOM policy, it does not make explicit consensus conclusions or recommendations.



The Food and Drug Administration (FDA) defines a surrogate endpoint as “a bio-marker that is used to predict clinical benefit (a direct measurement of how a patient feels, functions, or survives).”

Copyright © 2008, National Academy of Sciences.
Bookshelf ID: NBK53104


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