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Commentary

The Biomarkers Consortium: Public and Private Sectors Working in Partnership to Improve the Public Health

^aDirector, National Institutes of Health; ^bChairman, Foundation for the National Institutes of Health; and ^cCommissioner, Food and Drug Administration

Correspondence: Elias A. Zerhouni, M.D., Director, National Institutes of Health, Building 1, Room 126, One Center Drive, MSC 0148, Bethesda, Maryland 20892-0148, USA. Telephone: 301-496-2433; Fax: 301-402-2700; e-mail: ZerhounE{at}od.nih.gov

Received January 28, 2007; accepted for publication January 28, 2007.

The Biomarkers Consortium (BC), launched on November 5, 2006, is a public–private partnership whose goal is to identify and qualify new biological markers to accelerate the detection, diagnosis, and treatment of a range of diseases, including cancer. The Consortium is made up of a diverse list of partners with this common goal. It includes the Foundation for the National Institutes of Health (FNIH), the National Institutes of Health (NIH), the Food and Drug Administration (FDA), the Centers for Medicare & Medicaid Services (CMS), the Pharmaceutical Research and Manufacturers of America (PhRMA), the Biotechnology Industry Organization (BIO), and representatives of the public, including patient advocacy organizations.

The NIH and its partners have long recognized a need for robust and objective measures of disease risk, underlying pathobiological processes, diagnosis and stage of disease, prognosis, treatment response, recurrence, and clinical outcomes. However, despite significant advances in our molecular understanding of many diseases and treatment outcomes, there are very few biomarkers that are qualified for clinical use and used widely to address medical needs. Some of the most widely accepted biomarkers in use today include blood pressure, total cholesterol, and high-density lipoprotein to low-density lipoprotein (HDL/LDL) ratios as markers of cardiovascular risk and response to treatment; and HIV viral load and CD4⁺ T-cell counts to assess HIV/AIDS disease severity, stage, and treatment response.

The availability of such biomarkers would not only enable research, but also serve to streamline clinical care and potentially speed the development and availability of new drugs. Although the need is clear, there are several important impediments to developing reliable biomarkers. Biomarker development requires insight into disease risk, natural history, and outcomes. It also requires a sufficiently large number of adequate samples taken from well-characterized patients and handled in a standardized fashion. Analytical platforms that effectively and reproducibly measure the biomarker must also be available and standardized. Analytical approaches that assess the utility of biomarkers as signs or predictors of underlying biology or future outcomes must also be developed for the promise of biomarkers to be translated into clinical usefulness. Once such biomarkers and analytical approaches are developed, they will prove useful to promote and foster more discovery science and facilitate the conduct of translational and clinical research, all of which are activities central to the mission of the NIH.

The NIH is certainly not alone in recognizing the need for robust biomarkers. The FDA will benefit tremendously from having biomarkers that can be objectively assessed as markers for effectively stopping or ameliorating the disease process, as well as indicators that drugs are not having adverse effects as well. Biomarkers that are consensually qualified for a particular use provide an opportunity for the FDA to compare across trials and across treatments, without having to devote scarce resources to assessing distinct and separate proposed markers in the setting of each new drug application.

Industry, likewise, benefits from the development and qualification of biomarkers across the board. Useful markers will assist in the identification and stratification of human subjects to be enrolled in clinical trials, will shorten the duration of trials in which biomarkers can stand in as surrogates for more distant clinical endpoints, and may assist in excluding individuals at excessive risk for drug toxicity, thus translating to a more rapid, efficient, economical, and safer drug development process. In industry, as in the FDA and NIH, biomarkers can feed back into the discovery process, promoting the identification of new drug targets and facilitating the development of new drug entities.

The greatest benefit, however, will be to the public. The major beneficiaries of rapid, efficient, and economical drug development are patients and the public at large. They are also the major beneficiaries of new insights into disease risk, characterization, and treatment. Since no one partner in the BC can accomplish biomarker discovery, qualification, and implementation alone, the BC was developed to provide needed synergy to accomplish this ambitious aim.

The BC is structured to provide a fair and inclusive platform to discover, develop, and qualify biomarkers in a precompetitive environment, devoted to the generation of public resources. The FNIH serves as the managing partner and provides a home for this activity, consistent with its mandate to support the activities of the NIH. Other founding partners are the NIH, FDA, and PhRMA, all of whom must agree on the merits of a project for it to go forward in the BC.

Careful attention has been paid to developing and articulating policies for intellectual property, data sharing and data access, and antitrust to ensure that the public health benefit is served by BC activities. These policies are publicly available at http://www.fnih.org. Financial support for the BC is drawn largely from the private partners, while NIH and FDA provide significant intellectual and in-kind participation in all aspects of the BC. The BC also includes representatives from academia and patient advocacy organizations in both leadership and technical roles.

Oversight of BC projects will occur in part through steering committees, including an oncology steering committee. The first projects slated for implementation under the oncology steering committee are assessments of the role for fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in non-small cell lung cancer and lymphoma. In evaluating oncologic therapies, the oncology community and the FDA have come to rely on various endpoint biomarkers as correlates of clinical benefit. Anatomic imaging with computed tomography or magnetic resonance imaging, using one- or two-dimensional measurements of size to characterize cancers, has been traditionally used in all aspects of cancer patient management from diagnosis and staging to monitoring response to therapy and disease progression. However, standard anatomic imaging is often inadequate for characterizing cancers in settings in which drugs do not cause significant tumor shrinkage or for slow progressing tumors.

Newer functional imaging modalities, including FDG-PET, show significant promise as biomarkers, because they incorporate measurements of cancer viability. For example, since FDG-PET measures cancer's reliance on glycolysis, it promises to provide an early indication of therapeutic response (e.g., after one or two cycles of chemotherapy) that is correlated with clinical outcome. The lung and lymphoma projects are the first steps toward developing the standardized criteria, protocols, quality assurance of PET images, and endpoints needed to qualify FDG-PET as a biomarker. The clinical protocols for this qualification trial, developed by a collaborative group including oncologists and imaging scientists from the National Cancer Institute (NCI), FDA, academia, industry, and the Leukemia and Lymphoma Society, will serve as prototypes for evaluating FDG-PET and additional imaging-based biomarkers in other cancer settings. Images collected in the conduct of the study will be placed in a database held by the NCI and made available to all qualified investigators.

Other immediate areas for biomarker investigation, development, and qualification are in metabolic diseases and neuroscience. Projects in development in neuroscience include one focusing on whole genome association approaches to assessing the likelihood of responding to specific treatments in major depressive disorder as well as one intended to develop new PET tracers for neuroimaging. The metabolic diseases steering committee will initially engage in developing a project seeking proteomic markers for prediabetes and clinically evident diabetes as well as a project assessing the role for adiponectin as a biomarker in diabetes.

Proposals for new projects are sought from all sources, within and outside the BC members, and will be assessed for clinical and scientific merit, feasibility, and ability to attract support. The project concept submission form can be accessed at http://www.fnih.org. Each project concept approved by the BC will be developed into a more specific project plan, detailing the specifics of the scientific activity, participants, support, and budget. Projects can be initiated once the project plan is approved and funding is secured.

In summary, the BC is a novel partnership between the public sector and the private sector to work together in a synergistic fashion for the public good. It serves as both a way to move forward the science of biomarkers and a new way of leveraging the efforts of the medical research enterprise to this common goal.

	DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

Top Disclosure of Potential...

 
The authors indicate no potential conflicts of interest.

View larger version (80K): [in this window] [in a new window]   Figure 1. Dr. Charles A Sanders (left) and Dr. Elias Zerhouni announcing the Biomarkers Consortium.

View larger version (69K): [in this window] [in a new window]   Figure 2. Dr. Andrew von Eschenbach.

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