The Problem: We are living in a remarkable time. health care costs are projected to increase to an unsustainable $4.4 trillion (19.8% of the U.S. gross GDP) by 2020 (Centers for Medicare & Medicaid Services), yet much heralded molecularly based medicine, also known as precision or personalized medicine, represents a potentially transformative approach to disease diagnosis, treatment, and prevention that promises to significantly reduce these costs. So, what’s the problem? Biomarkers, measurable and reproducible specific indicators (signals) of normal or disease-related processes (or pharmacological responses to therapy), are critical to enable this transformation. There is no shortage of biomarkers today—more than 150,000 reported as “discovered” by 2012 alone—yet the FDA has approved less than 1.5 per protein biomarkers per year since the early 1990s and less than 100 biomarkers are routinely used in the clinic. Currently biomarker development is expensive, unpredictable, and fraught with failure. There is currently no predictable, reliable, evidence-based system for end-to-end biomarker development. This is a daunting challenge, but one that must be met. Otherwise, biomarkers will continue to fail, targeted therapeutics development will continue to be high risk and uncertain, the molecular diagnostics industry will remain an unattractive target for investors, and, most importantly, patients will fail to benefit from the promise of precision medicine. The NBDA: The NBDA is an independent nonprofit (within the new Research Collaboratory at ASU) that is dedicated to meeting this challenge. Through trans-sector networks, the NBDA will create “standards” (inclusive of best practices, guidelines, standard operating procedures, etc.) to support new models of end-to-end biomarker development. The Alliance will integrate existing knowledge, and/or create new knowledge where needed, and make its data, processes, and standards publicly available. The NBDA was founded on the principle that de-convoluting the complexity of transitioning biomarkers from discovery through development and delivery to patients is ultimately achievable. Moreover, this collaborative knowledge network model must become a “movement” engaging the entire health care ecosystem if the vision for precision medicine is to become reality for all patients. Status of the NBDA: The NBDA began as a question! “Could networks of organizations and individuals who will benefit from the successful development of biomarkers unite through a unique management construct to solve what has heretofore been an “unsolvable” problem?” Over the last 18 months the initial question has catalyzed the emergence of the NBDA; an organization committed to answering this question in the affirmative. Funded by ASU, the ASU Foundation, and Virginia G. Piper Charitable Trust and others that have provided planning and/or financial support, the NBDA has matured from concept to reality. Subsequently informed by several workshops involving large numbers of trans-sector groups of experts from across the biomarker discovery, development, and delivery continuum, inclusive of the FDA and the affected industries, the NBDA has achieved significant progress. Moreover, the NBDA was developed not just to relegate the current biomarker development processes to history, but also to serve as a working example of what convergence of purpose, scientific knowledge, and collaboration can accomplish. The NBDA Focus and Future Plans: Over the past two years, the NBDA leadership and management team has undertaken an unprecedented in-depth analysis of the barriers that exist in advancing biomarkers from initial discovery to successful delivery. Through this analysis, it has become clear that biomarker development occurs in overlapping but discrete “modules” – all of which represent decisions and investment points. These “modules” are captured in the figure below. Biomarker failure begins in discovery, where the field suffers from a lack of reproducibility due to factors ranging from poor and/or insufficient numbers of samples to a lack of technology standards to flawed design and inadequate analytics. In reality, only a small number of biomarkers are sufficiently robust and effective that they should ever advance beyond the discovery stage. Unfortunately, today there are thousands of putative protein biomarkers that move well beyond discovery - at great cost - and fail late in the development process. Given the investment needed to advance biomarkers beyond discovery, each phase is similarly limited by barriers that can only be solved by acceptance and use of standards in end-to-end models. Working with trans-sector teams, the NBDA has already undertaken the design of demonstration projects for major classes of biomarkers including genomic, proteomic, imaging, and complex biomarkers. Led and managed by the NBDA, collaborating partners, such as the ISPY-2 team, M.D. Anderson, ASU’s Biodesign Institute, and others will work through virtual teams to reach consensus on existing standards, create new ones, and/or develop “ideal” development pathways for emerging biomarkers such as next-gen sequencing profiles. The NBDA will also undertake efforts to create and/or assemble unique resources to serve the biomarker communities including a national biomarker-focused biorepository; a network to reproduce selected biomarker results; and a common biomarker database. As part of its mission, the NBDA will provide education initiatives for the research, provider, and advocacy communities. As part of its mission, the NBDA will provide education initiatives for the research, provider and advocacy communities. These latter activities will be performed in partnership with Arizona State University and other organizations that are dedicated to educating the industry and the public on the use of patient’s molecular profiles in precision medicine - and on the value of diagnostics. We are well underway, and will begin publishing our findings, standards, and recommendations as soon as they are finalized. Become Part of the Solution: Align With the NBDA: Join us to move beyond silos - to shift from a culture of acceptance of biomarker failure to one of transparent, predictable end-to-end processes based on scientifically robust processes that the FDA will welcome and patients will embrace. Become a partner or collaborator in one of NBDA’s networks. The NBDA needs financial resources, and we welcome investment from membership, philanthropy and support for national resources and/or special projects. Since NBDA will achieve solutions to shared problems through networks of stakeholders, we also need expertise and experienced collaborators to join our teams; participate in consensus conferences; and engage in NBDA’s educational initiatives. To request more information about the NBDA, email or call us as detailed in the box below. We look forward to working with you and to a future where biomarker-based precision medicine is available to all those in need.
