Abstract
As a result of the NIH investment in biomedical research, over the past 30 years we have seen many great advances impacting the health of our nation which have been fostered by the effective translation of scientific advances. However, rising costs for both research and health care mean that the NIH must make strategic decisions that maximize the return on its investment. Because treating end-stage disease is so costly, both personally and financially, learning how to pre-empt illness through molecular knowledge and behavioral interventions is the only viable strategy for maintaining the nation's health in the coming years.
In order to speed scientific discovery and its efficient translation to patient care, the NIH developed the Roadmap for Biomedical Research. The Roadmap provides an incubator space for funding innovative programs to address a panoply of scientific challenges and has engendered a new culture of cooperation among researchers seeking new avenues for collaboration. An important feature of the Roadmap is the Clinical and Translational Science Awards (CTSA). The program's goals are to eliminate growing barriers between clinical and basic research, to address the increasing complexities involved in conducting clinical research, and to help institutions nationwide create an academic home for clinical and translational science.
By adopting a strong strategic vision now, the NIH will be able to stand at the ready as future challenges and opportunities emerge. In keeping with our mission, the NIH's current and future actions will be defined by the requirements of the scientific community and the public health needs of the nation.
As a result of our investment in biomedical research, over the past 30 years we have seen many great advances impacting the health of our nation. In fact, life expectancy has increased by 1 year every 5 years for the past 30 years.1Americans are not only living longer, they are also healthier. For instance, the disability rate of American seniors dropped by 25% over a 17 year period from 1982-1999.2These great achievements in health have been fostered by the effective translation of scientific advances. Although the current budget climate is challenging, I feel strongly that we must never stray from our core mission: the pursuit of fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to extend healthy life and reduce the burdens of illness and disability.
In many ways, the scientific community is facing what some are calling a “perfect storm.” Just as the doubling was ending and the research community was primed with talented researchers who were submitting many more applications, we hit rough waters. Nationally, we have deep federal and trade deficits, rising expenditures for homeland security, unexpected economic and physical devastation from natural disasters such as Hurricane Katrina, and, to protect the nation, preparations for pandemic flu. Additionally, technological advances have emerged rapidly and altered the information landscape in dramatic ways. Further, we have an aging population with predominantly chronic diseases, and we are facing emerging public health challenges, such as obesity and diabetes.
It is clear to me that there is only one option for staying afloat. Because treating end-stage disease is so costly, both personally and financially, learning how to preempt illness through molecular knowledge and behavioral interventions is the only viable strategy for maintaining the nation's health in the coming years.
In 2002, when I became director of the National Institutes of Health (NIH), I immediately focused on two things: the support of clinical research and scientific problems that are common to many diseases and thus may benefit from a coordinated attack. Importantly, I arrived at these conclusions not in isolation but based on extensive consultation with the scientific community. I met with representatives from numerous professional societies and organizations, grantees, and other stakeholders to learn from the front line what is most needed to maintain research momentum in an era when science is changing at a breathtaking pace. From these discussions arose the NIH Roadmap, a framework for the NIH to speed discovery and its efficient translation to patient care.3The Roadmap provides an incubator space for funding innovative programs to address a panoply of scientific challenges.
The Roadmap contains three foci: “New Pathways of Discovery,” “Research Teams of the Future,” and “Re-engineering the Clinical Research Enterprise.” There is considerable—and intentional—intersection among each component. The Roadmap is not a single initiative but (in FY 2005) consisted of 345 individual awards at 133 institutions in 33 states. These awards are quite balanced among basic, translational, and what we call high-risk research. In total, the Roadmap accounts for only a relatively small proportion of the overall NIH budget: in FY 2005, 0.8%; in FY 2006, 1%; and in FY 2007, 1.2%. The question, then, is what will be the impact of the Roadmap?
One observation that is impossible to ignore is that today's science is not yesterday's science, and this is especially true for clinical research. Today's researchers cannot hope to master science and clinical medicine in the same ways that their counterparts did 50 years ago. It is impossible for one individual to absorb all of the necessary knowledge, and that makes innovative training and collaboration the keys to progress. We have seen that the biggest initial impact of the Roadmap process is in spurring change to the culture of research and in removing artificial barriers to greater synergy among scientific disciplines. A team approach to clinical research must also be the modus operandi of modern medicine. Today's scientists require mechanisms to work within interdisciplinary teams. The Roadmap has engendered a new culture of cooperation among researchers seeking new avenues for collaboration.
In October 2005, the National Center for Research Resources (NCRR), on behalf of the NIH, launched a new Roadmap initiative: the Clinical and Translational Science Awards (CTSAs). The program's goals are to eliminate growing barriers between clinical and basic research and to address the increasing complexities involved in conducting clinical research. Difficulties in recruiting and retaining clinical researchers, increasing regulatory burdens, and fragmented training programs are some of the challenges limiting professional interest in the field and hampering the clinical research enterprise at a time when it should be expanding. Developed with extensive input from the scientific community, the awards will help institutions nationwide create an academic home for clinical and translational science.
Over the years, the NIH has supported the conduct of translational and clinical research through multiple separate programs, such as General Clinical Research Centers (GCRCs), specialized laboratories and imaging facilities, funds for new and emerging fields such as research informatics, and the training of generations of translational scientists. These investments, however, fall short of recognizing the important linkages between these resources and the growing need to provide sustained interdisciplinary training in a supportive and dedicated academic environment beyond that provided by traditional academic structures. Support of the CTSAs will provide the financial resources and flexibility for institutions to establish an academic home for the discipline of clinical and translational research and enable institutions across the country to (1) captivate, advance, and nurture a cadre of well-trained multi- and interdisciplinary investigators and research teams; (2) create an incubator for innovative research tools and information technologies; (3) synergize multi- and interdisciplinary clinical and translational research; and (4) accelerate the application of new knowledge and techniques to clinical practice at the front lines of patient care. The CTSA program will provide additional resources toward training, especially by offering advanced degrees in clinical research. I see this as a core need if we are to strengthen clinical research as an independent discipline.
In addition to the GCRC program, the NIH has taken many steps in the past to advance clinical research. However, although important, these actions have not been sufficient. My hope is that the CTSA effort will complement existing programs that have benefited the clinical research community for many years. Loan repayment programs and career development awards for budding clinical researchers remain important ingredients for sustaining the clinical and translational research pipeline. The NIH's new Pathway to Independence program, which supports new investigators through a hybrid K-R01 (K99/R00) portable award, is a program that may be particularly suitable for new MD/PhD scientists who wish to perform laboratory research. This pilot program, which was just recently put into place, will be assessed to consider outcomes after its first year of implementation. And although it is not limited to PhDs, for physician researchers, NIH's 5-year K awards provide a longer term of support (compared with 2 years of K award support in the K99/R00 awards). Generally speaking, the NIH K awards remain critical to our efforts to attract talented medical students, physicians, dentists, and similar professionals to the challenges of clinical research or to help clinical investigators transition to independent research careers, and the NIH will continue to support them.
In particular, the Roadmap K12 initiative the Multidisciplinary Research Career Development Program is intended to produce new clinical research leaders who can cross the boundaries of their disciplines and draw on the strengths of other fields. The goal is to create leaders of various fields of clinical research critical to the overall NIH mission. Researchers funded through this initiative are the first generation to be educated, trained, and mentored to design and perform clinical research in a new, multidisciplinary, integrated environment. In designing the funding plan for the CTSA program, we took great care to preserve the investigator-initiated research support pool in this time of constrained budgets. As such, the CTSA program will be accomplished entirely through redirecting existing resources, including Roadmap funds. Researchers who perform patient-oriented research at institutions that do not receive CTSAs may apply for investigator-initiated NIH research supported by a variety of NIH grant mechanisms, including Research Project, Research Program Project, and Center grants. However, the 60 CTSAs that the NIH plans to make could support more than 90% of the institutions that currently have GCRCs.
Some in the research community have wondered why the NIH embarked on the CTSA and other Roadmap efforts in a constrained budget environment. It is important to remember that the creation of the CTSA program occurred in response to the needs of the research community. In May 2005, an NIH-sponsored meeting brought together more than 300 members of the biomedical research community, who shared information about the frustrations and obstacles they encountered, as well as their optimism about the promise of translating basic discoveries into improved medical care. Participants generally agreed that a significant change was needed to enhance clinical and translational science. According to many attendees, institutional and programmatic boundaries had created fragmented research efforts, training programs, and resources that would be more effective if integrated. Through the CTSA program, we aim to establishing a supportive habitat for clinical and translational research to thrive and grow. I believe strongly that this is the cornerstone to ensuring that rapid and fundamental advances in biomedical and behavioral sciences will be available for patient-oriented research and to provide well-structured career development pathways. Such efforts may be easier to accomplish if they were conducted within a true academic home, assembling dedicated faculty and staff with a transformative vision, mission, and strategies. This is why it is essential that we stay the course—working within our budgetary constraints—to implement the CTSA program.
The response to the CTSA request for applications (RFA) has been robust and generated wide-ranging reevaluation of programs of many institutions with innovative discussions. The NCRR Office of Review has been working closely with the trans-NIH CTSA Project Team to embody new principles into the review process. For example, the CTSA program will, when possible, support ongoing efforts to recognize multiple principal investigators on individual awards in future funding opportunities. This will provide an important impetus for interdisciplinary research. An essential facet of the success of the CTSA program is excellent peer review, and the NIH has instituted many measures over the years to optimize the review of clinical research applications. Recent findings suggest that although median funding scores for clinical research R01 grants are lower than those for basic research, the cause does not appear to be the cost of awards or reviewer bias.4Nonetheless, we are continuing to investigate and evaluate the review process, as well as bring it up to speed with the needs of today's reviewers. To that end, the NIH's Center for Scientific Review is experimenting with a range of pilot programs that aim to enhance and streamline the peer review process.
These are tough times, and the best outcomes will depend on how the NIH and the scientific community work together. We cannot afford to lose a new generation of scientists because of the markedly increased competition for funding that naturally occurs when there is a boom in capacity and corresponding growth in the number of competing grant applications—from 26,152 in 1998 to over 46,000 in 2006. Our most important treasure is our intellectual capital, and together we must work to sustain it.
In these challenging times, we must also have a strategic vision for the future. We are in an era of great scientific opportunity and, I believe, on the brink of transforming medicine and health in the twenty-first century. Our hope is to usher in an era in which medicine will be predictive, personalized, preemptive, and participatory. Toward this goal, the NIH is strategically investing in research to further our understanding of the fundamental causes of diseases at their earliest molecular stages so that we can reliably predict how and when a disease will develop and in whom. Because we now know that individuals respond differently to environmental changes according to their genetic endowment and their own behavioral responses, we can envision the ability to precisely target treatment on a personalized basis. Ultimately, this individualized approach, completely different from how we treat patients today, will allow us to preempt disease before it occurs. We must also work toward medicine that is more participatory, allowing for increased community involvement, feedback, and education in both health care and clinical research.
Finally, the NIH and all of its partners must strive to do a better job of communicating—at local, regional, and national levels—the positive impact of investing in medical research. This should be a natural consequence of blended efforts, such as the CTSA program, in which the entities funded can serve as magnets that concentrate basic, translational, and clinical investigators, community clinicians, clinical practices, networks, professional societies, and industry to facilitate the development of new professional interactions, programs, and research projects.
Teamwork thrives on mutual commitment. The NIH has a long history of working with key partners on clinical trials and other types of research projects. The collaborations are developed with clear delineation of responsibilities through formal agreements and cooperative research and development agreements. However, relationships can and do change with time. By adopting a strong strategic vision now, the NIH will be able to stand at the ready as future challenges and opportunities emerge. In keeping with our mission, the NIH's current and future actions will be defined by the requirements of the scientific community and the public health needs of the nation.