Dean's Newsletter

Archive of previous newsletters

Clinical and Translational Science at URMC

August 04 , 2006

In my experience, virtually all investigators involved in biomedical science are not only fascinated by the intrinsic scientific challenges of their work, but would love to see the day when their innovations are translated into clinical tools that can better prevent, diagnose or treat human disease.  Indeed, it is the mandate of the National Institutes of Health, which provides the funding for most of our fundamental research, to foster the translation of the remarkable scientific innovations we are witnessing into health gains for the nation.

It is this mandate that led to the NIH Roadmap for Medical Research, which represents the NIH response to the question:  "What novel approaches can be developed that have the potential to be truly transforming for human health?"  The Roadmap consists of three key themes. (1) develop novel approaches that will unravel the complexity of biologic systems and their regulation, called "New Pathways to Discovery;"  (2)  invoke an era in which scientists can cooperate in new and different ways, across disciplinary boundaries, called "Research Teams of the Future;"  and (3) "Re-engineering the Clinical and Translational Research Enterprise."

In this newsletter, I will review the steps we have taken to address the third of these themes, which also relates to the second theme.
 
To provide context, I will quote at length from an article written by Elias Zerhouni, MD, in the New England Journal of Medicine (Vol 353, pp.1621-23):  "Translational and clinical research are core components of a full-spectrum biomedical research enterprise. Yet, these critical arenas of research are hampered by increases in costs and complexity, a dearth of information systems, and increases in regulatory burden. An explosion in clinical-service demands and reduced financial margins have sharply cut protected research time for many clinical and translational researchers and diluted the time and attention devoted to the research mission of academic institutions. The inevitable result of these changes has been, for example, difficulties in the recruitment and retention of human subjects in clinical trials and, ultimately, considerable delay in the completion of critical studies. It is more and more difficult to recruit, mentor, and retain a critical mass of clinical and translational scientists. Proper training and mentoring of scientists capable of conducting truly innovative patient-oriented research require dedicated time away from the escalating pressures of clinical-service demands. At the same time, the increasingly complex resources needed to conduct modern clinical and translational research are either missing or scattered. There has been little investment in methodologic research to improve the tools used by clinical and translational scientists. Bioinformatics, bench-to-bedside laboratories, and statistical cores are not integrated in a manner that promotes, for example, both outstanding research and innovation in study design leading to a more efficient end result. At no other time has the need for a robust, bidirectional information flow between basic and translational scientists been so necessary. Advances in our understanding of biologic systems and the development of powerful new tools that can be applied at both the bench and the bedside -- genomics, proteomics, transgenic animal models, structural biology, biochemistry, and imaging technologies -- offer unprecedented prospects for advancing knowledge of human disorders in a translational context. Moreover, it has also become clear that available animal models of human disease are often inadequate, necessitating even more research on human populations and biologic samples. Today, there is good reason to believe that the scope of knowledge and expertise needed to be an effective translational or clinical scientist can no longer be acquired "on the job," as was done in the past. Although we have made every effort to provide the support functions for translational and clinical research, there is a call for training in a wider range of skill sets that span the biomedical and behavioral sciences and make use of far more advanced and more complex resources and methods than ever before. We may have failed to recognize that clinical and translational science is an emerging discipline that encompasses both the acquisition of new knowledge about health and disease prevention, preemption, and treatment and the methodologic research necessary to develop or improve research tools. Clinical and translational researchers require more dedicated and structured learning time and a clear path for both promotion and tenure, combined with opportunities for true scientific inquiry in an intellectual environment conducive to such endeavors. "

Shortly after publication of Dr. Zerhouni’s NEJM article, NIH released an RFA for Clinical and Translational Science Awards (CTSA), designed to foster the re-engineering described above, including enhanced infrastructure in biostatistics, regulatory support, training, novel methodologies, and the other elements described.  This came at just the right time for us at URMC, because indeed we felt that we shared a common vision with NIH about clinical and translational science.  Indeed, several steps that we had already taken, and several more that were planned, melded perfectly with the thrust of the RFA.  Our response to this RFA, submitted on March 27, 2006, reflects these ongoing ideas and efforts, and our vision for the future.

The RFA required that each institution create an academic home for clinical and translational science, and that the overall enterprise for clinical and translational science be given department, center or institute status.  We chose the "institute" designation, and proposed creation of the University of Rochester Clinical and Translational Science Institute (UR CTSI), which would contain a Clinical and Translational Science Building (CTSB) as its academic home.  The overall concept of the proposed UR CTSI is depicted in the figure below.  Elements to be located in the CTSB are shown as blue circles, while components located in other areas of the campus, to be coordinated under the CTSI, are shown as red circles.  Components that would be new under the CTSA are designated by a grid within the circle, while elements that would undergo upgrades under the CTSA are designated by outlining the circle in bold.  All of the elements of the CTSI are conceptually collected within an oval outlined in green.  CTSI partners are shown as yellow ovals intersecting the CTSI and its components.  The areas of overlap are meant to reflect areas of programmatic intersection and collaboration.  They are not meant to show explicitly all areas of overlap; rather, they are simply illustrative of much more frequent intersections between the various CTSI elements than can be shown in this type of schematic illustration.

Several aspects of Figure G1A1 are noteworthy.  First, many core components of the CTSI will be located under the CTSB (blue),yet, we will also take advantage of selected existing research centers in their current locations (red), which will be integrated into the CTSI as important components.  Second, the CTSI interacts with partner schools and colleges at the University, including Nursing, Dentistry, and Arts, Science and Engineering.  Third, the CTSI also interacts with basic science departments and research centers at the medical school.  Fourth, many existing clinical and translational research cores will be upgraded by the CTSA (outlined in bold) while others will be new under the CTSA (grid).  New initiatives that will be supported by the CTSA are a proposed T32 training program in translational science, and a K12 program for training junior faculty in clinical and translational science, new degree granting programs such as a PhD in translational science, new imaging and other translational cores, and infrastructure support for the development of novel methodologies.  Fifth, the figure conveys the interaction between the UR CTSI and our community and region.  In the Rochester community, we have links with the Monroe County Health Department, major employers, the Rochester School District and the Primary Care Practice-Based Network.  Across Upstate New York, a particularly innovative aspect of the UR CTSI is the creation of a consortium of universities and other research partners, which might serve as a national model for regional consortia.  Sixth, another innovative feature of the UR CTSI is the data sharing and dissemination plan, which might also be informative for a national approach to a logic model for such dissemination.  And Seventh, it can be seen that the UR CTSI is a trans-University entity.  Regulatory support functions such as the Institutional Review Board and the Office of Research and Project Administration are University-wide offices. 

University of Rochester Clinical and Translational Sciences Institute (CTSI)

Click on image to enlarge

Taken as a whole, we suggested in the grant proposal that the new organization illustrated above will transform clinical and translational science at UR by creating an academic home with the infrastructure, governance and institutional support needed to forge a new discipline that coalesces the two fields.  The UR CTSI will thus accelerate the generation of multidisciplinary clinical and translational science at UR.  In addition, the UR CTSI will provide significant contributions to a national consortium of CTSAs by providing innovative models for facilities, governance, regional collaboration and data sharing and dissemination.

According to the RFA, 4-7 of these grants were to be awarded nationally.  It should not be surprising, in view of their scope and projected budget (up to $6 million per year), that almost all of the major research-oriented medical schools submitted applications.  The NIH panel convened to review these applications, consisting of scientific peers from across the nation, met earlier this month.  This week, we learned that the panel had given an outstanding score to our grant.  Thus, there is reason to be optimistic that the grant will be funded; nothing is certain, however, because of overall NIH budget considerations, review by NIH Council, and other factors.  That said, whether or not we receive funding for this go-round, the principles of the CTSA initiative are in place at URMC, and will be an important part of our strategic planning going forward. 

Needless to say, this grant application, which amounted to 700 pages, represents the collective efforts of a large number of individuals who worked intensively together over many months.  The table shown below, which provides an overview of the components of the grant, conveys a sense of the depth and breadth of the research infrastructure development proposed under the CTSA.

From this table it should be clear that this initiative in clinical and translational science, if funded, will impact directly almost everyone doing research at the Medical Center.  It also addresses, directly and indirectly, our other missions.  In education, the T32 and K12 training awards will provide rigorous degree-granting and non-degree programs in clinical and translational research. Moreover, enhancements in clinical and translational science will enrich the resources that can be drawn on for education of medical students, graduate students, residents and fellows.  Clinically, fundamental discoveries that are translated into clinical application will more readily be incorporated by our clinical teams into their patient care.  And finally, community dissemination and application of translatable research findings will now also be facilitated by upgraded outreach resources, and creation of the Upstate Academic Consortium will promote even more far-reaching collaboration, as well as the potential for economic development.

Your waiting-for-the-NIH-award-notice Dean,

Meliora,

David S. Guzick, MD, PhD
Dean, School of Medicine and Dentistry