The Yellow Brick RoadMap:

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• The Yellow Brick RoadMap
• The Future of Clinical/Translational Research at
  UK
• Clinical Research Updates
• UK GCRC UKCRO
• C. William Balke, MD
• Senior Associate Dean for Research
• University of Kentucky
• College of Medicine
• October 19th, 2005

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• Goal of the CTSA
• Definition of Clinical/Translational Research
• Importance Relevance of Clinical/Translational
  Research
• Notable Example of the Impact of Clinical
  Translational Research
• Need for New Transformative, Novel and
  Integrative Programs.
• Team science
• Big Science
• Challenges to Implementation of CTSAs

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Goal of the CTSA

• The CTSA provides support for the establishment
  of a formal institutional infrastructure for the
  execution of and training in all aspects of
  clinical/translational research.
• Successful CTSAs will accelerate the application
  of basic science discoveries to clinical practice
  and facilitate the communication of observations
  at the bedside to drive new basic science
  investigations.

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Goal of the CTSA

• Clinical/Translational Research
  Bi-directional
• Bench-to-Bedside
• Discoveries from mechanistic studies from the
  basic science laboratory (bench)
• Translated into practical applications at the
  bedside and clinic
• Bedside-to-Bench
• Observations from the bedside and clinic drive
  mechanistic studies at the bench

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Importance of Clinical/Translational Research

• So defined, translational research can have a
  huge impact on advancing the public health of the
  nation .
• It can be argued that the work of Michael Brown
  and Joseph Goldstein on the regulation of
  cholesterol metabolism is the best example of the
  bi-directional aspects and potential impact of
  clinical/translational research.

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Joseph L. Goldstein Michael S. Brown

• Clinical observation advanced atherosclerosis
  in a pediatric patient.
• Basic science studies
• that the uptake of cholesterol-containing
  particles, namely low density lipoproteins (LDL),
  is mediated by cell surface receptors
• that the complete or partial lack of LDL
  receptors is the underlying mechanism of severe
  hereditary familial hypercholesterolemia
  characterized by premature atherosclerosis,
  myocardial infarction, and stroke.
• Clinical program new principles for the
  treatment and prevention of atherosclerosis and
  in the development of lifesaving,
  cholesterol-lowering statin drugs that are used
  by millions of people worldwide.
• Nobel Prize in Medicine or Physiology in 1985

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Importance of Clinical/Translational Research

• Considering the huge impact of the example of
  Brown and Goldstein, it is highly desirable to
  identify the factors that were required for its
  accomplishment and to duplicate them across the
  entire spectrum of biomedical research.
  Unfortunately, most of the notable examples of
  high-impact clinical and patient-oriented
  research are not the products of existing systems
  (e.g., NIHs General Clinical Research Centers
  (GCRC)) set up to promote discovery of this
  breadth and impact but rather seem to result from
  the serendipity of a clinical observation made by
  an investigator with the stubbornness,
  persistency, and skills needed to take that
  observation to its mechanistic conclusion and
  then back again to changes patient care.

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Importance of Clinical/Translational Research

• Clearly, the creation of a new workforce of
  clinical/translational investigators who lead
  multidisciplinary research teams is a key step in
  systematizing this process and thereby
  accelerating the pace of discovery of new
  knowledge in the prevention, detection,
  diagnosis, and treatment of disease and the
  translation of these discoveries into
  applications that will improve the health of the
  nation.

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Importance of Clinical/Translational Research

• CTSA - Wave of the Future
• Team science
• Multidisciplinary teams in basic clinical
  research
• Mentoring teams for clinical/translational
  research training

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Importance of Clinical/Translational Research

• Big Science
• The impact of the first wave of
  clinical/translational research is now sweeping
  the clinical and basic science communities of
  both the US and Europe.
• It is big science by scale, human resources,
  funding and complexity.
• It is predicted to be the mainstream of 21st
  century post-genomic biomedical science.

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Importance of Clinical/Translational Research

• The CTSA as the academic home for
  clinical/translational research is at the
  intersection and overlap of these traditional
  categories of biomedical research.

Basic Science Molecule Mechanism Research
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Importance of Clinical/Translational Research

• From man to mouse to molecule back again!
• Man
• Disease prevention, diagnosis, intervention
  reversal
• Mouse
• KO, KI TG models, in vivo physiology, cell
  signaling, etc.
• Molecules
• medical genetics high-thoughput gene sequencing
  proteomics

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Challenges to Implementation of CTSAs

• Transformation and consolidation of existing
  research and research training services/programs
  into an integrated center/department/institute
  for clinical/translational research
• NIH General Clinical Research Center (GCRC)
• Clinical Research Organization (CRO)
• NIH Multidisciplinary Clinical Research Career
  Development Program (Roadmap K12)
• NIH Predoctoral Clinical Research Training
  Program (Roadmap K30)
• NIH Clinical Research Curriculum Award (K30)
• Advanced degree programs in clinical/translational
  research

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Challenges to Implementation of CTSAs

• Transformation and consolidation of existing
  research and research training services/programs
  into an integrated center/department/institute
  for clinical/translational research
• Institutional Review Board (IRB)
• Office of Sponsored Programs Administration
  (OPSA)
• Institutional Core facilities/services
• Co-localization of
• Basic Scientists
• Clinical Scientists
• Translational Researchers
• Community clinicians, practices, networks
• Professional organizations and societies

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Challenges to Implementation of CTSAs

• Anxiety provoked by change even changes that
  are good and long overdue
• Preserve unique features of the nations
  biomedical research enterprise
• Entrepreneurial
• Diversity of institutions
• Merit-based

Grants Contracts
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Clinical Research Task Force Recommendations

• 1) Advisory Committee for Clinical Research
• Create a central institutional decision-making
  body responsible for establishing university
  policies, operational norms and business
  practices directing how all clinical research
  will be conducted within the University.

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Clinical Research Task Force Recommendations

• Definition of Clinical Trials and Clinical
  Research and Determination of Units engaged in
  Clinical Research
• The Advisory Committee for Clinical Research
  will review definitions of clinical research
  (NIH, Graylyn Development Conference, Association
  of Colleges of Medicine) and either select one or
  develop a University-wide definition to be used
  to identify units engaged in clinical research
  and therefore subject to compliance, monitoring
  and regulatory requirements. Care should be
  given to distinguish clinical research from
  clinical trials and different definitions of each
  term developed.

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Clinical Research Task Force Recommendations

• Expanded Centralized Organization to Provide
  Needed Services
• Expand the existing clinical research
  organization to include a clinical data
  management-biostatistics center, centralized data
  safety monitoring and additional expertise in
  such areas as clinical pharmacology,
  investigational drug services and dietary
  services with the goal of establishing a full
  service operation to support virtually all
  aspects of clinical research.

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Clinical Research Task Force Recommendations

• Expanded Electronic Infrastructure
• Identify and implement a centralized electronic
  clinical trials software system for regulatory,
  study management, patient information, study
  populations, and fiscal compliance. This
  software would be required for all clinical
  research and be compliant with the NCI Cancer
  Center Support Grant Guidelines.

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Clinical Research Task Force Recommendations

• Education Program
• Develop a coordinated program of education that
  can be continuously monitored and assessed.

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Clinical Research Task Force Recommendations

• Research Resources Issues
• Develop a Rapid Response IRB to rapidly schedule
  and review protocols where time elements for
  initiating the research is critical, such as in
  multi-center clinical trials where subject
  accrual times are of short duration.
• House Core Services together, including
• Office of Sponsored Programs Administration
  (OSPA),
• Institutional Review Board (IRB),
• General Clinical Research Center (GCRC), and
• Clinical Research Organization (CRO).