Enhancing%20Clinical%20and%20Translational%20Research%20at%20UNMC

1
Enhancing Clinical and Translational Research at
UNMC

• Lynell Klassen, Jennifer Larsen, Elizabeth
  Seaquist

2
What is Clinical Research?
3
What Clinical Research is NOT

• Research done by an MD
• Publication of clinical observations
• Post-marketing observational trials

4
NIH definition of Clinical Research (PHS 398)

• Patient-oriented research. Research conducted
  with human subjects (or of human origin -
  tissues, specimens and cognitive phenomena) for
  which an investigator (or colleague) directly
  interacts with human subjects (a) mechanisms of
  human disease, (b) therapeutic interventions, (c)
  clinical trials, or (d) development of new
  technologies.
• Epidemiologic and behavioral studies.
• Outcomes and health services research.

5
What is Translational Research?

• There are two types
• Type 1 Preclinical bench to bedside
• Pre-clinical modeling
• Clinically based hypothesis
• Type 2 Post-clinical trial to community (best
  practices)

6
UNMC Clinical Research Today

• State-of-the art clinical facilities and
  specialized regional centers for a variety of
  diseases with a Childrens Hospital for pediatric
  specialty care
• CRC to support investigator-initiated research
  with space, research nurses, lab, research
  support
• Clinical Trials Office for Pharma-driven trials

7
Current Clinical Research enterprise

• Additional research spaces Cruzan Center for
  Dental Research in Lincoln, Clinical research
  space at OVAMC but not Childrens Hospital
• Electronic medical record and nationally known
  medical informatics expertise
• Biostatistics/trial design previously in Prev Soc
  Med moved to the COPH additional qualitative
  analysis expertise at UNL
• Nationally known expertise in human studies
  regulation and bioethics

8
Current Clinical Research enterprise

• Growing bioinformatics and biotechnology
  expertise
• GMP facility for cellular therapies under
  construction
• Expertise in distance learning, web-based data
  entry, and long distance research collaborations
• Strong community partnerships with rural
  communities, minority groups in and outside NE
• Clinical research training in evolution
  Stats-Epi track in MPH, interdisciplinary
  Clinical Research track within MSIA, and Health
  Services PhD

9
Building clinical and translational research

• Elizabeth Seaquist MD
• Professor of Medicine
• Program Director, General Clinical Research
  Center
• Co-PI, CTSA
• University of Minnesota

10
BENCH
BEDSIDE
COMMUNITY
11
A Transforming Approach NIH Institutional
Clinical and Translational Science Awards (CTSA)

• Implementing biomedical discoveries made in the
  last 10 years demands an evolution of clinical
  science
• New prevention strategies and treatments must be
  developed, tested, and brought into medical
  practice more rapidly
• CTSA awards will lower barriers between
  disciplines, and encourage creative, innovative
  approaches to solve complex medical problems
• These clinical and translational science awards
  will catalyze change -- breaking silos, breaking
  barriers, and breaking conventions

12
How is this transformation achieved?

• Through the NIH Roadmap for Medical Research,
  create an integrated environment for the clinical
  and translational researcher that can provide
• an academic home for clinical research (a Center,
  Department, or Institute C/D/I)
• support for protocol preparation, regulatory
  compliance and data management
• support for participant recruitment, human
  subject safety monitoring
• education leading to advanced degrees in clinical
  research
• specialized cores and services for translational
  research

13
Where are we starting from?
Disease X Center
GCRC
K30
T32
Training Programs
Disease Y Center
K12
14
NIH CTSA Awards A Home for Clinical and
Translational Science
Clinical Research Ethics
Trial Design
Advanced Degree-Granting Programs
Biomedical Informatics
CTSA HOME
Participant Community Involvement
Clinical Resources
Biostatistics
Regulatory Support
15
NIH Clinical Translational Science Awards
(CTSA)

• By 2010 (2012?), all GCRCs and Roadmap training
  programs (T32/K30/K12) will disappear or be
  incorporated into a CTSA
• Approximately 60 CTSAs will be funded in total
• CTSA award will lower barriers between
  disciplines, and encourage creative, innovative
  approaches to solve complex medical problems
• CTSA award will provide new opportunities for
  institutions to be truly innovative in proposals
  to transform their programs and resources to
  foster clinical and translational science.
• Long term goal is to speed discoveries to
  improved patient care

16
CTSA Specific Objectives (RFA 3/07)

• Provide opportunities and resources for original
  research on novel methods and approaches to
  translational and clinical science
• Provide translational technologies and knowledge
  base for spectrum of clinical and translational
  science , including all types and sizes of
  studies and disciplines
• Integrate translational and clinical science by
  fostering collaboration between departments and
  schools within institution and between
  institutions and industry
• Provide a point a contact for partnerships with
  industry, foundations, and community physicians
• Provide research education, training and career
  development leading to a MS or PhD for the next
  generation of clinical and translational
  researchers
• Conduct self-evaluation activities and
  participate in a national evaluation of the CTSA
  program

17
CTSA components

1. Development of Novel Clinical and Translational
   Methodologies
2. Pilot and Collaborative Translational and
   Clinical Studies
3. Biomedical Informatics
4. Design, Biostatistics, Clinical Research Ethics
5. Regulatory Knowledge and Support
6. Participant and Clinical Interactions
7. Community Engagement
8. Translational Technologies and Resources
9. Research Education, Training, and Career
   Development

18
Organization CTSA resources
19
Budgetary constraints I.

• Only 1 application may be submitted from each
  degree granting institution
• Total cost Combined budgets of existing
  GCRC/T32/K30/K12 awards 6 million
• Institutions like UNMC without GCRC/T32/K30/K12
  can request up to 6 million
• IDC institutional rate U54 portion, 8 of
  K12/T32 portion

20
Budgetary constraints II.

• If more than 4 million total costs above
  existing GCRC/T32/K30/K12 is requested,
  applicants must
• discuss how they will develop and support
  translational research and career development in
  pediatrics
• discuss the opportunities that will carry their
  clinical and translational science endeavors into
  community settings
• describe the institutional commitments that match
  the increased scale of the program

21
Round one of applications

• 34 Applications
• Awards given to 12 centers
• Columbia University Health Sciences
• Duke University
• Mayo Clinic College of Medicine
• Oregon Health Science University
• Rockefeller University
• University of California, Davis
• University of California, San Francisco
• University of Pennsylvania
• University of Pittsburgh
• University of Rochester
• University of Texas Health Science Center at
  Houston
• Yale University

22
Round 2 of applications

• 27 are believed to have applied
• Up to 8 will be awarded (38
  million available)
• Review is in May
• Start date is September 2007

23
Elements of successful applications

• Strong institutional support
• ( equal to grant request new space, has
  gone gt100 million over grant period)
• Clear vision
• Well integrated
• Multidisciplinary
• Innovative

24
How has the University of Minnesota responded to
the RFA?

• Fall 2003 AHC Clinical Research Task Force
  starts
• 11/04 Task Force Report released
• 9/05 AHC Office of Clinical Research opened with
  Jas Ahluwalia as Executive Director
• First CTSA RFA released 10/05
• 10/05-3/06 - Grant planned, written, submitted
• Application incorporated 36 yr old GCRC with its
  specialized cores and research support services
  newly funded Roadmap K12 institutional support
  for industry protocols
• 66 million in total costs requested
• Institutional commitment 30,000 sq ft in
  renovated bldg for CTSA, renovation of existing
  10,000 sq ft GCRC, 50 million over 10 yrs

25
How has the University of Minnesota responded to
the RFA?

• Summer 06 Application not funded (249)
• Strengths
• Institutional commitment
• Training section
• Bioethics
• Creation of physical home
• Weaknesses
• organization complexity
• lack of details about implementation/integration
• all MDs in leadership
• unrealistic about potential problems
• poor bioinformatics

26
How has the University of Minnesota responded to
the RFA?

• October 06 Second RFA released
• 10/06-12/06 Draft prepared and rejected -
  decided to defer to 10/07
• 3/07 Third RFA released
• Plan to re-submit October 2007

27
CTSA Review

• Each application is assigned 8 reviewers and
  each reviewer is assigned one of following areas
• Significance, Approach, Innovation, Environment,
  and Implementation
• Staffing, Governance, Institutional Commitment,
  Evaluation Plans
• Biomedical Informatics
• Clinical Research Design and Biostatistics,Communi
  ty Engagement, Regulatory Knowledge and Support
• Translational Technologies and Resources, Pilot
  Studies
• Training
• 7,8. Overall (Integration, Impact, Anticipates
  problems)

28
ICTR Governance
Frank Cerra, MD Senior Vice President Academic
Health Center
External Advisory Committee
Deborah E. Powell, MD Assistant VP Clinical
Sciences
Jasjit S. Ahluwalia, MD, MPH, MS Principal
Investigator
Internal Advisory Committee Deans, Mark Paller,
Members
Eileen Harwood, PhD (SPH) Director, Evaluation
Community Engagement Mary Story, PhD (SPH) Co-PI
Education, Training Career Development Russell
Luepker, MD, MPH (SPH) Co-PI
Clinical Elizabeth Seaquist, MD (Med) Co-PI
Translational Jeff Miller, MD (Med) Tim Tracy,
PhD (Pharm) Bruce Blazar,MD (Med)
29
CTSA Challenges

• Balance - Finding balance between describing what
  you do well and what needs to change is difficult
  (i.e., Why should NIH give us grant if we already
  do everything well? vs. If we describe everything
  that needs changing, it seems negative.)
• Perspective All investigators believe what they
  do is most innovative and deserves highest
  priority. CTSA includes implicit judgment (e.g.,
  In what order does one list functions? How does
  the budget get allocated?)
• Budget - 6 million additional per year is not
  enough (especially since only 4 million is
  direct costs) to do all that is asked for in the
  RFA
• Change It is difficult to acknowledge that what
  we have been doing is not optimal (Clinical
  Research TF helped) and figuring out how to
  change it is even more so. Most people will agree
  to change in the abstract the devil is in
  details.

30
CTSA Lessons Learned

• Be flexible good ideas can come after initial
  decisions have been made
• Listen to the skeptics they will make your
  grant stronger
• Provide a structure for sections early on and
  dont let authors argue that the structure
  doesnt fit for my section
• Make a timeline that allows time for internal and
  external review and stick to it
• Its never too early to begin gathering
  biosketches
• The best sections were drafted early and went
  through many reviews
• The best sections incorporated ideas from many
  individuals
• Identify reviewers that are not intimately
  involved with the grant to provide feedback on
  ideas and to proof read

31
State of clinical and translational research 2013

• Clinical and translational research will be
  supported by a robust network of centers
  supported by CTSA program
• Funded centers will collaborate with each other
  and with unfunded institutions in their region to
  speed discovery into practice
• Clinical and translational research will become
  the preferred career path for talented health
  professionals

32
What dont we have?

• Current clinical research space
  inadequate-temporary, small, and at Childrens--
  nonexistent
• Clinical research training programs still being
  developed-clinical research mentor pool still
  small
• Clinical research processes are not
  transparent-no one place, no one person knows
  everything
• Processes not efficient time to contract and
  time to final IRB approval (benchmarklt4-6 weeks),
  biotechnology licensing, separate IRB approval
  and credentialing of research personnel at
  Childrens time consuming

33
What dont we have?

• New collaborations slowed by many factors
  faculty , type, or difficult to find
• No facility to manufacture drugs
• Mixed messages on value of interdisciplinary
  clinical research no space assigned for funded
  clinical research, only PI given credit for
  research performed by investigator teams
• Accountability less than clear who is in
  charge of clinical research?

34
What dont we have?

• Serving the larger community
• Health data in our hospital, county, or state not
  easily accessible to evaluate or study health
  concerns or outcomes
• CTSA RFA need to show how we can move basic
  research all the way to community implementation
  and take community concerns back to the
  laboratory- What will it take to do this?

35
Securing an NIH CTSA

• A physical and administrative home for Clinical
  research across UNMC
• Mentored interdisciplinary clinical research
  training
• New ways of organizing our research enterprise to
  speed up translation from bench ltgt bedside ltgt
  community better access to available data, new
  and innovative ways to gather new data, teams to
  address health issues, minority and rural
  community engagement
• This work can only be accomplished by a team of
  individuals who have been given institutional
  authority and committed to UNMCs success

36
A lot is at stake

• The final 60 CTSAs will be the driving force
  behind NIH-funded clinical research for the next
  40 years
• The CTSA is now the model of how clinical
  research should be done gt UNMC needs to
  transform its research enterprise just to keep
  in the game