The Vision of Translational Research

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The Vision of Translational Research

• James G. Krueger, MD PhD
• Co-Director, The Center for Clinical and
  Translational Science
• The Rockefeller University
• New York, New York
• jgk _at_rockefeller.edu

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The Translational Triad

• Bench to Bedside Research
• Reverse Translation Bedside to Bench and Back
• Mentoring new trainees in all aspects of clinical
  and translational science, as well as providing
  needed didactic education
• We have a small hospital which admits only
  research patients, so our main focus is
  Translation I (bench??bedside), rather than
  Translation II (bedside ??community).

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Bench to Bedside Translation-Our Vision

• Have ability to support PhD scientists (and their
  trainees) in accessing human subjects when they
  want to test a hypothesis in the clinic.
• Have a center with resources that will permit a
  scientist to carry a new therapeutic concept into
  humans with full support for IND application,
  study conduct under Good Clinical Practice, and
  housing of research data in FDA-compliant
  databases with ability for electronic data
  transfer.

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Case one Helping a basic scientist make the
clinical leap

• Provide an infrastructure to help with protocol
  design, regulatory issues, and informed consent
  writing
• Provide access to human subjects through a pool
  of research coordinators, where a subset of
  coordinators are nurse practitioners
• Medical oversight by a Hospitalist and Center
  Directors
• Study conduct oversight and monitoring by
  Clinical Research Support Office staff

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Case 2 Help a research team go from concept to
new drug

• One example

A team of basic scientists has discovered that
targeting an antigen to dendritic cells as an
antibody fusion protein (anti-DEC205Antigen) is
much more effective in inducing T-cell mediated
immune responses. They want to use this
technology to make a new vaccine for HIV, to be
developed and tested in human subjects.
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Help provided by our Center for Clinical and
Translation Science

• Help with submitting an IND to the FDA--provide
  advice about regulatory issues including product
  manufacturing, toxicity testing, stability
  testing, protocol design, and pre-IND
  discussions with FDA.
• Help with conducting study under GCP, including
  design of case report forms, tracking of adverse
  events, creation of FDA compliant databases, and
  study monitoring. Access to study coordinators,
  data mangers, an IT infrastructure, and study
  monitors is provided within CCTS structure.

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Deeper scientific resources for translational
research

• Our CCTS will establish a center for human immune
  monitoring. It will develop techniques and
  protocols to share with other CTS scientists and
  the scientific community at large
• Our center has wide ranging studies in human
  immunology across many medical disciplines with
  need for standardized cell-based assays, most of
  which are likely to use advanced flow cytometric
  methodologies
• The development of dendritic cell targeted
  vaccines also needs assay standardization to
  quantify T-cell responses to vaccine antigens and
  presence of specialized leukocyte subsets (e.g.,
  mature dendritic cells).

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Reverse Translation

• Have inpatient and outpatient facilities that
  permit investigators to study human physiology or
  patients with defined diseases, with a staff
  attuned to special needs of human subject studies
• Provide support for access to patients with rare
  diseases and study support at all levels (design,
  conduct, oversight and biostatistical analysis of
  studies), as well as outreach to patient
  communities with specific diseases

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A training environment with mentors and graduate
courses

• A center accessible to graduate (PhD) students,
  medical students, post-docs, medical residents
  and fellows and allied health professionals,
  including research nurses to learn about or
  engage in translational science
• Formal program for Masters or PhD in
  Translational Science

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Metrics to Measure Outcomes
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Priorities and Timelines

• New Masters (degree granting) program now open
  for application first K-12 supported students
  begin in 2007
• New translational graduate course started and
  open to PhD candidates as of Jan 2007 and will
  continue/expand going forward
• Actively building research coordination, GCP
  infrastructure, IT infrastructure, enhanced
  statistical support, and regulatory support
  elements now. Expect operational
  (interdependent) functionality within 1 year.

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Priorities and Timelines

• Immune Monitoring Core actively being assembled
  and director recruitment in progress
• New vaccine trials ongoing for some prototypes,
  but will introduce antibody fusion vaccines and
  new expression vaccines within 2 years
• Pilot project grants awarded for first grant
  year, with out reach to basic scientists will
  continue annually

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Collaboration

• We want to collaborate with as many CTS centers
  as possible across all functions of clinical and
  translational science.
• Collaboration should be stressed within
  educational opportunities
• We have an active plan for development and
  distribution of unique biostatistical and
  informatics tools. New tools already developed
  for biomedical statistics are accessible and can
  be used via a web interface/grid computing
  network maintained by our Center.