Translational Research Grants in Neurotrauma

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Translational Research Grants in Neurotrauma

• What?
• How?

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Purpose Translational research is needed to feed
the therapy development pipeline
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NINDS TR program established in 2002 to fill a gap
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What is Translational Research?
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Broad Definition of Translational Research

• Translational research is the process of applying
  ideas, insights, and discoveries generated
  through basic scientific inquiry to the treatment
  or prevention of human disease.

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NINDS Definition of Translational Research

• Goal - Interventions for screening, diagnosis,
  and prevention
• Begins with a disease-linked target
• Ends with IND/IDE
• Any type of intervention (e.g., drugs, biologics,
  surgical)
• Milestone-driven

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NINDS TranslationalResearch Program

• Support Therapy Development Projects
• Pre-clinical studies
• Only activities required for therapy development
• Level the Playing Field in Review
• Projects reviewed by NINDS Scientific Review
  Branch
• Special review criteria
• Orientation of reviewers

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Basic Research
Discovery-Oriented

• Hypothesis-Driven

Translational Research
Goal-Oriented
Milestone-Driven
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NINDS Translational Research Funding Mechanisms

• Exploratory/Developmental Projects in
  Translational Research (R21)
• Cooperative Program in Translational Research
• Single component projects (U01)
• Multi-compontent projects (U54)
• Small Business Awards in Translational Research
  SBIR (U44)
• Resource Centers (U24)
• Supplemental Awards in Translational Research -
  CAPTR

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Cooperative Program

• Heart of the Translational Research Program
• Cooperative Agreements Support
• Single-component projects
• Multi-component projects
• Resource centers
• Drugs, Biologics, and Devices

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Milestone-Driven Cooperative Agreements

• Only aims required for therapy development
• Overall plan for therapy development, including
  IND or IDE
• Milestones toward therapeutic intervention

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Milestones

• Not the same as aims
• Go/No go decision makers
• Quantitative success criteria

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Cooperative ProgramScope

• Required
• A focused effort at therapy development for a
  neurological disorder
• Milestones toward therapeutic intervention
  leading to an IND
• Excluded
• Basic/mechanistic work
• Human studies

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Exploratory/Developmental

• For Investigators Not Quite Ready for the
  Cooperative Program
• Goal-Oriented Projects
• Specific Purposes
• Creation and validation of assays
• Creation of animal models for therapy development
• Identification of candidate therapeutics
• Preliminary data on animal efficacy

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Small Business Cooperative Agreements

• Phase II or Fast-Track Awards
• Identical Scope to Other Mechanisms in the Program

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How to submit a successful application

• Select a really promising therapy
• Lay out steps required for optimization prior to
  a clinical trial
• Write milestones for each step
• Include pre-IND or IDE meeting

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Developing Milestones

• Describe precise study outcomes
• Example
• No adverse events observed in two species at drug
  levels at least 5x gt than therapeutic dose at 28
  days
• Not
• Completion of 28 d toxicology study in two species

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Developing Milestones

• Provide quantifiable measures of success
• Example
• Compound analogue will have an EC50 lt 10 nM and
  LD50 gt 5 x above EC50
• Not
• Compound analogue will have improved potency and
  reduced toxicity

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Developing Milestones

• Include the rationale for your choices of in
  vitro or in vivo models, parameters tested, and
  quantitative values for go/no go milestones
• If there are consensus guidelines for preclinical
  testing, cite them

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Developing Milestones

• Be aggressive yet realistic
• Fail fast
• Define milestones for each year of funding
• Clearly identify the milestones
• Include FDA interactions

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Example

• Year 1
• Aim optimize dose and define therapeutic window
  for drug x
• Milestone drug x will improve latencies on
  Morris Water Maze test by 50 compared to vehicle
  when delivered up to 6 hours post-injury
• Rationale Six hour treatment window is feasible
  for patients with TBI. If you cant achieve this
  milestone, then the study stops.

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Contact For Translational Research Program

• Thomas Miller
• 301-496-1779
• tm208y_at_nih.gov

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Summary

• NINDS has multiple funding mechanisms for
  translational research
• Limited to preclinical therapy development
• Focus is on efficacy, not mechanisms
• Neurodegenerative Disorders and Stroke research
  are more successful than Neurotrauma Why?

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Questions