WG6 Endpoint Predictivity 19 July 2012 Meeting Minutes

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When: 11:00AM (EDT) , 19Jul2012
Place: Teleconference/Webconference
Facilitator: Paul Cornwell
Scribe: Paul Cornwell
Attendance: Shree Nath, Paul Cornwell, Jane Reed, Martha Lee, Paul Bradley, Joelle Ibanes, Rich Khan-Malek, Tim Gartner, Tim Kropp, Jeremy Wally, Dave Seyler, Sue Dehaven

  1. FDA resource commitment (Tim Kropp)
  2. Narrow list of use cases to 3-5 ideas

Potential Use Case Classifications

Target Organ Systems

  • Liver
  • Cardiovascular
    • Heart
    • Vasculature
  • Male reproductive system
  • Bone marrow
  • Nervous system
    • CNS
    • PNS
  • Bone
  • Skin

Predictive vs. Retrospective

Value of Models

Molecule Type

  • Small molecule
  • Large molecule

Reproduce previous literature on predictivity

  • Olsen analysis
  • JPMA analysis

Project difficulty

  • Easy
  • Moderate
  • High

General discussion

  1. Agenda Item 1 - Summary of comments from Tim Kropp: We define the problem. FDA runs analysis and returns results. Need to be sure that problem doesn't require confidential data/information disclosure.
  2. Agenda Item 2 - Narrow use cases to 3-5 ideas
    • Easier question: Do hERG changes in nonclinical models correlate with x, y or z clinical effects?
    • Moderate question: Do transaminase changes in rodents correlate with changes in transaminases in humans?
      • Follow-up: Analyze histopath changes and other clin path changes in rodents, Determine if rodents are the appropriate species for hepatic injury
    • Hard question: Are newer kidney biomarkers (e.g. KIM1) more predictive of clinical effects than classic renal injury biomarkers (e.g. creatinine, BUN)?
    • Really hard question: Do / Which CNS findings in nonclinical species translate to clinical observations?
    • Other potential projects: Ask the Db what is the best content. e.g. which organ has the most findings? (Db may not be in appropriate format for this question currently)

Follow up

Team to submit high level questions (above) to WG6 Core Team to use as a tool to recruit additional participants to project

Last revision by Pacorn,07/26/2012