Proposal for End-of-Phase 2A (EOP2A) Meetings Advisory Committee for Pharmaceutical Sciences Clinical Pharmacology Subcommittee November 17-18, 2003 - PowerPoint PPT Presentation

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Proposal for End-of-Phase 2A (EOP2A) Meetings Advisory Committee for Pharmaceutical Sciences Clinical Pharmacology Subcommittee November 17-18, 2003

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Informal review of E-R data in over 100 NDAs submitted between 1995-2001 ... Rationale for Meeting Time. Complete information on preclinical pharmacology and E-R ... – PowerPoint PPT presentation

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Title: Proposal for End-of-Phase 2A (EOP2A) Meetings Advisory Committee for Pharmaceutical Sciences Clinical Pharmacology Subcommittee November 17-18, 2003


1
Proposal for End-of-Phase 2A (EOP2A) Meetings
Advisory Committee for Pharmaceutical
SciencesClinical Pharmacology SubcommitteeNovemb
er 17-18, 2003
  • Lawrence J. Lesko, Ph.D., FCPOffice of Clinical
    Pharmacology and Biopharmaceutics, CDER, FDA

2
New Drug Development
3
What Problems Need Solving?
  • Costs 800 million to develop a new drug
  • Almost 50 of phase 3 trials dont succeed
  • Only 20 of new drugs entering clinical testing
    are approved

4
FDA Strategic Plan
New Drug Development A Need for Greater
Productivity Steps to reduce the time, cost and
uncertainty of developing new drugs is an
important public health priority
5
Proposal End-of-Phase 2A Meeting
  • Hypothesis
  • meetings with sponsors early in the drug
    development process will focus greater attention
    on analysis of exposure-response information and
    will improve dose selection and study design for
    later clinical trials
  • Prior discussions
  • Dr. McClellan (4/03), Drs. Woodcock and Jenkins
    (5/03), OND Office Directors (7/03), OND Division
    Directors (9/03) and CDER All-Hands Guidance
    Training (10/03)

6
Philosophy Driving Hypothesis
There is more to do with regard to dose choice
from E-R studies and there is much to gain from
better use of biomarkers (PD) and more efficient
study designs Dr. Robert T. Temple, CDER
Associate Director for Medical Policy,
DIA Annual Meeting, June 16, 2003
7
Guidances Driving Hypothesis
Exposure-Response Relationships Study Design,
Data Analysis and Regulatory Applications
(2003)Providing Clinical Evidence of
Effectiveness for Human Drug and Biological
Products (1998)Dose-Response Information to
Support Drug Registration (1995)
8
Data Driving Hypothesis
  • Informal review of E-R data in over 100 NDAs
    submitted between 1995-2001
  • identified important missing data related to the
    quality of submission and approval rates
  • Prospective evaluation of over 10 NDAs submitted
    in 2002-2003
  • evaluated the impact of review including the
    re-analysis of E-R information
  • could this review been carried out early in the
    IND period and would it have saved costs and time
    in drug development?

9
Results of E-R Re-Analysis
  • Avoided potential requests for sponsors to
    conduct additional clinical trials
  • Approved lower doses or different dosing regimens
    than proposed by sponsor
  • Identified missing data on specific doses or in
    special populations that impacted review times

10
Additional Goal
Efficient and Effective Use of ResourcesInteract
ions with sponsors early in the drug development
process provides an opportunity for FDA to assist
sponsors and provide advice on the development of
information on E-R and other clinical
pharmacology issues, rather than identify
important missing data or studies during the
review of NDAs.
11
Timing of Meeting
EOP2
Pre-NDA
Labeling
Pre-IND
NDA Submission
Action Letter
Preclinical
Phase 1
Phase 4
Phase 2A
Phase 2B
Phase 3
Phase 1
12
Rationale for Meeting Time
  • Complete information on preclinical pharmacology
    and E-R
  • Complete dose-tolerance (safety) data in healthy
    volunteers
  • Initial efficacy (proof-of-concept) and safety
    data in patients
  • Prior to so-called registration or label
    studies on special populations, drug
    interactions and food studies
  • Discuss study designs using emerging technologies
    such as pharmacogenetics

13
Opportunity to Apply Mechanistic and Quantitative
Methods
  • Modeling and simulation to analyze all E-R data
    and explore dose choices
  • Design of studies using computer-assisted
    clinical trial simulation
  • Design of PPK studies to efficiently identify
    co-variates affecting E-R
  • Discuss therapeutic equivalence boundaries based
    on E-R to interpret special population studies

14
End of Phase 2 Meeting Differences
  • Final decision made on choice of doses and/or
    dose range
  • Formal meeting to discuss study design, endpoints
    and statistics of phase 3 AWC efficacy studies as
    basis for approval
  • Special population and drug interactions studies
    complete

15
Which Drug Development Programs Would Benefit the
Most?
Limited resources- first-in-class or
significant therapeutic advancement-
well-understood pathophysiology and
pharmacology- completeness of EOP2A background
package- experience of sponsor in drug
development
16
Plan
  • Draft guidance for industry
  • background, objectives, examples of topics,
    procedure for requesting meetings, information
    package, process for conducting meetings,
    documentation
  • Meetings are voluntary, relatively informal and
    interdisciplinary
  • Evaluation of impact after years of experience

Concept paper in the background package
17
Summary Goals of EOP2A Meeting
  • Decrease uncertainty in further drug development,
    e.g., phase 3
  • Quantitative analysis of E-R data to suggest dose
    ranges for clinical study
  • Identify missing or discuss necessary information
    prior to submission
  • Improve informational quality and minimize delays
    in NDA review

18
Input from CPSC
  • Do you consider the goals of the EOP2A meeting
    appropriate and what do you see as obstacles to
    achieving those goals?
  • Comment on the analytic methods used in examples
    of E-R to be presented how can these approaches
    be improved?
  • What metrics can be used to measure the impact or
    success of this initiative?
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