Transcript Analgesic Clinical Trials Project (ACTP) Proposal for

ANALGESIC CLINICAL TRIAL
INNOVATIONS, OPPORTUNITIES, AND
NETWORKS (ACTION)
ACTION Inaugural Workshop
6-15-11
Evolution of the ACTION Initiative and
Public Private Partnerships in the
Context of FDA’s Public Health Mission
and Regulatory Science
Wendy R. Sanhai, Ph.D., M.B.A.
Senior Scientific Advisor
Office of Chief Scientist
Office of the Commissioner, FDA
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FDA’s Mission Statement
• “The FDA is responsible for protecting the public
health by assuring the safety, efficacy, and
security of human and veterinary drugs, biological
products, medical devices, our nation’s food
supply, cosmetics, and products that emit
radiation.
• The FDA is also responsible for advancing the
public health by helping to speed innovations that
make medicines and foods more effective, safer,
and more affordable; and helping the public get
the accurate, science-based information they
need to use medicines and foods to improve their
health.”
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Public Health Context: “Unmet Need”
• The most widely used analgesics are opioids,
NSAIDs and acetaminophen
– All have serious toxicities, even when used properly
• Development of novel analgesic products has been
slow and challenging
– Clinical trials frequently fail to show efficacy
– Pharmaceutical industry is reluctant to take on the risk
of developing of novel analgesics due to hurdle of
achieving successful outcomes in expensive clinical trials
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Current State of Affairs
• Clinical studies, particularly efficacy trials,
notoriously flawed for analgesic drug development
– Frequent studies failures with drugs known to be
effective
– Extremely small treatment effects even when successful
– Multiple causes, e.g.:
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Large placebo effect
Missing data
Study design flaws
Study analysis flaws
Investigator quality
Frequent use of foreign sites
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Overall ACTION Objectives
• To conduct critical research, including
analysis of existing data to:
– improve the success rates of analgesic
trials and guide the design of future trials
– facilitate efficient development of safer and
more effective analgesic drug products
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Why Public Private Partnerships?
• Any single party: limited resources (staff, funds,
infrastructure, equipment…), time and expertise
– Leverage resources and expertise among stakeholders
to minimize costs (time and money)
– Align missions toward mutually beneficial goals
– Open new lines of communication among partners
– Create value added for all stakeholders: optimizing
economies of scale…advancing public health
• Whole = Greater than sum of individual
parts/partners
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…It will take a village
• Pain researchers and clinicians
(academia, other research institutions)
• Professional organizations
• Government agencies
• Pharmaceutical and device companies
• Patients and patient advocacy organizations
• Non-profit foundations
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Building the Foundation for ACTION
(prior to ACTION PPP launch; All funding from CDER)
• Three initial projects
– 1 data reanalysis project
– 1 clinical protocol development project
– 1 data transformation/standardization project
• Partners
– Univ. Pennsylvania
– SAS Institute/Executive Information Services (EIS)
• Funding:
– FY ’07: $50K; FY ’08: $250K; FY ’09: $500K
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ACTION Timeline
First
ACTION
Discussions
(FDA)
Q3
Q4
ACTP
Workshop
(Ashburn)
2009 Q2
ACTION/
IMMPACT
Discussions
Q3
Q4
ACTION
Contract
Solicitation
2010 Q2
FDA-internal
ACTION
contract
process begun
Q3
ACTION
Manuscript
published
Q4
ACTION
Contract to U
Rochester
ACTION
Inaugural
Workshop
2011 Q2
ACTION
Cooperative
Agreement
RFP
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2010 ACTION Contract
• Issued in September 2010, under the Critical
Path Initiative
• Aggressive 1-year timeline
• Goals:
– Establish ACTION PPP: robust foundation for future
activities
• Governance board
• Operating principles
• Scientific oversight committee
– Perform analysis of selected pain trial data
– Conduct scientific workshop (June 15, 2011)
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PPP Operating Principles
• Transparency: maintain public trust
• Inclusion of interested/affected stakeholders
– FDA, industry, academia, professional societies,
patient advocates, NIH, other gov’t, …
• Leveraging resources
– Existing and prospective data
– Claims data
– Personnel & scientific expertise
– Project funding
• Focused on public health and efficient product
development
• Mutually beneficial to partners
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ACTION PPP Governance Structure
Executive Committee (EC)
Board of
Advisors
(BOA)
Scientific and Professional
Advisory and
Recommendations
Committee (SPARC)
ACTION Coordinating
Center /
Steering Committee
Working Groups (WGs):
EC and SPARC approved
projects and activities
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Basic Steps in Collaborating with FDA
(not comprehensive! not consecutive!)
Start with the Public Health Need, SCIENCE!
Identify Priorities for multiple stakeholders
Identify gaps/opportunities
(avoid duplication)
Identify partners: define roles/responsibilities
Co-develop: proposals, budgets, timelines etc.
Leverage resources/expertise
Implement joint Proof of Concept projects
Share data in public domain as quickly as appropriate: Pre & Pro-competitive tools
Some Benefits
PRIVATE PARTNERS: Regulatory Knowledge, Predictive Tools & Input in Project
Selection
FDA: Guidances, Standard-setting, Evaluative Tools
PAITENTS: Faster, Safer and Cheaper Medical Products!!!!
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Elements of a PPP
SCIENCE
PPP
•Develop protocols, timelines
•Determine public health questions
•Obtain stakeholder input
•Identify other efforts: join, expand
•Coauthor scientific articles
•Interpret scientific data
BUSINESS
•Develop business plan/strategy
•Create governance/Adm Oversight
•Identify & recruit partners
•Negotiate agreements, IP etc
•Administer/manage contracts
•Manage conflicts of interest
•Develop data sharing guidelines
•Develop reports/output analysis
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Some Elements of Business Model
• Pooling: IP, resources, expertise…
• Share Data: Proprietary, Pre-clinical, clinical, procompetitive?
• Models: Sematech, SNP & Biomarker Consortia, C-Path
Institute
• Contracts/Agreements with timelines, deliverables,
specific terms and conditions? (Licenses: non-exclusive
commercial, research-use?)
• Implement POC project/s
• Develop: Research/predictive tools, know-how,
guidances
• Employ multiple mechanisms
Data/Deliverables
FDA Guidances
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R&D, CMS, Clinical Decisions
ACTION Plan
• RFI issued on 12/18/09
• Responses reviewed and elements
incorporated into ACTION RFP
• ACTION Initiative RFP issued on
7/22/10
• Elements of the RFP….
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ACTION RFP
Develop Strategic Plan in order to:
• Identify and establish relationships with key
experts in the field
• Create an Executive Committee with
representation from key stakeholders
• Establish an independent scientific oversight
body to coordinate the overall scientific mission
of the ACTION Initiative
• Develop methodologies for the transformation of
pooled trial data from multiple analgesic trials
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General Funding Model
Whole is greater than sum of parts/partners
Private Only
Individually or
in groups
launch project/s
Private
Public
Launch PPPs with combination
of public/private funds
with mutually beneficial
goals and objectives
Public Only
FDA, NIH, CMS
Other government
Data, new guidances, best practices, informed clinical decisions, evidence based medicine
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Effective & safe medical products to patients faster, and more efficiently
Potential Sources of Funding
Private Funders
State Funds
Grants
Appropriations
ACTION
Other…
Project 3
Project 1
Project 2
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ACTION Executive Committee Co-Chairs
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American Academy of Neurology
American Academy of Pain Medicine
American College of Rheumatology
American Pain Society
American Society of Anesthesiologists
Initiative on Methods, Measurement, and Pain Assessment in
Clinical Trials (IMMPACT)
• International Association for the Study of Pain
• Outcome Measures in Rheumatology (OMERACT)
• ACTION liaisons:
• EuroPain
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• German Neuropathic Pain Research Network
Partners
Projects
Partnership
Agreements
Public Health Need
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ACTION ongoing activities
1. Methodologically-focused meta-analyses of publiclyavailable randomized clinical trials
• e.g., neuropathic pain, osteoarthritis
2. Methodologically-focused retrospective analyses of
patient-level raw data provided by FDA and by industry
3. STandardized ANalgesic DAtabase for Research, Discovery,
and Submissions (STANDARDS)
• development of CDISC-compliant database format for
retrospective pooling and prospective use
4. Request for Information
Draft Strategic Plan
Request for Proposals
5. Scientific Workshop at FDA White Oak facility (6/15/11)
• identify obstacles and finalize Strategic Plan
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FUTURE “ACTIONS”
• Research
• Facilitate collaborations among stakeholders
• Sponsor analyses of pooled legacy data
• Develop more efficient clinical trial designs
• Reduce patient burden and study costs
• Explore biomarkers and patient phenotyping
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2011 FDA Strategic Priorities
1.
Transforming development of medical countermeasures against threats
to US and global health and security
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Innovation in product development and evaluation: biomarkers,
personalized medicine and effective clinical studies
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Harnessing diverse data through information science to improve
public health
4.
Modernizing toxicology and risk assessment to better predict safety
5.
Supporting new approaches to improve product manufacturing and
quality
6.
Protecting the food supply
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Assuring FDA’s readiness to evaluate new and emerging technologies
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Advancing behavioral science to empower informed decision making and
use of products by professionals and consumers
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