RE-ENGINEERING THE CLINICAL
RESEARCH ENTERPRISE
Co-Chairs
Working Groups and Co-Chairs
Stephen Katz, NIAMS
Stephen E. Straus, NCCAM
Subgroups
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Harmonization of Clinical Research Regulatory Processes
Amy Patterson, OSP
Integration of Clinical Research Networks, including NECTAR
Larry Friedman, NHLBI
Stephen Katz, NIAMS
Enhance Clinical Research Workforce Training
Duane Alexander, NICHD
Rob Star, NIDDK
Enabling Technologies for Improved Assessment of Clinical Outcomes
Deborah Ader, NIAMS
Larry Fine, OBSSR
Stephen Katz, NIAMS
Regional Translational Research Centers
Stephen E. Straus, NCCAM
Steve Zalcman, NIMH
Translational Research Service Cores
Josephine Briggs, NIDDK
Stephen E. Straus, NCCAM
Re-engineering the Clinical
Research Enterprise
Stephen Katz, M.D., Ph.D
Amy Patterson, M.D.
Stephen E. Straus, M.D.
Re-engineering Clinical Research
Interdisciplinary
Research
Pioneer Award
Bench
Public-Private Partnerships
Bedside
Practice
Building Blocks
and Pathways
• Translational • Integrated Research Networks
Molecular Libraries
Research
• Clinical Research Informatics
Bioinformatics and
Cores
• National Clinical Research Associates
Computational
• Regional
• Patient-reported clinical outcomes
Biology
Centers
Structural Biology
Nanomedicine Cross cutting: Harmonization, Training
Integration of Clinical Research
Networks
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Link existing networks
so clinical studies and
trials can be conducted
more effectively
Ensure that patients,
physicians and scientists
form true “Communities
of Research”
Typical NIH Network
Academic Health Center Sites
& Data Coordinating Center
Interoperable Networks
Share Sites and Data
Integration of Clinical
Research Networks
 Create interoperable ‘Network of Networks’
 National Electronic Clinical Trials/Research Network
(NECTAR)
 Common data standards, informatics
 Software application tools for Protocol preparation, IRB
management, adverse event reports
 Use existing networks to rapidly address questions
beyond their traditional scope
BAA-RM-04-23: Feasibility of Integrating and Expanding Clinical Research Networks
Inventory and Evaluation of Clinical Research Networks: NIH Task Order 169
NIH Career Development Programs
College
Professional
Grad School
•NIH CR Training Program;
•Advanced Degree Program?
Post-Doc
Prof. Advancement
Trans-NIH K12 CR Career Dev;
National CR Associates Program
Trans-NIH Multidisciplinary K12
Career Development Program (RFA)
Promote development of investigators from a
variety of disciplines (M.D., Ph.D., R.N.-Ph.D.,
D.P.H., Pharm.D., D.C., …)
 To be trained in multidisciplinary team settings
Goal:
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Features:
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Up to 5 years of training
 Core didactic courses, Project-specific training
 Mentored research experience in team settings
 Faculty and mentor support to protect their time
 Tuition support
 Annual meetings
National Clinical Research Associates
Goal:
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Steps:
Diverse national group of trained and certified
community healthcare providers
Will enroll and follow their own patients
Accelerate translation of results into practice
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Determine feasibility: Barriers? Communities?
Incentives needed?
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Inventory training methods, best practices
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Develop core competencies, certification
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Future: Training programs
Dynamic Assessment of PatientReported Chronic Disease Outcomes
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Background:
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Assessment of chronic diseases relies heavily on subjective reports
of symptoms and health related quality of life items
PROMIS – Patient-Reported Outcomes Measurement
Information System:
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A collaborative network of investigators charged to develop and
implement a publicly available system of a large item bank and a
Computerized Adaptive Tests for more sensitive and efficient testing
of major chronic disease symptoms and functioning.
RFA-RM-04-011: Dynamic Assessment of Patient-Reported Chronic Disease
Outcomes
Re-engineering Clinical Research
Interdisciplinary
Research
Pioneer Award
Bench
Public-Private Partnerships
Bedside
Practice
Building Blocks
and Pathways
• Translational • Integrated Research Networks
Molecular Libraries
• Clinical Research Informatics
Research
Bioinformatics and
Cores
• National Clinical Research Associates
Computational
• Regional
• Patient-reported clinical outcomes
Biology
Centers
Structural Biology
Nanomedicine Cross cutting: Harmonization, Training
Clinical Research Policy
Analysis and Coordination
“Harmonization Initiative”
Clinical Research:
Navigating the Roadway
 Clinical research impeded
by multiple and variable
requirements to address
fundamentally the same
oversight concerns
 Variability among and within
agencies
 Creates uncertainty
about how to comply
 Hampers efficiency and
effectiveness
Clinical Research Policy
Analysis and Coordination Initiative
 AIM:
Promote clear, effective, and
coordinated policies and regulations
for the conduct and oversight of
clinical research
Priority Issues
1.
Diverse adverse event reporting requirements
2.
Confusion regarding roles and responsibilities of
Data Safety and Monitoring Boards, IRBs, and other
review mechanisms
3.
Variable requirements for auditing and monitoring of
clinical trials
4.
Absence of uniform standards for electronic
submission of safety and clinical research
information
Priority Issues
5.
Confusion regarding applicability of privacy
requirements and HIPAA to clinical research
6.
Variability in interpretation of the human subjects
regulations
7.
Central vs. local IRB review
8.
Best practices in informed consent
9.
Investigator financial disclosure and conflicts of
interest
Methods
 Establish formal NIH program to:
 Work in concert with sibling agencies to catalyze the
federal-wide coordination of policies pertaining to
clinical research
 Consult with key stakeholders including IRB, patient,
industry, and research communities
 Develop tools and resources to facilitate
understanding of and compliance with clinical
research policies and requirements
Harmonized Adverse Event
Reporting Requirements
Gene Therapy Example
 Prior to January 2002:
 Principal Investigators had to report to NIH all serious
adverse events immediately
 At variance with FDA requirements (21 CFR 312)
 Current harmonized requirement:
 Possibly associated, unexpected events reported within 15
days - or within 7 days if fatal or life threatening
 Scope, timeframe, and definitions for safety reporting are
same for NIH and FDA
Analysis and Communication of
CR Information
 Prevailing paradigm
 Paper based
 Varied information and diverse formats and vocabularies
 Inefficient transmission and limited comparison of data sets
 Model approach
 Electronic data capture, analysis and reporting
 Uniform data elements and format accepted by multiple agencies
 Rapid transmission and ready comparison of data sets
 Objectives
 Facilitate investigator compliance
 Enhance agency oversight
 Optimize data sharing and analysis
Outcomes
 Clear, effective, and coordinated rules for clinical
research
 Maximally effective human subjects protections
 More comprehensive analysis and sharing of
research data
 Enhanced quality and productivity of the
research enterprise
Translational Research
 Definition:
Research at the bench-bedside interface designed to
define disease pathobiology and to explore innovative
approaches to treatment and prevention
 A Problem:
Academic investigators too often lack the resources and
expertise to study diseases or evaluate novel drugs and
biologics in early phase (I-II) human studies using stateof-the-art tools
Facilitating Translational Research
Interdisciplinary
Research
Pioneer Award
Bench
Public-Private Partnerships
Bedside
Practice
Building Blocks
and Pathways
• Translational • Integrated Research Networks
Molecular Libraries
Research
• Clinical Research Informatics
Bioinformatics and
Cores
• National Clinical Research Associates
Computational
• Regional
• Patient-reported clinical outcomes
Biology
Centers
Structural Biology
Nanomedicine Cross cutting: Harmonization, Training
Translational Research:
Goals for the Initiatives
 Stimulate research at the bench-bedside interface
 Implement mechanisms to prepare novel products
for pre-clinical and clinical studies
 Ensure adequate support for regulatory oversight,
data management, and specimen analyses
 Increase the sensitivity and impact of early phase
clinical studies
 Invest sufficiently in a modest number of programs
to facilitate research at many institutions
Translational Research Core Services
 Extensive consultations with leaders in academia and
industry
 Pilot program will support early pre-clinical development
of small molecules for therapeutic applications
 Modeled on NCI RAID program – Provides investigators
access to contractor facilities for key services
 Requires extensive decision-making expertise, process
controls, and regulatory oversight
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Funded ~25% by Roadmap; ~75% by sponsoring IC
 Current status: Pilot initiative for implementation in
FY2005
Regional Translational
Research Centers
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Current options for resources:
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Regulatory, statistical, bioethics & data management support
Support bench-to-bedside and pilot projects, translational
research fellows program
Cores in some sites for pharmacology, immunology, genetics,
microarray, bioinformatics and other highly technical services
 Could complement NCRR’s GCRC program, and support
phase I studies of products made by the Core Services program
Next Steps:
 National meeting of academic opinion leaders in summer 2004
 Goal is to call for and fund planning grants in FY2005, and rounds of
new centers starting in FY2006
Re-engineering Clinical Research
Interdisciplinary
Research
Pioneer Award
Bench
Public-Private Partnerships
Bedside
Practice
Building Blocks
and Pathways
• Translational • Integrated Research Networks
Molecular Libraries
• Clinical Research Informatics
Research
Bioinformatics and
Cores
• National Clinical Research Associates
Computational
• Regional
• Patient-reported clinical outcomes
Biology
Centers
Structural Biology
Nanomedicine Cross cutting: Harmonization, Training
Re-engineering Clinical Research:
A Work in Progress
Re-engineering Clinical Research:
Progress To Date (as of February 2004)
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Multidisciplinary Clinical Research Career
Development (K12) programs: RFA-RM-04-006
Dynamic Assessment of Patient-Reported
Chronic Disease Outcomes: RFA-RM-04-011
Inventory and Evaluation of Clinical Research
Networks: NIH task order 169
Feasibility of Integrating and Expanding
Clinical Research Networks: BAA-RM-04-23
Re-engineering Clinical Research:
Future ‘05 Initiatives
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Translational Research
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Translational Research Core Services pilot
program
Planning grants for Regional Translational
Research Centers
Clinical Research
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Feasibility of the National Clinical Research
Associates program
NIH
Ideas
People
Resources
Leadership