RE-ENGINEERING THE CLINICAL RESEARCH ENTERPRISEWorking Groups and Co-ChairsCo-Chairs
Stephen Katz, NIAMS Stephen E. Straus, NCCAM
Subgroups Harmonization of Clinical Research Regulatory Processes
Amy Patterson, OSP Integration of Clinical Research Networks, including NECTAR
Larry Friedman, NHLBIStephen Katz, NIAMS
Enhance Clinical Research Workforce Training Duane Alexander, NICHD Rob Star, NIDDK
Enabling Technologies for Improved Assessment of Clinical Outcomes Deborah Ader, NIAMSLarry Fine, OBSSRStephen Katz, NIAMS
Regional Translational Research Centers Stephen E. Straus, NCCAMSteve Zalcman, NIMH
Translational Research Service Cores Josephine Briggs, NIDDK Stephen E. Straus, NCCAM
Re-engineering the Clinical Research Enterprise
Stephen Katz, M.D., Ph.DAmy Patterson, M.D.Stephen E. Straus, M.D.
Bench Bedside Practice
Building Blocks and PathwaysMolecular LibrariesBioinformatics and Computational BiologyStructural BiologyNanomedicine
• Translational Research Cores• Regional Centers
Interdisciplinary Research
Pioneer Award Public-Private Partnerships
Cross cutting: Harmonization, Training
• Integrated Research Networks• Clinical Research Informatics• National Clinical Research Associates• Patient-reported clinical outcomes
Re-engineering Clinical Research
Integration of Clinical Research Networks
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 NetworkAcademic Health Center Sites & Data Coordinating Center
Interoperable NetworksShare Sites and Data
Integration of ClinicalResearch 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 scopeBAA-RM-04-23: Feasibility of Integrating and Expanding Clinical Research NetworksInventory and Evaluation of Clinical Research Networks: NIH Task Order 169
NIH Career Development Programs
College Professional Post-Doc Prof. AdvancementGrad School
•NIH CR Training Program; Trans-NIH K12 CR Career Dev; •Advanced Degree Program? National CR Associates Program
Trans-NIH Multidisciplinary K12 Career Development Program (RFA)
Goal: 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
Features: 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: Diverse national group of trained and certified community healthcare providers
Will enroll and follow their own patients Accelerate translation of results into practice
Steps: Determine feasibility: Barriers? Communities? Incentives needed?
Inventory training methods, best practices
Develop core competencies, certification Future: Training programs
Dynamic Assessment of Patient-Reported Chronic Disease Outcomes
Background: 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: 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
Bench Bedside Practice
Building Blocks and PathwaysMolecular LibrariesBioinformatics and Computational BiologyStructural BiologyNanomedicine
• Translational Research Cores• Regional Centers
Interdisciplinary Research
Pioneer Award Public-Private Partnerships
Cross cutting: Harmonization, Training
• Integrated Research Networks• Clinical Research Informatics• National Clinical Research Associates• Patient-reported clinical outcomes
Re-engineering Clinical Research
Clinical Research PolicyAnalysis 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
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
Outcomes
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 state-of-the-art tools
Bench Bedside Practice
Building Blocks and PathwaysMolecular LibrariesBioinformatics and Computational BiologyStructural BiologyNanomedicine
• Translational Research Cores• Regional Centers
Interdisciplinary Research
Pioneer Award Public-Private Partnerships
Cross cutting: Harmonization, Training
• Integrated Research Networks• Clinical Research Informatics• National Clinical Research Associates• Patient-reported clinical outcomes
Facilitating Translational Research
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
Funded ~25% by Roadmap; ~75% by sponsoring IC
Current status: Pilot initiative for implementation in FY2005
Regional Translational Research Centers
Current options for resources:
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 supportphase 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
Bench Bedside Practice
Building Blocks and PathwaysMolecular LibrariesBioinformatics and Computational BiologyStructural BiologyNanomedicine
• Translational Research Cores• Regional Centers
Interdisciplinary Research
Pioneer Award Public-Private Partnerships
Cross cutting: Harmonization, Training
• Integrated Research Networks• Clinical Research Informatics• National Clinical Research Associates• Patient-reported clinical outcomes
Re-engineering Clinical Research
Re-engineering Clinical Research:A Work in Progress
Re-engineering Clinical Research:Progress To Date (as of February 2004)
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
Translational Research Translational Research Core Services pilot
program Planning grants for Regional Translational
Research Centers Clinical Research
Feasibility of the National Clinical ResearchAssociates program
IdeasPeople
ResourcesLeadership
NIH