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