Restructuring the National Cancer Clinical Trials Enterprise

1. Restructuring the National Cancer Clinical Trials Enterprise Clinical Trials Working Group Implementation Update for the CCOP, MBCCOP and Research Base Meeting Sheila A. Prindiville, MD, MPH September 17, 2007

2. CTWG Restructuring Initiatives • Enterprise-Wide/Integrated Management • Coordination • Prioritization/Scientific Quality • Standardization • Operational Efficiency CTWG Report, June 2005 - http://integratedtrials.nci.nih.gov

3. Enterprise-Wide: Integrated Management CTWG Recommendation: • Establish an external clinical trials oversight committee to advise NCI Director • Develop a coordinated organizational structure within NCI to manage the clinical trials enterprise

4. NCI Federal Advisory Groups http://deainfo.nci.nih.gov/advisory/ctac/ctac.htm

5. Clinical Trials Advisory Committee (CTAC) • Provide extramural oversight for the implementation of the CTWG recommendations and initiatives • Provide strategic advice regarding NCI’s entire clinical trials portfolio including resources associated with clinical trials • Advise on the use of new correlative science and quality of life funds • Advise on the formal evaluation of the impact of the restructuring plan • Membership: • Chair, Dr. John Niederhuber • Ten members current Boards (NCAB, BSA, BSC, DCLG) • Fourteen new members from extramural clinical trials community • Next meeting November 14, 2007

6. Internal Clinical Trials Operations • Clinical Trials Operations Committee (CTOC) • Internal NCI committee established in December, 2005 to provide strategic oversight for NCI clinical trials programs and infrastructures • Reviews and prioritizes clinical trial programs proposed by Divisions, Centers, and Offices to coordinate efforts Institute-wide • Membership from all NCI Divisions, Offices, and Centers involved in NCI-supported clinical trials • Chair, Dr. John Niederhuber • Coordinating Center for Clinical Trials (CCCT) • New office in the Office of NCI Director established in 2006 (http://ccct.nci.nih.gov) • Supports the implementation of the CTWG initiatives in conjunction with NCI’s Divisions/Centers/Offices • Supports CTOC and CTAC

7. Integrated Management Extramural Clinical Trials Community Clinical Trials Advisory Committee (CTAC) Coordinating Center for Clinical Trials (CCCT) NCI Director Clinical Trials Operations Committee (CTOC) Divisions, Centers, and Offices

8. CTWG Restructuring Initiatives • Enterprise-Wide/Integrated Management • Prioritization/Scientific Quality Involve all stakeholders in design and prioritization of clinical trials that address the most important questions, using the tools of modern cancer biology • Coordination • Standardization • Operational Efficiency

9. Prioritization /Scientific Initiative #1 • Establish an Investigational Drug Steering Committee (IDSC) for early phase trial prioritization • IDSC has been established to provide strategic input to CTEP drug development planning • Co-Chairs: Drs. David Gandara and Mark Ratain • Task Forces • Clinical Trial Design • Angiogenesis • Signal Transduction • Biomarker • Pharmacology • Gap Analysis • CTEP Career Development Letter of Intent (LOI) Program for Young Investigators

10. Prioritization /Scientific Initiative #2 • Establish Disease-Specific Scientific Steering Committees (SC’s) for phase III trials • Responsibilities of the Disease-Specific SC’s • Prioritize phase III concepts for therapeutic clinical trials • Convene State-of-the-Science meetings to identify critical questions to prioritize key strategies and future concepts for NCI supported clinical trials • Develop phase III concepts for new clinical trials utilizing Task Forces • Periodically review accrual and unforeseen implementation issues

11. Initial Disease-Specific Steering Committees • Gastrointestinal Cancer (Co-Chairs: Joel Tepper, MD and Daniel Haller, MD) • Gynecologic Cancer (Co-Chairs: William Hoskins, MD and Gillian Thomas, MD) • Head and Neck Cancer (Co-Chairs: Arlene Forastiere, MD, David Schuller, MD, and Andrew Trotti, MD) • Symptom Management and Health-Related Quality of Life (Co-Chairs: Deborah Bruner, RN, PhD and Michael Fisch, MD, MPH)

12. Prioritization /Scientific Initiative #3 • Increase community oncologist and patient advocate representation on steering committees • Community oncologists • GI: Drs. Phillip Kuebler and Roscoe Martin • GYN: Drs. Michael Method and Margaret Wilmoth • H & N: pending • SxQOL: Drs. James Wade and James Bearden

13. Prioritization /Scientific Initiative #4 • Establish a funding mechanism and prioritization process for correlative science and quality of life studies • Separate budget has been established to support this initiative • Primary purpose is to fund studies conducted in association with phase III trials when the cost of studies is too large to be covered by the Cooperative Group mechanisms in a timely manner • Task Force of the Program for the Assessment of Clinical Cancer Tests (PACCT), DCTD has developed criteria for prioritization of correlative science studies (essential marker and imaging) • Symptom Management SC developing develop criteria for prioritization of QOL studies • Divisions/Centers/Offices will recommend studies approved by Scientific Steering Committees to CTOC and CTAC for prioritization and funding

14. CTWG Restructuring Initiatives • Enterprise-Wide/Integrated Management • Prioritization/Scientific Quality • Coordination Coordinate clinical trials research through data sharing and providing incentives for collaboration • Standardization • Operational Efficiency

15. Coordination Initiatives • Establish a comprehensive database containing regularly-updated information on all NCI-funded clinical trials https://cabig.nci.nih.gov/workspaces/CTMS • Realign NCI funding, academic recognition, and other incentives to promote collaborativeteam science and clinical trial cooperation • Cooperative Group program guidelines are in the process of modification to reflect collaboration with SPOREs and Cancer Centers positively • CTAC Coordination Subcommittee formed with initial focus on harmonizing program guidelines to enhance collaborations • Evaluating feasibility of accruing patients to SPORE and Cancer Center clinical trials through NCI’s Cancer Trials Support Unit (CTSU)

16. CTWG Restructuring Initiatives • Enterprise-Wide/Integrated Management • Coordination • Prioritization/Scientific Quality • Standardization Standardize informatics infrastructure and clinical research tools • Operational Efficiency

17. Standardization Initiatives • Informatics infrastructure interoperable with caBIGTM • Standard Case Report Forms incorporating Common Data Elements • Credentialing repository for investigators and sites that is recognized and accepted by NCI, industry sponsors, clinical investigators and clinical trial sites • Establish commonly accepted clauses for clinical trial agreements https://cabig.nci.nih.gov/workspaces/CTMS

18. CTAC Public-Private Partnerships Subcommittee • Chair: Dr. David Parkinson • Function: Provide advice to the Director, NCI on how to enhance NCI-sponsored clinical trials through collaborative interactions with the private sector • Initial focus: Oversight for the implementation of the CTWG initiative to establish commonly accepted clauses for clinical trial agreements

19. Common Themes of the Restructuring Plan • Enterprise-Wide/Integrated Management • Prioritization/Scientific Quality • Coordination • Standardization • Operational Efficiency: Use resources most efficiently through improved cost-effectiveness and accrual rates, and more rapid trial initiation

20. Operational Efficiency New Initiative #1 • Restructure the funding model for phase III efficacy trials to provide incentives for more rapid rates of patient accrual while preserving the funding flexibility of the present system • Rationale: • Current system – large differential between NCI per-case costs and actual clinical trial costs is not sustainable over time for the Coop Groups nor CCOPs • There may be some cost inefficiencies in the current system • Sites that accrue only a few patients per year may result in a high per-case cost because of fixed costs

21. Implementation Plan • Conduct a financial analysis of clinical trials costs • Evaluate data quality as a function of patient accrual • Develop a new phase III trial funding model collaboratively with the Cooperative Groups • Align reimbursement with trial complexity • Reduce duplication of administrative functions • Incentivize high accruing, cost-efficient sites • Establish minimum accrual standards

22. Operational Efficiency Initiative #2 Identify the institutional barriers that prolong the time from from concept approval to accrual of the first patient, and develop solutions for overcoming these barriers Dilts, D. M. et al. J Clin Oncol; 24:4553-4557 2006

23. Operational Efficiency Initiative #3 • Develop approaches for enhancing adoption of centralized Institutional Review Board processes • An analysis of the barriers to utilization of the Central IRB has been initiated • Preliminary findings will be presented at the November 2007 CTAC meeting

24. Evaluation and Outcome Measures • Structured evaluation system • Designed by experienced evaluation specialists • Blend of quantitative and qualitative measures • External clinical trials expert panel has reviewed the proposed measures • Baseline evaluation conducted in FY07; analyses underway • Periodic evaluations to assess impact of restructuring