Funds Available

1. Clinical Epidemiology and Validation Centers for the Early Detection Research NetworkPresubmission MeetingMarch 15, 2004Paul Wagnerwagnerp@mail.nih.gov

2. The information presented in following slides is a general overview. Applicants must consult RFA CA-5-005 for detailed information on the scope of this RFA, application procedures, and review criteria.

3. Funds Available • $7 million in FY 2005 to fund 8-15 new and/or competitive continuation grants in response to this RFA • May request up to five years of support

4. Mechanism of Support • Cooperative Agreement award mechanisms (U01 and U24) • The Principal Investigators retain the primary responsibility for planning, directing, and executing the proposed projects • NIH Program Coordinator is substantially involved as a partner with the Principal Investigators

5. Roles of the Clinical and Epidemiology Centers within the Early Detection Research Network • Validate biomarkers for early cancer detection • Perform epidemiological research into the application of biomarkers

6. Three Ways to Participate Participate in collaborative network validation studies by providing specimens Participate in collaborative studies with another CEC or with a Biomarker Developmental Laboratory Conduct clinical research on the validation of biomarkers developed in your own or collaborators’ laboratories

7. Two Types of Applications • U24 for those who wish to serve as a Resource Center and participate in collaborative validation studies but do not wish to propose a particular research project to validate biomarkers • U01 for those who wish to both 1) serve as a Resource Center and participate in collaborative validation studies and 2) propose clinical research projects to validate biomarkers

8. Participation in Collaborative Network Validation Studies Investigators submit a proposal to the EDRN Steering Committee for a collaborative network validation study. If the proposal is approved, the appropriate CECs will be asked to provide specimens or active patient accrual for the validation study. The CECs will also participate in data quality control, analysis and interpretation. Applicable to both U24 and U01 grantees. Reimbursement for subject accrual will be on a per case basis from EDRN core funds.

9. Participation in Individual Collaborative Validation Studies Investigators are encouraged to establish collaborative validation projects with other EDRN investigators. (Applicable to both U24 and U01 grantees.) These projects are usually funded by the set aside funds of the individual CEC or BDL U01 grantees.

10. Investigator Initiated Biomarker Validation Studies Conduct clinical research on the validation of biomarkers for early cancer detection and risk assessment. This research will be Phase II and III validation studies as described in the RFA. These studies are supported by the individual U01 grants. This proposed research needs to be presented in your U01 application and will be evaluated by the review panel convened to review these applications.

11. Phase II and Phase III Studies Phase II: Studies to determine the capacity of biomarkers for distinguishing people with cancer. Phase III: Studies to assess the capacity of a biomarker to detect preclinical disease by testing the marker against tissues collected longitudinally from research cohorts. Pepe, MS, et al (2001) Phases of biomarker development for early detection of cancer. J Natl Cancer Inst. 93, 1054-1061.

12. Phase III Studies Protocols for Phase III proposals must be approved by the EDRN Steering Committee and NCI before the study begins. Data for all Phase III studies must be collected using EDRN Common Data Elements and submitted to the Data Management and Coordination Center.

13. Phase I Studies are Not Appropriate for this RFA Phase I: Exploratory studies to identify potentially useful biomarkers – discovery. For example, the use of DNA microarrays to discover new biomarkers for early cancer detection.

14. Submitting an Application Use the standard PHS 398 form. The research plan (sections A to D) should be replaced with the following three sections: Collaborative Clinical Validation Studies (both U01 & U24) Research Plan for Clinical Biomarkers Validations Studies (only U01) Compliance with terms of EDRN Cooperative Agreement (both U01 & U24)

15. Section 1: Collaborative Clinical Validation Studies (U01 & U24)(10 page maximum) Applicant: Describe your group’s expertise, facilities, and core resources that are available to support your participation in EDRN collaborative validation studies. Patient accrual: Document your ability to recruit patients and procure specimens. Describe specimen repositories which you are willing to make available to the EDRN. Quality assurance: Describe procedures for quality assurance and laboratory quality control.

16. Section 2: Research Plan for Clinical Biomarkers Validations Studies(25 page maximum) • This section only applies to those applications proposing to develop a scientific agenda to validate biomarkers (U01). • Describe the proposed research objectives and the significance, background, rationale, and approaches for the proposed studies. • Define the major research questions and opportunities related to objectives of EDRN.

17. Section 2 of Competitive Renewal U01 Applications • Describe the goals of the previous grant and progress made during the previous project period. • Indicate the status of developed markers according to the biomarker developmental phases.

18. Section 3: Compliance with terms of Cooperative Agreement (U01 & U24)(10 page maximum) • State your willingness to collaborate with other EDRN members, to participate in workshops, and to serve on the Steering Committee and be bound by its decisions. • Provide a letter describing your institution’s policies for sharing of data. • Provide a letter on your research tools and resources sharing plan. • Describe the approach to be used for licensing patented inventions developed through EDRN activities.

19. Budgets for U24 Applications • Travel: Budget for the PI and one senior investigator to attend two EDRN Steering Committee meetings and one workshop or symposia per year. • Administrative costs: Applicants may request funds to cover the costs of their participation in EDRN activities (e.g., attending steering committee meetings, participating collaborative group conference calls, and entering information on the EDRN secure website). • EDRN core funds will be used to cover costs of specimen collection, clinical testing, and data management, when you join an EDRN collaborative network study.

20. Budgets for U01 Applications • Same as for U24 applications plus • Funds to cover the investigator initiated biomarker validation studies described in Section 2 • Request set aside funds for collaborative projects (use and release of these must be approved by the Steering Committee and NCI)

21. Set Aside Funds for Collaborative Studies • New applicants must set aside 20% of their annual budgets from the second year onward. • Competing renewal applicants must set aside funds that were approved by the NCI program staff for the years of ongoing studies, otherwise they must set aside 20% of their annual budgets.

22. Review • Applications will be evaluated by a peer review group convened by NCI’s Division of Extramural Activities in accordance with the review criteria described in the RFA. • All applications (both U24 and U01) will be evaluated on issues related to patient accrual and their willingness to participate in EDRN activities. • Applications proposing to conduct clinical research on biomarker validation (U01) will be evaluated on the proposed research.

23. Award Criteria • Scientific merit as determined by peer review • Availability of funds • Programmatic priorities

24. Questions Cancer Biomarkers Research Group Dr. Sudhir Srivastava Dr. Mukesh Verma Dr. Jacob Kagan Dr. Padma Maruvada Dr. Wendy Wang Donald Johnsey 301-435-1594 Grants Administration Branch Karen Chuang Emily Linde