1. Future Approaches to NIAMS Clinical Trials * As presented to the NIAMS Advisory Council on June 2, 2009

2. Goals To increase the impact and quality of clinical trials supported by the NIAMS

3. Background The NIAMS investment in clinical trials increased with the doubling of the NIH budget. A recent institute review of the currently funded studies suggested the need to examine: The identification of opportunities and priorities for the NIAMS clinical trials portfolio Approaches for implementing high-quality trials

5. 46 total clinical trials 10% solicited (through Broad Agency Announcements) 90% unsolicited, Investigator-initiated (~70% under $500,000*) Current Funded Clinical Trials * Note that there is no pre-approval process for applications under $500,000

6. NIAMS Scientific Retreat April 7, 2009 Session goals: To explore and analyze some approaches that NIAMS can use to more effectively identify, solicit, support and manage high-quality and significant clinical trials. At the retreat we examined and discussed a variety of models used by other institutes to accomplish these goals

7. For Discussion Today Should NIAMS implement any new strategies for clinical trials selection and implementation to support trials of higher impact and quality? PART 1. Identification of opportunities for Institute and Investigator-initiated trials PART 2. Changes to the process used for Investigator-initiated clinical trials

8. Part 1. Opportunities STRATEGIES: Identifying Opportunities –Engage scientific organizations, networks and research centers, advocacy groups and the private sector –Roundtables and scientific retreats Structured Discussion of Opportunities –Establish external advisory groups –Sub-committee of council DISCUSSION

9. Investigator-Initiated Clinical Trials Part 2.

10. Currently Applications with budgets >$500 K: criteria for acceptance include relevance to Institute’s mission, evidence of feasibility and budget. Applications under $500 K: all are accepted as long as they are within the mission of NIAMS. Funding mechanisms is R01, some U01s. Reviewed by CSR or NIAMS. Planning grant/phase not a requirement.

11. For Discussion Option 1. No change in approach to Investigator-initiated clinical trials. Option 2. Support solicited clinical trials (RFPs or RFAs) only. Option 3. Structure the process by expanding the use of the planning grants or similar structured planning phases for all clinical trials and manage by cooperative agreements.

12. Option 2. RFPs and RFAs ONLY Advantages: –Allows the concentration of resources in selected areas of greatest need and feasibility. –Use of the contract mechanism allows greater cost accountability. Disadvantages: –May not capture effectively emerging opportunities. –Narrows the areas of investigation.

13. Option 3. Structuring New Investigator-initiated Applications for Clinical Trials STRATEGY: Two step process: –Planning grant is a pre-requisite for submission of a multi-center clinical study (funding of planning grant does not commit the NIAMS to funding of actual trial) –Trial is submitted using the Cooperative Agreement mechanism and requires pre-approval by the NIAMS

14. Why Use Planning Grants? Permit early peer review of the rationale for the proposed study Assessment of the design of the study Support the development of a protocol and manual of operating procedures Provide support for other elements of coordination and decision making necessary to the conduct of a high quality study

15. Why Use Cooperative Agreements for Multi-Center Clinical Studies? Allows NIAMS to accept, peer review and consider funding applications from planning grant awardees only. There will be substantial NIH programmatic involvement with the grantee during the conduct of the clinical study – without assuming direction of the study or a dominant role.

16. For Discussion Option 1. No change in approach to Investigator-initiated clinical trials. Option 2. Support solicited clinical trials (RFPs or RFAs) only. Option 3. Structure the process by expanding the use of the planning grants or similar structured planning phases for all clinical trials and manage by cooperative agreements.