1. Fishing in DoD Waters Medical Research Playbook & Beyond Dr. James K. Gilman, MD Executive Director Johns Hopkins Military & Veterans Health Institute 1

2. Guest Appearances Dr. Eva Lai Mike McLoughlin Dr. Steve Kaminsky 2

3. Contracting Activities, Regulatory Compliance, Funding Vehicle, Etc. Not Approved PROGRAM DECISIONS SOLICITATIONS RESEARCH PROPOSALS EVALUATIONS Strategic Guidance and Requirements, Good Ideas Program Defined INTERNAL PROGRAMMATIC REVIEW JPC / IIPT / RAD conduct programmatic review and integration Comprised of Army, Air Force, Navy, DoD, NIH, VA, Others RADs coordinate and integrate with each other, CDMRP, and TATRC RADs maintain research portfolios for research areas Evaluates programmatic relevance Comparison-based evaluation Evaluates proposals evaluated across multiple disciplines Considers External Scientific Peer Review (criteria-based) Integrates across research areas and capability gaps Not Approved TAM: Task Area Manager PM: Program / Project Mgr SME: Subject Matter Expert JPC: Joint Program Committee IIPT: Integrating Integrated Products Team RAD: Research Area Directorate START INTRAMURAL & EXTRAMURAL RESEARCH (1) Basic Research, (2) Applied Research, and (3) Advanced Technology Development to prove tech-base concepts for medical products (drugs, biologics & devices) and information Slide Courtesy of USAMRMC 3

4. Yin & Yang Framework Requirement Capability Requirements Driven Hypothesis Driven Core Program Congressional Special Interest Grants Cooperative Agreements Scientific Review Programmatic Review Science & Technology Advanced Development BAA PA Proposal Pre-proposal Research Project Research Program 4 ACQUISITION

5. Just a Few Acronyms (at least to me) DoD – Department of Defense (Department) MHS – Military Health System DHP – Defense Health Program DARPA – Defense Advanced Research Projects Agency DTRA – Defense Threat Reduction Agency ONR – Office of Naval Research USAMRMC – US Army Medical Research & Materiel Command Services – Army, Navy, Air Force, Marines 5

6. Yin & Yang Framework Requirement Capability Requirements Driven Hypothesis Driven Core Program Congressional Special Interest Grants Cooperative Agreements Scientific Review Programmatic Review Science & Technology Advanced Development BAA PA Proposal Pre-proposal Research Project Research Program 6

7. Requirement vs Capability Requirement Problem to be solved Determined by the funding organization More requirements than money Prioritization is key Not determined by research community Priorities may shift Capability Solution to a problem Not the solution that works in the lab Not the solution that works once Solution has to work at scale under operational conditions 7

8. Yin & Yang Framework Requirement Capability Requirements Driven Hypothesis Driven Core Program Congressional Special Interest Grants Cooperative Agreements Scientific Review Programmatic Review Science & Technology Advanced Development BAA PA Proposal Pre-proposal Research Project Research Program 8

9. Fundamental Nature of Research Hypothesis Driven Researcher’s bright ideas Knowledge focused Stable long-term funding Must answer the question and determine mechanism Publication & presentations are the coin of the realm Requirements Driven Customer specified Acquisition model Problem focused Solve problem with fewest resources Empiric problem solving accepted Publications, presentations are by- products Requirements driven and sponsored research are synonymous. 9

10. Yin & Yang Framework Requirement Capability Requirements Driven Hypothesis Driven Core Program Congressional Special Interest Grants Cooperative Agreements Scientific Review Programmatic Review Science & Technology Advanced Development BAA PA Proposal Pre-proposal Research Project Research Program 10

11. Grants vs Cooperative Agreements Grants used by NIH No pre-specified deliverables Major risk is to next grant Other than reports, the gov’t is hands off Used extensively by NIH Cooperative Agreement - used by DoD Specific deliverables Periodic reviews can result in loss of funds Gov’t is a participant in planning work Used by DoD Contracts (DARPA) are the most prescriptive. 11

12. Yin & Yang Framework Requirement Capability Requirements Driven Hypothesis Driven Core Program Congressional Special Interest Grants Cooperative Agreements Scientific Review Programmatic Review Science & Technology Advanced Development BAA PA Proposal Pre-proposal Research Project Research Program 12

13. Core Program vs Congressional Special Interest Core program Money requested by DoD in Pres Budget Enduring military requirement Money available over a number of years (aka programmatic funding) Plans cover multiple years Intramural expertise CSI Money not requested by DoD Money added by Congress Not a military requirement (priority) No assurance of money in subsequent years Very little goes inside DoD CSI:$$ with disease attached. Earmark:$$ with Zipcode attached. 13

14. Research Priorities Core programs Behavioral health TBI,Cognition Suicide prevention Infectious diseases (malaria, dengue, diarrhea, HIV) Orthopedics Combat casualty care Congressional Special Interest Breast cancer Prostate cancer Ovarian cancer ALS Spinal cord injury Autism CSI programs much more like civilian priorities. 14

15. Yin & Yang Framework Requirement Capability Requirements Driven Hypothesis Driven Core Program Congressional Special Interest Grants Cooperative Agreements Scientific Review Programmatic Review Science & Technology Advanced Development BAA PA Proposal Pre-proposal Research Project Research Program 15

16. Scientific vs Programmatic Review Scientific Review Much like NIH processes Usually done outside the DoD (AIBS) Done by subject matter experts when available Objective –criteria known Pick the best projects Programmatic Review Unique to DoD Done by group inside DoD Criteria are more subjective Pick the best group of projects based on a plan (program) 16

17. Yin & Yang Framework Requirement Capability Requirements Driven Hypothesis Driven Core Program Congressional Special Interest Grants Cooperative Agreements Scientific Review Programmatic Review Science & Technology Advanced Development BAA PA Proposal Pre-proposal Research Project Research Program 17

18. PA vs BAA Program announcement Boundary conditions specified Relatively specific Money has been allocated and will be awarded Broad agency announcement Trolling for good ideas Fewer constraints Boundaries may be vague No dollar limit May be little (or no) money to spend All will appear on grants.gov 18

19. Yin & Yang Framework Requirement Capability Requirements Driven Hypothesis Driven Core Program Congressional Special Interest Grants Cooperative Agreements Scientific Review Programmatic Review Science & Technology Advanced Development BAA PA Proposal Pre-proposal Research Project Research Program 19

20. Pre-proposal vs Proposal Pre-proposal Short Focused – easy to read Screened – not necessarily by SME’s Can someone reading this quickly understand its relevance Proposal More detailed Focused – easy to read Scientific and programmatic reviews Will both appeal to SME’s and have obvious relevance 20

21. Yin & Yang Framework Requirement Capability Requirements Driven Hypothesis Driven Core Program Congressional Special Interest Grants Cooperative Agreements Scientific Review Programmatic Review Science & Technology Advanced Development BAA PA Proposal Pre-proposal Research Project Research Program 21

22. Project vs Program Stand alone effort If designed well, can answer important questions Works well for simple problems, incremental benefit Requires assurances of money before beginning Linear, stepwise, each step complete before next one starts Group of projects Must be arranged in proper sequence – some processes in parallel, others in sequence Usually required for complex problems Multi-year funding profile Completing a group of projects in non-linear fashion to achieve results while conserving resources Understanding DoD’s programs is paramount for success. 22 The most expensive resource is time.

23. Multicenter Pivotal Trial? (n=300+) DoD/VA HBO 2 Research Program Jan ‘11Jan ‘13Jul ‘12Jan ‘12Jul’11Jul ‘13 HOPPS IND Pilot Study (n=96) USAFSAM Pilot Study (n=50) VA/VCU/USN Dose Ranging Study (n=60) Outcomes in Normals Study (n=75) Mechanisms of Action Study (BIMA) (n=60) Outcome Validation Project Jan ‘14Jul ‘14Jan ‘15 DSMB IND Filed Type C meeting Chambers Installation at 4 MTFs We must know these before we start pivotal trial: - sham method validated - dose selection of HBO 2 - outcome measure validated to detect change after intervention - establish range of placebo effect to determine sample size TMA & UHMS Submission DSMB End Phase II Long Term Follow-Up Courtesy of COL Robert S. Miller 23

24. Consortium Awards AFIRM – regenerative medicine CAP / STRONGSTAR – PTSD CENC – TBI May request proposals from outside the consortia but loyalty to charter members is certainly an expectation. 24

25. Contracting Activities, Regulatory Compliance, Funding Vehicle, Etc. Not Approved PROGRAM DECISIONS SOLICITATIONS RESEARCH PROPOSALS EVALUATIONS Strategic Guidance and Requirements, Good Ideas Program Defined INTERNAL PROGRAMMATIC REVIEW JPC / IIPT / RAD conduct programmatic review and integration Comprised of Army, Air Force, Navy, DoD, NIH, VA, Others RADs coordinate and integrate with each other, CDMRP, and TATRC RADs maintain research portfolios for research areas Evaluates programmatic relevance Comparison-based evaluation Evaluates proposals evaluated across multiple disciplines Considers External Scientific Peer Review (criteria-based) Integrates across research areas and capability gaps Not Approved TAM: Task Area Manager PM: Program / Project Mgr SME: Subject Matter Expert JPC: Joint Program Committee IIPT: Integrating Integrated Products Team RAD: Research Area Directorate START INTRAMURAL & EXTRAMURAL RESEARCH (1) Basic Research, (2) Applied Research, and (3) Advanced Technology Development to prove tech-base concepts for medical products (drugs, biologics & devices) and information Slide Courtesy of USAMRMC 25

26. Congress approves a budget Program Announced Pre- proposal Proposal Scientific Review Programmatic Review Award is Made Cooperative Agreement is Negotiated USAMRMC Basic Process Slide Preparing to Fish Starting to Fish Got a bite Got a Fish! 26

27. Preparation Today is part of it Determine whether DoD is interested in the kind of research you do (or get ready to do research they want done) Find the people doing research inside DoD – connect Attend the Military Health System Research Symposium 27

28. 28 2013 Military Health System Research Symposium Hopkins – 1 abstract, 1 podium presentation, 4 attendees $1.2 Billion (2013)

29. The Competition Other academic centers Commercial laboratories Not-for-profit labs (e.g. Battelle) In contrast to NIH, no preliminary data required Played this game longer 29

30. DARPA & ONR Michael McLoughlin Senior Scientist JHUAPL jgilman5@jhu.edu 443-287-5060 30