Partnership for Effective Research for Veterans Health VA’s Model Clinical Trial-Cooperative Research and Development Ag

1. Partnership for Effective Research for Veterans HealthVA’s Model Clinical Trial-Cooperative Research and Development Agreement (CT CRADA) Our Panel • Amy Centanni, Director, Technology Transfer Program (TTP), VHA • Barbara West, Executive Director, National Association of Veterans’ Research and Education Foundations (NAVREF) • Paul Hutter, Assistant General Counsel, Office of General Counsel (OGC)

2. Partnership for Effective Research for Veterans HealthVA’s Model Clinical Trial-Cooperative Research and Development Agreement Partnership – (VHA, Nonprofit Research Corporations, Office of General Counsel) • April 2005 • November 2005 • February 2006

3. Partnership for Effective Research for Veterans HealthVA’s Model Clinical Trial-Cooperative Research and Development Agreement • CT-CRADA - the first product of this strong partnership • Our Agenda • The CRADA itself – Amy Centanni • The CT-CRADA Guidelines – Amy Centanni

4. Partnership for Effective Research for Veterans HealthVA’s Model Clinical Trial-Cooperative Research and Development Agreement • The Cooperative Technology Administration Agreement Amendments/Guidelines – Paul Hutter • The Implementation Plan – Paul Hutter • Suggested Talking Points/Conclusion – Paul Hutter • Questions throughout and at the conclusion

5. CRADA BASICS What is a Cooperative Research and Development Agreement (CRADA)? A CRADA is a legal agreement between VA and one or more non-Federal parties. Title 15 USC § 3710a

6. CRADA BASICS Protection of background inventions, trade secrets and confidential information Access to VA research resources including personnel, services and property

7. CRADA BASICS Establishment of intellectual property ownership and licensing options in advance of an invention Leveraging federal expertise to develop products with commercialization potential Enforceable

8. When to use the CT CRADA When the collaborator: Holder of the investigational new drug (IND) Designs the protocol; and Funds the project

9. Who negotiates the CT CRADA? VAMC / PI (principal investigator) NPC (nonprofit corporation) RC (regional counsel) as needed

10. Looking at the actual agreement

11. Article 2: Definitions Affiliate vs. Affiliated University (University Partners) Background Invention vs. CRADA subject Invention Clinical Investigator = PI Collaborator = Sponsor

12. Article 2: Definitions CRADA Data Dual Appointment Personnel Protocol and Statement of Work

13. Article 2: Definitions Raw Data VA Employee(s) without compensation (WOCs) intergovernmental personnel agreement (IPAs)

14. Article 5. Inventions and Intellectual Property 5.1 Ownership of CRADA Subject Inventions – VA RETAINS OWNERSHIP 5.2 Reporting – VA and Collaborator invention disclosure obligations.

15. Article 6. Licensing 6.2 Collaborator’s License Option to CRADA Subject Inventions “… VA will grant to Collaborator a nonexclusive royalty free license.” NERF available only for CT CRADAs

16. Article 6. Licensing Rationale for the NERF Protects collaborator’s rights to use background intellectual property Grants collaborator license to use new intellectual property Does not affect ownership under language of the CT-CRADA

17. Article 6. Licensing 6.3 VA also grants the Collaborator an option to elect an exclusive or partially exclusive commercialization license on any CRADA Subject Invention License will comply with Federal requirements

18. Article 7. Ownership and Rights of Access to Data and Publication 7.1 Ownership of Data and Records 7.2 Right of Access to CRADA Data and CRADA Materials 7.4 Presentations and Publications

19. Article 8. Confidentiality 8.1 Confidential Information 8.2 Protection of Confidential Information 8.3 Disclosure of Confidential Information 8.4 Duration of Confidentiality Obligation

20. Article 12. Liability 12.1 Collaborator’s Indemnification and Liability 12.2 VA’s Indemnity and Liability

21. What’s negotiable? Refer to CT-CRADA Guidelines Use RCs to guide determination as to whether negotiated changes are substantive Substantive changes must be cleared by TTP

22. What if there are substantive changes to the model CT CRADA? RC will forward those clauses to TTP for review and approval with a cc to the NPC.

23. Steps after RC Review PI signs acknowledgement All parties sign CRADA Collaborator NPC Medical Center Director (last to sign) Disseminate originals to all parties and provide a copy to PI and RC.

24. How are Foreign Partners/Sponsors handled under CT CRADAs? CRADAs involving foreign partners have additional requirements. Prior to entering such negotiations please call TTP office to discuss these additional requirements.

25. Other Resources CT CRADA Registry Registration is mandatory (AO or NPC) Consists of an Excel spreadsheet listing all past and current CT CRADAs updated weekly Complete as much as possible as soon as negotiations are initiated

26. Other Resources *Future of the Registry online submission of CT CRADAs Body of the CRADA and Appendix C will be available to VHA and RCs under password protection.

27. Where to go for help? Technology Transfer Website www.research.va.gov/ programs/tech_transfer/ Technology Transfer Program Regional Counsels NPC Executive Directors

28. Questions I would like to confirm my understanding that the review by the Regional Counsel and the TTP, if necessary, will be completed in the 30 day time frame?

29. Questions Currently our clinical trial agreements reference the protocol and usually consider it one of the appendices but the actual protocol remains with the clinical trial investigator. What is VA thinking about the Statement of Work (SOW)?

30. CTAA Amendment Guidelines CTAAs • Clearly identify the relationship between VA and University Partners • Establish joint ownership of potential intellectual property between VA and Universities • Allowed universities to take the lead with respect to developing, marketing and promoting intellectual property

31. CTAA Amendment Guidelines Amending the CTAAs • Still establish relationship between VA and University Partners • CRADA terms require VA to take the lead regarding intellectual property development

32. CTAA Amendment Guidelines • VA looks to amend existing CTAAs to ensure VA takes the lead for CRADAs • No change in ownership of potential intellectual property • VA and University Partners retain undivided interests in the intellectual property

33. CTAA Amendment GuidelinesNegotiating the Amendments Field partners (VHA, NPCs, OGC) should take the lead • Negotiations are best initiated locally with TTP as backup • VAMC negotiators notify TTP when negotiations begin with a particular University Partner • Don’t wait – time is of the essence

34. CTAA Amendment GuidelinesNegotiating the Amendments Negotiation – a suggested approach • Determine what is important to the University • Begin negotiation with the position that VA will take the lead (patenting, marketing, licensing and commercialization) in all research subject to CRADAs (Clinical Trials and otherwise)

35. CTAA Amendment GuidelinesNegotiating the Amendments Recall the language from Santa Monica: “Where the VA enters into a CRADA under the FTTA, then VA undertakes to file such patent applications and/or market and license the Subject Invention as it deems appropriate.”

36. CTAA Amendment GuidelinesNegotiating the Amendments “In that event, what otherwise would have been UNIVERSITY’s financial and other rights and obligations to VA under this Agreement, with respect to such a Subject Invention, thereafter shall become VA’s rights and obligations to UNIVERSITY.” Amendments must be signed by the original signatories or their successors.

37. CTAA Amendment GuidelinesNegotiating the Amendments Should the UNIVERSITY fail to agree to the above clause, then propose the following alternative clause: “Where the VA enters into a phase II, III or IV clinical trial CRADA, then VA undertakes to file such patent applications and/or market and license the Subject Invention as it deems appropriate.”

38. CTAA Amendment GuidelinesNegotiating the Amendments “In that event, what otherwise would have been UNIVERSITY’s financial and other rights and obligations to VA under this Agreement, with respect to such a Subject Invention, thereafter shall become VA’s rights and obligations to UNIVERSITY.”

39. CTAA Amendment GuidelinesNegotiating the Amendments The Options in Order of Preference 1)University allows VA to take the lead for all CRADAs 2)University agrees to VA taking the lead on phase II-IV Clinical Trials 3)University agrees to VA taking the lead in Phase III and IV clinical trials 4)University reviews on a case by case basis

40. Implementation PlanVA’s Model Clinical Trial-Cooperative Research and Development Agreement How do we implement the CT CRADA? • Implementation Date: March 15, 2006 - with the following guidance and exceptions: • All existing executed CRAs are grandfathered • A CRA may be used for any studies for which negotiations were initiated before March 15, 2006

41. Implementation PlanVA’s Model Clinical Trial-Cooperative Research and Development Agreement • If PI/Co-PI are not Dual Appointment Personnel (DAP), CT CRADA used for all clinical trials where negotiations start on or after March 15, 2006

42. Implementation PlanVA’s Model Clinical Trial-Cooperative Research and Development Agreement New clinical trials - PI is a DAP - negotiations are initiated after March 15, 2006, CT CRADA used as soon as A or B is satisfied: A. Where there is a CTAA: The CTAA allows - or has been amended to allow - VA to take the lead on intellectual property developed under a CT CRADA.

43. Implementation PlanVA’s Model Clinical Trial-Cooperative Research and Development Agreement B. Where there is no CTAA or where the CTAA has not been amended: A process has been worked out between VA and the university for a case-by-case review of CT CRADAs allowing VA to take the lead in any intellectual property developed. A or B above must be in place no later than June 1, 2006. If not, TTP may provide the site with a waiver to continue to use CRAs past June 1,

44. Talking PointsIntroducing the Model CT-CRADAs to Stakeholders • Advantages of CRADAs • Protect background inventions, trade secrets and confidential information • Offer access to VA research resources including personnel, services and property • Establish intellectual property ownership and licensing options in advance of an invention

45. CT CRADA Present CRADAs positively Track interactions Complete a short evaluation

46. Questions If we don’t have a CTAA, should we remove that paragraph from the CT-CRADA?

47. Questions “I was advised by one of the OGC Corporation Panel Attorneys not to sign the clinical trial agreement until the protocol had received IRB approval… some NPCs do like me and wait until the IRB has approved the protocol whereas other NPCs have had a practice of signing as soon as a final draft has been negotiated and approved regardless of the status of the IRB approval. Is there any guidance as to the timing of signing the CT CRADAs?

48. Questions Are we going to have to insist on the VAMC Director being the last signatory with the sponsors?

49. Questions Article 3.1 Please explain the reasoning behind the last sentence in this paragraph? 3.1 Any Collaborator employee(s) who will work at VA facilities shall be required to have a Without Compensation Appointment.

50. Questions 3.6 Human Subject Protection. We should be allowed to delete this paragraph if no human subjects are involved?