A CCESS TO C LINICAL T RIALS (ACT) FOR VETERANS

1. ACCESS TO CLINICAL TRIALS (ACT) FOR VETERANS NAVREF Annual Meeting September 17, 2019

2. Panelists Krissa Caroff, MS, ACT for Veterans Program Coordinator and NAVREF Clinical Trials Facilitator Molly Klote, MD, CIP, Director, Office of Research Protections, Policy and Education (ORPP&E), VHA Office of Research and Development Robin Rusconi, JD, Executive Director, Midwest Veterans’ Biomedical Research Foundation; Chair, NAVREF Board of Directors

3. History • Multi-year collaborative effort designed to provide Veterans with more access to industry sponsored clinical trials within the VA health care system. • Recognize that much of VA’s clinical trials tradition was borne out of an intramural research model that regarded research as the product of clinician-investigator inquiries. While parts of the system were developed to conduct trials with external partners, those processes were adapted through available capabilities and policies on a more study by- study basis. • Activities are focused on establishing a dedicated system for initiating and conducting these clinical trials efficiently within VA ​

4. Progress to Date December 2017 Steering Committee Established

5. Steering Committee • Provides the strategic direction for the initiative. • Initial charge: Determine the goals and objectives for a workshop which would bring together VA and non-VA stakeholders interested in improving the efficiency of VA clinical trials. • Responsible for identifying individuals both within and outside of VA who would be appropriate to participate in the workshop and the subsequent workgroups that would be created. Initial Membership included representatives from : • ORD • NAVREF • VA Central IRB

6. Progress to Date April 2018 Kickoff- Stakeholders’ Summit December 2017 Steering Committee Established

7. Stakeholders’ Summit • April 2018 • Over 60 individuals representing industry, VA Central Office, VA medical centers, patient advocacy groups, and the NPCs • Goal: Enhancing Veteran access to clinical trials. • Facilitated discussions centered around three key areas: • Initiating Partnerships • Business Operations and; • Study Approvals and Considerations.

8. Progress to Date April 2018 Kickoff- Stakeholders’ Summit July 2018 Top 5 Priorities Identified/Workgroups Established December 2017 Steering Committee Established

9. 5 Key Priorities/Workgroups Developing the single point of contact (SPOC) model to facilitate the communication of trial opportunities, processes, and requirements. Establishing a standard set of basic information that VA can provide to industry regarding VA assets (e.g., patients, investigators, capabilities, etc.) and processes (e.g., approvals, requirements, etc.) in order to initiate partnerships. Establishing a set of requirements that outlines the specific information that VA needs from industry to initiate conversations Creating and maintaining a process map related to study start up (from initiation of the relationship through site initiation) which includes and delineates centralized functions from those that are local responsibilities. Developing the capability for the VA Central IRB to accommodate more industry-sponsored trials. *Revised to compliance with Single IRB mandate

10. 5 Key Priorities/Workgroups • Workgroup Membership designed to include representatives from: • ORD • NPCs • VA ACOS • VA Investigators • Industry (Pharma and CROs) • Wanted to ensure that varying stakeholders’ perspectives were involved in the process.

11. Progress to Date April 2018 Kickoff- Stakeholders’ Summit February 2019 Workgroup Summit July 2018 Top 5 Priorities Identified/Workgroups Established December 2017 Steering Committee Established

12. Workgroup Summit

13. Workgroup Summit • Allowed each workgroup to present its deliverables • Allowed for open discussion/feedback among and between workgroup members • Allowed for fine tuning of key deliverables

14. Workgroup Summit-Key Deliverables • Workgroup 1: • Need for a “Clinical Trials Office” (CTO) to serve as the Single Point of Contact and assume responsibilities for various aspects of study start up. • Workgroup 2: • List of VA assets • Site Profile Template • Workgroup 3: • List of requirements needed from industry • Identification of Industry Benchmarks • Specialty Review Committees

15. Workgroup Summit-Key Deliverables • Workgroup 4: Process Map • Obtain appropriate leadership approval for central sign off of Non-Disclosure Agreements • Partner with NAVREF Clinical Trials Committee on lead NPC definition and centralized budgeting • Get ACOS feedback on which local assurances can be moved further up in the start up process • Workgroup 5: Compliance with Single IRB mandate • Prepare multisite IRB network for an electronic platform • Optimize current Central IRB function • Execute Master Services Agreement with 2 commercial IRBs

16. Workgroup Summit-Key Themes • Need for a Central Coordinating Office – communications, managing activities, expertise in system/process • Tools to be built to help with activities • VA needs to indicate its priorities for Clinical Trials – topic/disease areas • Take proactive approach to engaging sponsors • Internally – to support time/effort to serve on groups critical to process (e.g., IRB, clinical review committees) • Time for processes need to be kept to minimum • Processes can be done in parallel • Engage VA as soon as possible • Removing bottlenecks is key responsible for “system managers”

17. Progress to Date April 2018 Kickoff- Stakeholders’ Summit February 2019 Workgroup Summit July 2018 Top 5 Priorities Identified/Workgroups Established December 2017 Steering Committee Established Summer 2019 Fine Tuning of Workgroup Deliverables

18. Post Summit Activities • Workgroup 1: • Single Point of Contact (SPOC) Standard Operating Procedures drafted: • Designed to provide guidance and lay out expectations for industry partners. • Incorporates the products from the other workgroups • .

19. Post Summit Activities • Workgroup 2: • Finalizing List of VA Assets • Finalizing Site Profile Template • Working to identify a platform to host information on sites and developing a database that will facilitate the exchange of information on sites and assets with external partners. • Exploring data sources that may provide more information about site-specific data regarding prevalent diseases/conditions.

20. Post Summit Activities • Workgroup 3: • Finalized list of key information needed from industry to facilitate discussions regarding a new trial and to determine if it would be a good fit with VA. • Establishing guidelines for specialty review committees that may be involved in the evaluation of a given protocol. • Reviewing industry start-up timelines which will inform benchmarks for start-up activity timelines within VA.

21. Post Summit Activities • Workgroup 4: • Successfully obtained VA leadership approval for a central VA sign-off of Non-Disclosure Agreements (NDAs) on behalf of the agency eliminating the need for each medical center to execute its own CDA for a multisite clinical trial. A work flow diagram has been drafted and the proposed process is currently being piloted. • With assistance from NAVREF Clinical Trials Committee, a guidance document for the selection of the lead site NPC has been drafted. This will be undergoing additional revisions and shared with NPCs for comment.

22. Post Summit Activities

23. On the Horizon • Creation of Tools/Job Aids • Test Run/Pilot • Determination of SPOC structure ( VA vs. non-VA, resources, etc.) resources • Identification of Specialty Review Committee Members • Refinement • Implementation

24. Workgroup # 5 - Regulatory Modernization • Goals: • Improve Veteran access to Pharma trials through a network of VA IRBs capable of multisite research operations and developing criteria for use of commercial IRBs. • Standardize the review process through the use of an electronic platform and harmonized process • Prepare the VHA for changing responsibilities between IRBs, Institutions, and Research and Development Committees (R&DC).

25. Workgroup # 5Key Recommendations Key Recommendation(s):VA requires policy changes, infrastructure improvements, educational efforts, and guidance development to successfully enhance Veteran access to Pharma trials.

26. Workgroup # Policy Changes 1200.05: Remove restriction on use of commercial IRBs; allow for use of any non-affiliated IRB where the requisite medical expertise is present to approve biomedical or behavioral research 1200.01: Adjust language to encourage single IRB review; adjust the role of the R&DC to focus on institutional requirements and take on determination responsibilities for exempt research.

27. Workgroup #5 Infrastructure • 1. Enhance the capability of the Central VA IRB • - streamline initial review process • - augment the support staffing • - develop additional IRB panels to increase capacity • 2. Expand use of non affiliated IRBs • - Utilize Commercial IRBs for Industry sponsored studies where a commercial IRB as been chosen for the study • - Utilize other non-affiliated IRBs with expertise to review clinical • trials

28. Workgroup # 5Cultural Changes - Need to define/standardize institutional responsibilities vs IRB responsibilities - establish standard protocol pre-review process for relying facilities -Omnibus Institutional Agreement for IRB Reliance among VHA facilities with internal IRBs - Encourage VA to VA collaborative research - Networking - Expand use of centralized ISSO and PO reviews for multi-site projects - Education on reliance on non-affiliated IRBs – dispel fear - Master Services Agreements with commercial IRBs - Streamline process for new IRB reliance

29. Workgroup # 5Resources • Staffing Needs: • CIRB – 4 FTEs (full time) to stabilize current operation • May be scaled back once government positions hired • ORPP&E - 3 FTE (full time) - admin staff to support educational platform, non affiliated IRB application process, meeting coordination • ORD – 3 FTE electronic platform support personnel • Electronic IRB Platform that is 21 CFR part 11 compliant • Sole source request approved – pending award • VA Electronic Determination Aid • Decrease burden on IRBs, increase efficiency of exempt and bench lab research

30. Workgroup # 5 Challenges Communication – ensuring that a clear/consistent message is released with intentions and timelines Policy Change – use exceptions to policy where needed, technical amendments and policy revision. Supplement with guidance. Authority To Operate (ATO) an electronic research platform in cloud or on government servers; access non affiliated IRBs and commercial IRBs Staffing – stable workforce to support administrative tasks and IRB

31. Questions?

32. Resources ACT for Veterans Website: www.actforveterans.org Interested in subscribing to the ACT for Veterans Monthly Stakeholder Update? Or, have general questions about the initiative? Email Krissa at clinicaltrials@navref.org