1. VA Central IRB Annette Anderson, MS, CIP VA Central IRB Administrator Updated: September 21, 2015

2. 2 2 Purpose of VA Central IRB Primary Purpose Improve human research protections in VA multi-site studies by ensuring: Consistent expert ethical and scientific review Local issues are still addressed Secondary Purpose Enhance efficiencies of IRB review in multisite studies

3. 3 3 VA Central IRB Implementation Established as part of the VHA Central Office Human Research Protection Program (HRPP) in 2008 Institutional Official (IO) is the Principal Deputy Under Secretary for Health First study reviewed in August 2008 and approved in October 2008 As of September 20, 2015, the VA Central IRB is overseeing or is in the process of reviewing a total of 173 multi-site studies involving a little over 990 sites The VA Central IRB also approves Requests for Exemptions – have approved 7; 1 in process

4. 4 4 VA Central IRB Composition 15 voting members including 2 Co-Chairs 1 non-scientist alternate 4 non-voting members Ethics Privacy with 2 alternates Information Security with 1 alternate Legal Ad Hoc Consultants as needed

5. 5 5 VA Central IRB Operations Staffed by PRIDE 1 VA Central IRB Administrator 4 VA Central IRB Managers 1 Regulatory Analyst 2 Program Administrators Meetings held twice monthly via teleconference; two meetings each year in Washington, DC SharePoint used for submitting and distributing documents and tasking Reviewers ACCESS and shared drive data base for tracking and storing data

6. 6 6 What Studies are Reviewed by VA Central IRB? Studies that receive funding from the VA Office of Research and Development (ORD) in which multiple VA sites (2 or more) are engaged; currently limiting the number and types of studies accepted due to ongoing hiring freeze A charter is being developed to more clearly delineate the types of ORD studies to be reviewed and to expand to non-ORD funded studies; piloted a NIH-sponsored study with 25 VA sites participating No charge for use of VA Central IRB for VA-funded studies

7. 7 7 Local VA Facility Requirements to Use the VA Central IRB Local VA Facilities must: Amend Facility Federalwide Assurance to list the VA Central IRB as an IRB of Record; affiliated NPCs must amend FWAs as well Enter into a Memorandum of Understanding (MOU) with the VHA Central Office and affiliated NPC if applicable Develop Standard Operating Procedures (SOPs) for using the VA Central IRB as an IRB of Record Amend affiliate MOU if applicable

8. 8 8 Memorandum of Understanding (MOU) Spells out the respective authorities, roles, and responsibilities of the VHA Central Office HRPP, the VA Central IRB, the local VA facility, and the affiliated NPC if applicable VA facilities that do not use the VA Central IRB will not be able to participate in studies reviewed by the VA Central IRB As of September 20, 2015, the VHA Central Office HRPP has MOUs with 104 of the 109 VA facilities with FWAs

9. 9 9 Local Accountability for Research The MOU requires the VA Facility Medical Center Director to Appoint local Site Representatives to: Provide local comments to the VA Central IRB regarding the VA Central IRB’s review of the Principal Investigator New Project Application Serve as the Local Site Liaison with the VA Central IRB

10. 10 Engagement and Exemptions Prior to submission of a new project for review by the VA Central IRB the PI may request: An Engagement determination An Exemption from IRB Review A Human Subjects Research determination Administrative Pre-Reviews are also available and highly recommended

11. 11 Application Processes – 2 Types Principal Investigator (PI) Application – Based on IRB approval criteria Co-PI and Coordinating Center Supplements Protocol and other documents (i.e., surveys, scripts, investigator drug brochures) Waiver requests Vulnerable Population Supplements Model Documents (i.e., informed consent form, recruitment materials, HIPAA Authorization) COI statements from personnel in investigator roles only CVs of investigators only Local ACOS/R&D certification

12. 12 Application Processes – 2 Types Local Site Investigator (LSI) Application – based on and mirrors PI/SC Application Local study team Local resources Local recruitment practices Local participant compensation practices Customize model documents All differences from PI Application must be justified Signed by LSI and local ACOS/R&D

13. 13 VA Central IRB Review Model – 7 Steps Step 1 - PI completes and submits PI Application Contact VA Central IRB Administrator prior to completing application Forms on VA Central IRB website PI enlists local sites and lists them if known Local Conflict of Interest determination if feasible PI/SC signs form and obtains certification from local ACOS/R&D

14. 14 VA Central IRB Review Model – 7 Steps Step 2 – VA Central IRB reviews PI Application Initial Reviews Administrative Information Security Privacy Primary Reviewer System Primary, Secondary, and Informed Consent Reviewers for studies reviewed at convened IRB Meetings Primary Reviewer only for studies reviewed under expedited review procedures VA Central IRB Co-Chair reviews and signs all approval letters for new PI Applications

15. 15 VA Central IRB Review Model – 7 Steps 3a - Local Site Review VA Central IRB staff provide a copy of the approved PI/SC application to sites along with the VA Central IRB determination Sites have up to 15-days to submit comments for consideration by the VA Central IRB 3b - Submission of Applications Local Site Investigators complete the LSI Application for their site All site applications must be reviewed and submitted through PI/SC unless PI/SC indicates LSIs can submit directly to VA Central IRB Note: Local Review is not performed by local IRB Step 3 - Local Site Review and Submission of Local Site Investigator Applications Note: These two functions can take place simultaneously

16. 16 VA Central IRB Review Model – 7 Steps Step 4 – Review of Local Site Comments and Local Site Investigator Applications Step 4a – The VA Central IRB reviews local comments and may do one of the following: Refer comments to PI Require changes in PI and/or LSI Applications Administratively respond to comments Step 4b – Review Local Site Investigator Applications Include modifications from step 4a if applicable

17. 17 VA Central IRB Review Model – 7 Steps Step 5 – PI and LSI Submit Revisions as applicable PI can submit answers to questions, clarifications, or a PI amendment for approval LSIs submit revisions to their LSI Application Step 6 – VA Central IRB Makes Final Approval Decision on LSI Application Approved documents made available on VA Central IRB Secure SharePoint system E-mail sent to PI, LSI, and VA Central IRB Liaison

18. 18 VA Central IRB Review Model – 7 Steps Step 7 – Local Site Final Approval Local Site reviews and approves study in accordance with local policies and procedures (i.e., R&D Committee approval) At local sites, approved application package consists of approved PI Application and the approved LSI Application Note: A study cannot begin at any given local facility until the PI and, if applicable, the LSI Application, has been approved by the VA Central IRB and the VA facility has complied with the requirements of VHA Handbook 1200.01

19. 19 Amendments and Updates PI Amendments Made available to all sites through SharePoint Local Site Investigator Amendments/Updates Specific Site Amendment Updates based on approved PI Amendments or change in model field (i.e., room or phone numbers) Addition of a Site Sites added after approval of PI/SC Application will not get 15-day comment period but still may make comments through local R&D process

20. 20 Continuing Review Continuing Review date is set for overall study, not for each site Two step application and submission process: LSI submits a report to PI by PI established deadline PI/SC submits summary report, along with copies of all LSI reports Local Site Applications cannot be approved, even if no further modifications, until PI Application is approved

21. 21 Reportable Events VA Central IRB Table of Reporting Requirements Specific Reporting forms available on VA Central IRB website Reported to VA Central IRB, not local IRB Separate SharePoint site for uploading reports

22. 22 RCO Audits and Other Local Site Audits or Reports Submitted at Continuing Review: Routine Research Compliance Officer (ROC) audits (informed consent and triennial) if no findings require review by the IRB; MVP exception – Quarterly summary from ORO Central Office Submitted immediately (By RCO, PI, LSI) Any reports of apparent serious noncompliance Any other issues identified that require IRB review

23. 23 Role of VA Central IRB Administrator Main Point of Contact Prior to Submission Maintenance of SOPs and Forms Supervises VA Central staff Assists VA Central IRB Co-Chairs with meeting management and IRB member management Maintains website and provides training Serves as POC for outside audits, site visits, and annual review of VHA Central Office HRPP

24. 24 Role of VA Central IRB Managers Serve as main point of contact after study is officially submitted to VA Central IRB and assigned a study number Performs administrative review and coordinates all other required reviews, to include local site review After initial approval, oversees all other study actions (cradle to grave) in coordination with Primary Reviewer and other staff processing CRs and SAEs/PDs)

25. 25 Roles of Other PRIDE Personnel Program Administrators Process SAE/Protocol Deviations Meeting Logistics to include member travel IRB Member Training and Appointments SharePoint and ACCESS system development and maintenance Regulatory Analyst Perform Pre-Reviews, Engagement Determinations Advises IRB and study teams on regulatory issues Fills in as needed for other staff

26. 26 Contact Information Annette R. Anderson, MS VA Central IRB Administrator Annette.anderson3@va.govAnnette.anderson3@va.gov or 202-443-5649 E-mail: va.central.irb@va.govva.central.irb@va.gov Toll Free Number: 877-254-3130 Website: http://www.research.va.gov/vacentralirb/default.cfmhttp://www.research.va.gov/vacentralirb/default.cfm Note: See next slide for additional contact information.

27. 27 VA Central IRB Managers and Other Staff Current VA Central IRB Managers Hector Ramirez202-443-5656hector.ramirez@va.govhector.ramirez@va.gov Christie O’Brien202-443-5660christie.obrien@va.govchristie.obrien@va.gov Jeffrey Rollins202-443-5652jeffrey.rollins@va.govjeffrey.rollins@va.gov Evangela Covert202-443-5788evangela.covert@va.govevangela.covert@va.gov SharePoint, ACCESS, MOUs, and Reportable Event Reporting Lindsey Martin202-443-5653lindsey.martin2@va.govlindsey.martin2@va.gov Erica Doruska Remoteerica.doruska@va.goverica.doruska@va.gov Regulatory Analyst Soundia Duche202-443-5658soundia.duche@va.govsoundia.duche@va.gov