VA's Single IRB Mandate Implementation: Requirements & Actions

Dial in: (415) 655-0052 Access Code: 420-066-648 Slides in Handout Tab One of the sessions will be recorded VA s Implementation of the Single IRB Mandate in the 2018 Requirements (the Revised Common Rule): What You Need to Know and Do Office of Research Protections, Policy, & Education VHA Office of Research and Development Department of Veterans Affairs January 22, 2020

Objectives Describe when the single IRB requirement of 38 CFR 16.114 in the 2018 Requirements (revised Common Rule) applies in VA research. Describe what considerations and actions must be taken when the single IRB requirement applies in VA research. How to apply for an exception to the single IRB requirement How to request a change in IRB arrangements for use of the single IRB

Where are we? July 19, 2018 January 21, 2019 Jan 20, 2020 January 23, 2018 January 19, 2018 January 19, 2017 September 2016 June 19, 2018 Six month delay in effective date to July 19, 2018 Effective date Three burden- reducing provisions Final Rule revising the Common Rule Six month delay in compliance to January 21, 2019 Compliance date 2018 Common Rule Original effective/ compliance date Final Provision* Compliance date NPRM *38 CFR 16 .114 Cooperative Research Provision (also referred to as the Single IRB Requirement ) 3

What the .114 Cooperative Research Provision States (a) Cooperative research projects are those projects covered by this policy that involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for safeguarding the rights and welfare of human subjects and for complying with this policy. (b) (1) Any institution located in the United States that is engaged in cooperative research must rely upon approval by a single IRB for that portion of the research that is conducted in the United States. The reviewing IRB will be identified by the Federal department or agency supporting or conducting the research or proposed by the lead institution subject to the acceptance of the Federal department or agency supporting the research. 4

What the .114 Cooperative Research Provision States (cont.) (2) The following research is NOT subject to this provision: (i) Cooperative research for which more than single IRB review is required by law (including tribal law passed by the official governing body of an American Indian or Alaska Native tribe); or (ii)Research for which any Federal department or agency supporting or conducting the research determines and documents that the use of a single IRB is not appropriate for the particular context. 5

What Does This Mean? 6

When Does the Single IRB Requirement Apply to Human Subjects Research in the United States? All Federally Conducted or Supported Human Subjects Research in the United States All Federally Conducted or Supported Non- Exempt Human Subjects Research in the United States Engaging More than One (1) Institution** All Human Subjects Research Conducted in the United States

When Does the Single IRB Requirement Apply to Human Subjects Research that are Conducted or Supported by the VA? All VA Non-Exempt Human Subjects Research All VA Non-Exempt Human Subjects Research With More than One Institution Engaged All VA Exempt and Non-Exempt Human Subjects Research All VA Non-Exempt Human Subjects Research With More than One Institution Engaged and the Other Institution(s) is a Federal Institution (including another VA Facility) or the other non-Federal Institution(s) is a Recipient of Federal Government Funding or Support for that Research Activity Single IRB Required Unless Exception Applies

Evaluating when the Single IRB Requirement Applies in VA: When the VA Research Activity is Exempt - - - - - The Single IRB Requirement in the 2018 Requirements (revised Common Rule) does not apply to exempt research activities.

Poll #1: True or False: If a VA Facility is conducting a non-exempt human subjects research activity with another institution that is engaged in the research, a single IRB is always required unless an exception to the single IRB requirement applies: Possible answers: 1. 2. True False 10

Poll #1: Answer & Rationale True or False: If a VA Facility is conducting a non-exempt human subjects research activity with another institution that is engaged in the research, a single IRB is always required unless an exception to the single IRB requirement applies: Answer: 1. 2. True False 11

Lets Go Back to Poll #1: Answer & Rationale True or False: If a VA Facility is conducting a non-exempt human subjects research activity with another institution that is engaged in the research, a single IRB is always required unless an exception to the single IRB requirement applies: Answer: 1. 2. True False 12

Why is a Single IRB Not Always Required When a VA Facility is Conducting a Non-Exempt Human Subjects Research Activity with Another Institution Engaged in the Research? An exception is not needed when the single IRB requirement doesn t apply. The single IRB requirement applies to all federally conducted or supported non-exempt human subjects research involving more than one (1) institution engaged in human subjects research. The single IRB requirement does not apply if the non-exempt human subjects research involving the VA and another engaged institution is Not funded or supported by VA or another Federal agency or department at the other non-VA institution, or The other non-VA institution is not another federal agency or department s institution. 13

Poll #2: Applying the Single IRB Requirement Answer Yes or No. An industry collaborator is funding a multi-site clinical trial involving an investigational drug. The industry collaborator is funding the study at your VA Facility and 4 academic universities. Is a single IRB required for the 5 engaged institutions because the VA as a federal agency is involved in the conduct of the multi-site clinical trial? Possible answers: 1. 2. Yes No 14

Poll #2: Applying the Single IRB Requirement Answer Yes or No. An industry collaborator is funding a multi-site clinical trial involving an investigational drug. The industry collaborator is funding the study at your VA Facility and 4 academic universities. Is a single IRB required for the 5 engaged participating institutions because the VA as a federal agency is involved in the conduct of the multi-site clinical trial? Possible answers: 1. 2. Yes No Rationale: A single IRB is not required for the multi-site clinical trial. The 4 academic universities are not supported or funded by a Federal agency or department and the VA Facility is the only Federal Institution participating in the study. 15

Poll #3: Applying the Single IRB Requirement Answer Yes or No. A VA Investigator at your VA Facility with a dual appointment at the academic affiliated University has been awarded a VA merit to conduct a clinical study. The VA research activity is a non-exempt human subjects research study. ORD has approved an off-site waiver to allow a portion of the research to be conducted at the University. The University is engaged in the non-exempt human subjects research study. Is a single IRB required for this VA merit research activity because both the VA and the University are engaged in non-exempt human subjects research? Possible answers: 1. 2. Yes No 16

Poll #3: Applying the Single IRB Requirement Answer Yes or No. A VA Investigator at your VA Facility with a dual appointment at the academic affiliated University has been awarded a VA merit to conduct a clinical study. The VA research activity is a non-exempt human subjects research study. ORD has approved an off-site waiver to allow a portion of the research to be conducted at the University. The University is engaged in the non-exempt human subjects research study. Is a single IRB required for this VA merit research activity because both the VA and the University are engaged in non-exempt human subjects research? Possible answers: 1. Yes Rationale: VA is supporting the research at the non-VA site by granting an off-site waiver for the ORD-funded research. 2. No 17

ORDs Key Mechanisms for Funding or Supporting Human Subjects Research: Implications for Evaluating When the Single IRB Requirement Applies Unless an Exception Applies PEOPLE CENTERS Research Career Scientist Awards Personnel Salaries Pilot Awards ORD Merit Awards Career Development Awards 18

Implementing the Single IRB Requirement July 19, 2018 January 21, 2019 Jan 20, 2020 January 23, 2018 January 19, 2018 January 19, 2017 September 2016 June 19, 2018 Six month delay in effective date to July 19, 2018 Effective date Three burden- reducing provisions Final Rule revising the Common Rule Six month delay in compliance to January 21, 2019 Compliance date 2018 Common Rule Original effective/ compliance date Final Provision* Compliance date NPRM *38 CFR 16 .114 Cooperative Research Provision 19

ORDs Data Request Sent on January 2, 2020: Implementation of the .114 Cooperative Research Provision in VA Research VA received recent clarification on the date when the single IRB cooperative research provision in .114 (single IRB requirement) became effective. As of July 19, 2018, all federally funded or supported non-exempt human subjects studies with more than one engaged institution were required to be reviewed by a single IRB. The Single IRB requirement did not apply if more than one IRB were required by law or an exception to the single IRB requirement had been determined and documented by the Federal agency or department conducting or supporting the research. Many cooperative (more than one engaged institution) non-exempt human VA research studies have been approved with more than one IRB since July 19, 2018. 20

ORDs Data Request Sent on January 2, 2020: Implementation of the .114 Cooperative Research Provision in VA Research ORD requested identification of these projects from each VA Facility s research program so that an exception determination can be given by ORD and documentation sent to the VA Facility. Spreadsheets were to be completed and sent to ORD by January 13, 2020. ORD will send documentation of exception determinations for the individual studies to your VA Facilities by January 20, 2020. 21

Example of ORD Sample Template for Documentation of Exception from Single IRB Requirement for VA Research

As of January 20, 2020: Process for Requesting an Exception from the Single IRB Requirement for Cooperative Non-Exempt Human Subjects Studies ORD supports use of a single IRB when possible, but ORD also recognizes that mandating use of a single IRB in all cases is not logical or feasible. The .114 cooperative research provision also recognizes that use of a single IRB is not always required. ORD has established a process for VHA facilities (not investigators) to submit a request and justification for exception from the Cooperative Research Provision for individual studies. Possible exception: An IRB reliance agreement cannot be established due to technical (ISSO) reasons. 23

As of January 20, 2020: Process for Requesting an Exception from the Single IRB Requirement for Cooperative Non-Exempt Human Subjects Studies The exception request spreadsheet titled PROSPECTIVE CHNE RESEARCH EXEMPTIONS REQUEST must be sent to ORD by the ORD funding service, ACOS/R&D, AO/R&D, VA Human Research Protections Administrator or the VA Facility s IRB Administrator. Requests should be sent when the research plan is being developed and before IRB review. Email subject line should reference that it is a request for single IRB exception with the name of the study and the VA Principal Investigator. Example: Request for sIRB exception: Comparison of X vs. Y, A. Investigator, M.D. Requests are to be sent to: IRBRelianceandSIRBExceptions@va.gov. Requests will be reviewed by ORD with an expected response time no later than 10 business days. 24

Example #1 of Exception Request from the Single IRB Requirement To: IRBRelianceandSIRBExceptions@va.gov Subject Line: Request for sIRB exception: Project title: Sepsis and Septic Shock: Patient satisfaction with experiences in the ICU, B. Well, M.D. Text: Please find our attached spreadsheet requesting an exception for use of a single IRB for the above-named study involving our VA Facility and the ABC VA Facility. If you have any questions, please contact me at the following email address. IRB Administrator VA Facility Name 25

Example #1 of Exception Request from the Single IRB Requirement Justification LEAD VA SITE, IF APPLICABLE, OR LOCAL SITE VA VA VA LOCAL STUDY # (if applicable) ACOS/R NAME, DEGREE(s) SPECIFIC FUNDING SOURCE VA FACILITY Street Facility City Faculty State Facility Zip Code ACOS/R EMAIL ADDRESS STUDY PI NAME STUDY NAME Palo Alto 1234 palo Alto Street Palo alto CA 02134 Joe Acos, MD joe.acos@va.gov 23456 B. Well, M.D. Sepsis and Septic Shock: Patient satisfaction with experiences in the ICU No We do not have an IRB reliance agreement for the ABC VA Facility to use our VA Facility s IRB, and it will take longer to negotiate an IRB agreement for the ABC VA Facility to use our IRB for this single study than for each our of VA Facilities to use its own IRB of Record. The ABC VA s IRB of Record is the University, which will not agree to be the single IRB for this study. 26

Example #1: Justification for the Exception Request from the Single IRB Requirement We do not have an IRB reliance agreement for the ABC VA Facility to use our VA Facility s IRB, and it will take longer to negotiate an IRB agreement for the ABC VA Facility to use our IRB for this single study than for each our of VA Facilities to use its own IRB of Record. The ABC VA s IRB of Record is the University, which will not agree to be the single IRB for this study. 27

Example #2 of Exception Request from the Single IRB Requirement To: IRBRelianceandSIRBExceptions@va.gov Subject Line: Request for sIRB exception: Project title: Comparison of Two Methods of Conducting Spontaneous Breathing Trials, Y. I. Wirk, M.D. Text: Please find our attached spreadsheet requesting an exception for use of a single IRB for the above-named study involving our VA Facility and our University. If you have any questions, please contact me at the following email address. HRPP Administrator VA Facility Name 28

Example #2 of Exception Request from the Single IRB Requirement Justification LEAD VA SITE, IF APPLICABLE, OR LOCAL SITE VA Facility City VA Faculty State VA Facility Zip Code ACOS/R NAME, DEGREE(s) LOCAL STUDY # (if applicable) SPECIFIC FUNDING SOURCE VA FACILITY Street ACOS/R EMAIL ADDRESS STUDY PI NAME STUDY NAME CAVHS 4300 West 7th Street Little Rock AR 72205 Josephine Acos, MD josephine.va.gov NA Y.I. Wirk, M.D. Comparison of Two Methods of Conducting Spontaneous Breathing Trials Department of Defense I am requesting an exception for use of a single IRB for the above-named study currently approved at our VA and our affiliated University. Dr. Wirk is the Lead PI for he study, and we are adding the ABC VA Facility as a participating site in this study. Our VA IRB does not have the capacity or the infrastructure to be the IRB for other VA Facility. We are requesting an exception for the above-named study by Dr. Wirk. 29

Example #2: Justification for the Exception Request fromthe Single IRB Requirement I am requesting an exception for use of a single IRB for the above-named study currently approved at our VA and our affiliated University. Dr. Wirk is the Lead PI for he study, and we are adding the ABC VA Facility as a participating site in this study. Our VA IRB does not have the capacity or the infrastructure to be the IRB for other VA Facility. We are requesting an exception for the above-named study by Dr. Wirk. 30

Pending Publication: VA List of Exceptions to the Single IRB Requirement in the .114 Cooperative Research Provision VA is in the process of publishing a list of exceptions to the single IRB requirement. This list has been reviewed by other Common Rule agencies. The list must be published in the Federal Register. Once the list is published, a mechanism will still remain for requesting exceptions to the single IRB requirement.

VAs Facilitation for Use of a Single IRB Standardizing requests and processing Negotiating to facilitate use of the SMART IRB platform: Pending VHA Directive 1200.05 policy change: Use of Commercial IRBs approved by ORD for industry-sponsored clinical trials when sponsor contracts with the commercial IRB Pending VHA Directive 1200.01 policy changes: Adjust language to encourage single IRB review when possible; role and timing of R&D committee review and approval, clarification of timing for privacy and ISSO reviews

VAs Facilitation for Use of a Single IRB: Current ORD Policy Regarding IRBs The January 20, 2020 compliance date for the .114 cooperative research provisions does not change ORD policy regarding the types of IRBs VA Facilities can use or the types of IRBs that VA Facilities IRBs can serve as an IRB of Record for as described in VHA Directive 1200.05 (January 7, 2019).

VAs Facilitation for Use of a Single IRB: Types of IRBs VA Facilities May Use VA Facility IRBs of Record may include the VA facility s own IRB(s), VHA Central Office IRB (VA Central IRB), an IRB of another VA facility, the IRB(s) of an affiliated medical or dental school, or the IRB of another Federal agency. A facility may also use for multi-site protocols an IRB from a non- affiliated medical or dental school if that IRB has been specifically designated by ORD as an IRB that may serve as a multi-site IRB for VA facilities. Reference: VHA Directive 1200.05, Paragraph 5.f.(8)(a)

VAs Facilitation for Use of a Single IRB: Use of VA IRBs by Non-VA Entities A VA facility s own IRB, also known as an internal IRB, and the VA Central IRB, cannot serve as an IRB of Record for any non-VA entity except: Department of Defense (DoD) facility, Department of Energy laboratory, or a VA Nonprofit Corporation. Reference: VHA Directive 1200.05, Paragraph 5.f.(8)(b)

VAs Facilitation for Use of a Single IRB: Standardizing Requests for Changes in IRB Arrangements ORD policy requires that the VA Medical Center Director request approval from the Chief Research and Development Officer (CRADO) approval when the VA facility wants to establish a new HRPP, change its IRB(s) of Record, or wants its internal IRB to serve as an IRB of Record for a non-VA entity. To standardize the application process for VA Facilities to request changes in IRBs of Record, an Application Form titled: Institutional Review Board (IRB) Reliance Request Form has been developed and piloted. The Application Form will be placed on the ORD Polices and Guidance webpage. This Application Form can also be obtained by emailing Ms. Sarah Rule at sarah.rule@va.gov., the VHA IRB Reliance/Single IRB Exceptions Box at IRBRelianceandSIRBExceptions@va.gov. and the VHA Regulatory Box at vhacoordregulatory@va.gov. This Application Form cannot be used by VA Facilities requesting to start a research program. A dialogue with both ORO and ORD is required before any documentation is sent by a VA Facility wishing to start or re-initiate a research program. Reference: VHA Directive 1200.05, Paragraph 5.f.(9)

Institutional Reliance Request Form

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Dissemination of ORD Approval of non-VA IRBs Many institutions do not want to be a single IRB or only want to be a single IRB for a single study. ORD is currently processing requests from VA Facilities for non-VA IRBs that specifically request reliance for a specific study. ORD will publish on its website approval in consultation with ORO the non-VA IRBs that will allow VA Facilities to enter into IRB reliance agreements for multiple studies. Example: VA is working with non-VA IRBs for use of IRB services to support VA Facilities participating in clinical studies supported by the Trial Innovation Network. Example: Commercial IRBs will be listed that have been approved by ORD and ORO after the VHA Policy allowing use of Commercial IRBs is published and the applicable Master Service Agreements have been executed.

Key Points VA Facilities should ask the following for every Non-Exempt Human Subjects Study that follows the 2018 Requirements to determine whether the .114 Cooperative Research Provision Applies Does the research involve more than one engaged institution? If the answer is no, the single IRB requirement does not apply. If the answer is yes, proceed to the next question. Are any of the other participating institutions a Federal institution (including another VA) or are any of the participating institutions receiving federal funding or support for the research activity? If the answer is no, the single IRB requirement does not apply. If the answer is yes to either part of that question, proceed to the next question. Does ORD policy allow the use of the single IRB for the study, has an exception to the single IRB requirement already been determined and documented, or will the single IRB allow the VA Facility to rely upon it for IRB review? The answers to these questions will help determine whether the VA Facility needs to evaluate whether to send an application to ORD for requesting use of the single IRB for the study or whether a request for an exception to the single IRB requirement should be sent to ORD and/or the applicable Federal agency or department.

NO Single IRB regulation does not apply Does the non-exempt human subjects research involve more than one engaged institution? Key Questions to Ask for Every Non-Exempt Human Subjects Study that Follows the 2018 Requirements: Determining Whether the .114 Cooperative Research Provision Applies YES NO Are any of the other participating institutions a Federal institution (including another VA) or are any of the participating institutions receiving federal funding or support for the research activity? Single IRB regulation does not apply YES Send a request for an exception to the single IRB requirement to ORD and/or the applicable Federal agency or department. Send an application to ORD for requesting approval of the single IRB for the study if an IRB Reliance Agreement or MOU is not present. Does ORD policy allow the use of the single IRB for the study, has an exception to the single IRB requirement already been determined and documented, or will the single IRB allow the VA Facility to rely upon it for IRB review?

Key Points VA supports use of a single IRB when it is possible regardless of whether the .114 cooperative research provision applies to the research activity. The implementation of the .114 cooperative research provisions is going to be an ongoing process among investigators, VA research offices, VA Central Office, other federal agencies, and the entire United States research regulated community. Communication is key. Please contact ORD if you have questions about whether the single IRB requirement in the .114 cooperative provisions applies to a multi-site VA study. .

Questions? Presenters: C. Karen Jeans, PhD, CCRN, CIP at c.karen.jeans@va.gov Sarah Rule, MPH, CCRP at sarah.rule@va.gov Send Questions to: VHA IRB Reliance/Single IRB Exceptions Box at IRBRelianceandSIRBExceptions@va.gov VHA ORD Regulatory Box at vhacoordregulatory@va.gov. 47