Dial in: (415) 655-0060 Access Code: 143-332-858 Slides in

Dial in: (415) 655-0060 Access Code: 143-332-858 Slides in “Handout” Tab Karen Jeans, PhD, CCRN, CIP Associate Director of Regulatory Aff airs, ORPP&E VHA Offi ce of Research and Development VA R e s e a r c h a n d D e v e l o p m e n t C o m m i t t e e Fr e q u e n t l y A s k e d Q u e s t io n s June 6, 2019

Objectives Dial in: (415) 655-0060 Access Code: 143-332-858 Slides in “Handout” Tab Identify issues requiring clarification in VHA Directive 1200.01 by reviewing R&D Committee Frequently Asked Questions (FAQs) released on May 24, 2019 and revised on June 5, 2019 2

Topics of R&D FAQs Dial in: (415) 655-0060 Access Code: 143-332-858 Slides in “Handout” Tab R&D Committee Review of Subcommittee and Committees R&D Committee Quality Assurance Reviews R&D Continuing Review R&D Committee Approval of Inclusion of NonVeterans in VA Research VA Central IRB Single Patient Expanded Access Protocols R&D Committee Chair and Members’ Required Training – CITI modules 3

VHA Directive 1200.01: Research and Development (R&D) Committee 16, June 2009 VHA Handbook 1200.01 Issued January 24, 2019 VHA Directive 1200.01 Issued January 24 to April 30, 2019 Discretionary Enforcement of new requirements in VHA Directive 1200.01 or substantial alterations until May 1,2019 April 19, 2019 September 1, 2019 Signed Concurrence Memorandum from DUSH-DEAN for Discretionary Enforcement of three specific policy areas until September 1, 2019. All other policies in VHA Directive must be complied with as of May 1, 2019. Discretionary Enforcement ends. All policies in VHA Directive 1200.01 must be complied with as of this date. 4

Three Policy Areas in VHA Directive 1200.01 under Discretionary Enforcement until September 1, 2019 Paragraphs 5.h.(9); 5.i., and 5.l.(3 Paragraphs 5.h.(6), 5.j, and 5.k Establishment of Research & Development Committee Conflict of Interest Committees for review of the OGE Form 450 Alternative – VA, Research Financial Conflict of Interest Statement. Completion of Information System Security Officer (ISSO) and Privacy Officer (PO) review before any VA study is given final approval Paragraph 10.c Use of Material Transfer Agreements (MTA) for transfer of biospecimens from VA in collaborative research activities 5

R&D Committee Review of Subcommittee and Committees Question #1: Is the R&D Committee required to “approve” subcommittee minutes as part of the requirement for it to review subcommittees as described in VHA Directive 1200.01, Paragraph 6.f.? “The R&D Committee reviews all research related committees and subcommittees at least annually in part by: reviewing the minutes of each subcommittee that reviews VA research protocols; by close communication with the subcommittees; and through Quality Assurance and Quality Improvement activities . . .” 6

R&D Committee Review of Subcommittee and Committees Answer: No. The R&D Committee is not required to approve subcommittee minutes, but it must document in its minutes its review of the subcommittee minutes within 60 days of the subcommittee’s finalization of the minutes (VHA Directive 1200.01, Paragraph 8.a.(3)). An example of documentation of the R&D Committee’s review of minutes when no issues required action is as follows: “The IRB’s minutes were reviewed by the R&D Committee; there were no issues requiring discussion or action.” An example of documentation of the R&D Committee’s review of minutes when issues required action is as follows: “The IRB’s minutes were reviewed by the R&D Committee; the IRB reviewed 101 protocol deviations for Dr. “121” in its last meeting, but there Is no indication that any actions were taken by the IRB. Additional information will be requested from the IRB regarding its review of the protocol deviations for Dr. “121” and any required reporting.” 7

R&D Committee Review of Subcommittee and Committees Question #2: What are the quality assurance and quality improvement activities the Office of Research and Development (ORD) requires the R&D Committee to conduct as part of its review of research related committees and subcommittees as stated in VHA Directive 1200.01, Paragraph 6.f.: “The R&D Committee reviews all research related committees and subcommittees at least annually in part by: reviewing the minutes of each subcommittee that reviews VA research protocols; by close communication with the subcommittees; and through Quality Assurance and Quality Improvement activities. . . .” ? 8

R&D Committee Review of Subcommittee and Committees Answer: ORD does not prescribe the specific number or types of quality assurance and quality improvement activities that the R&D Committee uses for its periodic review (at least annually) of its research-related committees and subcommittees. The R&D Committee has discretion to select the quality indicators or quality measures it considers most meaningful to its review. 9

R&D Committee Review of Subcommittee and Committees Examples of Quality Indicators or Quality Measures: Comparison of VA studies approved by the research-related committee or subcommittee against the VA studies approved by the R&D Committee to ensure that all studies approved by a research-related committee or subcommittee to be conducted as VA research are approved by the R&D Committee; Attendance of subcommittee or committee members; Documentation in the minutes of information specified by regulatory requirements, such as attendance and voting; Length of time required for the committee or subcommittee to review and approve modifications to previously approved research; Number of actions taken by the committee or subcommittee during a convened meeting, and the duration of the meeting; and Reviewing a subset of standard operating policies of its research-related committees and subcommittees to evaluate whether documentation reflects implementation of the reviewed standard operating policies. 10

R&D Committee Approval of Inclusion of Non-Veterans in VA Research Question #3: Why is the R&D Committee required to review and approve recruitment of non-Veterans in VA research instead of an Institutional Review Board (IRB)? 11

R&D Committee Approval of Inclusion of Non-Veterans in VA Research Answer: VA research focuses on health issues that affect Veterans. A Veteran as defined in 38 U.S. Code §101(2) “. . . means a person who served in the active military, naval, or air service, and who was discharged or released therefrom under conditions other than dishonorable.” The R&D Committee is responsible for ensuring that all research in which the facility is engaged is consistent with the VA mission. The evaluation of whether the inclusion of non-Veterans in a proposed VA research activity is consistent with meeting the VA mission cannot be delegated to an Institutional Review Board (IRB) because the evaluation is not a human subjects protections issue; it is an institutional evaluation. Not all exempt human subjects research activities require IRB approval. 12

R&D Committee Approval of Inclusion of Non-Veterans in VA Research Answer: For VA studies involving subjects receiving treatment as inpatients or outpatients, VA has strict regulations in 38 CFR §17.45 and 38 CFR §17.92 stating that non-Veterans may only be included in VA research involving VA outpatient or VA inpatient treatment when there are insufficient Veteran patients suitable for the study. For VA studies involving subjects receiving treatment as inpatients or outpatients, VA has strict regulations in 38 CFR §17.45 and 38 CFR §17.92 stating that non-Veterans may only be included in VA research involving VA outpatient or VA inpatient treatment when there are insufficient Veteran patients suitable for the study. The R&D Committee should evaluate who will be responsible for paying for any medical care or treatment for non-Veterans included in research activities involving VA hospital inpatient or outpatient treatment because VA’s medical dollars appropriated for the care of Veterans cannot be used to provide care for non-Veterans. 13

R&D Committee Approval of Inclusion of Non-Veterans in VA Research Question #4: When can the R&D Committee approve the inclusion of non-Veterans through a designated review process? 14

R&D Committee Approval of Inclusion of Non-Veterans in VA Research Answer: VHA Directive 1200.01, Paragraph 13.a. describes the specific responsibilities of the VA Investigator and the R&D Committee when non-Veterans are proposed to be included in VA research. “. . . The investigator must justify including nonVeterans, and the R&D Committee must review the justification and provide specific approval for recruitment of non-Veterans.” If the VA research activity can be approved by a R&D Committee through a designated review process, such as exempt human subject research protocols and protocols approved by expedited review by the IRB, the review and approval for inclusion of non-Veterans in a VA research protocol can be done by designated review. 15

List of Activities that May be Approved by Designated Review Designated Review. The following activities may be approved by the Chair, R&D Committee or a voting member designated by the Chair: (1) Minor changes to a protocol required by the R&D Committee, following full board review. (2) Final approval for protocols approved contingent on the full approval of a subcommittee if the subcommittee had not required major changes (as defined in local SOPs) to the protocol since the R&D Committee conducted its review. (3) Final approval for protocols approved contingent upon completion of the PO and ISSO review. (4) Exempt human subject research protocols and protocols approved by expedited review by the IRB. (5) Single patient expanded access protocols approved by the IRB Chair or another appropriate IRB voting member. (6) Protocols that do not involve human subjects, biosafety level (BSL-3) or higher containment, use of select agents or non-exempt quantities of select toxins, United States Department of Agriculture (USDA)-regulated animal species, or any animal research involving more than momentary pain or distress to animals. 16

R&D Committee Review of Subcommittee and Committees Question #5: Is the R&D Committee required to review and approve all subcommittee standard operating policies and procedures (SOPs)? 17

R&D Committee Review of Subcommittee and Committees Answer: No. The R&D Committee is not required to review and approve all subcommittee SOPs. ORD’s requirement of the policy statement in VHA Directive 1200.01, Paragraph 9.b.(1) related to review of subcommittee SOPs is that the R&D Committee must have a way to ensure that each of its subcommittees has effective standard operating procedures (SOPs) for protocol review. ORD does not prescribe the method used by each of the VA Facility’s applicable subcommittees to establish these SOPs. The subcommittee’s method for reviewing and approving its SOPs can be done by the subcommittee members or by other methods. To meet the ORD policy requirement, the R&D Committee should document how it evaluates the adequacy of each subcommittee’s review procedures 18

R&D Committee Quality Assurance Reviews Question #6: Is the ACOS/R&D (or Coordinator for Research in a smaller VA medical facility) required to continue conducting the following quality assurance reviews described in the rescinded VHA Handbook 1200.01 (January 15, 2009) even though they are not included in VHA Directive 1200.01 (January 24, 2019)? a. Conducting an annual quality assurance review of publications assessing the acknowledgement of VA support and affiliation: b. Providing an annual quality assurance review of research employees involved in human subject research to ensure the employees are working within their scopes of practice and their privileges allowed by the facility’s bylaws and granted to them by the facility; and c. Providing an annual quality assurance review of Cooperative Research and Development Agreements (CRADAs) and other agreements in support of the research program or specific research projects and an assessment of the impact of these agreements on the research program, when applicable. 19

R&D Committee Quality Assurance Reviews Answer: No. The ACOS/R&D (or Coordinator for Research in a smaller VA medical facility) is not required by ORD policy in VHA Directive 1200.01 to be responsible for the referenced quality assurance activities described in VHA Handbook 1200.01. The R&D Committee is required at least annually to conduct quality assurance and quality improvement activities as part of its review of all research related committees and subcommittees as described in VHA Directive 1200.01, paragraph 6. 20

VA Central IRB Question #7: Is the VA Central IRB a subcommittee of the R&D Committee? 21

VA Central IRB Answer: The VA Central IRB is not a subcommittee of the R&D Committee. It is an external committee established by a Memorandum of Understanding (MOU) between it and a VA Facility for VA Central IRB services. As stated in the Note in VHA Directive 1200.0 , Paragraph 8.a., “External committees established by MOUs or other agreements in lieu of required subcommittee(s) are not considered subcommittees and are governed by the agreement (e.g. the VA Central IRB).” However, it is an internal VA IRB. 22

VA Central IRB Question #8: VA Central IRB: Is the VA Central IRB an internal IRB or an external IRB? 23

VA Central IRB Answer: The VA Central IRB is an internal IRB. As stated in the Note in VHA Directive 1200.01, Paragraph 5.h. (7): “For purposes of this directive, use of the VACO [VA Central IRB] or another VA facility’s internal IRB is not considered to be an external IRB. See VHA Handbook 1200.05(2).” Internal IRBs include two types of IRBs: (a) a VA facility’s IRB supported, and staffed within the VA Facility, including registration of the IRB; and (b) the VA Central IRB. 24

Single Patient Expanded Access Protocols Question #9: When is the R&D Committee approval required for single patient expanded access protocols for investigational drugs or biologics or investigational medical devices? 25

Single Patient Expanded Access Protocols Answer: The R&D Committee approval is required for single patient expanded access protocols for investigational drugs or investigational medical devices when IRB approval is required by FDA regulations for an expanded access protocol prior to the investigational medical product (drug, biologic, or medical device) being administered to the patient. The R&D Committee approval can be granted using a designated review procedure as permitted in VHA Directive 1200.01, Paragraph 9.e. (5) or the convened R&D Committee review procedure. 26

R&D Continuing Review Question #10: Is the R&D Committee required to conduct continuing review for human subjects research activities approved by expedited review or transitioned to the 2018 Requirements of the Federal Policy for the Protection of Human Subjects (Common Rule) when the IRB does not conduct continuing review of the research activity? 27

R&D Continuing Review Answer: No. The R&D Committee is not required to conduct continuing review of the non-exempt human subjects research activities because the research activities remain under the continuing oversight of the IRB. 28

R&D Committee Chair and Members’ Required Training – CITI Modules Question #11: Which two modules in the Collaborative Institutional Training Initiative (CITI) are required by ORD for the R&D Committee Chair and voting members to complete to meet the ORD training requirement in VHA Directive 1200.01 for training on ethical protections of human research protections? 29

R&D Committee Chair and Members’ Required Training – CITI Modules Question #11: VHA Directive 1200.01, Paragraph 14, states “Every 3 years the Chair and voting members of the R&D Committee are required to complete two modules from ORD and Collaborative Institutional Training Initiative (CITI) on ethical principles of human research protection. See https://www.research.va.gov/pride/training/options.cfm for approved courses and VHA Handbook 1200.05(2) for additional information.” There are two stages (basic and refresher) in CITI for VA’s Human Subjects Protections course. The required modules in the Human Subjects Protection course are: For the basic stage: History and Ethics of Human Subjects Research (ID: 498) Informed Consent (ID: 3) For the refresher stages: History and Ethical Principles (ID: 511) History and Ethical Principles – Research vs. Practice (ID 993) 30

R&D Committee Chair and Members’ Required Training – CITI Modules Answer: ORD has set up the above modules as a separate course for R&D Committee members at each of the VA Facilities. Learners can get to it via the “add a course” link in their own accounts. Those who have already taken the VA Human Subjects Protection training in CITI, which includes the training required of R&D Committee members, will not have to take additional training; CITI will automatically grant those individuals credit for having already completed the training for R&D Committee members, when they enroll in the new course. Please contact Dr. Alice Huang at [email protected] with any questions about this training. 31

QUESTIONS? 32