TABLE C-3INDIVIDUAL IRB STRUCTURE AND OPERATIONS

RequirementElementData SourceMethod
IRB 1 The IRB's structure and composition are appropriate to the amount and nature of research reviewed and meet regulatory requirements
1.A. The IRB maintains, or has access to, information about each IRB member.
Regulation/Source
38 CFR 16.103(b)(3)
38 CFR 16.115 (a)(5)
M-3, Part 1, 9.09 (g)(l)(e)
45 CFR 46.103(b)(3)
45 CFR 46.115(a)(5)
21 CFR 56.115(a)(5)
IRB-GB, (I)(B)
FDA-IS, (CL)(VI)
ICH-GCP, (3.21)
Information about each IRB member includes the following:
1.A.1. Name and address.
1.A.2. Earned degrees.
1.A.3. Representative capacity (e.g., physician, non-scientist, ethicist, community member, etc.).
1.A.4. Indications of experience, such as board certifications, licensures, certifications, etc.
1.A.5. For community members, past or present association with the VA (including academic affiliates) or its employees.
1.A.6. Statement of financial and other interests which may constitute a conflict of interest.
1.A.7. Documentation of training in human subject protection.
1.A.8. Documentation of the voting status of each member.
1.A.9. Documentation of alternate status.
Files maintained by the institution on each IRB member including but not limited to: curriculum vitae; disclosure documentation; copies of training certificatesReview of IRB files shows compliance with requirements for current and past IRB members for the past one year
1.B. The IRB consists of the appropriate number, type, and diversity of members.
Regulation/Source
38 CFR 16.107 (a)(b)(c)(d)
M-3, Part l, 9.08(a)
45 CFR 46.107 (a)(b)(c)(d)(f)
21 CFR 56.107 (a)(b)(c)(d)
IRB-GB, (I)(B)
FDA-IS, (FAQ)(II)
FDA-IS, (CL)(VI)
ICH-GCP, (3.2.1)
The IRB includes:
1.B.1. At least five members.
1.B.2. At least one member whose primary area of interest is nonscientific (e.g., lawyer, clergy, and ethicist).
1.B.3. At least one member whose primary area of interest is scientific.
1.B.4. At least one member who does not have any past or present association with the VA or university affiliate that would negate the status of a community, non-affiliated member.
1.B.5. Diversity of membership based on gender, cultural background, and sensitivity to community issues and/or community attitudes.
1.B.6. Members of more than one profession.
1.B.7. Affiliate IRBs have at least one member who is a VA representative.
1.B.8. Officials with responsibility for development and oversight of the HRPP are non-voting, ex-officio members.
Policies and procedures
IRB membership lists, from the past year
Review of policies and procedures reflects compliance with regulations
Review of IRB files shows compliance with requirements for current and past IRB members
1.C. The IRB meets regularly and with sufficient frequency, and members have sufficient time to review the materials prior to the meeting. Materials include the full protocol, a proposed informed consent form, any relevant merit review or grant applications, the investigator's brochure (if one exists), and any advertising intended to be seen or heard by potential subjects.1.C.1. IRB meetings have the following arrangements:
      1.C.1.1. The IRB has a set meeting schedule.
      1.C.1.2. Except under specified “emergency” conditions, IRB members receive meeting materials far enough in advance of the scheduled meeting to allow for sufficient review.
Policies and procedures
IRB meeting schedule
Review of policies and procedures shows evidence of requirements
Confirm existence of meeting schedule or regularly scheduled meeting date and time (e.g., first Monday of the month at 8:00 a.m.)
Regulation/Source
38 CFR 16.108(a)(1)
45 CFR 46.108(a)(1)
21 CFR 56.108(a)(1)
      1.C.1.3. The IRB has established timelines for receipt by the IRB office and distribution of materials to members.
1.C.2. The IRB follows its established timelines.
1.C.3. The IRB periodically evaluates established timelines and it updates timelines to ensure effective participation of IRB members.
Distribution schedule
IRB submission deadline schedule
IRB member interview
IRB minutes
QI results
Ask IRB member how soon before scheduled meetings they typically receive materials. Ask them whether they believe this is enough time to allow for sufficient review.
Review of IRB minutes for evidence of actual meeting dates conforming to scheduled dates
Review of QI results for evidence of compliance with meeting schedules
1.D. The IRB has a system for assigning reviewers to protocols prior to initial review (e.g., primary/secondary reviewer system), if applicable.
Regulation/Source
38 CFR 16.107(a)
1.D.1. The IRB has a systematic process to assign review responsibility that is consistent with protocol content and reviewer expertise.
1.D.2. The IRB periodically evaluates the reviewer assignment system.
Policies and procedures
IRB member interview
QI results
Review of policies and procedures for evidence of primary reviewer system, if applicable
IRB member is able to articulate the process for assigning protocols
Review of QI results for evidence of compliance with, and appropriateness of, outlined protocol review system
IRB 2 The IRB systematically evaluates each research protocol to ensure adequate protection of human subjects in research
2.A. There are written policies and procedures that describe IRB operations and functions.
Regulation/Source
38 CFR 16.103(b)(4)(5)
38 CFR 16.108(a)(e)
38 CFR 6.115(a)(b)(6)
45 CFR 46.103(b)(4)(5)
45 CFR 46.115(a)(b)
21 CFR 56.108(a)(b)(c)
21CFR 50.24
M-3, Part I, 9.09(c)(a)
IRB-GB, (I)(B)
FDA-IS, (CL)
ICH-GCP, (3.3)
MPA
VA Handbook
2.A.1. These polices and procedures shall be consistent with all applicable VA and federal requirements and include the following:
      2.A.1.1. Procedures and required information for conducting initial review and continuing review activities.
      2.A.1.1.1. Procedures for reporting findings and actions to the investigator, the R&D Committee, and institutional officials as required.
      2.A.1.1.2. Procedures for determining which projects require review more often than annually and which projects need verification from sources other than the investigators that no material changes have occurred since previous IRB review.
2.A.1.2. Procedures and criteria for making the following determinations for a research protocol: approval; require modifications in (to secure approval); or disapproval.
2.A.1.3. Procedures and criteria for suspension or termination of IRB approval of research protocols.
2.A.1.4. Criteria for when research protocols should include a Data Safety Monitoring Board (DSMB) as required by VA, DHHS, and FDA.
2.A.1.5. Review of protocol amendments, including procedures for determining criteria for what type of changes require full IRB review versus expedited review.
Policies and proceduresReview of policies and procedures shows evidence of requirements for IRB operations and functions
2.A.1.6. Procedures and criteria for determining if an expedited review process can be used.
2.A.1.7. Investigator reporting requirements, including:
      2.A.1.7.1. Providing IRB required data for continuing review.
      2.A.1.7.2. Submitting proposed changes in research protocol and/or consent forms for approval.
      2.A.1.7.3. Reporting deviations from approved protocol or other regulations and policies.
      2.A.1.7.4. Reporting adverse events.
      2.A.1.7.5. Reporting unanticipated problems involving risks to subjects.
      2.A.1.7.6. Submitting termination/completion reports.
2.A.1.8. Continuing review occurs at the specified time interval.
2.B. The IRB reviews required and relevant information to make evaluations on research proposals during initial review.
Regulation/Source
38 CFR 16.115(a)
45 CFR 46.115(a)
21 CFR 56.115(a)
FDA-IS, (FDA)(IV)
FDA-IS, (CL)(XI)
ICH-GCP, (3.1.2)(4.9.4)(8.0)
OHRP-CFG
HHS-IGR
2.B.1. The IRB considers the following at initial review:
      2.B.1.1. Attestation, when required, by the investigator as to whether the proposal, or one substantially similar to it, has been disapproved by another IRB.
      2.B.1.2. Scientific evaluations (if any) that accompany the proposal.
      2.B.1.3. Research design.
      2.B.1.4. Scientific rationale.
      2.B.1.5. Statement of known and suspected risks and benefits.
Initial review submission forms and checklists used by the IRB
Sample of IRB initial review files
IRB communications to investigators
Review of submission form and checklists for requirements
Review of protocols for evidence of content of requirements
Review of IRB communications or other guidance for notice of submission requirements
      2.B.1.6. Procedures to minimize risks.
      2.B.1.7. Recruitment and enrollment procedures, including payment to subjects.
      2.B.1.8. Subject selection criteria.
      2.B.1.9. Procedures to protect subject privacy and confidentiality.
      2.B.1.10. Where appropriate, additional safeguards planned to protect the rights and welfare of potentially vulnerable subjects.
      2.B.1.11. Process for monitoring and reporting adverse events.
      2.B.1.12. Presence of a Data Safety Monitoring Board (DSMB) if applicable.
      2.B.1.13. Other information to be used for recruitment or to inform subjects or potential subjects about the nature of the research.
      2.B.1.14. Scientific training and qualifications of investigator and research staff.
      2.B.1.15. Human subject protection training of investigators and research staff.
      2.B.1.16. Investigator potential financial conflicts.
      2.B.1.17. Proposed informed consent documents.
2.B.2. Based on its review of the information above, the IRB approves, requires modifications, or disapproves proposed research.
2.B.3. The IRB conducts audits of the adequacy of information at initial review. Results are used for QI purposes and actions taken, as needed.
IRB minutes
QI results
Review of IRB minutes shows IRB consideration of requirements as appropriate, and decisions to approve are not pro forma
Review of QI results shows evidence of assessment of requirements for initial submission
2.C. The IRB uses required and relevant information to conduct continuing review of research proposals and makes recommended changes.
Regulation/Source
38 CFR 16.1.09 (e)
M-3, Part 1, 9.09 (f)
45 CFR 46 1.09 (e)
21 CFR 56 1.09 (f)
2.C.1. In addition to copies of the documents required for the initial review, the IRB considers the following information, where applicable, for continuing review:
      2.C.1.1. Currently approved informed consent documents.
      2.C.1.2. Approved or proposed amendments, including minor changes (if any), and the IRB action on each amendment.
      2.C.1.3. Research findings to date.
      2.C.1.4. Reports of injuries to subjects.
      2.C.1.5. All serious adverse events or unanticipated problems involving risks to subjects.
      2.C.1.6. Recent published medical or scientific studies applicable to the protocol.
      2.C.1.7. Review of information that may change risk/benefit ratio, including adverse events or unanticipated problems.
      2.C.1.8. Documentation of protocol violations and/or deviations.
      2.C.1.9. Documentation of non-compliance with applicable regulations.
      2.C.1.10. Number of subjects enrolled and entered into the study.
      2.C.1.10.1. Gender and minority status of subjects entered into the protocol.
      2.C.1.10.2. Number of subjects in each of the following categories: children, prisoners, pregnant women, economically disadvantaged, decisionally impaired, or homeless.
      2.C.1.11. Number of subjects withdrawn by self and by investigator, and reasons for withdrawal.
      2.C.1.12. Review of a summary of the DSMB meetings (if applicable) or findings based on information collected on AEs, UAEs, and SAEs as required by the approved data and safety monitoring plan.
Policy and procedures
Continuing review submission forms
Checklists and forms used by IRB
Sample of IRB continuing review files
IRB communications to investigators
IRB minutes
Review of policies and procedures shows evidence of requirements for submission of continuing review
Forms have requirements listed
IRB checklists show evidence of IRB consideration of required information
Protocols reviewed show evidence of IRB consideration of required information and that continuing review was submitted and considered within the required time frame for the protocol
IRB communications list requirements for continuing review submission
IRB minutes reflect consideration of requirements
      2.C.1.12.1. An assurance that all SAEs and UAEs have been reported as required.
      2.C.1.12.2. Review of IND/IDE safety reports and MedWatch reports.
      2.C.1.13. Any new recruitment documents.
2.C.2. Based on its review of the above information, the IRB decides that the research can be continued, continued with modifications, suspended, or terminated.
2.C.3. Based on its continuing review, the IRB requires appropriate changes to the following:
      2.C.3.1. Informed consent form content.
      2.C.3.2. Frequency of continuing review.
      2.C.3.3. Level of safety monitoring.
2.C.4. The IRB conducts audits of the adequacy of information considered at continuing review.
      2.C.4.1. Results are used for QI purposes and actions taken, as needed.
2.D. The IRB has policies and procedures for the conduct of expedited review (if applicable) and appropriately utilizes such review.
Regulation/Source
38 CFR 16.110
M-3, Part I, 9.10
45 CFR 46.110
21 CFR 56.110
2.D.1. The IRB's policies and procedures for expedited review conform to VA and federal regulations and include:
      2.D.1.1 The IRB identifies categories of research for which expedited review is allowed.
      2.D.1.2. There are established qualifications and experience criteria for those IRB members who serve as chairperson's designee(s) in conducting expedited review.
      2.D.1.3. The IRB must have criteria for establishing that research involves no more than minimal risk.
Policies and procedures
IRB submission forms and checklists used by the IRB
Sample of IRB expedited review files
Review of policies and procedures for evidence of requirements for expedited review
Review of IRB submission forms for requirements for expedited review
Review of protocols approved through expedited review shows that the protocols met criteria
FDA-IS, (FAQ)(20)
FDA-IS, (CL)(IX)(C)
OHRP-CFG (B)
      2.D.1.4. The IRB must have criteria for establishing that changes in previously approved research are “minor.”
      2.D.1.5. The IRB has methods to keep IRB members advised of research proposals approved under expedited review that include documentation of specific permissible categories justifying expedited review.
2.D.2. The IRB conducts expedited review of protocols in conformance with its policies and procedures.
      2.D.2.1. Expedited review shall be conducted by IRB Chairperson or by one or more experienced IRB members designated by the IRB Chairperson.
      2.D.2.2. Expedited reviews comply with the IRB policies and procedures and applicable VA and federal regulations.
2.D.3. The IRB conducts audits or self-assessments of compliance with VA and federal regulations and its policies and procedures on expedited review.
      2.D.3.1. Results are used for QI purposes and actions taken, as needed.
IRB minutesIRB minutes show that protocols reviewed through expedited review were presented to full committee for consideration
2.E. The IRB has policies and procedures for determining whether research involving human subjects is exempt from IRB review and correctly makes such determinations.
Regulation/Source
38 CFR 16.101(b)
M-3. Part I, 9.06
45 CFR 46.101(b)
IRB-GB, (I)(A)
2.E.1. The IRB policies and procedures for determining exempt status conform to VA and federal regulations and include:
      2.E.1.1. Definition of all categories of research that are exempt from IRB review.
      2.E.1.2. Process for determining exempt status.
2.E.2. The IRB makes determination of exempt status in accordance with federal regulations.
2.E.3. The IRB conducts audits or selfassessments of compliance with VA and federal regulations and its policies and procedures on exempt status.
      2.E.3.1. Results are used for QI and actions taken, as needed.
Policies and procedures
IRB minutes
IRB Chair interview
IRB coordinator interview
QI results
Review of policies and procedures for presence of requirements for exempt status
IRB minutes show evidence of evaluation of protocols for exempt status.
IRB Chair is able to discuss application of exempt status at the institution
IRB coordinator is able to discuss process for determining exempt status
QI results show evidence of compliance with VA and federal regulations and IRB policies and procedures on the determination of exempt status
2.F. The IRB has policies and procedures for determination of risk level of investigational devices, appropriately makes such determinations, and implements any resulting actions.
Regulation/Source
21 CFR 812.62, 66
FDA-IS, (SR/NSR)
2.F.1. The IRB's policies and procedures for the review of investigational devices address the following:
      2.F.1.1. The IRB decision is based on proposed use of the device and not the device alone.
      2.F.1.2. The IRB may agree or disagree with the sponsor's assessment of significant risk or nonsignificant risk.
      2.F.1.3. The IRB notifies the sponsor and investigator when it determines the device is a significant risk device and proceeds to review the study only after an IDE is obtained by the sponsor.
Policies and procedures
IRB minutes
Sample of device protocols
Review of policies and procedures for determination of risk level of devices
IRB minutes reflect evaluation of risk level of device
Review of device protocols contains evidence of risk level of device
      2.F.1.4. The IRB proceeds to review the study under requisite criteria for any study when the device is determined to be nonsignificant risk.
2.F.2. The IRB conducts audits or self-assessments of compliance with VA and federal regulations for assessing whether the investigational devices are significant or nonsignificant risk.
      2.F.2.1. Results are used for QI and actions taken, as needed.
QI resultsQI results show evidence of compliance with VA and federal regulations and IRB policies and procedures on the determination of risk level of devices
IRB 3 The IRB maintains documentation of its activities
3.A. The IRB documents discussions and decisions on research proposals and activities.
Regulation/Source
38 CFR 16.115(a)(2)
M-3, Part 1,
9.09(g)(1)(b)
45 CFR 46.115(a)(2)
21 CFR 56.115(a)(2)
IRB-GB, (I)(B)
FDA-IS, (CL)(X)
ICH-GCP, (3.4)
OHRP-CFG (G64)
3.A.1. Minutes of IRB meetings contain sufficient detail to show:
      3.A.1.1. Attendance.
      3.A.1.2. Approval of previous meeting minutes.
      3.A.1.3. Actions taken by the IRB at the meeting.
      3.A.1.4. The vote on actions, including the number of members voting for, against, and abstaining.
      3.A.1.4.1. Names of members abstaining.
      3.A.1.4.2. Quorum requirements were met at each recorded vote or for the entire meeting, including circumstances in which members recused themselves due to conflicts of interest.
      3.A.1.4.3. A non-scientific member of the IRB was present during the entire meeting.
3.A.2. When an IRB member has a real or potential conflict of interest relative to the proposal under consideration, the minutes will document that the IRB member did not participate in the deliberations or voting on the proposal and that the quorum was maintained.
3.A.3. Minutes document the basis for requiring changes in or disapproving research and documentation of resolution of these issues when resolution occurs.
Policies and procedures
IRB minutes
IRB communications
R&D Committee minutes
Review of policies and procedures shows evidence of evaluation of requirements for content of IRB minutes
IRB minutes contain required information
IRB communications to investigators, R&D Committee, or other institutional officials document decisions made by the IRB
R&D Committee minutes document acknowledgement of IRB decisions
3.A.4. Minutes document required IRB findings where needed to approve exceptions, waivers, or use of vulnerable populations.
3.A.5. Minutes include a written summary of the discussion of:
      3.A.5.1. Controverted issues and their resolution.
      3.A.5.2. Risk/benefit analysis.
      3.A.5.3. Informed consent.
      3.A.5.4. Risk level of investigational devices.
      3.A.5.5. Additional safeguards to protect vulnerable populations if entered as study subjects.
3.A.6. Minutes reflect results of expedited reviews and the eligibility category serving as justification for meeting expedited review criteria.
3.A.7. Minutes include items approved as exempt from review and documentation of the eligibility category serving as justification for the exemption.
3.A.8. Minutes document the frequency of continuing review of each research project, based upon the degree of risk, as determined by the IRB.
3.A.9. IRB decisions are reported promptly and in writing to the investigator and appropriate institutional officials. In addition, suspensions and terminations are reported to the department or agency head.
3.A.10. IRB minutes are completed in a timely manner and forwarded to the R&D Committee.
3.B. The IRB retains required records for at least 3 years from study completion.
Regulation/Source
38 CFR 16,115(b)
M-3, Part 1, 9.09(g)(2)
45 CFR 46, 115(b)
21 CFR 56.115(b)
IRB-GB, (I)(B)
FDA-IS, (CL)(X)(I)
ICH-GCP (3.4)
3.B.1. Required records are retained for a minimum of 3 years following the completion of the study, in accordance with VHA's Records Control Schedule, applicable FDA and DHHS regulations, or as required by sponsors.
3.B.2. All records shall be accessible for inspection and copying by authorized representatives of VA, including accreditors and appropriate federal departments or agencies, at reasonable times and in a reasonable manner.
3.B.3. IRB records are the property and the responsibility of the local research office and are maintained and/or stored as required to protect the privacy and confidentiality of subjects. Records must be stored in a secure environment (e.g., locking file cabinets).
3.B.4. There must be limited access to the files.
      3.B.4.1. There must be logs or records of access to restricted files, including:
      3.B.4.1.1. Who accessed the files, with the exception of IRB and research office staff;
      3.B.4.1.2. What files were accessed;
      3.B.4.1.3. When the files were accessed;
      3.B.4.1.4. For what purpose the files were accessed.
Policies and procedures
IRB files
IRB coordinator interview
IRB file access log
Review of policies and procedures shows evidence of requirements for record retention and access
IRB files are kept in a secure location
Staff demonstrates filing system to show that files are kept in an organized fashion in a secure location
Review of access log reflects access by appropriate individuals or groups
Additionally, all research proposals and IRB minutes requested for the survey process were available.

Rationale

Institutional Review Boards (IRB) are the administrative bodies established to protect the rights and welfare of human research subjects through prospective and concurrent review of research. IRB structure, composition, and function must be sufficient to allow for thorough and expert review of research to ensure that subjects are adequately protected. This standard contains the requirements for IRB membership and processes to provide adequate supervision of research.

KEY:

CFR = Code of Federal Regulations

M-3, Part 1 = The Veterans Affairs Manual, Chapter 9

IRB-GB = OPRR IRB Guidebook

FDA-IS = FDA Information Sheets

FDA-IS, (CL) = Appendix H: A Self-Evaluation Checklist for IRBs

FDA-IS, (FAQ) = Frequently Asked Questions

FDA-IS, (ICG) = The Guide to Informed Consent

FDA-IS, (CR) = Continuing Review After Study Approval

FDA-IS, (SR/NSR) = Significant Risk and Nonsignificant Risk Medical Device Studies

ICH-GCP = International Conference on Harmonization, Good Clinical Practice Guideline

OHRP-CFG = Office of Human Research Protection Compliance Activities: Common Findings and Guidance 9/1/2000

HHSIGR = HHS Inspector General's Report

From: C, VA Human Research Protection Accreditation Program Draft Accreditation Standards

Cover of Preserving Public Trust
Preserving Public Trust: Accreditation and Human Research Participant Protection Programs.
Institute of Medicine (US) Committee on Assessing the System for Protecting Human Research Subjects.
Washington (DC): National Academies Press (US); 2001.
Copyright © 2001, National Academy of Sciences.

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