Source: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/minutes-institutional-review-board-irb-meetings
Timestamp: 2020-02-17 04:48:48
Document Index: 2737887

Matched Legal Cases: ['art 46', 'arts 50', 'art 46', 'art 50', 'art 46', 'art 56', 'art 46']

Minutes of Institutional Review Board (IRB) Meetings | FDA
Minutes of Institutional Review Board (IRB) Meetings Guidance for Institutions and IRBs September 2017
FDA-2015-D-3638
OHRP's and FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe OHRP's and FDA's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word must in joint OHRP and FDA guidance means that something is required under the HHS regulations at 45 CFR part 46 or the FDA regulations at 21 CFR parts 50 and 56. The use of the word should in joint OHRP and FDA guidance means that something is recommended or suggested, but not required.
IRBs have been cited in OHRP Determination Letters1 and FDA Warning Letters2 for failing to prepare and maintain adequate minutes. For this reason, OHRP and FDA believe providing recommendations on the type and amount of information to include in minutes will help IRBs meet the regulatory requirements for minutes.
Minutes are incomplete and only describe voting actions as "passed unanimously."
When reviewing proposed research, the IRB must document the information required by 45 CFR 46.115(a)(2) and 21 CFR 56.115(a)(2) in the minutes. However, there are other findings and determinations the IRB must make to fulfill other regulatory requirements (e.g., the IRB must review research involving children as subjects that is covered by 45 CFR part 46, subpart D and/or 21 CFR part 50, subpart D, and approve such research only if it satisfies the conditions of all applicable sections of those subparts). While we recommend that IRBs document these additional findings and determinations in the minutes, these can be documented elsewhere in the IRB records to avoid redundancy (e.g., IRB reviewer form/checklist, database entries, other forms of physical or electronic records). Documentation should include relevant summary information when such information contributes to an understanding of the IRB's findings and determinations (e.g., a brief rationale for the IRB's pediatric risk determination).
IRBs may invite consultants to assist in the review of a particular study when expertise is required beyond or in addition to that available on the IRB (45 CFR 46.107(f); 21 CFR 56.107(f)). If the IRB uses a consultant and the consultant is present at the convened meeting, the minutes must include the name of the consultant (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)), and should include a brief description of the consultant's expertise. In accordance with 45 CFR 46.107(f) and 21 CFR 56.107(f), the consultant may not vote with the IRB on the study.
The institution and the IRB may establish written procedures covering the use of alternate members, the use of consultants, and attendance of non-members and guests at a convened meeting. Such written procedures may help to ensure that those who attend an IRB meeting understand their role, and to promote respect for the IRB's advice and counsel in safeguarding the rights and welfare of human subjects.
IRBs often calculate majority by using the "half-plus-one" technique. This technique works well for IRBs with an even number of IRB members. For example, if the total IRB membership is 10, then the majority is 6 (half of 10 is 5, plus 1 equals 6). However, if the IRB has an odd number of members, then the majority should be calculated by taking half of the total number of IRB members, and rounding up to the next whole number. For example, if the IRB membership is 15, then majority is 8 (half of 15 is 7.5, and rounding up to the next whole number is 8)3 .
The minutes of IRB meetings must be in sufficient detail to show the actions taken by the IRB at the convened meeting (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)). OHRP and FDA interpret "actions taken by the IRB" (also called "IRB actions") to refer to any vote taken by the IRB related to a proposed research activity. Accordingly, to be in sufficient detail to show actions taken by the IRB, the minutes must provide sufficient information to identify the research activities being reviewed and voted on by the IRB at that meeting (e.g., initial review of protocol title/protocol number). The minutes should serve as a central repository for IRB actions on proposed research activities.
OHRP and FDA regulations require that an IRB review and have the authority to approve, require modifications in (to secure approval), or disapprove all proposed research activities covered by the regulations (45 CFR 46.109(a); 21 CFR 56.109(a)). Any IRB action to approve, require modifications in (to secure approval), or disapprove proposed research activities that occurs at a convened meeting must be documented in the minutes (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)). Additionally, the IRB or institution may develop a range of other allowable actions the IRB may take when reviewing proposed research activities (e.g., approve with conditions4 , defer a decision until additional information can be obtained). The IRB's written procedures should describe the range of possible actions the IRB can take.
The minutes must be in sufficient detail to show the actions taken by the IRB at the convened meeting (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)). In order to approve research covered by the regulations in 45 CFR part 46 and/or 21 CFR part 56, the IRB must determine that all of the criteria for IRB approval of research are satisfied (45 CFR 46.111; 21 CFR 56.111). We recommend that the minutes, or other IRB record (e.g., correspondence with the investigator), identify the effective date of approval and the approval period (continuing review interval) for any research approved by the IRB. IRBs must determine which projects require review more often than annually (45 CFR 46.103(b)(4)(ii); 21 CFR 56.108(a)(2)). Both OHRP and FDA have issued guidance on continuing review of research to assist the IRB in determining the effective date of the initial approval and the subsequent date of continuing review.5
Both OHRP and FDA regulations authorize an IRB to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects (45 CFR 46.113; 21 CFR 56.113). Any IRB action to suspend or terminate IRB approval that occurs at a convened meeting must be documented in the minutes (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)). Any suspension or termination of approval must include a statement of the reasons for the IRB's action (45 CFR 46.113; 21 CFR 56.113). Any decision to suspend or terminate the study that occurs outside of a convened IRB meeting (e.g., as determined by the IRB Chair or Institutional Official for subject safety reasons) should be reported to the convened IRB and the discussion summarized in the minutes. Any subsequent action taken by the convened IRB (e.g., to lift the suspension or to terminate the study) must be documented in the minutes (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)).
As previously mentioned, in addition to the findings and determinations the IRB must make and document in the minutes (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)), there are other findings and determinations the IRB must make to fulfill other regulatory requirements. While we recommend that IRBs document these additional findings and determinations in the minutes, these can be documented elsewhere in the IRB records to avoid redundancy (e.g., IRB reviewer form/checklist, database entries, other forms of physical or electronic records). Again, we recommend that documentation include relevant summary information when such information contributes to an understanding of the IRB's findings and determinations.
In order to approve research, the IRB must determine that all of the criteria for IRB approval of research are satisfied (45 CFR 46.111; 21 CFR 56.111). The process the IRB follows for considering the approval criteria should be addressed in the IRB's written procedures. The IRB's consideration of these criteria applies to both initial review and continuing review of research and provides the framework for the IRB's evaluation of research. The minutes must document actions taken by the IRB (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)).
In order to approve a study, the IRB must determine that informed consent will be sought from each prospective subject or the subject's legally authorized representative (LAR) in accordance with the regulations (45 CFR 46.111(a)(4); 21 CFR 56.111(a)(4)). The IRB must also determine that informed consent will be appropriately documented in accordance with the regulations (45 CFR 46.111(a)(5); 21 CFR 56.111(a)(5)). The minutes should indicate that, as part of its review and approval of a study, the IRB reviewed the informed consent form(s) and determined that the form(s) meet the applicable regulatory requirements.6
Both OHRP and FDA regulations permit an IRB to waive the requirement that the subject or the subject's LAR sign a written consent form if the IRB determines that certain criteria are met (45 CFR 46.117(c); 21 CFR 56.109(c) and (d)). We recommend that any such waiver of documentation of informed consent be documented in the minutes or other IRB record.
In addition, for HHS-conducted or -supported research, the regulations at 45 CFR 46.116(c) and (d) permit an IRB to approve a consent procedure that does not include, or which alters, some or all of the elements of informed consent, or waive the requirement to obtain informed consent provided the IRB finds and documents that certain criteria are met.7 When an IRB approves a waiver or alteration of consent for research reviewed by the convened IRB, these findings must be documented (45 CFR 46.116(c) and (d)). OHRP recommends that IRB decisions for waiver or alteration of consent be documented in the minutes or other IRB record.
In its review of proposed research involving children, the IRB must find that the research meets the conditions of 45 CFR 46.404 and/or 21 CFR 50.51 (research/clinical investigations not involving greater than minimal risk); 45 CFR 46.405 and/or 21 CFR 50.52 (research/clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects); or 45 CFR 46.406 and/or 21 CFR 50.53 (research/clinical investigations involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subjects' disorder or condition). If the IRB determines that the proposed research cannot be approved under these categories, then additional regulatory requirements under 45 CFR 46.407 and/or 21 CFR 50.54 (research/clinical investigations not otherwise approvable that present an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children) must be met. Both OHRP and FDA have issued guidance to assist IRBs with handling clinical investigations that include children as subjects and that have been referred under 45 CFR 46.407 or 21 CFR 50.54.8
OHRP and FDA recommend that the IRB's findings and determinations for studies involving children be documented in the minutes.
If the IRB reviews a proposal for research involving an exception from informed consent requirements for emergency research, the IRB must find and document that the proposed research satisfies the criteria found in OHRP's Secretarial Waiver9 and/or FDA's regulations at 21 CFR 50.24.
FDA has issued guidance on the exception from informed consent requirements for emergency research.10 As outlined in FDA's guidance, FDA anticipates that an emergency research study in which informed consent is not obtained for all subjects is, by its very nature, controversial. Therefore, IRBs must summarize their discussions and decisions about the required elements for these studies in the minutes (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)).
Unless FDA has already made a risk determination for a device study (e.g., significant risk (SR), or nonsignificant risk (NSR)), or the study is exempt in accordance with 21 CFR 812.2(c), sponsors are responsible for making the initial risk determination and presenting it to the IRB. In that case, the IRB must then make its own SR/NSR determination about the study, and either agree or disagree with the sponsor's determination by reviewing relevant information provided by the sponsor at a convened meeting (21 CFR 56.108(a)(1); 21 CFR 812.66). FDA considers this determination to be part of the IRB's responsibilities for conducting its initial review of a study. FDA recommends that the IRB document each SR/NSR determination, along with the reason for the determination, in the minutes.
IRBs should be aware that FDA regulations do not require specific findings for research involving prisoners as subjects. If an IRB reviews an FDA-regulated study that is not HHS-conducted or -supported research, and the study is expected to involve prisoners as subjects, IRBs may find 45 CFR part 46, subpart C, and OHRP's guidance on prisoners in research11 to be helpful.
If at a convened meeting, the IRB reviews an issue that requires prompt reporting to the IRB under 45 CFR 46.103(b)(5) or 21 CFR 56.108(b) (e.g., an unanticipated problem involving risk to human subjects or others), the minutes should summarize the report and must document the IRB's action, if any, resulting from that review (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)). Any review of such information and any decisions made outside of a convened meeting (e.g., as determined by the IRB Chair or Institutional Official for subject safety reasons) should be reported to the convened IRB and the discussion summarized in the minutes. Any subsequent action taken by the convened IRB (e.g., to lift suspension or to terminate the study) must be documented in the minutes (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)).
The minutes should identify any member who has a conflicting interest in a research study, and as such, is excluded (recused) from participation in the IRB's review of that particular research including the reason for the recusal. As shown in the examples above, the minutes of the meeting must reflect a vote count (i.e., for, against, and abstaining) that is consistent with the number of non-conflicted IRB members present (45 CFR 46.107(e); 21 CFR 56.107(e); 45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)).
If the IRB requires that the investigator make specified changes to the research protocol or informed consent document(s) and resubmit such documents to the convened IRB for subsequent review, the IRB's action, along with the basis for requiring changes must be documented in the minutes (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)).
If the IRB disapproves a research activity, the IRB must include a statement of the reasons for its decision in the written notification to the investigator and the institution, and provide the investigator an opportunity to respond in person or in writing (45 CFR 46.109(d); 21 CFR 56.109(e)). The minutes must document the IRB's action along with the basis for disapproving the research (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)).
IRB members may resolve controverted issues and concerns with continued discussion and deliberation, decide to seek further clarification from the investigator or sponsor of the proposed research, or decide to settle the issue by vote. The minutes must summarize the IRB's discussion and resolution of any controverted issues (45 CFR 46.115(a)(2); 21 CFR 56.115(a)(2)).
We recommend that institutions and IRBs decide who is responsible for preparing and maintaining minutes at their institutions and outline the process in the IRB's written procedures. While there is no regulatory requirement for IRBs to approve or accept minutes of IRB meetings, if the institution and IRB choose to adopt a process for review and approval/acceptance of minutes, this process should be covered in the IRB's written procedures. Institutions and IRBs may consider creating a standard template to assist in the preparation of their minutes.
OHRP and FDA recognize that in addition to documenting the IRB's findings and determinations in the minutes, or elsewhere in the IRB records, IRBs may also choose to document other activities that occur during the meeting. For example, some IRBs provide continuing education and training to the IRB members at a convened meeting and document such training in the minutes. IRBs may also communicate announcements or other information to the IRB members and attendees at the meeting and document this in the minutes (e.g., upcoming meeting schedule, staff or membership changes). This practice is acceptable to OHRP and FDA.
IRBs may choose to record IRB meetings (e.g., video, audio tape) and use the recording as a tool to assist in the preparation of written minutes.12 However, retention of complete recordings of meetings is not required nor does it relieve an IRB of its obligation to keep written minutes in accordance with the requirements of 45 CFR 46.115(a)(2) and 21 CFR 56.115(a)(2). We do not expect the minutes to include a verbatim transcription of what each member said during the course of the meeting.
This guidance represents the Office for Human Research Protections' (OHRP's) and the Food and Drug Administration's (FDA's) current thinking on this topic. This guidance does not create or confer any rights for or on any person and does not operate to bind OHRP, FDA, or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the appropriate OHRP or FDA staff responsible for implementing this guidance. If you cannot identify the appropriate OHRP or FDA staff, call the appropriate number listedbelow.
OHRP Guidance, Alphabetical List
1. OHRP Determination Letters are posted on the HHS.gov website and can be viewed by the date issued.
2. FDA Warning Letters are posted on the FDA.gov website and can be viewed via multiple browsing options (e.g., by date, by company, by subject).
3. Note that the regulations do not prohibit IRBs from having more stringent requirements for quorum.
4. OHRP's Guidance on IRB Approval of Research with Conditions can be found at Approval of Research With Conditions: OHRP Guidance (2010); FDA's Guidance on IRB Continuing Review after Clinical Investigation Approval can be found at Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Continuing Review after Clinical Investigation Approval.
5. OHRP's Guidance on Continuing Review can be found at Continuing Review Guidance (2010); FDA's Guidance on IRB Continuing Review after Clinical Investigation Approval can be found at Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Continuing Review after Clinical Investigation Approval.
6. See 45 CFR 46.116, 45 CFR 46.117, 21 CFR 50.20, 21 CFR 50.25 and 21 CFR 50.27.
7. On December 13, 2016, the President signed the 21st Century Cures Act (P.L. 114-255) into law. Title III, section 3024 of the 21st Century Cures Act amended sections 520(g)(3) and 505(i)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) to provide FDA with the authority to permit an exception from informed consent when the proposed clinical testing poses no more than minimal risk to the human subject and includes appropriate safeguards to protect the rights, safety, and welfare of the human subjects. FDA intends to promulgate regulations to permit this exception and to specify appropriate human subject protection safeguards. FDA issued guidance in July 2017 for sponsors, investigators, and IRBs on enforcement of FDA regulations governing informed consent requirements for clinical investigations that involve no more than minimal risk to human subjects – see IRB Waiver or Alteration of Informed Consent for Clinical Investigations Involving No More Than Minimal Risk to Human Subjects.
8. OHRP's guidance on Children as Research Subjects and the HHS "407" Process can be found at Children as Research Subjects and the HHS "407" Process; FDA's guidance on the Process for Handling Referrals to FDA Under 21 CFR 50.54, Additional Safeguards for Children in Clinical Investigations can be found at Guidance for Clinical Investigators, Institutional Review Boards and Sponsors: Process for Handling Referrals to FDA Under 21 CFR 50.54, Additional Safeguards for Children in Clinical Investigations.
9. Information about OHRP's Informed Consent Requirements in Emergency Research can be found at Informed Consent Requirements in Emergency Research (OPRR Letter, 1996)
10. FDA's guidance on the Exception from Informed Consent Requirements for Emergency Research can be found at Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Exception from Informed Consent Requirements for Emergency Research.
11. OHRP's guidance on Prisoner Involvement in Research can be found at Prisoner Involvement in Research (2003), and the Prisoner Research FAQs can be found at Prisoner Research FAQs.
12. Institutions and IRBs should ensure recording is permitted by institutional policy and, if applicable, state law. All members, and any others attending the meeting, should be informed that the meeting is being recorded and how the recording(s) will be used.
All written comments should be identified with this document's docket number: FDA-2015-D-3638.