New draft guidance ("Draft Guidance") from the U.S. Food and Drug Administration ("FDA") and the Office for Human Research Protections ("OHRP") strongly highlights the need for Institutional Review Boards ("IRBs") overseeing human subject research to keep detailed minutes of their meetings. Doing so, according to the Draft Guidance, will demonstrate to the IRBs' research institutions and to the FDA and OHRP the IRBs' understanding of applicable federal regulations and help those IRBs to keep potential sanctions and/or liability to a minimum.
On November 5, 2015, FDA and OHRP (collectively the "Agencies") issued the Draft Guidance on the best practices for recording the meeting activities of IRBs. The Draft Guidance is intended for institutions and IRBs that are responsible for the review and oversight of human subject research conducted or supported by the U.S. Department of Health and Human Services ("HHS") or regulated by the FDA and is aimed at assisting institutions and IRBs to prepare and maintain IRB minutes that are compliant with FDA and HHS regulations.1
The Draft Guidance emphasizes that keeping adequate and thorough minutes of all IRB activities is important as these minutes serve to provide information to individuals not present at the meeting, including institutional officials and regulators. Minutes must be detailed enough for the Agencies to determine attendance at IRB meetings, actions taken by the IRB, the votes on IRB actions and the basis for requiring any changes in approving or disapproving research, as required by FDA and HHS regulations.
A summary of the Draft Guidance requirements follows. The Agencies are currently seeking public comment from industry stakeholders on the Draft Guidance. The 60-day comment period closes on January 4, 2016. A copy of the Draft Guidance can be found here.
Attendance at IRB Meetings: According to the Draft Guidance, an IRB is responsible for keeping an accurate record of the attendees of each convened meeting of the IRB. For each IRB meeting, the minutes must demonstrate that the required quorum was met and maintained at all times.
Members, Alternates and Guests. In the Draft Guidance, the Agencies recommend that the minutes include the full names of the IRB members present and participating in the meeting and the representative status for each member. The minutes should also document any circumstances in which an alternate member is substituting for a primary member. The minutes must provide the alternate's name and representative status, the name of the primary member for whom the alternate is substituting and the reason for the substitution. The minutes must also provide the names of all guests and non-members.
Quorum. Quorum must be maintained throughout the meeting in order for the IRB to conduct business. If quorum is lost during a meeting, the IRB may not take any further action or vote on proposed research. Because IRB members may occasionally enter or leave the room throughout the meeting, the Draft Guidance recommends that the minutes provide sufficient information to indicate that a quorum is present throughout the duration of the meeting.
Actions Taken by the IRB: According to the Draft Guidance, minutes must be in sufficient detail to show actions taken by the IRB. The Agencies interpret "actions taken by the IRB" to refer to any vote taken by the IRB related to a proposed research activity. The minutes must summarize all research activities being reviewed and document all subsequent actions taken. According to the Agencies, "the minutes should serve as a central repository for IRB decisions on proposed research activities."
Approve, Require Modifications to Secure Approval, Disapprove. The minutes should show that the IRB made all the findings and determinations required for approval under the regulations. If a proposed research activity is conditionally approved, the minutes should state the process to be followed to ensure the conditions are met. The minutes should also identify the effective date of approval and the length of the approval period. Finally, the IRB must determine and document which study protocols require continuing review more often than annually.
Suspension or Termination of IRB Approval. Any IRB action to suspend or terminate IRB approval that occurs at a convened meeting must be summarized in the minutes along with the reasons for the IRB's actions and any follow-up action items. Any decision to suspend or terminate IRB approval that occurs outside of a convened meeting should be reported to the convened IRB and the discussion summarized in the minutes.
Other IRB Regulatory Determinations and Review Responsibilities. The Draft Guidance emphasizes that the IRB meeting minutes should summarize the IRB's consideration of all approval criteria required for a research study and should include a determination as to whether such criteria were met. This is especially important for research on vulnerable populations, including prisoners, pregnant women and fetuses, children and emergency research.
With regards to informed consent, it should be indicated that the IRB reviewed the informed consent form and found it in compliance with applicable regulations. The minutes must also summarize any changes to the informed consent forms required by the IRB. If at any time the IRB approves a waiver of the regulatory informed consent requirements, this should be documented along with protocol-specific information justifying the IRB's decision.
For FDA regulated research involving an investigational medical device, the IRB must make an independent determination of whether the device study is significant risk ("SR") or nonsignificant risk ("NSR") by reviewing relevant information provided by the study sponsor. Because the FDA considers this determination to be part of the IRB's responsibilities for conducting its initial review of a study, the FDA recommends that the IRB document each SR/NSR determination in the minutes.
Finally, when a report of expedited review actions is presented during a convened IRB meeting, the minutes should describe what was presented to the IRB, indicate that the IRB members had an opportunity to ask questions or raise concerns and summarize the questions or concerns, if any, raised by the IRB members.
The Vote on IRB Action: The minutes of IRB meetings must be detailed enough to show the vote on IRB actions, including the number of members voting for, against and abstaining; the names of IRB members need not accompany the voting record. The Draft Guidance provides the following example as an acceptable documentation of the voting record:
Total Voting = 15, Vote: For = 14, Opposed = 0, Abstained = 1
Members with a conflict of interest should be identified in the minutes and reflected in the vote count as "Recused." Members who are recused from voting on a specific study because of conflicting interests may not be counted toward the quorum (i.e., a recusal may not be counted as an abstention).
Requiring Changes or Disapproving Research: The Draft Guidance provides that minutes of IRB meetings must be sufficient in detail to show the basis for requiring changes in approving or disapproving research. If an investigator is required to make changes to the research protocol or informed consent documents and to resubmit such documents to the convened IRB for subsequent review, these IRB decisions must be documented in the minutes. If the IRB disapproves of a research activity, the minutes should summarize the IRB's discussion and deliberations for its decision to disapprove proposed research and clearly indicate the IRB's reasoning for disapproval.
Controverted Issues and Their Resolution: For issues that cause controversy and dispute among IRB members, the minutes must summarize the IRB's discussion and plans for seeking resolution if resolution is not reached during a convened meeting. When resolution of a controverted issue is reached, the minutes must summarize the IRB's discussion and how they were resolved. If there were no controverted issues, this should also be noted in the minutes.
The Agencies recommend that institutions and IRBs decide who is responsible for preparing and maintaining minutes and outline the process in the IRB's written procedures. Institutions and IRBs may consider creating a standard template to assist in the preparation of their minutes. The Agencies also note that while recordings of IRB meetings are acceptable to help in the preparation of meeting minutes, this does not relieve the IRB of its obligation to keep written minutes in accordance with regulatory requirements.
Meeting minutes must be retained for at least three years after completion of the reviewed research and must be accessible for inspection and copying by authorized representatives of the Agencies. It is important to understand that IRB minutes from meetings during which multiple studies were reviewed must be retained until all of the studies that were reviewed at that meeting have been completed for at least three years.
The Draft Guidance emphasizes that failing to prepare and maintain adequate minutes could result in IRBs being cited in OHRP determination letters and FDA warning letters. Continued noncompliance can eventually lead to debarment from participation in research or even civil monetary penalties. Examples of noncompliance related to minutes include:
- Missing minutes;
- Minutes lacking sufficient detail to show the vote on actions taken by the IRB, including the number of members voting for, against and abstaining;
- Minutes that are incomplete and only describe voting actions as "passed unanimously";
- Minutes that do not clearly indicate, or contain discrepancies about, what the IRB approved;
- The IRB maintains multiple sets of minutes with different information for the same meeting; and
- Minutes fail to include a summary of the discussion of controverted issues.
The Draft Guidance makes clear that the Agencies and their representatives will review IRB minutes and other appropriate IRB records very closely to assess compliance with all applicable regulations. Therefore, it is recommended that institutions and IRBs begin to review their procedures in anticipation of the release of final guidance to ensure that their documentation includes the required elements and a sufficient level of detail.