Put 'painful details' into IRB documentation, experts say

Meeting minutes can be weak spot

IRBs often do a good, or at least adequate, job of maintaining required documentation for studies they review, but there are several key documentation areas in which many IRBs need to improve, according to experts.

Two of these involve communication with clinical investigators and clinical research staff and preparing minutes of IRB meetings, says Jean Toth-Allen, PhD, biophysicist in the Office of Good Clinical Practice, Office of the Commissioner, Food and Drug Administration (FDA) in Silver Springs, MD.

"The minutes are a window into how an IRB functions," Toth-Allen says.

IRBs also need to maintain thoroughly documented policies and procedures, suggests Glen D. Drew, MS, JD, health policy analyst with the Office for Human Research Protections (OHRP) in Rockville, MD.

"The policies and procedures are the guidebook, map, and owners' operating manual for the IRB," Drew says.

"'Painful detail' is the phrase we use," Drew says. "Having things spelled out reduces the uncertainty of what to do in any given situation. It promotes fairness, reduces uncertainty, and allows transparency so investigators can see the policies and procedures and know what the rules are."

Toth-Allen and Drew offer these suggestions for how IRBs can improve their documentation from prior to when an IRB meets to review a protocol to after the decision is made:

• Make communication with research staff more precise and clear: IRBs are required to notify investigators in writing about their decision to approve or disapprove a research protocol, and they should outline the modifications necessary for approval. Or, when the study is declined, the IRB must include a rationale and give the investigator an opportunity to respond.

The most essential detail in communications with research staff is the date of the IRB's approval of a protocol. This is the date from which the protocol's continuing review is set, Toth-Allen says.

For studies with high risk, IRBs might choose to hold a continuing review at a shorter interval than one year. If this is the case, communication with research staff should make it clear when the continuing review will be held, she adds.

"Also, tell investigators what the principal investigator's responsibilities are," she says. "The more the IRB can put in writing what is expected from the investigator, the better."

Here are examples of other items that need to be included in investigator communications:

– Describe what the investigator should send to the IRB between continuing reviews,

– Identify the date and precise copy of the approved informed consent document,

– List continuing review conditions,

– Explain what it is the IRB wants the investigator to do next,

– Reiterate the regulations that apply to this particular study.

• Write policies and procedures (P&Ps) that provide transparency for regulatory auditors, IRB staff, and researchers: Investigators should be able to look at the policies and procedures and understand what the rules are and how communications between the IRB and research staff will be handled.

"The policies and procedures are living documents," Drew says. "If you encounter a situation that's not described in your P&Ps, then the IRB can create a new P&P that will ensure the situation is handled the same way in the future."

Or if the research institution made a mistake, the P&Ps will outline how future actions will prevent this error.

Here are some examples of items to include in the P&Ps:

– How the IRB appoints members,

– Information the IRB needs from researchers,

– Development of submission forms,

– Policies on how submissions are handled and who receives these,

– How to log in protocol submissions,

– Roles of IRB staff and their authority with regard to sending submissions back to investigators,

– How reviews are assigned – whether they are rotated or whether there's a primary reviewer system,

– Defining the meeting schedule for the committee,

– Describing what is done if there's a need for an ad hoc or emergency meeting about a study,

– Outlining how the institution handles and conducts IRB meetings,

– Show what type of vote is required, how the quorum might be comprised, and whether it's a simple majority needed to approve a protocol or some other proportion,

– Explain when it is permissible for IRB members to abstain from voting,

– Address whether the IRB chair votes or breaks tie votes or has no votes,

– When consultants are used and how they're hired and paid,

– Set policy on whether investigators are invited or allowed in meetings,

– How IRB handles continuing reviews and notifying investigators of such reviews,

– How it is handled if studies fail to apply for a continuing review,

– Giving a description of the types of conflicts of interest that would result in an IRB member recusing himself/herself from voting.

"What does an IRB consider a conflict of interest?" Drew says. "It's good to have the policies and procedures define what would constitute a conflict of interest."

The P&Ps should include details about financial conflicts of interest, professional COIs, and fraternal COIs.

"If you're a drinking buddy of the investigator, do you have a conflict?" Drew asks. "There are some issues that can be hard to define because if you define conflicts of interest too expansively, you won't have any members on your committee."

• Put explanations and detailed discussions in IRB meeting minutes: Unfortunately, FDA auditors sometimes find that IRB meeting minutes lack some essential details, Toth-Allen says.

For example, IRB meeting minutes from the review of a study involving a vulnerable population might not even mention that the study has a vulnerable population, she adds.

"If a study involves children, they have to record in their minutes how they looked at various required aspects during the review," Toth-Allen explains. "They should not just say, 'We reviewed it and approved it.'"

"If a sponsor thinks their device study presents a nonsignificant risk to subjects, then the sponsor is not required to send an application for the IDE to the FDA, but the sponsor still needs IRB approval," Toth-Allen says.

"It is therefore essential that meeting minutes include a summary of the IRB's discussion regarding the risk of any device study submitted to it by the sponsor as a non-significant risk study," she explains. "If the IRB agrees it presents a non-significant risk and approves the study, it is considered to have an IDE [investigational device exemption]."

When the IRB agrees with the sponsor that the study poses nonsignificant risk, the sponsor can proceed with the IDE based on the IRB's approval of the study.

"It's very important the IRB makes the correct decision and then say why they made it," Toth-Allen says. "We've found that many IRBs don't know how to make a decision about the device study's risk, and we've tried to educate them about it."

Other details that should be spelled out in the meeting minutes are as follows:

– Attendance,

– IRB actions,

– Votes, including the number of people who voted for, against, and who abstained,

– Listing IRB members who did not participate because of conflicts of interest,

– Details about why changes were required or research was not approved,

– A summary of the meeting's discussion of any controverted issues and how these were resolved,

– Waiver of informed consent and other IC issues,

– Discussion of a study's population, specifying any vulnerable population issues.

IRBs also should take certain actions to ensure all of their documentation are protected and adequately stored.

"Make sure your system is protected and your documentation is accessible," Toth-Allen says. "Documents need to be in place, and IRBs could very well be inspected by the FDA or OHRP."