Make sure you address all stipulations or clarifications requested by the IRB
Failing to do so will get the review item returned to the Investigator for the item to be addressed.
Deferred vs. Modifications to Secure Approval
Federal regulations and OHSP Policy 402: RSRB Meetings give Institutional Review Boards (IRBs) the authority to:
- Approve submissions as submitted;
- Approve submissions with modifications required (also referred to as ‘approved with stipulations’ and ‘modifications to secure approval’);
- Defer submissions (also referred to as ‘table’); or
- Disapprove submissions.
Often, when the boards require modifications to the research, study teams fail to understand the implications for a review item that is approved with modifications required versus one that is deferred.
Approved with modifications required
A review item that is ‘approved with modifications required’ means that the IRB determined that the criteria for approval, as defined by 45 CFR 46.111 and OHSP Policy 404: Criteria for Approval of Research, will be met provided the study team:
- Makes minor changes specifically requested by the convened board to the review item; or
- Confirms specific assumptions made by the convened board regarding how the research will be conducted.
Examples of modifications that might be required to secure approval include:
- Confirming that routine MRI screening procedures will be conducted;
- Requiring editorial revisions to the consent document(s); and/or
- Requesting documentation that confirms the 30 day IND (Investigational New Drug) waiting period has passed without any clinical holds.
Once the study team makes the specific revisions requested by the board, the board chair or their designee is able to approve the research on behalf of the convened board without the item having to go back to the convened board for review.
Revisions made to the research that go beyond simply concurring with the board’s request require re-review by the convened board.
For example, a new study may be approved with the stipulation that the subject payment information in the consent document be updated to be consistent with the study protocol. After the Investigator makes this simple revision, the board chair can review the revision to confirm it meets the board’s original request, and approve the research. On the other hand, if the Investigator makes further changes to the subject payment schedule (e.g., modifying how much subjects are paid and when), the submission would require re-review by the convened board at a subsequent meeting.
Deferred research
Anytime the board is unable to make a determination about whether a review item satisfies all the criteria for IRB approval, the review of the item will be deferred (tabled) to a future board meeting pending the resolution of substantive issues. Unlike approving a review item with modifications required, deferring an item generally means that:
- Not enough information was included in the initial submission, modification or continuing review for the board to understand how the research will be conducted (therefore confirming an assumption is not possible);
- The changes required by the board in order for the item to meet the criteria for approval are substantial; or
- There are so many inconsistencies between the review materials that the board is unsure of what the research involves.
Examples of clarifications that might defer a review item include:
- Clarifying how and when data and safety monitoring will occur;
- Identifying study procedures that the control group will undergo; and/or
- Requiring an additional consent or assent form be created.
All studies that are deferred by an IRB require re-review by the convened board at a subsequent meeting.
Avoiding unnecessary pitfalls
Any time the IRB requests modifications or clarifications to research (meaning, the review item was either approved with modifications required or it was deferred), keep the following points in mind:
When appropriate, provide written responses to the IRB to clarify where, how and why changes were made.
This is particularly important when:
a) modifications beyond those requested by the board are made to research that has been approved with modification; or
b) the Investigator disagrees with a modification requested by the board.
Plan for plenty of review time
Modifications that require re-review by the convened board can take 2–8 weeks to review, depending on board scheduling and workload.
If a tracked document (e.g., consent form) is provided by the board, review it the revisions; do not blindly accept the board’s revisions.
While tracked documents are provided as a courtesy to ease the review process, it is the Investigator’s responsibility to review the revisions to ensure they are accurate and complete. Board comments and/or questions included in tracked documents must be addressed prior to re-submission.