Question
How do primary investigators (PIs) report promptly reportable information (PRI) in a blinded* study? How can they report unblinded information without unblinding themselves?
*While in ophthalmology studies the term “masked” is used, blinded will be used here as it is the most commonly used terminology.
Answer
For WCG’s Institutional Review Board (IRB), reporting protocol deviations are required if the deviation harmed a participant or placed a participant at risk of harm. You can review our list of events that require reporting, when disclosing through our portal, on our Promptly Reportable Information Form (HRP-204) or in our Guide for Researchers.
When reporting PRI in a blinded study, there are two issues to consider:
- Unblinding the participant to see the randomization, e.g., whether they were assigned a placebo or the investigational product (IP).
- Unblinding a blinded clinical study team member as a result of reporting the participant’s clinical information as a PRI.
For the first issue, WCG’s IRB doesn’t require universal unblinded reporting. In most cases, sufficient information is available without unblinding to allow the IRB to determine if the issue requires further follow up and action. If insufficient information is provided, we will follow up and ask for specifics. If unblinding is required, we will request that information with a rationale. For example, if an overdose occurs, unblinding is not necessary for reporting as the issue is the overdose. Overdosing is a problem because it’s the process that led to the overdose that is the risk. In this case, the most important information to provide is the Corrective and Preventive Action (CAPA) plan that identify and address the root causes of noncompliance and prevent future occurrences.
Unblinding the participant to manage an adverse event would only be necessary if the clinical information is required for corrective actions to address the immediate problem. If the participant or staff were unblinded, WCG’s IRB would need to be informed of this.
Out of respect for persons and to encourage trust through transparency in research, we believe it is important to inform participants about research errors. That does not require you to unblind to inform the participant. For example, if the site is aware that a participant in a double-blind, randomized study received the IP that was intended for another participant, unblinding isn’t necessary to tell the participant that they received the study drug intended for another participant. Instead, inform them of the importance of blinding to address the reason for not providing more detail.
For the second point, the issue is unblinding blinded study staff. This could occur either because of a blinded study team member being unblinded or unblinding themselves, or this could be due to the reporting of an event where the details or data included in the report could unblind a staff member. In the case where a staff member is unblinded, the act of unblinding them wouldn’t have to be reported unless the unblinding put a participant at risk or met one of the other reportable categories. If in doubt, the event can be reported that a blinded study staff was unblinded, without the specific data that would unblind others.
In the case where the reporting of the event details might unblind staff, this is best managed through reporting events in a way that doesn’t include the specifics which would unblind. There are very few and limited circumstances in which the site or sponsor would need to report an event to the IRB that would unblind the site where the site wasn’t already needing to be unblinded.
In either situation, good communication with the IRB is important. If you have any questions, please don’t hesitate to contact us. Our experts are always ready to assist you with your questions. Whether you have additional questions about reporting PRI in a blinded study or other IRB inquiries, our team is here to provide the guidance you need. Submit your questions to our IRB experts here.