Blinding
Item 24c: If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s allocated intervention during the trial.
Example
“We expect the need for emergency unblinding to be relatively rare. Nevertheless, we have the following procedure in case emergency unblinding is required: If unblinding is deemed to be necessary for the intraoperative event of significant safety concerns, the principal investigator will be notified immediately. If the principal investigator considers emergency unblinding necessary, a request will be directed to the responsible anesthesiologist. The requested information and details of emergency unblinding will be recorded in the case report form and well-documented. The actual allocation must not be disclosed to the participant or other trial personnel since the trial is placebo controlled-double-blind ” [370].
“This study defines three unblinding situations: (1) when data entry is completed, (2) when statistical analysis is completed, and (3) when serious adverse events occur. All adverse events will be reported to the data and safety monitoring committee (DSMC), who will decide whether the patient’s participation needs to be discontinued and whether the patient should be unblinded immediately ” [379].
Explanation
Emergency unblinding reveals the assigned intervention of a trial participant, typically when experiencing potential harm of the intervention. It is important that emergency unblinding procedures are constrained to a single participant, and that unblinding of additional participants is avoided (Item 24b). In some cases (e.g., minor, reversible harms), stopping the assigned intervention, and then cautiously re-introducing it, can avoid both unblinding and further harm.
Reviews of two samples of 108 and 292 trial protocols from 2016 found that 81% and 90% addressed the conditions when unblinding was permissible [9, 10].
A clear protocol description of the circumstances and procedures for emergency unblinding helps to prevent unnecessary unblinding, facilitates implementation by trial personnel when indicated, and enables evaluation of the appropriateness of the planned procedures
Summary of key elements to address
For blinded trials:
-
Circumstances under which unblinding is permissible during the trial (e.g., to reduce immediate risk for a participant)
-
Procedure for revealing a participant’s allocated intervention during the trial