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Unblinding

Blinding is used in the design of some clinical trials and other research studies to try to eliminate the bias of expectation influencing the research findings.

Unblinding, sometimes referred to as code-break, is the process by which the treatment/allocation details are made available either purposefully (i.e according to the code-break procedures) or accidently.

Risks associated with retaining the blind should be considered in the initial /bespoke risk assessment with plans on how risks will be mitigated in the study-specific monitoring plan.

Blinding /unblinding procedures should be clearly documented in the protocol, study specific standard operating procedures or study manual. Sites should be trained in the study specific unbinding procedures at site initiation.

Definition of a blind trial

A blind trial is a trial where the participants do not know which treatment/intervention they have been allocated.

A double blind trial is a trial where neither the researchers nor the participants know which treatment/intervention they have been allocated. 

Maintaining the blind

When designing a blinded trial is important to consider how blinding will be maintained (centrally by the study team and locally at sites).

The responsibilities and procedures for the production, dissemination and location of the randomisation schedule (electronic and paper versions) should be documented the Study/Trial Master File (S/TMF)

For double blind trials where the study team are to retain blindness, the master randomisation schedule/ records should be retained separately (under the care of the person delegated  responsible – often the trial statistician) to the rest of the trial documentation until the end of trial when they should be placed in the Study/Trial Master File (S/TMF).   A file note should be placed on file to detail the location of the master randomisation schedule until the end of the trial. An audit trail should be available to support/track the dissemination and location of the randomisation schedule.

Procedures for unblinding

Unblinding procedures should be documented either in the protocol or in supporting study documentation (such as study specific standard operating procedures or study manual).  These procedures should include :

  • details of where code break details are located and their security (who has/should have access to codes)
  • the process for emergency (and out of hours) contact and unblinding at site ( where possible the trial team should not be informed).  This may be via code break envelopes with restricted access to dedicated unblinded personnel at sites or via a centralised code break system
  • where dedicated unblinded personnel are to be used at site they should be trained and delegated responsibility to perform unblinding activities on the delegation log
  • unblinding process for IDMCs for interim data analysis/safety monitoring should be documented
  • the formal process for unblinding at the end of the trial for data analysis (when, how and who)

Whatever system is used for out-of-hours contact and emergency unblinding at site it should be tested periodically to ensure that it works as intended. Any tests should be documented in the Investigator Site File (ISF).

An audit trail should be available at site pertaining to any code breaks carried out during the trial (as per the study specific procedures as to where the unblinded information should be documented and reported).