What is it? Why is it important?

Emergency unblinding (EUB) is the act of revealing the blinded intervention of a participant during study conduct. This might become necessary in order to ensure participant safety including any required clinical management.

For EUB procedures:

  • Indicate emergency circumstances that necessitate an EUB
  • Define a system that allows for ongoing 24hr EUB (e.g. by phone, scratch cards, sealed envelope, IVRS)
  • Allow for rapid identification of participant treatment (e.g. intervention of placebo)
  • Allow for unblinding procedures in unexpected circumstances (e.g. electronic system with access to treatment allocation is out of order)
  • Describe how to document EUBs
  • Define how the Site-INV informs the SP-INV
  • Guarantee that blinding is maintained for all other study participants
  • Describe conditions where after EUB a participant can remain in the study (e.g. unblinding is not necessarily a reason for study drug discontinuation)

More

Circumstances that might necessitate an EUB can include:

  • Treatment of an AE
  • Occurrence of a SUSAR
  • A child has accidently ingested the IMP in a participant household
  • A request by the DSMB based on study-risk assessment

What do I need to do?

As a SP-INV of a blinded study:

  • Describe EUN procedures in an SOP or WI
  • Train Site-INV on EUB procedures, including how to document an EUN (e.g. EUN date, time, reason, result, name and role of the person requesting an EUN, name of the blind breaker) and how to notify the SP-INV
  • Define other circumstances where unblinding is allowed (premature study termination, interim analysis, statistical analysis at study end)

As a Site-INV:

  • Once during study conduct, document and notify the SP-INV regarding any cases of premature unblinding (e.g. both accidental or cases performed as per procedure)

To maintain the overall quality and legitimacy of the study, EUB should only occur under exceptional circumstances.

Where can I get help?

Your local CTU can support you with experienced staff regarding this topic

References

ICH GCP E6(R2) – see in particular guideline

  • 4.7 Randomization procedures and unblinding
Abbreviations
  • AE – Adverse Event
  • CTU – Clinical Trials Unit
  • DSMB – Data Safety Monitoring Board
  • EUB – Emergency Unblinding
  • ICH GCP – International Council for Harmonisation - Good Clinical Practice
  • IMP – Investigational Medicinal Product
  • IVRS – Interactive Voice Response System
  • Site-INV – Site-Investigator
  • SOP – Standard Operating Procedures
  • SP-INV – Sponsor-Investigator
  • SUSAR – Suspected Unexpected Serious Adverse Reaction
  • WI – Working Instructions
Set-Up ↦ Safety ↦ Safety Management ↦ Emergency Unblinding
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Completion Biobanking
Current Path (click to copy): Set-Up ↦ Safety ↦ Safety Management ↦ Emergency Unblinding

Please note: the Easy-GCS tool is currently under construction.