SOP-305
Randomization, Blinding and Emergency Unblinding
- Number
- SOP-305
- Category
- Study Conduct
- Edition
- Reference Edition 1.3
- Approx. pages
- 4
[YELLOW] the site fills in. [DEFAULT: green] a value the site may keep or change.
On this page
1. Purpose
This SOP describes how [SITE NAME] randomizes participants, keeps treatment assignments blinded, separates blinded and unblinded staff, breaks the blind in an emergency, and handles accidental unblinding.
2. Scope
This SOP applies to every randomized or blinded study at [SITE NAME] and to all staff who use the sponsor's Interactive Response Technology (IRT) or who could see treatment assignment information. It partly replaces the blinding and code-break text in AIM SOP-304.01.
Out of scope: IP receipt, storage and accountability (SOP-304); eligibility confirmation before randomization (SOP-303); safety reporting of the event that led to unblinding (SOP-500, SOP-501).
Where the protocol, IRT manual, pharmacy manual, sponsor or IRB sets a stricter requirement than this SOP, the stricter requirement applies.
3. Responsibilities
| Role | Responsibilities |
|---|---|
| Principal Investigator (PI) | Follows the randomization procedures and keeps the blind. Decides with the treating clinician whether emergency unblinding is needed. Documents and explains any premature unblinding to the sponsor. Assigns blinded and unblinded roles on F-302-01. |
| Sub-Investigator (Sub-I) | May perform emergency unblinding where delegated and IRT access is granted. Assesses participants as a blinded investigator. |
| Research Pharmacist or IP Manager | In studies with an unblinded IP role: prepares and dispenses blinded IP, keeps unblinded records apart from blinded staff, and does not take part in efficacy or safety assessments. |
| Clinical Research Coordinator (CRC) | Randomizes participants in IRT where delegated. Keeps IRT confirmations in the participant file. Reports any accidental unblinding at once. |
| Regulatory Coordinator | Keeps IRT user access aligned with F-302-01 and asks the sponsor to remove access when staff leave or change roles. |
| Quality Lead | Reviews unblinding events and blinding deviations for trends and CAPA (SOP-703). |
4. Definitions
| Term | Definition |
|---|---|
| Randomization | The process of deliberately including an element of chance when assigning participants to groups that receive different treatments, to reduce bias. |
| Blinding (Masking) | A procedure in which one or more parties to the trial are kept unaware of the treatment assignment. Single blinding usually means the participant is unaware; double blinding usually means the participant, investigators and, where appropriate, other site and sponsor staff are unaware. |
| Interactive Response Technology (IRT) | The sponsor's web or voice system (IWRS/IVRS) that randomizes participants, assigns IP kits and provides emergency unblinding. |
| Blinded Staff | Staff who must not know treatment assignment, including all staff who assess efficacy or safety or who make medical decisions about study treatment, unless the protocol states otherwise. |
| Unblinded Staff | Staff whom the protocol or sponsor permits to know treatment assignment to do a defined task (for example IP preparation of visibly different products), and who are named as unblinded on F-302-01. |
| Emergency Unblinding | Disclosure of an individual participant's treatment assignment by an investigator because knowing it is needed for that participant's medical care. |
| Accidental Unblinding | Any disclosure of treatment assignment to a blinded person, or to the participant, that the protocol does not allow. |
5. Procedure
5.1 Study Set-up
5.1.1
Before activation, the PI and Lead CRC read the protocol, IRT manual and pharmacy manual sections on randomization, blinding and unblinding, and record the training on F-103-01.
5.1.2
The PI assigns blinded and unblinded roles on F-302-01. A person with an unblinded role does not perform blinded assessments in the same study, unless the protocol allows it.
5.1.3
The Regulatory Coordinator requests IRT accounts that match each person's role. Unblinded IRT roles are given only to staff named as unblinded. At least [DEFAULT: 2] investigators who can perform emergency unblinding have working IRT access at all times. Where the site has only one investigator on the study, the PI records the back-up route (section 5.1.4) for times the PI cannot be reached.
5.1.4
The Lead CRC records the IRT help desk number and the sponsor's medical monitor contact on the study contact sheet, and confirms the back-up unblinding route (for example sealed envelopes or the IRT help desk) if IRT is unavailable.
5.1.5
Where an unblinded role is required, the Site Director arranges physical separation of unblinded records and preparation areas: separate locked file or restricted electronic folder, and an area where blinded staff cannot see IP preparation.
5.2 Randomization
5.2.1
The CRC or investigator randomizes a participant only after consent is documented and an investigator has confirmed eligibility (SOP-303).
5.2.2
The delegated staff member enters the required data in IRT, checks it before submitting, and randomizes the participant within the visit window the protocol sets.
5.2.3
The staff member prints or saves the IRT confirmation and files it in the participant's source record. Blinded staff file only the blinded confirmation.
5.2.4
If a participant is randomized in error (for example wrong stratum, ineligible participant, wrong participant ID), the staff member does not re-randomize or alter IRT data. The staff member notifies the PI and sponsor, follows the sponsor's instruction, and records the event as a deviation (SOP-308).
5.2.5
If IRT is unavailable at a visit, staff follow the IRT manual back-up process. Staff do not assign kits by any method the sponsor has not authorized.
5.3 Keeping the Blind
5.3.1
Unblinded staff keep unblinded information (unblinded IRT reports, preparation records showing treatment, unblinded monitor correspondence) in the restricted file and do not discuss it with blinded staff or participants.
5.3.2
Unblinded staff do not record treatment assignment in shared source documents, the EHR, EDC fields visible to blinded staff, or email to blinded staff.
5.3.3
Blinded staff do not ask unblinded staff about treatment assignment and do not try to deduce it from IP appearance, lab results the protocol keeps hidden, or IRT screens.
5.3.4
Where the sponsor uses an unblinded monitor, only unblinded staff meet with that monitor about unblinded records.
5.3.5
When a participant's treating clinician outside the study asks about treatment, staff give the IRB-approved participant wallet card or contact information and refer the question to an investigator, who follows section 5.4 if unblinding is needed.
5.4 Emergency Unblinding
5.4.1
An investigator unblinds a participant only when knowing the treatment assignment is needed to make a decision about that participant's medical care. Unblinding is not done for convenience or curiosity, or because the participant is withdrawing, unless the protocol requires it.
5.4.2
If time allows without delaying care, the investigator first contacts the sponsor's medical monitor to discuss the need, as the protocol directs. The protocol may allow or require the investigator to unblind without first contacting the sponsor. The investigator never delays care to wait for sponsor agreement.
5.4.3
The investigator performs the unblinding in IRT using their own account. If IRT is unavailable, the investigator uses the back-up route recorded at set-up.
5.4.4
The investigator completes F-305-01 at the time of unblinding or as soon as the emergency is under control, recording:
- participant ID, date and time of unblinding
- name of the investigator who unblinded
- the clinical reason and why knowledge of assignment was needed
- whether the sponsor was contacted before unblinding, and who
- the persons told the assignment and why each needed to know
- IRT confirmation number or back-up record
5.4.5
The investigator tells the treatment assignment only to those who need it for the participant's care (for example the treating physician). The investigator does not tell blinded study staff unless the protocol requires it, and records the reason on F-305-01 if they do.
5.4.6
The investigator notifies the sponsor of the unblinding within the time the protocol sets. IRT notifications do not replace this notification unless the protocol says so. The investigator files proof of notification with F-305-01.
5.4.7
The investigator follows the protocol on whether the participant continues IP or the study after unblinding, and records the decision in source.
5.4.8
Where the unblinding relates to an adverse event, the event is recorded and reported under SOP-500 and SOP-501.
5.4.9
F-305-01 is kept in the restricted unblinded file if it shows treatment assignment. A blinded version stating only that unblinding occurred, the date and the reason is filed in the participant's source record.
5.5 Accidental Unblinding
5.5.1
Any staff member who becomes aware of accidental unblinding reports it to the PI and, where relevant, the unblinded IP Manager the same day.
5.5.2
The PI records what was disclosed, to whom, how and when on F-305-01 (marked as accidental unblinding) and logs it as a deviation under SOP-308, and notifies the sponsor within [DEFAULT: 1 business day] of discovery, or the protocol or sponsor time if shorter. The PI assesses with the sponsor whether the staff member who learned the assignment can continue blinded assessments for that participant.
5.5.3
The event is recorded as a deviation on F-308-01 (SOP-308). The Quality Lead reviews whether a process failure caused it and opens CAPA where needed (SOP-703).
5.6 Unblinding at Study End
5.6.1
Staff do not seek treatment assignments at study end until the sponsor releases them. When the sponsor provides assignments or results, the investigator informs participants who wish to know, as the protocol and IRB-approved materials describe (SOP-601).
5.7 Access Changes
5.7.1
When a staff member leaves or changes role, the Regulatory Coordinator asks the sponsor to change or revoke IRT access [DEFAULT: the same business day] the change takes effect, and updates F-302-01 and F-401-01.
6. Related Forms and SOPs
- F-305-01 Emergency Unblinding Record
- F-302-01 Delegation of Authority Log
- F-308-01 Protocol Deviation Log
- F-103-01 Staff Training Log
- F-401-01 Computerized System Inventory and Access Log
- SOP-302 Delegation of Authority
- SOP-303 Screening, Eligibility Verification and Enrollment
- SOP-304 Investigational Product Management
- SOP-308 Protocol Deviations and Noncompliance
- SOP-401 Computerized Systems and Electronic Records
- SOP-500 Adverse Event Identification, Assessment and Recording
- SOP-501 Serious Adverse Event and Expedited Safety Reporting
- SOP-601 Study Closeout
- SOP-703 Corrective and Preventive Action (CAPA)
- SOP-904 Shared Staff, Cross-Site Coverage and Central Services (Model N only)
- Appendix B Central and Site Responsibility Matrix (Model N only)
7. References
| Reference | Title |
|---|---|
| 21 CFR 312.62 | Investigator recordkeeping and record retention |
| 21 CFR 812.140 | Records |
| ICH E6(R3) Annex 1, 2.11 | Randomisation Procedures and Unblinding |
| ICH E6(R3) Annex 1, 2.12.10 | Records: computerised systems |
| ICH E6(R3) Annex 1, 4.1 | Safeguard Blinding in Data Governance |
| ICH E6(R3) Annex 1, 2.9.3 | End of Participation in a Clinical Trial |
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