SOP-05
Pre-Screening, Screening, Eligibility, Randomization and Blinding
- Number
- SOP-05
- Category
- Core
- Edition
- Lean Edition 2.0
- Approx. pages
- 7
[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] pre-screens candidates before consent, screens consented participants, verifies and documents eligibility before randomization or first dose, registers and randomizes participants in the sponsor's interactive response technology (IRT), keeps the blind, and handles emergency and accidental unblinding.
2. Scope
This SOP applies to every study at [SITE NAME] from first contact with a candidate until the participant is enrolled or recorded as a screen failure, and to blinding for the life of each blinded study. Advertising, recruitment materials, recruitment vendors and volunteer databases are in SOP-M3 (if adopted). Consent is in SOP-04. IP handling is in SOP-06. Safety reporting is in SOP-09. The protocol defines when a participant counts as enrolled, and this SOP uses that definition.
Where the protocol, IRT manual, pharmacy manual, sponsor or IRB requirement is stricter than this SOP, the site follows the stricter requirement.
3. Responsibilities
| Role | Responsibilities |
|---|---|
| Principal Investigator (PI) | Enrolls only eligible participants. Signs F-303-02 or delegates sign-off to a Sub-I. Confirms the HIPAA pathway for record review. Assigns blinded and unblinded roles. Decides on emergency unblinding. Reports eligibility and blinding errors to the sponsor. |
| Sub-Investigator (Sub-I) | Confirms eligibility and signs F-303-02 when delegated. Performs emergency unblinding when delegated and given IRT access. |
| Clinical Research Coordinator (CRC) | Pre-screens when delegated. Performs delegated screening procedures after consent. Prepares F-303-02, maintains F-300-01 and F-303-01, registers and randomizes participants in IRT, and completes enrollment documentation. |
| Recruitment Specialist | Optional role. Pre-screens and maintains F-300-01 when delegated. |
| Research Pharmacist or IP Manager | Performs unblinded IP tasks where the protocol requires an unblinded role, and keeps unblinded records apart from blinded staff. |
| Regulatory Coordinator | Confirms activation and the current protocol version before screening. Keeps IRT access aligned with F-302-01. |
| Quality Lead | Includes eligibility, pre-screening and blinding in QC (SOP-14). Opens CAPA when needed (SOP-08). |
4. Definitions
| Term | Definition |
|---|---|
| Pre-screening | Activities before consent that identify people who may be eligible, using information that already exists or that the person volunteers. It never includes study-specific procedures. |
| Preparatory to research | A HIPAA permission (45 CFR 164.512(i)(1)(ii)) that lets a covered entity use PHI to identify potential participants, on the researcher's representation that the PHI is needed for that purpose and will not leave the covered entity. |
| Screening | Protocol-required procedures, done after consent, to determine whether a participant meets the eligibility criteria. |
| Screen failure | A consented participant who does not meet the eligibility criteria, or who withdraws or is withdrawn before enrollment. |
| Interactive response technology (IRT) | The sponsor's system for registration, randomization, IP assignment and emergency unblinding (also called IWRS or IxRS). |
| Participant identification code | The unique code used in place of identity in data reported to the sponsor (ICH E6(R3) Annex 1, 2.12.8). |
| Blinding | Keeping one or more parties to the trial unaware of the treatment assignment. |
| Unblinded staff | Staff whom the protocol or sponsor permits to know treatment assignment for a defined task, and who are named as unblinded on F-302-01. |
| Emergency unblinding | Disclosure of one 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 Pre-screening rules
5.1.1
This section is the site's single rule on pre-screening before IRB approval and activation. Pre-screening for a study starts only after the IRB has approved the pre-screening script or questionnaire and every material used to contact candidates. F-300-01 entries for a study start on or after that approval date. Nothing that requires consent happens before the study is activated (SOP-03) and the participant has consented (SOP-04).
5.1.2
Record review for feasibility under the preparatory-to-research provision may happen before activation if no PHI leaves the covered entity and no candidate is contacted. Feasibility results are recorded as counts only, on F-200-01 (SOP-M2, if adopted) or in the feasibility file.
5.1.3
Before anyone reviews medical records to find candidates, the PI records in the study file which HIPAA pathway applies (site HIPAA status: SOP-12):
- the patient's own treating clinician raises the study as part of care
- preparatory to research (45 CFR 164.512(i)(1)(ii)): workforce members of the covered entity holding the records may review PHI to identify candidates, not only to count them, once the Privacy Officer accepts the researcher's written representation of purpose (preparing a protocol or a similar purpose, such as identifying candidates), necessity, and that no PHI leaves the covered entity. The record is the Preparatory-to-Research Representation, signed by the PI and accepted by the Privacy Officer. No one contacts a candidate about the study until the IRB has approved the recruitment method and materials (5.1.1). It is not an IRB approval and does not let outside researchers contact patients or take PHI away
- a partial waiver of authorization from the IRB or a Privacy Board (45 CFR 164.512(i)(1)(i))
- the patient's signed HIPAA authorization
5.1.4
Reviewers use the minimum necessary information and do not copy or export records. Substance use disorder program records (42 CFR Part 2) are not used unless the Privacy Officer confirms a permitted pathway.
5.1.5
Only staff delegated pre-screening on F-302-01 and trained on the criteria pre-screen, using only the IRB-approved script or questionnaire. They add no questions and do not test, measure, collect specimens or ask a candidate to change any medication. Staff tell the candidate that pre-screening does not decide eligibility and that taking part is voluntary.
5.1.6
Staff record each candidate on F-300-01 under a site-assigned pre-screening ID not derived from name, date of birth or medical record number, with date, initials, study, referral source (for example ad name and version), outcome (referred for consent, not eligible, not interested, unable to contact, other), reason category without clinical detail, and screening number if the candidate later screens.
5.1.7
Names, contact details, medical record numbers and pre-screening answers are kept in a separate access-controlled key linked by pre-screening ID, never on F-300-01. The key and answers are destroyed under SOP-12 [DEFAULT: when the study closes to enrollment] unless the IRB-approved protocol or the person's database agreement says otherwise.
5.1.8
F-300-01 is minimum necessary but not de-identified, because dates linked to a person are PHI (45 CFR 164.514(b)(2)). A sponsor asking for pre-screening data receives aggregate counts. The log itself goes to a sponsor only after the Privacy Officer confirms a HIPAA basis (for example a limited data set under a data use agreement).
5.1.9
Candidates who appear eligible are offered a consent appointment; others are told they do not qualify, without saying which answer excluded them unless the script allows. Staff do not exclude a candidate for language, literacy or disability unless the protocol requires it. Where the site cannot support a candidate's language, the PI decides with the sponsor and IRB and the outcome is recorded on F-300-01.
5.2 Study set-up
5.2.1
Before screening starts, the Regulatory Coordinator confirms the study is activated and the protocol version in use is IRB-approved. After any amendment that changes eligibility, the CRC updates F-303-02 and the PI or Lead CRC trains the team before the amendment is used.
5.2.2
The CRC builds F-303-02 from the current protocol: each criterion verbatim or by number, with columns for met or not met, source used, source date and whether it is within the protocol window, and verifier's initials. A sponsor checklist may be used if it has these columns or they are added.
5.2.3
Before activation, the PI and Lead CRC read the protocol, IRT manual and pharmacy manual sections on randomization and blinding, and record the training on F-103-01. The PI assigns blinded and unblinded roles on F-302-01 and names a backup for each unblinded role. A person in an unblinded role does not perform blinded assessments in that study unless the protocol allows it.
5.2.4
The Regulatory Coordinator requests IRT accounts matching each role; unblinded IRT roles go only to staff named as unblinded. At least [DEFAULT: 2] investigators have working emergency-unblinding access. Where the study has one investigator, the PI records a back-up route (IRT help desk or sealed envelopes) on the study contact sheet, with the sponsor medical monitor contact.
5.2.5
Where an unblinded role is required, the Site Director provides a locked file or restricted folder for unblinded records and a preparation area blinded staff cannot see.
5.3 Screening and the screening log
5.3.1
No screening procedure is done before the participant signs consent, including research-only tests, questionnaires and medication washouts, unless it is part of normal care and the protocol allows its results to be used.
5.3.2
The CRC assigns the screening number per the protocol or IRT and records the participant on F-303-01 at consent: screening number and participant identification code, consent date and version, visit dates, outcome (enrolled, screen failure with primary reason, or withdrawn), any earlier screening number, and initials. Identity is held only on the site's confidential participant identification code list, which is never sent to the sponsor.
5.3.3
Screening procedures are done only by delegated staff, within the protocol window and in protocol order. Adverse events during screening are handled under SOP-09.
5.4 Verifying each criterion
5.4.1
The CRC completes F-303-02 as results arrive. Every criterion is supported by source a monitor can find. Self-report counts only where the protocol allows it, and the source note says so.
5.4.2
An investigator reviews outside records (signing and dating them or noting the review) before they are used as source, and assesses criteria that need clinical judgment in a signed and dated note.
5.4.3
The CRC checks each test value against the protocol limits and units, using the laboratory's reference ranges on file (SOP-11), and records the actual value. A test is repeated only where the protocol allows a retest, never to produce a qualifying result.
5.4.4
The CRC checks concurrent research participation by asking the participant and reviewing records. A research participant registry is checked [DEFAULT: only where the protocol or sponsor requires it] and the result filed.
5.4.5
If a criterion is unclear and the protocol does not resolve it, the PI asks the sponsor for a written interpretation, filed in the ISF. An interpretation is not permission to enroll someone who does not meet the criterion.
5.5 Investigator sign-off and no waivers
5.5.1
The PI, or a Sub-I delegated eligibility confirmation on F-302-01, reviews F-303-02 with the source, confirms every inclusion criterion is met and no exclusion criterion applies, and signs and dates F-303-02 (with the time where dosing is the same day). Where the signing investigator also prepared F-303-02, a delegated CRC or Sub-I checks it against source first.
5.5.2
Sign-off is complete before randomization, treatment-assigning IRT registration or first dose, whichever comes first. Sponsor review of an eligibility packet does not replace it. Criteria that can change before dosing (for example a same-day pregnancy test) are rechecked as the protocol requires and confirmed by the investigator before dosing.
5.5.3
The site does not request or accept an eligibility waiver or exception for an individual participant. The investigator must follow the investigational plan (21 CFR 312.60; 21 CFR 812.100 and 812.110(b)); changing eligibility needs an IRB-approved amendment. If a sponsor representative offers an exception, the CRC declines, tells the PI and records the communication in the study file.
5.6 Screen failures and rescreening
5.6.1
The investigator confirms each screen failure and tells the participant, and with their agreement their own doctor, of any clinically significant findings. The CRC records the primary reason on F-303-01 and completes the IRT and EDC entries the protocol requires.
5.6.2
Rescreening happens only where the protocol allows it, with written sponsor approval where required. The CRC assigns a new screening number if required, links it on F-303-01, confirms consent is still valid or re-consents (SOP-04), and completes a new F-303-02.
5.7 Registration and randomization in IRT
5.7.1
Only staff delegated IRT tasks on F-302-01, using their own accounts, register or randomize participants, after investigator sign-off and within the visit window. The CRC checks stratification factors and other entries against source before submitting.
5.7.2
The CRC saves the IRT confirmation in the research record as source or a certified copy (SOP-07). Blinded staff file only the blinded confirmation.
5.7.3
If an IRT entry is wrong or a participant is randomized in error, staff do not re-randomize or alter IRT data. The CRC tells the PI, contacts the sponsor or IRT help desk the same day, follows their instructions and records a deviation on F-308-01 (SOP-08).
5.7.4
If IRT is unavailable, staff follow the IRT manual back-up process and never assign kits by an unauthorized method.
5.8 Enrollment documentation
5.8.1
On enrollment, the CRC:
- records the enrollment date and number on F-303-01
- writes a source note confirming consent before any study procedure, the consent version, the investigator sign-off date and the randomization number
- enters the participant in EDC (SOP-07) and notes participation in the medical record where the site keeps one
- gives the participant the study contact information and any sponsor card, and, with their agreement, informs their primary care physician (ICH E6(R3) Annex 1, 2.7.1(d))
5.9 Keeping the blind
5.9.1
Unblinded staff keep unblinded information in the restricted file. They do not record assignment in shared source, the EHR, EDC fields blinded staff can see, or email, and do not discuss it with blinded staff or participants. Only unblinded staff meet the unblinded monitor.
5.9.2
Blinded staff do not ask about or try to deduce assignment, and refer an outside clinician's treatment question to an investigator.
5.9.3
When a staff member leaves or changes role, the Regulatory Coordinator asks the sponsor to change IRT access within the SOP-02 timing and updates F-302-01 and F-401-01.
5.10 Emergency unblinding
5.10.1
An investigator unblinds a participant only when knowing the assignment is needed for that participant's medical care. If time allows, the investigator first contacts the sponsor medical monitor as the protocol directs, but never delays care for sponsor agreement. The investigator unblinds in IRT with their own account, or by the back-up route.
5.10.2
The investigator completes F-305-01 at the time or as soon as the emergency is controlled: participant ID, date and time, investigator, clinical reason, whether the sponsor was contacted first, each person told and why, and the IRT confirmation or back-up record. Blinded study staff are told only where the protocol requires it.
5.10.3
The investigator notifies the sponsor within the protocol's time (an IRT notification counts only where the protocol says so), files proof with F-305-01, records the decision on continuing in source, and reports any related adverse event under SOP-09.
5.10.4
F-305-01 is kept in the restricted file if it shows assignment. A blinded note of the date and reason goes in the participant's source.
5.11 Accidental unblinding and study end
5.11.1
Any staff member who learns of accidental unblinding tells the PI, and the unblinded IP Manager where relevant, the same day.
5.11.2
The PI records what was disclosed, to whom, how and when on F-305-01 marked as accidental unblinding, records a deviation on F-308-01 (SOP-08), and notifies the sponsor within [DEFAULT: 1 business day] of discovery, or the protocol or sponsor time if shorter. The PI decides with the sponsor whether the person told can continue blinded assessments for that participant.
5.11.3
Staff do not seek assignments at study end until the sponsor releases them. The investigator then informs participants who wish to know, as the IRB-approved materials describe (SOP-15).
5.12 Eligibility errors found after enrollment
5.12.1
Anyone who finds that an enrolled participant did not meet a criterion tells the PI the same day.
5.12.2
The PI assesses the participant's safety and notifies the sponsor within [DEFAULT: 1 business day] of discovery, or the protocol or sponsor time if shorter. The PI decides with the sponsor whether the participant continues, decides what to tell the participant, and records both decisions in source.
5.12.3
The CRC records a deviation on F-308-01 (SOP-08), and the Regulatory Coordinator reports it to the IRB where [CENTRAL IRB NAME] policy requires (SOP-09). Records are never changed to make a participant appear eligible.
6. Related Forms and SOPs
- F-300-01 Pre-Screening Log
- F-303-01 Screening and Enrollment Log
- F-303-02 Eligibility Verification Checklist
- F-305-01 Emergency Unblinding Record
- F-302-01 Delegation of Authority Log
- F-103-01 Staff Training Log
- F-200-01 Study Feasibility Assessment (SOP-M2, if adopted)
- F-308-01 Protocol Deviation Log
- F-401-01 Computerized System Inventory and Access Log
- SOP-02 Roles, PI Oversight, Delegation and Conflicts of Interest
- SOP-03 IRB Oversight, Essential Records and Study Activation
- SOP-04 Informed Consent
- SOP-06 Investigational Product Management
- SOP-07 Source Documentation and EDC
- SOP-08 Protocol Deviations and CAPA
- SOP-09 Safety Reporting (AEs, SAEs, IRB-Reportable Events, Pregnancy)
- SOP-11 Specimens, Equipment and Laboratories
- SOP-12 Privacy, Electronic Systems and Record Retention
- SOP-14 Quality Control and Quality Review
- SOP-15 Study Closeout
- SOP-M2 Feasibility, Contracts, Budgets and Research Billing (if adopted)
- SOP-M3 Recruitment and Advertising (if adopted)
7. References
| Reference | Title |
|---|---|
| 21 CFR 312.60 | General responsibilities of investigators |
| 21 CFR 812.100 and 812.110(b) | Investigator responsibilities (devices) |
| 45 CFR 164.512(i) | Uses and disclosures for research purposes |
| 45 CFR 164.514 | De-identification; limited data set |
| 42 CFR Part 2 | Confidentiality of Substance Use Disorder Patient Records |
| ICH E6(R3) Annex 1, 2.7 | Participant Medical Care and Safety Reporting |
| ICH E6(R3) Annex 1, 2.11 | Randomisation Procedures and Unblinding |
| ICH E6(R3) Annex 1, 2.12 | Records |
| ICH E6(R3) Appendix C | Essential Records (participant identification code list and enrolment log; screening log) |
| FDA Guidance (1998) | Screening Tests Prior to Study Enrollment |
| HHS OCR HIPAA FAQ 317 | Preparatory research provision and recruitment |
| Reference Edition SOP-300, SOP-303, SOP-305 | Background and full text |
Independent Site SOP Library. Licensed CC BY-NC 4.0 by the American Institute for Medical Research (AIMR), with added permission for any site's internal use (license terms). Not legal advice: each adopting site confirms state law, IRB and sponsor requirements with its own counsel and owns every step it approves.