SOP-601
Study Closeout
- Number
- SOP-601
- Category
- Monitoring and Closeout
- Edition
- Reference Edition 1.3
- Approx. pages
- 6
[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] closes a trial at the site, whether at planned completion or after early termination or suspension, so that participants are informed and cared for, data and records are complete, investigational product and specimens are reconciled, IRB and financial obligations are met, and records are archived.
2. Scope
This SOP applies to all trials at [SITE NAME] when the last participant completes the last visit, when the sponsor closes the site, or when the sponsor, investigator, site or IRB terminates or suspends the trial early.
Out of scope: archiving and destruction procedures (SOP-402) and sponsor-investigator obligations to FDA (SOP-800).
Follow the protocol, CTA, sponsor or IRB requirement where it is stricter than or more specific than this SOP.
3. Responsibilities
| Role | Responsibilities |
|---|---|
| Principal Investigator (PI) | Signs off the casebook, makes sure participants are informed and transitioned to appropriate care, submits or approves the final IRB report, provides the final report to the sponsor, and updates financial disclosure for one year after completion. |
| Lead CRC or CRC | Completes data entry and queries, completes participant end-of-study activities and notifications, coordinates the close-out visit and completes F-601-01. |
| Regulatory Coordinator | Reconciles the ISF, submits the final report and closure request to the IRB, and prepares records for archiving. |
| Research Pharmacist or IP Manager | Completes final IP and device reconciliation, returns or destroys IP as the sponsor directs, and returns sponsor equipment and supplies. |
| Finance / Contracts Lead | Reconciles payments received against work performed, invoices outstanding items and holdback, and closes participant payment accounts. |
| Site Director | Approves early termination decisions by the site, closes out vendor arrangements, and confirms archiving arrangements and costs. |
| Quality Lead | Performs a closeout QC review and confirms all CAPAs and open findings are closed or transferred. |
4. Definitions
| Term | Definition |
|---|---|
| Last participant last visit (LPLV) | The date the last participant at the site completes the last protocol-required visit or contact. |
| Close-out visit (COV) | The final monitoring visit, on site or remote, at which the sponsor confirms that site close-out activities are complete. |
| Database lock | The sponsor's action that prevents further changes to the trial database. |
| Casebook sign-off | The investigator's electronic signature in EDC attesting to the review of each participant's CRF data. |
| Holdback | A portion of payments that the sponsor retains under the CTA until close-out conditions are met. |
| Early termination | Ending of the trial, or of the site's participation, before planned completion, by decision of the sponsor, investigator, site, IRB or a regulatory authority. |
| Suspension | Temporary halt of all or part of a trial (for example, enrollment or dosing) pending further review. |
| Essential records | Records that individually and collectively permit evaluation of the conduct of the trial and the quality of the data (ICH E6(R3) Appendix C). |
5. Procedure
5.1 Planning closeout
5.1.1
When the sponsor announces the end of enrollment or LPLV, the Lead CRC opens F-601-01 and assigns an owner and target date to each item.
5.1.2
The Lead CRC confirms with the sponsor: expected database lock date, close-out visit date and format, IP and supply return instructions, specimen instructions, record retention instructions, and whether participants will be given results.
5.2 Participant end of study
5.2.1
The CRC completes each participant's end-of-study visit as the protocol requires and records end-of-study status in EDC.
5.2.2
The investigator discusses ongoing care with each participant at the final visit, including what treatment options exist after the trial and whether any post-trial access to IP is offered by the sponsor. The investigator arranges transfer of care to the participant's own physician where needed and documents it.
5.2.3
Ongoing AEs and SAEs are followed as the protocol requires (SOP-500, SOP-501). Pregnancies are followed to outcome (SOP-503).
5.2.4
The CRC tells participants how they will be informed of the trial results and, for blinded trials, of the treatment they received, if the sponsor provides this information, and records their preference (ICH E6(R3) Annex 1, 2.9.3). When the sponsor supplies a participant results summary, the Regulatory Coordinator obtains IRB approval if the IRB requires it, and the CRC sends it to participants who wanted it.
5.2.5
For blinded trials, the Lead CRC asks the sponsor when and how treatment assignments will be released to the investigator after unblinding (for example, a treatment code list or portal report). When received, the investigator reviews it, the Regulatory Coordinator files it in the ISF, and the CRC informs each participant who asked to know, with due respect to the participant's preference. Any information that matters for a participant's ongoing care is shared with the participant's physician with the participant's agreement. Emergency unblinding during the trial follows SOP-305.
5.3 Data and query completion
5.3.1
The CRC enters all outstanding data and answers all queries by the sponsor's deadline (SOP-307).
5.3.2
The CRC reconciles the source with EDC for each participant, including AEs, concomitant medications, deviations and end-of-study status.
5.3.3
The PI (or a Sub-I where the sponsor allows) reviews and signs each casebook in EDC by the sponsor's deadline. The PI signs only after reviewing the data. If data change after signature, the PI re-signs as the system requires.
5.3.4
The Lead CRC confirms with the sponsor that the site will receive a copy of its participants' eCRF data, including the audit trail (for example, PDF casebooks with audit trail on durable media or through a secure portal), after database lock, and files the confirmation. When the copy arrives, the Regulatory Coordinator checks that it opens, covers every participant at the site and includes the audit trail, records the check on F-601-01, and files it with the ISF for retention under SOP-402. Missing or unreadable data are raised with the sponsor in writing.
5.3.5
Access for site staff and monitors to sponsor systems is removed at the time the sponsor specifies. Monitor access to site systems is removed at close (SOP-401, F-401-01).
5.4 Investigational product and supplies
5.4.1
The Research Pharmacist or IP Manager completes the final accountability on F-304-01, reconciling received, dispensed, returned, destroyed and on-hand quantities, and explains every discrepancy.
5.4.2
After the monitor verifies accountability, unused IP is returned to the sponsor or destroyed only on the sponsor's written instruction (21 CFR 312.62(a); 21 CFR 312.59). Investigational devices are returned or disposed of as the sponsor directs (21 CFR 812.110(e)). Destruction records or return shipping records are filed in the ISF.
5.4.3
Controlled substance IP is returned or destroyed according to DEA requirements and sponsor instructions, with records kept under 21 CFR 1304.
5.4.4
Sponsor-owned equipment (for example, ECG machines, tablets, freezers, temperature loggers) is returned as instructed, and its F-312-01 entry is marked returned with the date (the record is kept, SOP-312). Unused lab kits and supplies are returned or destroyed as instructed.
5.4.5
Temperature logs for the full storage period are complete and filed (F-304-02).
5.5 Specimens
5.5.1
The CRC confirms that all specimens have been shipped to the central lab, and reconciles F-311-01 with the sponsor's specimen receipt records.
5.5.2
Specimens remaining at the site are shipped, retained or destroyed only according to the sponsor's written instructions and the participant's consent for storage and future use. Destruction is recorded.
5.6 Essential records
5.6.1
The Regulatory Coordinator reconciles the ISF against F-204-01 and the sponsor's list of expected essential records, and files missing items or notes to file explaining their absence.
5.6.2
The Regulatory Coordinator confirms that all safety report acknowledgments, IRB correspondence, delegation and training records, consent versions, signed consent forms, monitoring letters and deviation logs are complete through study end.
5.6.3
The Quality Lead performs a closeout QC review using F-700-01, and confirms that all CAPAs and open monitoring actions (F-600-02) are closed or have a documented owner after close.
5.7 Close-out visit
5.7.1
The Lead CRC schedules the close-out visit and records it on F-600-01. Preparation and conduct follow SOP-600.
5.7.2
At the close-out visit, the monitor confirms IP reconciliation, record completeness, and retention arrangements. Open items are recorded on F-600-02 and completed before the site is closed in the sponsor's systems.
5.7.3
The Regulatory Coordinator files the sponsor's close-out letter in the ISF.
5.8 IRB final report and closure
5.8.1
The Regulatory Coordinator submits the final report or closure request to the IRB, with the PI's approval, when the IRB's closure criteria are met. Most IRBs allow closure when all participant interaction and follow-up is complete and no further collection or analysis of identifiable data will occur at the site. Where the sponsor is still sending queries, the study stays open with the IRB unless the IRB says otherwise.
5.8.2
The report gives a summary of the trial's outcome at the site in the format the IRB requests (ICH E6(R3) Annex 1, 2.13).
5.8.3
For device studies, the investigator submits a final report to the sponsor and the reviewing IRB within 3 months after termination or completion of the investigation or the investigator's part of it (21 CFR 812.150(a)(6)).
5.8.4
For drug studies, the investigator provides the sponsor with an adequate final report shortly after completion of the investigator's participation (21 CFR 312.64(c)). The sponsor's close-out documentation usually serves this purpose; the Regulatory Coordinator confirms with the sponsor.
5.8.5
The IRB closure letter is filed in the ISF and a copy is sent to the sponsor.
5.9 Financial closeout
5.9.1
The Finance / Contracts Lead reconciles payments received with visits, procedures and invoiceable items performed, using the CTA payment schedule.
5.9.2
The Finance / Contracts Lead invoices all outstanding items (for example, screen failures, unscheduled visits, IRB fees, close-out and archiving fees) and requests release of holdback when the sponsor's conditions are met. Final invoices are sent within the CTA's invoicing deadline.
5.9.3
The Finance / Contracts Lead confirms that all participant payments and reimbursements are complete and closes participant payment cards or accounts (SOP-310).
5.9.4
Research billing for the study is reconciled so that no sponsor-paid item has been billed to a participant or insurer (SOP-202).
5.9.5
The PI and each Sub-I listed on the 1572 or investigator agreement update financial disclosure information to the sponsor if relevant changes occur during the study and for 1 year after completion (21 CFR 312.64(d); 21 CFR 812.110(d); SOP-104).
5.10 Archiving
5.10.1
The Regulatory Coordinator prepares records for archiving under SOP-402 and records them on F-402-01. The retention period is set under SOP-402, 5.1.2, and records are not destroyed without the sponsor notice SOP-402 requires.
5.10.2
The sponsor is informed of the archive location and of any later change, including change of ownership or closure of [SITE NAME] (ICH E6(R3) Annex 1, 2.12.13).
5.11 Early termination or suspension
5.11.1
If the sponsor terminates or suspends the trial, the Regulatory Coordinator files the sponsor's notice, and the PI confirms with the sponsor which party will notify the IRB. The IRB is informed promptly (ICH E6(R3) Annex 1, 2.6.3).
5.11.2
If the PI or [SITE NAME] decides to end participation without the sponsor's prior agreement, the PI informs the sponsor and the IRB promptly with a detailed explanation (ICH E6(R3) Annex 1, 2.6.2). The Site Director approves site-initiated termination and the Finance / Contracts Lead reviews CTA termination terms.
5.11.3
If the IRB suspends or terminates approval, the PI informs the sponsor promptly, and for device studies within 5 working days (21 CFR 812.150(a)(2)). Research activities stop except those the IRB permits for participant safety.
5.11.4
The PI decides, with the sponsor's input, how IP will be stopped for each participant. Where abrupt cessation could harm a participant (for example, tapering requirements), the PI arranges a safe transition.
5.11.5
The CRC contacts every active participant promptly to inform them of the termination or suspension and of the reason as far as known, using IRB-approved language where the IRB requires it, and records each contact (ICH E6(R3) Annex 1, 2.6.1).
5.11.6
The investigator arranges appropriate therapy and follow-up for each participant, including transfer of care to the participant's own physician and a written summary of trial treatment where helpful. Safety follow-up continues as the sponsor and protocol require.
5.11.7
After participants are safe, the closeout steps in sections 5.3 to 5.10 are completed.
5.11.8
A suspended trial resumes only after the sponsor's written instruction and IRB approval where required. A significant risk device study terminated for an unreasonable risk under 21 CFR 812.46(b) may not resume without IRB and FDA approval (21 CFR 812.46(c)).
5.12 Completion
5.12.1
When all items on F-601-01 are complete, the Lead CRC signs it, the PI signs to confirm closeout, and the Regulatory Coordinator files it in the ISF. After archiving under SOP-402, the PI signs the archive-complete line on F-601-01 (SOP-402, 5.2.2) and the signed checklist is filed with the archive record on F-402-01.
6. Related Forms and SOPs
- F-601-01 Study Closeout Checklist
- F-204-01 Investigator Site File Index
- F-304-01 Investigational Product Accountability Log
- F-304-02 Temperature Monitoring Log
- F-311-01 Specimen Processing and Shipment Log
- F-312-01 Equipment Inventory and Calibration Log
- F-401-01 Computerized System Inventory and Access Log
- F-402-01 Record Archiving and Retrieval Log
- F-600-01 Monitoring Visit Log
- F-600-02 Monitoring Follow-Up Action Tracker
- F-700-01 Internal QC Review Checklist
- SOP-104 Conflict of Interest and Financial Disclosure
- SOP-202 Medicare Coverage Analysis and Research Billing Compliance
- SOP-204 Essential Documents and the Investigator Site File
- SOP-304 Investigational Product Management
- SOP-305 Randomization, Blinding and Emergency Unblinding
- SOP-307 Case Report Forms, EDC Entry and Query Resolution
- SOP-310 Participant Payments and Reimbursement
- SOP-311 Biological Specimen Collection, Processing and Shipping
- SOP-401 Computerized Systems and Electronic Records
- SOP-402 Record Retention, Archiving and Destruction
- SOP-500 Adverse Event Identification, Assessment and Recording
- SOP-501 Serious Adverse Event and Expedited Safety Reporting
- SOP-503 Pregnancy Reporting in Clinical Trials
- SOP-600 Sponsor Monitoring Visits
- Appendix A State Law Worksheet
- SOP-901 Member Site Onboarding, Integration and Exit (Model N only)
- SOP-902 Network Study Feasibility, Allocation and Central Contracting (Model N only)
- Appendix B Central and Site Responsibility Matrix (Model N only)
7. References
| Reference | Title |
|---|---|
| 21 CFR 312.59 | Disposition of Unused Supply of Investigational Drug |
| 21 CFR 312.62 | Investigator Recordkeeping and Record Retention |
| 21 CFR 312.64(c), (d) | Investigator Reports: Final Report; Financial Disclosure Reports |
| 21 CFR 812.46(c) | Resumption of Terminated Studies |
| 21 CFR 812.110(d), (e) | Specific Investigator Responsibilities: Financial Disclosure; Disposing of Device |
| 21 CFR 812.140(d) | Records: Retention Period |
| 21 CFR 812.150(a) | Investigator Reports |
| 21 CFR 1304 | Records and Reports of Registrants (controlled substances) |
| ICH E6(R3) Annex 1, 2.6 | Premature Termination or Suspension of a Trial |
| ICH E6(R3) Annex 1, 2.9 | End of Participation in a Clinical Trial |
| ICH E6(R3) Annex 1, 2.12 | Records |
| ICH E6(R3) Annex 1, 2.13 | Reports |
| ICH E6(R3) Appendix C | Essential Records for the Conduct of a Clinical Trial |
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