Standard Operating Procedure for Contingency Planning for Subject Withdrawal in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/140/2025 |
| Supersedes | SOP/BA-BE/140/2022 |
| Page No. | Page 1 of 9 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define a systematic approach for handling subject withdrawals during BA/BE clinical trials, including documentation, notification, replacement strategies, and regulatory compliance to ensure study continuity and integrity.
2. Scope
This SOP applies to all clinical trials conducted at the site under the BA/BE program, covering both voluntary and investigator-mandated subject withdrawals at any stage of the study.
3. Responsibilities
- Principal Investigator (PI): Makes final decision on subject withdrawal, oversees documentation, and notifies sponsor/regulatory authorities.
- Study Coordinator: Assists in documentation, tracks subject disposition, and maintains logs.
- Medical Officer: Conducts safety assessments and records medical justifications, if applicable.
- QA Officer: Ensures protocol compliance and verifies withdrawal records during audits.
4. Accountability
The Principal Investigator is accountable for ensuring that subject withdrawals are handled ethically, documented properly, and evaluated for impact on study validity.
5. Procedure
5.1 Reasons for Subject Withdrawal
- Subjects may withdraw from the study for the following reasons:
- Voluntary withdrawal (personal reasons, discomfort, etc.)
- Medical reasons (e.g., adverse events, abnormal lab results)
- Non-compliance with study procedures
- Protocol deviations
- Investigator’s discretion for subject safety
5.2 Initial Assessment and Reporting
- Immediately upon a subject expressing intent to withdraw, the Study Coordinator must notify the Medical Officer and PI.
- Conduct a medical evaluation to assess safety or adverse events leading to withdrawal.
- Document the event in Annexure-1: Subject Withdrawal Form, including:
- Subject ID
- Date and study period
- Reason for withdrawal
- Medical findings, if any
- Investigator and subject signatures
- Update the Subject Disposition Log accordingly.
5.3 Follow-Up and Safety Monitoring
- Offer voluntary follow-up visit to withdrawn subjects to assess health status.
- Record outcomes of the follow-up in Annexure-2: Post-Withdrawal Safety Report, if applicable.
- If adverse event is related to IMP, initiate SAE reporting per SOP/BA-BE/68/2025.
5.4 Replacement of Withdrawn Subjects
- Check protocol-specific replacement criteria:
- Pre-dose withdrawals: Replace with reserve subjects, if enrolled.
- Post-dose withdrawals: Generally not replaced unless protocol allows.
- Activate standby subjects if identified prior to dosing.
- Update randomization records and ensure blinding is maintained, if applicable.
- Record new subject inclusion in Annexure-3: Replacement Subject Log.
5.5 Notification to Sponsor and Ethics Committee
- Send written notification to the sponsor within 24 hours for all withdrawals.
- If withdrawal is related to safety or protocol deviation, notify IEC/IRB as per their SOPs.
- Maintain copies of all communications in the Trial Master File (TMF).
5.6 Final Documentation and Archival
- Update eCRF or paper CRF with withdrawal status and date.
- Ensure all associated logs (dispensing, lab samples, consent) are reconciled and closed.
- Archive withdrawal forms in subject file for minimum 5 years or as per regulatory requirement.
6. Abbreviations
- BA/BE: Bioavailability / Bioequivalence
- PI: Principal Investigator
- IMP: Investigational Medicinal Product
- SAE: Serious Adverse Event
- IEC: Institutional Ethics Committee
- TMF: Trial Master File
7. Documents
- Subject Withdrawal Form – Annexure-1
- Post-Withdrawal Safety Report – Annexure-2
- Replacement Subject Log – Annexure-3
8. References
- ICH E6(R2) – Good Clinical Practice
- Schedule Y – Drugs and Cosmetics Rules, India
- CDSCO Bioavailability/Bioequivalence Guidelines
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Subject Withdrawal Form
| Subject ID | Date | Study Period | Reason | Investigator Signature |
|---|---|---|---|---|
| SUB123 | 17/04/2025 | P1 | Personal reason | Dr. Meena Joshi |
Annexure-2: Post-Withdrawal Safety Report
| Subject ID | Follow-Up Date | Symptoms | Treatment | Outcome |
|---|---|---|---|---|
| SUB123 | 20/04/2025 | None | NA | Recovered |
Annexure-3: Replacement Subject Log
| Withdrawn ID | Replaced By | Period | Date | Remarks |
|---|---|---|---|---|
| SUB123 | SUB129 | P1 | 17/04/2025 | Used reserve subject |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP release | New procedure | QA Head |
| 17/04/2025 | 2.0 | Expanded procedure for follow-up and annexures | Regulatory alignment | QA Head |