Standard Operating Procedure for Protocol and SAP (Statistical Analysis Plan) Integration in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/027/2025 |
| Supersedes | SOP/BA-BE/027/2022 |
| Page No. | Page 1 of 13 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define the procedure for ensuring accurate and consistent integration between the study protocol and the Statistical Analysis Plan (SAP) in Bioavailability/Bioequivalence (BA/BE) studies, maintaining alignment between study design and statistical methodology.
2. Scope
This SOP applies to all BA/BE studies involving human subjects where a separate SAP is created or revised in conjunction with the clinical protocol, including submissions to regulatory agencies such as CDSCO, USFDA, EMA, and WHO PQ.
3. Responsibilities
- Biostatistician: Prepares and reviews the SAP ensuring consistency with the protocol.
- Medical Writer: Ensures alignment between protocol objectives and statistical sections.
- Clinical Project Manager: Coordinates inputs from clinical and statistical teams.
- Quality Assurance: Verifies final documents for consistency and audit readiness.
4. Accountability
The Head of Biostatistics is accountable for the final integration of protocol and SAP and ensuring that all endpoints, methods, and populations are harmonized prior to database lock and analysis.
5. Procedure
5.1 Development of SAP
- Initiate SAP development once the final or near-final version of the protocol is available.
- The SAP must include:
- Objectives and endpoints (primary, secondary)
- Statistical hypothesis
- Sample size justification
- Population definitions (PP, ITT, Safety)
- Bioequivalence criteria and confidence intervals
- Handling of missing data and outliers
5.2 Cross-Referencing with Protocol
- Ensure consistency between:
- Inclusion/exclusion criteria (SAP vs Protocol)
- Study design (e.g., crossover, parallel)
- Pharmacokinetic parameters (Cmax, AUC, Tmax)
- Timing of assessments
- Log cross-verification in Annexure-1: Protocol-SAP Consistency Checklist.
5.3 Review and Approval Process
- Circulate draft SAP to cross-functional teams (Clinical, QA, Regulatory) for feedback.
- Document all review comments and version updates in Annexure-2: SAP Review Log.
- Obtain final sign-off prior to database lock and statistical programming.
See also BA-BE Studies: SOP for Review of Bioequivalence Waiver Justifications (BCS Class I) - V 2.0
5.4 Amendment Handling
- Any protocol amendment impacting endpoints or statistical methods must be reflected in a revised SAP.
- Ensure the amended SAP is clearly versioned and submitted to EC/Regulatory if required.
5.5 Filing and Archiving
- Archive both protocol and SAP in the Trial Master File (TMF/eTMF) with clear version history.
- Maintain document metadata in Annexure-3: SAP Finalization and Filing Log.
6. Abbreviations
- SAP: Statistical Analysis Plan
- PP: Per Protocol
- ITT: Intent to Treat
- TMF: Trial Master File
- eTMF: Electronic Trial Master File
- CDSCO: Central Drugs Standard Control Organization
7. Documents
- Protocol-SAP Consistency Checklist – Annexure-1
- SAP Review Log – Annexure-2
- SAP Finalization and Filing Log – Annexure-3
8. References
- ICH E9 – Statistical Principles for Clinical Trials
- ICH E6(R2) – Good Clinical Practice
- Schedule Y – Drugs and Cosmetics Rules
- USFDA and EMA BE Guidances
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Protocol-SAP Consistency Checklist
| Section | Protocol Description | SAP Description | Verified By | Date |
|---|---|---|---|---|
| Endpoints | Cmax, AUC0-t, AUC0-∞ | Same | Dr. Arvind Shah | 15/04/2025 |
Annexure-2: SAP Review Log
| Reviewer | Department | Date Reviewed | Comments | Resolved (Y/N) |
|---|---|---|---|---|
| Sunita Reddy | QA | 14/04/2025 | Clarify imputation method | Yes |
Annexure-3: SAP Finalization and Filing Log
| SAP Version | Date Finalized | Filed In | Filed By |
|---|---|---|---|
| V2.0 | 16/04/2025 | eTMF/BE036/Stat | Rajesh Kumar |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 10/01/2022 | 1.0 | Initial SOP | New SAP Process | QA Head |
| 17/04/2025 | 2.0 | Updated annexures and added amendment handling | GCP Alignment | QA Head |