BA-BE Studies: SOP for Protocol and SAP (Statistical Analysis Plan) Integration – V 2.0

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BA-BE Studies: SOP for Protocol and SAP (Statistical Analysis Plan) Integration – V 2.0

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.
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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

  1. Initiate SAP development once the final or near-final version of the protocol is available.
  2. 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

  1. Ensure consistency between:
    • Inclusion/exclusion criteria (SAP vs Protocol)
    • Study design (e.g., crossover, parallel)
    • Pharmacokinetic parameters (Cmax, AUC, Tmax)
    • Timing of assessments
  2. Log cross-verification in Annexure-1: Protocol-SAP Consistency Checklist.
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5.3 Review and Approval Process

  1. Circulate draft SAP to cross-functional teams (Clinical, QA, Regulatory) for feedback.
  2. Document all review comments and version updates in Annexure-2: SAP Review Log.
  3. Obtain final sign-off prior to database lock and statistical programming.

5.4 Amendment Handling

  1. Any protocol amendment impacting endpoints or statistical methods must be reflected in a revised SAP.
  2. Ensure the amended SAP is clearly versioned and submitted to EC/Regulatory if required.

5.5 Filing and Archiving

  1. Archive both protocol and SAP in the Trial Master File (TMF/eTMF) with clear version history.
  2. 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

  1. Protocol-SAP Consistency Checklist – Annexure-1
  2. SAP Review Log – Annexure-2
  3. SAP Finalization and Filing Log – Annexure-3

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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
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