SOP for Statistical Principles and Deviations (ICH E9/E9(R1))

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Published on 22/12/2025

Standard Operating Procedure for Statistical Principles and Deviations (ICH E9/E9(R1))

SOP No.	CR/OPS/157/2025
Supersedes	NA
Page No.	X of Y
Issue Date	26/08/2025
Effective Date	01/09/2025
Review Date	01/09/2026

Table of Contents

Purpose

The purpose of this SOP is to provide guidance for the application of statistical principles in clinical trials in accordance with ICH E9

and E9(R1). It defines processes for developing statistical analysis plans, handling deviations, applying the estimand framework, and ensuring robust data interpretation that supports regulatory submissions and scientific validity.

Scope

This SOP applies to sponsors, CROs, biostatisticians, investigators, QA staff, and regulatory affairs professionals engaged in statistical planning, monitoring, and reporting of clinical trial data. It covers development of the Statistical Analysis Plan (SAP), handling protocol deviations, and compliance with ICH E9/E9(R1).

Responsibilities

Sponsor: Oversees statistical compliance with ICH E9/E9(R1) and ensures SAP approval.
CRO: Executes statistical analyses and ensures timely reporting of deviations.
Biostatistician: Develops SAP, applies estimand principles, and conducts statistical analyses.
Investigator: Documents site-level deviations impacting statistical analyses.
QA: Audits statistical processes for compliance.

Accountability

The Sponsor’s Head of Biostatistics is accountable for ensuring compliance with statistical principles and deviation management in line with ICH E9/E9(R1).

Procedure

1. Statistical Planning
1.1 Develop SAP before database lock.
1.2 Define endpoints, estimands, and statistical methodologies.
1.3 Record in SAP Development Log (Annexure-1).

2. Handling Protocol Deviations
2.1 Identify and classify deviations (major/minor).
2.2 Assess impact on statistical analyses.
2.3 Document in Deviation Impact Log (Annexure-2).

3. Estimand Framework (ICH E9R1)
3.1 Define treatment effect of interest considering intercurrent events.
3.2 Align estimands with trial objectives and endpoints.
3.3 Document in Estimand Framework Log (Annexure-3).

4. Statistical Analysis
4.1 Conduct primary and secondary analyses per SAP.
4.2 Implement sensitivity analyses to account for missing data.
4.3 Document in Analysis Execution Log (Annexure-4).

5. Reporting and Archiving
5.1 Prepare statistical sections of the CSR.
5.2 Archive SAP, deviations, and statistical outputs in TMF.
5.3 Record in Statistical Archiving Log (Annexure-5).

Abbreviations

SOP: Standard Operating Procedure
SAP: Statistical Analysis Plan
ICH: International Council for Harmonisation
CSR: Clinical Study Report
CRO: Contract Research Organization
QA: Quality Assurance
TMF: Trial Master File
Estimand: A precise description of the treatment effect to be estimated

Documents

SAP Development Log (Annexure-1)
Deviation Impact Log (Annexure-2)
Estimand Framework Log (Annexure-3)
Analysis Execution Log (Annexure-4)
Statistical Archiving Log (Annexure-5)

References

Version: 1.0

Approval Section

Prepared By	Ravi Kumar, Biostatistician
Checked By	Sunita Reddy, QA Officer
Approved By	Dr. Anil Sharma, Head Biostatistics

Annexures

Annexure-1: SAP Development Log

Date	Protocol ID	Activity	Prepared By	Status
01/09/2025	STAT-2025-01	SAP Drafted	Biostatistician	Completed

Annexure-2: Deviation Impact Log

Date	Deviation	Impact Assessment	Reviewed By	Status
03/09/2025	Missed Visit	No Impact	Statistician	Closed

Annexure-3: Estimand Framework Log

Date	Protocol ID	Estimand Defined	Prepared By	Status
05/09/2025	STAT-2025-01	Treatment Effect Adjusted for Dropouts	Biostatistician	Approved

Annexure-4: Analysis Execution Log

Date	Analysis Type	Conducted By	Status
07/09/2025	Primary Endpoint	Statistician	Completed

Annexure-5: Statistical Archiving Log

Date	Document	Archived By	Location	Status
10/09/2025	SAP and Outputs	QA	TMF	Archived

Revision History

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
26/08/2025	00	Initial version	New SOP creation	Head Biostatistics

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