Non-inferiority and equivalence comparisons in clinical trials - Scientific guideline

This document provides guidance on the planning, conduct, analysis and interpretation of non-inferiority and equivalence comparisons in clinical trials. It replaces the 'Guideline on the choice of the non-inferiority margin' (EMEA/CPMP/EWP/2158/99) and ‘Points to consider on switching between superiority and non-inferiority' (CPMP/EWP/482/99).

Current version

Draft guideline on non-inferiority and equivalence comparisons in clinical trials

Draft: consultation open Consultation dates: 13/11/2025 to 31/05/2026 Reference Number: EMA/301654/2025 Summary:

This guideline replaces the 'Guideline on the choice of the non-inferiority margin' (EMEA/CPMP/EWP/2158/99) and ‘Points to consider on switching between superiority and non-inferiority' (CPMP/EWP/482/99).

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Document history

Concept Paper for the Development of a Guideline on Non-Inferiority and Equivalence Comparisons in Clinical Trials

Draft: consultation closed Consultation dates: 16/02/2024 to 31/05/2024 Reference Number: EMA/65012/2024

Points to consider on switching between superiority and non-inferiority

Adopted Reference Number: CPMP/EWP/482/99 Legal effective date: 01/02/2001

Guideline on the choice of the non-inferiority margin

Adopted Reference Number: EMEA/CPMP/EWP/2158/99 Legal effective date: 01/01/2006