# Basic Considerations for the Consistency Evaluation Based on ICH E17 Guideline

## TL;DR

This paper outlines key considerations for evaluating treatment consistency across regions in global clinical trials, aiming to improve regulatory alignment and trial implementation.

## Contribution

The paper provides a comprehensive framework for consistency evaluation in multi-regional clinical trials under the ICH E17 guideline.

## Key findings

- Design and statistical considerations for evaluating consistency in pharmacokinetics, efficacy, and safety are detailed.
- Strategies for addressing challenges like non-inferiority and adaptive designs are proposed.
- An exploratory framework is introduced for investigating potential inconsistencies observed in trials.

## Abstract

In the International Council for Harmonisation (ICH) guidance on General Principles for Planning and Design of Multi-Regional Clinical Trials (E17), it is important to evaluate the consistency of treatment effect across regions in a multi-regional clinical trial (MRCT). In this paper, we elaborated on some basic considerations to evaluate consistency. We first list the design considerations, and then provide consistency evaluation and interpretation on pharmacokinetics, pharmacodynamics, efficacy, safety, and benefit-risk. Furthermore, we consider special situations including non-inferiority, multiple primary endpoints, interim analyses with delayed treatment effect, adaptive design, single-arm studies, rare diseases, and statistical methods for regional treatment effect estimate and consistency evaluation. Finally, if potential inconsistency is anticipated or observed in the MRCT, an exploratory framework is provided for further investigations. Overall, this paper elaborates on consistency evaluation in MRCT, discusses possible challenges in reality and also provides strategies and methods to overcome these challenges. This could help consensus across health authorities, industries, and academic societies, which could further facilitate consistency evaluation and MRCT implementation. Effective communication with regulatory authorities is encouraged to obtain an acceptance of a global approach.

The online version contains supplementary material available at 10.1007/s43441-024-00737-z.