ICH E9 statistical principles for clinical trials - Scientific guideline

This document provides guidance on the design, conduct, analysis and evaluation of clinical trials of an investigational product in the context of its overall clinical development. It also assists with preparing application summaries or assessing evidence of efficacy and safety, principally from clinical trials in later phases of development.

The addendum provides clarification on some of the concepts explained in ICH E9. It presents a structured framework for clinical trial planning, conduct, data collection and interpretation of data analyses. The addendum also refines the role of sensitivity analysis to explore robustness of conclusions from the main statistical analysis, both aligned to the same estimand.

Keywords: Statistical methodology, clinical trial design.

Current version

ICH: E 9: Statistical principles for clinical trials - Step 5

AdoptedLegal effective date: 01/09/1998Reference Number: CPMP/ICH/363/96

ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials - Step 5

AdoptedLegal effective date: 30/07/2020Reference Number: EMA/CHMP/ICH/436221/2017

Document history

ICH: E 9: Statistical principles for clinical trials - Step 5

AdoptedLegal effective date: 01/09/1998Reference Number: CPMP/ICH/363/96

ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials - Step 5

AdoptedLegal effective date: 30/07/2020Reference Number: EMA/CHMP/ICH/436221/2017

Draft ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials, step 2b - Revision 1

Consultation dates: 31/08/2017 to 28/02/2018Draft: consultation closedReference Number: EMA/CHMP/ICH/436221/2017Summary:

Having clarity in the trial objectives and accounting explicitly for intercurrent events when describing the treatment effect of interest at the planning stage of a clinical trial are crucial for a clear description of the effects of a medicine. The E9(R1) addendum aims to clarify and extend ICH E9 by elaborating on the choice of estimand and sensitivity analysis in clinical trials, providing a framework to align its planning, design, conduct, analysis and interpretation. The proposed framework aims to facilitate dialogue for the disciplines involved at the planning level of the trial and also between sponsors and regulators regarding the treatment effects of interest that a clinical trial should address. The statistical analysis, aligned to the estimand, will be associated with assumptions and data limitations, the impact of which can be investigated through sensitivity analysis, whose definition and role are clarified in this addendum.

Overview of comments received on draft ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials (EMA/CHMP/ICH/436221/2017)

Reference Number: EMA/744060/2017Summary:

Overview of comments received on draft ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials (EMA/CHMP/ICH/436221/2017)