Adjustment for baseline covariates in clinical trials - Scientific guideline

This document provides advice on how to address important baseline covariates in designing, analysing and reporting clinical trials. It mainly focuses on confirmatory randomised trials.

Keywords: Baseline covariates, stratification, dynamic allocation, multicentre trials, baseline imbalance

Current effective version

Guideline on adjustment for baseline covariates in clinical trials

AdoptedReference Number: EMA/CHMP/295050/2013Summary:

Baseline covariates impact the outcome in many clinical trials. Although baseline adjustment is not always necessary, in case of a strong or moderate association between a baseline covariate(s) and the primary outcome measure, adjustment for such covariate(s) generally improves the efficiency of the analysis and avoids conditional bias from chance covariate imbalance.

Document history

Guideline on adjustment for baseline covariates in clinical trials

AdoptedReference Number: EMA/CHMP/295050/2013Summary:

Baseline covariates impact the outcome in many clinical trials. Although baseline adjustment is not always necessary, in case of a strong or moderate association between a baseline covariate(s) and the primary outcome measure, adjustment for such covariate(s) generally improves the efficiency of the analysis and avoids conditional bias from chance covariate imbalance.

Overview of comments received on 'Guideline on adjustment for baseline covariates'

Reference Number: EMA/40143/2014

Draft guideline on adjustment for baseline covariates

Draft: consultation closedConsultation dates: 28/06/2013 to 31/12/2013Reference Number: EMA/295050/2013Summary:

Baseline covariates impact the outcome in many clinical trials. Although baseline adjustment is not always necessary, in case of a strong or moderate association between a baseline covariate(s) and the primary outcome measure, adjustment for such covariate(s) generally improves the efficiency of the analysis. Besides editorial changes the major change with this revision of the guideline relates to the use of dynamic allocation methods.

Concept paper on the need to revise the points to consider on adjustment for baseline covariates

Draft: consultation closedConsultation dates: 29/02/2012 to 30/05/2012Reference Number: EMA/CHMP/965150/2011Summary:

The Committee for Medicinal Products for Human Use points to consider on adjustment for baseline covariates came into operation in 2003. Since then, they have been widely used by both industry and regulators when planning and assessing confirmatory clinical trials. Changes to the current text are intended to reflect the current state of scientific knowledge in this document which could evolve into a guideline.

Points to consider on adjustment for baseline covariates

AdoptedReference Number: CPMP/EWP/2863/99Legal effective date: 01/11/2003