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

Adopted Reference Number: EMA/CHMP/295050/2013 Summary:

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

Adopted Reference Number: EMA/CHMP/295050/2013 Summary:

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 closed Consultation dates: 28/06/2013 to 31/12/2013 Reference Number: EMA/295050/2013 Summary:

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 closed Consultation dates: 29/02/2012 to 30/05/2012 Reference Number: EMA/CHMP/965150/2011 Summary:

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

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