Considerations on Analysis of Covariance with a Baseline Covariate: Application in Randomized Clinical Trials

Abstract

In randomized clinical trials, last observation or change from baseline (last observation -baseline) is frequently adopted as an endpoint. In two-arm comparison trials in Japan, a two-sample t-test is often employed in the primary analysis whereas an analysis of covariance (ANCOVA) with baseline covariate assuming equal slopes between the groups is seldom employed. This paper discusses the adoption of the ANCOVA as the primary analysis and recommends its use provided that the assumptions for AN-COVA are satisfied. First, the powers of the t-test and the ANCOVA are presented in order to investigate the extent of how the ANCOVA can increase power. Next, several reasons for not employing the ANCOVA are discussed. Percentage change is also briefly discussed. The power of the ANCOVA with baseline covariate is dependent on the correlation coefficient between baseline and last observation, and on the magnitude relation of variances of baseline and last observation. This paper presents several factors that are responsible for reducing the correlation coefficient and several factors which influence the magnitude relation.