THE APPLICATION OF REML IN CLINICAL-TRIALS

Residual maximum likelihood (REML) is a technique for estimating varia nce components in multi-classified data. In contrast to analysis of va riance it can be routinely applied to unbalanced data and avoids some of the problems of biased variance estimates found with standard maxim um likelihood estimation. The full REML method is of particular value for the analysis of unbalanced clinical trials as it allows recovery o f all the available information on treatment effects which can lead to significant improvements in their precision. The use of REML has unti l recently been limited by heavy computational requirements and lack o f readily available software. This is no longer such a restriction, ho wever, as REML procedures are now available in several widely-used sta tistical packages, including BMDP, Genstat and SAS. This paper describ es the REML technique and discusses its application to three common ty pes of clinical trial: crossover, repeated measures and multicentre.