Model validity range in multicentre clinical trials

Analyses of multicentre trials consider the estimated treatment effect differences of the individual centres and combine them into an estimate of the overall treatment effect. There has been much debate in the literature concerning the best way to combine these treatment effect differences. We emphasize that first of all one should define the combined response to treatment (CRT), the object that has to be estimated from the results of a multicentre clinical trial. Having the defined target in mind, the least squares estimators of the CRT under three possible models of increasing complexity for multicentre data axe derived. We compare these estimators in terms of their mean squared errors. It is shown that the choice of CRT determines not only the best estimator, but also the allocation of patients among the centres that minimizes the MSE.