Methods for pooling results from multi-center studies.

Abstract

A multi-center study is one conducted simultaneously in several participating centers following an agreed protocol, where the randomization has been carried out independently within each center. The main consideration for pooling the data from the individual centers is the choice between a weighted analysis, which weights centers relative to the number of patients in them, or an unweighted analysis as the primary statistical method. The unweighted analysis is used to investigate whether there was an interaction between the centers and study groups. Another issue is whether a fixed- or random-effects model should be used. There is unresolved controversy among statisticians about whether to use a weighted (type II) or unweighted analysis (type III), since there are advantages and disadvantages to the use of either method. The weighted analysis provides the most powerful test of the treatment contrast if there is no interaction between treatment and center. If there is an interaction, the unweighted analysis leads to unbiased estimates. Although, from an estimation and hypothesis testing standpoint, there is no need to balance the number of patients between the sites, it is sensible to avoid major imbalances among the study sites. There is agreement among statisticians that a fixed-effects model should be used.