| Abstract: | Two-treatment multicentre clinical trials are very common in practice. In cases where a non-parametric analysis is appropriate, a rank-sum test for grouped data called the van Elteren test can be applied. As an alternative approach, one may apply a combination test such as Fisher's combination test or the inverse normal combination test (also called Liptak's method) in order to combine centre-specific P-values. If there are no ties and no differences between centres with regard to the groups’ sample sizes, the inverse normal combination test using centre-specific Wilcoxon rank-sum tests is equivalent to the van Elteren test. In this paper, the van Elteren test is compared with Fisher's combination test based on Wilcoxon rank-sum tests. Data from two multicentre trials as well as simulated data indicate that Fisher's combination of P-values is more powerful than the van Elteren test in realistic scenarios, i.e. when there are large differences between the centres’ P-values, some quantitative interaction between treatment and centre, and/or heterogeneity in variability. The combination approach opens the possibility of using statistics other than the rank sum, and it is also a suitable method for more complicated designs, e.g. when covariates such as age or gender are included in the analysis. |
