  The purpose of this paper is to investigate and develop methods for analysis
of multi-center randomized clinical trials which only rely on the randomization
process as a basis of inference. Our motivation is prompted by the fact that
most current statistical procedures used in the analysis of randomized
multi-center studies are model based. The randomization feature of the trials
is usually ignored. An important characteristic of model based analysis is that
it is straightforward to model covariates. Nevertheless, in nearly all model
based analyses, the effects due to different centers and, in general, the
design of the clinical trials are ignored. An alternative to a model based
analysis is to have analyses guided by the design of the trial. Our development
of design based methods allows the incorporation of centers as well as other
features of the trial design. The methods make use of conditioning on the
ancillary statistics in the sample space generated by the randomization
process. We have investigated the power of the methods and have found that, in
the presence of center variation, there is a significant increase in power. The
methods have been extended to group sequential trials with similar increases in
power.
