A rank-based mixed model approach to multisite clinical trials.

New rank-based methods for analyzing data from multisite clinical trials are presented in the context of "mixed" linear models. In contrast to current rank methods, the new procedures test for a drug main effect in the presence of a random drug by site interaction (or drug by investigator interaction when there is only one investigator per site). Analogous procedures are also provided for the "fixed-effects" situation, and comparisons are made with current methods. The rationale for an analysis that assumes random investigator effects is described.