Analysis of data from multiclinic trials

Abstract

Because the clinics in a multiclinic randomized clinical trial represent neither fixed stratification effects nor random classificatory effects, the appropriate analysis of data from such a trial has been the subject of controversy and debate. The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed. Is it ever valid to ignore the effects of clinics in the analysis? Is it ever valid to drop clinics from the analysis? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor? Assuming that clinics will be taken account of in the analysis, should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments? How should the data be analyzed if there is evidence of treatment-by-clinic interaction?