title: Review of rank-based procedures for multicenter clinical trials.
abstract: This article reviews nonparametric alternatives to the mixed model normal theory analysis for the analyses of multicenter clinical trials. Under a mixed model, the traditional analysis is based on maximum likelihood theory under normal errors. This analysis, though, is not robust to outliers. Robust, rank-based, Wilcoxon-type procedures are reviewed for a multicenter clinical trial for the mixed model but without the assumption of normality. These procedures retain the high efficiency of Wilcoxon methods for simple location problems and are based on a fitting criterion which is robust to outliers in response space. A simple weighting scheme can be employed so that the procedures are robust to outliers in factor (design) space as well as response space. These rank-based analyses offer a complete analysis, including estimation of fixed effects and their standard errors, and tests of linear hypotheses. Both rank-based estimates of contrasts and individual treatment effects are reviewed. We illustrate the analyses using real data from a clinical trial.
authors.affiliation: a Food and Drug Administration , Silver Spring , Maryland , USA.
authors.forename: M Mushfiqur
authors.initials: MM
authors.lastname: Rashid
authors.forename: Joseph W
authors.initials: JW
authors.lastname: McKean
authors.forename: John D
authors.initials: JD
authors.lastname: Kloke
mesh_terms: D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003627:Data Interpretation, Statistical; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D016013:Likelihood Functions; D015233:Models, Statistical; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D018401:Sample Size; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents