title: Estimation of the treatment difference in multicenter trials.
abstract: The three fixed effects estimators of a treatment,difference are compared under conditions of random enrollment in a multicenter clinical trial. These comparisons are performed by assuming five different enrollment schemes. The estimators are compared via simulation using their expected mean squared errors. Unlike previous discussions of these three estimators, we take explicit account of the effect of centers that fail to enroll patients to one or both treatment arms. Within each center, we assume enrollment follows a Poisson process and consider the two situations in which the mean rate of this process is the same in every center and in which the mean rates are sampled from a gamma distribution. The effect of patient dropout is studied as well as the effect of increasing the number of centers. Simulations show that for many sound scenarios, the simpler estimator corresponding to the simplest model works better, even for the cases when data are generated by more complex models.
authors.affiliation: Department of Biometrics, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA.
authors.forename: Valerii
authors.initials: V
authors.lastname: Fedorov
authors.forename: Byron
authors.initials: B
authors.lastname: Jones
authors.forename: Matthew
authors.initials: M
authors.lastname: Jones
authors.forename: Anatoly
authors.initials: A
authors.lastname: Zhigljavsky
mesh_terms: D000465:Algorithms; D003627:Data Interpretation, Statistical; D006801:Humans; D015233:Models, Statistical; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data*; D010352:Patient Dropouts; D018579:Patient Selection; D016012:Poisson Distribution; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results