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Linear mixed‐effects models for central statistical monitoring of multicenter clinical trials
Author(s) -
Desmet L.,
Venet D.,
Doffagne E.,
Timmermans C.,
Burzykowski T.,
Legrand C.,
Buyse M.
Publication year - 2014
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.6294
Subject(s) - computer science , context (archaeology) , clinical trial , mixed model , variance (accounting) , generalized linear mixed model , sample size determination , statistics , data quality , statistical model , data mining , econometrics , medicine , mathematics , artificial intelligence , machine learning , operations management , geography , metric (unit) , economics , business , archaeology , accounting , pathology
Multicenter studies are widely used to meet accrual targets in clinical trials. Clinical data monitoring is required to ensure the quality and validity of the data gathered across centers. One approach to this end is central statistical monitoring, which aims at detecting atypical patterns in the data by means of statistical methods. In this context, we consider the simple case of a continuous variable, and we propose a detection procedure based on a linear mixed‐effects model to detect location differences between each center and all other centers. We describe the performance of the procedure as a function of contamination rate and signal‐to‐noise ratio. We investigate the effect of center size and variance structure and illustrate the use of the procedure using data from two multicenter clinical trials. Copyright © 2014 John Wiley & Sons, Ltd.