Estimation of the Treatment Difference in Multicentre Trials Taking into Account Random Enrolment
Estimation of the Treatment Difference in Multicentre Trials Taking into Account Random Enrolment
Valerii Fedorov, Byron Jones, Matthew Jones and Anatoly Zhigljavsky
ABSTRACT. The three fixed effects estimators of a treatment difference are compared under conditions of random enrolment in a multicentre clinical trial. These comparisons are done assuming five different enrolment 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 centres that fail to enrol patients to one or both treatment arms.
Within each centre we assume enrolment follows a Poisson process and consider the two situations where the mean rate of this process is the same in every centre and where the mean rates are sampled from a gamma distribution. The effect of patient drop-out is studied as well as the effect of increasing the number of centres.
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.
