Assessing heterogeneity in multicenter clinical trials using the frailty model

Abstract

The key idea of this thesis is that although patients treated within large multicenter trials are all treated according to the same protocol, there could still remain some " heterogeneity" between centers and that such heterogeneity, either in outcome, in the size of the treatment effect or in prognostic index effect, deserves further investigation. The main objective of this thesis is to demonstrate how frailty model methodology can be used to quantify such heterogeneity, to interpret it based on medically relevant quantities, and to identify center and patient specific factors explaining this heterogeneity. ...