International Journal of Statistics in Medical Research

Evaluating Treatment Effect in Multicenter Trials with Small Centers Using Survival Modeling
Pages 8-25
Usha S. Govindarajulu and Elizabeth J. Malloy
Published: 27 January 2015

Abstract: Clinical trials of rare diseases commonly enlist several centers to achieve recruitment goals. The aim of this study is to examine the estimation of treatment effects for survival outcomes in multicenter clinical trials with varying numbers of centers and few patients per center for rarer disease outcomes (i.e. rare cancers). We modeled the heterogeneity between centers using Cox frailty models to account for the variability in patients and patient care between centers and examined measures of model fit via smoothed functions of a prognostic factor. Through a simulation study, we were able to examine the consequence of having only a few centers or a few patients per center on the treatment and prognostic factor effects and model performance indices. Overall, we found it is preferable to have more patients per site and more sites in a multicenter trial as expected. However, having a few patients per site is feasible if there are many sites in a trial.

Keywords: Frailty, survival, clinical trial, prognostic factor, rare disease.
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