Re-estimation of Recruitment Duration with Adjustment of Center Effects in Multicenter Clinical Trials

Abstract

Recruitment of patients is one of main issues of clinical trials, but there are neither standard statistical methods of monitoring nor those of decision-making. Methods for predicting future accrual of patients and re-estimating recruitment duration in a midpoint of trial seem useful. However, there is no method that considers a variability of recruitment rate in participating site (center effects). In this study, we propose a method for re-estimation of recruitment duration with adjustment of center effects in multicenter clinical trials utilizing an empirical Bayes approach and a normal approximation of posterior predictive distribution using Edgeworth expansion. We applied our methods to the randomized clinical trial of adjuvant therapy for breast cancer. In the application, the observed number of patients in the end of trial can be predicted closer with adjustment of center effects than without adjustment, because the effect of the increase of participating sites was modeled explicitly with adjustment of center effects.