title: Bayesian modeling and prediction of accrual in multi-regional clinical trials.
abstract: In multi-regional trials, the underlying overall and region-specific accrual rates often do not hold constant over time and different regions could have different start-up times, which combined with initial jump in accrual within each region often leads to a discontinuous overall accrual rate, and these issues associated with multi-regional trials have not been adequately investigated. In this paper, we clarify the implication of the multi-regional nature on modeling and prediction of accrual in clinical trials and investigate a Bayesian approach for accrual modeling and prediction, which models region-specific accrual using a nonhomogeneous Poisson process and allows the underlying Poisson rate in each region to vary over time. The proposed approach can accommodate staggered start-up times and different initial accrual rates across regions/centers. Our numerical studies show that the proposed method improves accuracy and precision of accrual prediction compared to existing methods including the nonhomogeneous Poisson process model that does not model region-specific accrual.
authors.affiliation: 1 Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Deng
authors.affiliation: 2 Pfizer Inc., New York, NY, USA.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1 Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
mesh_terms: D001499:Bayes Theorem; D056808:Biostatistics / Q000379:methods; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D015179:Colorectal Neoplasms / Q000628:therapy; D003198:Computer Simulation; D006801:Humans; D015233:Models, Statistical; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D016012:Poisson Distribution; D018709:Statistics, Nonparametric
keywords: Bayesian modeling; clinical trials; multi-regional trials; nonhomogeneous Poisson process; patient accrual