Bayesian design of superiority clinical trials for recurrent events data with applications to bleeding and transfusion events in myelodyplastic syndrome.

TitleBayesian design of superiority clinical trials for recurrent events data with applications to bleeding and transfusion events in myelodyplastic syndrome.
Publication TypeJournal Article
Year of Publication2014
AuthorsChen, Ming-Hui, Joseph G. Ibrahim, Donglin Zeng, Kuolung Hu, and Catherine Jia
JournalBiometrics
Volume70
Issue4
Pagination1003-13
Date Published2014 Dec
ISSN1541-0420
KeywordsAlgorithms, Bayes Theorem, Blood Transfusion, Clinical Trials as Topic, Computer Simulation, Data Interpretation, Statistical, Hemorrhage, Humans, Models, Statistical, Myelodysplastic Syndromes, Outcome Assessment, Health Care, Prevalence, Recurrence, Reproducibility of Results, Research Design, Risk Factors, Sample Size, Sensitivity and Specificity
Abstract

In many biomedical studies, patients may experience the same type of recurrent event repeatedly over time, such as bleeding, multiple infections and disease. In this article, we propose a Bayesian design to a pivotal clinical trial in which lower risk myelodysplastic syndromes (MDS) patients are treated with MDS disease modifying therapies. One of the key study objectives is to demonstrate the investigational product (treatment) effect on reduction of platelet transfusion and bleeding events while receiving MDS therapies. In this context, we propose a new Bayesian approach for the design of superiority clinical trials using recurrent events frailty regression models. Historical recurrent events data from an already completed phase 2 trial are incorporated into the Bayesian design via the partial borrowing power prior of Ibrahim et al. (2012, Biometrics 68, 578-586). An efficient Gibbs sampling algorithm, a predictive data generation algorithm, and a simulation-based algorithm are developed for sampling from the fitting posterior distribution, generating the predictive recurrent events data, and computing various design quantities such as the type I error rate and power, respectively. An extensive simulation study is conducted to compare the proposed method to the existing frequentist methods and to investigate various operating characteristics of the proposed design.

DOI10.1111/biom.12215
Alternate JournalBiometrics
Original PublicationBayesian design of superiority clinical trials for recurrent events data with applications to bleeding and transfusion events in myelodyplastic syndrome.
PubMed ID25041037
PubMed Central IDPMC4276515
Grant ListR01 CA082659 / CA / NCI NIH HHS / United States
CA 74015 / CA / NCI NIH HHS / United States
R37 GM047845 / GM / NIGMS NIH HHS / United States
R01 GM070335 / GM / NIGMS NIH HHS / United States
GM 70335 / GM / NIGMS NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
R01 CA074015 / CA / NCI NIH HHS / United States
Project: