Modeling event count data in the presence of informative dropout with application to bleeding and transfusion events in myelodysplastic syndrome

• Published in: Statistics in medicine Vol. 36; no. 22; pp. 3475 - 3494
• Main Authors: Diao, Guoqing, Zeng, Donglin, Hu, Kuolung, Ibrahim, Joseph G.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 30.09.2017
• Subjects: Bias; Biomedical research; Biometry - methods; Blood diseases; Blood Transfusion; Blood transfusions; Clinical trials; Computer Simulation; Cox model; Hemorrhage; Humans; informative dropout; Likelihood Functions; Medical statistics; Models, Statistical; Myelodysplastic Syndromes; nonparametric maximum likelihood estimators; Patient Dropouts; Poisson regression model; Proportional Hazards Models; Randomized Controlled Trials as Topic; Research Subjects; semiparametric efficiency; Simulation; Statistics, Nonparametric; Treatment Outcome; Poisson regression model; Cox model; nonparametric maximum likelihood estimators; semiparametric efficiency; informative dropout
• ISSN: 0277-6715; 1097-0258; 1097-0258
• DOI: 10.1002/sim.7351

In many biomedical studies, it is often of interest to model event count data over the study period. For some patients, we may not follow up them for the entire study period owing to informative dropout. The dropout time can potentially provide valuable insight on the rate of the events. We propose a joint semiparametric model for event count data and informative dropout time that allows for correlation through a Gamma frailty. We develop efficient likelihood‐based estimation and inference procedures. The proposed nonparametric maximum likelihood estimators are shown to be consistent and asymptotically normal. Furthermore, the asymptotic covariances of the finite‐dimensional parameter estimates attain the semiparametric efficiency bound. Extensive simulation studies demonstrate that the proposed methods perform well in practice. We illustrate the proposed methods through an application to a clinical trial for bleeding and transfusion events in myelodysplastic syndrome. Copyright © 2017 John Wiley & Sons, Ltd.