title: Estimation of summary protective efficacy using a frailty mixture model for recurrent event time data.
abstract: Recurrent event time data are common in experimental and observational studies. The analytic strategy needs to consider three issues: within-subject event dependence, between-subject heterogeneity in event rates, and the possibility of a nonsusceptible fraction. Motivated by the need to estimate the summary protective efficacy from recurrent event time data as seen in many infectious disease clinical trials, we propose a two-part frailty mixture model that simultaneously accommodates all the three issues. In terms of vaccine action models, the proposed model is a combination of the 'all-or-none' and the 'leaky' models, and the summary protective efficacy is a unified measure of the vaccine's twofold effects in completely or partially protecting the vaccinated individuals against the study event. The model parameters of interest are estimated using the expectation-maximization algorithm with their respective variances estimated using Louis's formula for the expectation-maximization algorithm. The summary protective efficacy is estimated by a composite estimand with its variance estimated using the delta method. The performance of the proposed estimation approach is investigated by a simulation study. Data from a trial of malaria prophylaxis conducted in Ghana are reanalyzed.
authors: Centre for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore. tina.xu@scri.edu.sg
authors: Ying
authors: Y
authors: Xu
authors: Yin Bun
authors: YB
authors: Cheung
authors: K F
authors: KF
authors: Lam
authors: Paul
authors: P
authors: Milligan
mesh_terms: D000465:Algorithms; D000962:Antimalarials / Q000627:therapeutic use*; D003198:Computer Simulation; D004338:Drug Combinations; D005869:Ghana; D006801:Humans; D007223:Infant; D008288:Malaria / Q000401:mortality / Q000517:prevention & control*; D015233:Models, Statistical; D009010:Monte Carlo Method; D016012:Poisson Distribution; D011739:Pyrimethamine / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D013413:Sulfadoxine / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine