A discrete-time survival model with random effects for designing and analyzing repeated low-dose challenge experiments.

ABSTRACT: Repeated low-dose (RLD) challenge designs are important in HIV vaccine research. Current methods for RLD designs rely heavily on an assumption of homogeneous risk of infection among animals, which, upon violation, can lead to invalid inferences and underpowered study designs. We propose to fit a discrete-time survival model with random effects that allows for heterogeneity in the risk of infection among animals and allows for predetermined challenge dose changes over time. Based on this model, we derive likelihood ratio tests and estimators for vaccine efficacy. A two-stage approach is proposed for optimizing the RLD design under cost constraints. Simulation studies demonstrate good finite sample properties of the proposed method and its superior performance compared to existing methods. W

SUBMITTER: Kang C 

PROVIDER: S-EPMC4786638 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature