Statistical inferences for data from studies conducted with an aggregated multivariate outcome‐dependent sample design

Outcome‐dependent sampling (ODS) scheme is a cost‐effective sampling scheme where one observes the exposure with a probability that depends on the outcome. The well‐known such design is the case‐control design for binary response, the case‐cohort design for the failure time data, and the general ODS design for a continuous response. While substantial work has been carried out for the univariate response case, statistical inference and design for the ODS with multivariate cases remain under‐developed. Motivated by the need in biological studies for taking the advantage of the available responses for subjects in a cluster, we propose a multivariate outcome‐dependent sampling (multivariate‐ODS) design that is based on a general selection of the continuous responses within a cluster. The proposed inference procedure for the multivariate‐ODS design is semiparametric where all the underlying distributions of covariates are modeled nonparametrically using the empirical likelihood methods. We show that the proposed estimator is consistent and developed the asymptotically normality properties. Simulation studies show that the proposed estimator is more efficient than the estimator obtained using only the simple‐random‐sample portion of the multivariate‐ODS or the estimator from a simple random sample with the same sample size. The multivariate‐ODS design together with the proposed estimator provides an approach to further improve study efficiency for a given fixed study budget. We illustrate the proposed design and estimator with an analysis of association of polychlorinated biphenyl exposure to hearing loss in children born to the Collaborative Perinatal Study. Copyright © 2016 John Wiley & Sons, Ltd.