Fitting additive hazards models for case-cohort studies: a multiple imputation approach

In this paper, we consider fitting semiparametric additive hazards models for case-cohort studies using a multiple imputation approach. In a case-cohort study, main exposure variables are measured only on some selected subjects, but other covariates are often available for the whole cohort. We consider this as a special case of a missing covariate by design. We propose to employ a popular incomplete data method, multiple imputation, for estimation of the regression parameters in additive hazards models. For imputation models, an imputation modeling procedure based on a rejection sampling is developed. A simple imputation modeling that can naturally be applied to a general missing-at-random situation is also considered and compared with the rejection sampling method via extensive simulation studies. In addition, a misspecification aspect in imputation modeling is investigated. The proposed procedures are illustrated using a cancer data example.