Estimation of Stratified Mark‐Specific Proportional Hazards Models with Missing Marks

Abstract. An objective of randomized placebo‐controlled preventive HIV vaccine efficacy trials is to assess the relationship between the vaccine effect to prevent infection and the genetic distance of the exposing HIV to the HIV strain represented in the vaccine construct. Motivated by this objective, recently a mark‐specific proportional hazards (PH) model with a continuum of competing risks has been studied, where the genetic distance of the transmitting strain is the continuous ‘mark’ defined and observable only in failures. A high percentage of genetic marks of interest may be missing for a variety of reasons, predominantly because rapid evolution of HIV sequences after transmission before a blood sample is drawn from which HIV sequences are measured. This research investigates the stratified mark‐specific PH model with missing marks where the baseline functions may vary with strata. We develop two consistent estimation approaches, the first based on the inverse probability weighted complete‐case (IPW) technique, and the second based on augmenting the IPW estimator by incorporating auxiliary information predictive of the mark. We investigate the asymptotic properties and finite‐sample performance of the two estimators, and show that the augmented IPW estimator, which satisfies a double robustness property, is more efficient.