NONPARAMETRIC INFERENCE FOR IMMUNE RESPONSE THRESHOLDS OF RISK IN VACCINE STUDIES.

An important objective in vaccine studies entails identifying an immune response which is predictive of disease risk. Nonparametric methods are developed for inference on immune response thresholds that are associated with specified levels of disease risk, including where the risk level is zero. This threshold is defined as the minimum immune response value above which disease risk is less than or equal to the desired level. The proposed nonparametric methods are compared to previously developed parametric methods in simulation studies. The methods are extended for use in studies that only measure the immune response in a subset of participants, such as case-cohort or case-control studies, and with right censored time to disease outcomes. Finally, these methods are used to estimate neutralizing antibody thresholds for virologically confirmed dengue risk using data from two recent dengue vaccine trials.