Nonparametric variable importance for time-to-event outcomes with application to prediction of HIV infection

In survival analysis, complex machine learning algorithms have been increasingly used for predictive modeling. Given a collection of features available for inclusion in a predictive model, it may be of interest to quantify the relative importance of a subset of features for the prediction task at hand. In particular, in HIV vaccine trials, participant baseline characteristics are used to predict the probability of infection over the intended follow-up period, and investigators may wish to understand how much certain types of predictors, such as behavioral factors, contribute toward overall predictiveness. Time-to-event outcomes such as time to infection are often subject to right censoring, and existing methods for assessing variable importance are typically not intended to be used in this setting. We describe a broad class of algorithm-agnostic variable importance measures for prediction in the context of survival data. We propose a nonparametric efficient estimation procedure that incorporates flexible learning of nuisance parameters, yields asymptotically valid inference, and enjoys double-robustness. We assess the performance of our proposed procedure via numerical simulations and analyze data from the HVTN 702 study to inform enrollment strategies for future HIV vaccine trials.