Replica analysis of overfitting in regression models for time to event data: the impact of censoring

Abstract

We use statistical mechanics techniques, viz. the replica method, to model the effect of censoring on overfitting in Cox’s proportional hazards model, the dominant regression method for time-to-event data. In the overfitting regime, Maximum Likelihood (ML) parameter estimators are known to be biased already for small values of the ratio of the number of covariates over the number of samples. The inclusion of censoring was avoided in previous overfitting analyses for mathematical convenience, but is vital to make any theory applicable to real-world medical data, where censoring is ubiquitous. Upon constructing efficient algorithms for solving the new (and more complex) Replica Symmetric (RS) equations and comparing the solutions with numerical simulation data, we find excellent agreement, even for large censoring rates. We then address the practical problem of using the theory to correct the biased ML estimators without knowledge of the data-generating distribution. This is achieved via a novel numerical algorithm that self-consistently approximates all relevant parameters of the data generating distribution while simultaneously solving the RS equations. We investigate numerically the statistics of the corrected estimators, and show that the proposed new algorithm indeed succeeds in removing the bias of the ML estimators, for both the association parameters and for the cumulative hazard.