Replica analysis of overfitting in regression models for time-to-event data

The purpose of this paper is to construct confidence intervals for the regression coefficients in high-dimensional Cox proportional hazards regression models where the number of covariates may be larger than the sample size. Our debiased estimator construction is similar to those in Zhang and Zhang (2014) and van de Geer et al. (2014), but the time-dependent covariates and censored risk sets introduce considerable additional challenges. Our theoretical results, which provide ...

New methods for time-to-event prediction are proposed by extending the Cox proportional hazards model with neural networks. Building on methodology from nested case-control studies, we propose a loss function that scales well to large data sets, and enables fitting of both proportional and non-proportional extensions of the Cox model. Through simulation studies, the proposed loss function is verified to be a good approximation for the Cox partial log-likelihood. The proposed ...

To go beyond standard first-order asymptotics for Cox regression, we develop parametric bootstrap and second-order methods. In general, computation of $P$-values beyond first order requires more model specification than is required for the likelihood function. It is problematic to specify a censoring mechanism to be taken very seriously in detail, and it appears that conditioning on censoring is not a viable alternative to that. We circumvent this matter by employing a refere...

This paper introduces the R package INLAjoint, designed as a toolbox for fitting a diverse range of regression models addressing both longitudinal and survival outcomes. INLAjoint relies on the computational efficiency of the integrated nested Laplace approximations methodology, an efficient alternative to Markov chain Monte Carlo for Bayesian inference, ensuring both speed and accuracy in parameter estimation and uncertainty quantification. The package facilitates the constr...

With the growing availability of large-scale biomedical data, it is often time-consuming or infeasible to directly perform traditional statistical analysis with relatively limited computing resources at hand. We propose a fast subsampling method to effectively approximate the full data maximum partial likelihood estimator in Cox's model, which largely reduces the computational burden when analyzing massive survival data. We establish consistency and asymptotic normality of a ...

The modeling of time-to-event data, also known as survival analysis, requires specialized methods that can deal with censoring and truncation, time-varying features and effects, and that extend to settings with multiple competing events. However, many machine learning methods for survival analysis only consider the standard setting with right-censored data and proportional hazards assumption. The methods that do provide extensions usually address at most a subset of these cha...

We study parametric inference on a rich class of hazard regression models in the presence of right-censoring. Previous literature has reported some inferential challenges, such as multimodal or flat likelihood surfaces, in this class of models for some particular data sets. We formalize the study of these inferential problems by linking them to the concepts of near-redundancy and practical non-identifiability of parameters. We show that the maximum likelihood estimators of th...

It's regarded as an axiom that a good model is one that compromises between bias and variance. The bias is measured in training cost, while the variance of a (say, regression) model is measure by the cost associated with a validation set. If reducing bias is the goal, one will strive to fetch as complex a model as necessary, but complexity is invariably coupled with variance: greater complexity implies greater variance. In practice, driving training cost to near zero does not...

Repeated measures of biomarkers have the potential of explaining hazards of survival outcomes. In practice, these measurements are intermittently measured and are known to be subject to substantial measurement error. Joint modelling of longitudinal and survival data enables us to associate intermittently measured error-prone biomarkers with risks of survival outcomes. Most of the joint models available in the literature have been built on the Gaussian assumption. This makes t...

The Cox model is an indispensable tool for time-to-event analysis, particularly in biomedical research. However, medicine is undergoing a profound transformation, generating data at an unprecedented scale, which opens new frontiers to study and understand diseases. With the wealth of data collected, new challenges for statistical inference arise, as datasets are often high dimensional, exhibit an increasing number of measurements at irregularly spaced time points, and are sim...