The aim of this article is to propose a novel kernel estimator of the baseline function in a general high-dimensional Cox model, for which we derive non-asymptotic rates of convergence. To construct our estimator, we first estimate the regression parameter in the Cox model via a Lasso procedure. We then plug this estimator into the classical kernel estimator of the baseline function, obtained by smoothing the so-called Breslow estimator of the cumulative baseline function. We propose and study an adaptive procedure for selecting the bandwidth, in the spirit of Gold-enshluger and Lepski (2011). We state non-asymptotic oracle inequalities for the final estimator, which reveal the reduction of the rates of convergence when the dimension of the covariates grows.
For statistical inference on regression models with a diverging number of covariates, the existing literature typically makes sparsity assumptions on the inverse of the Fisher information matrix. Such assumptions, however, are often violated under Cox proportion hazards models, leading to biased estimates with under-coverage confidence intervals. We propose a modified debiased lasso approach, which solves a series of quadratic programming problems to approximate the inverse information matrix without posing sparse matrix assumptions. We establish asymptotic results for the estimated regression…
Recently the shape-restricted inference has gained popularity in statistical and econometric literature in order to relax the linear or quadratic covariate effect in regression analyses. The typical shape-restricted covariate effect includes monotonic increasing, decreasing, convexity or concavity. In this paper, we introduce the shape-restricted inference to the celebrated Cox regression model (SR-Cox), in which the covariate response is modeled as shape-restricted additive functions. The SR-Cox regression approximates the shape-restricted functions using a spline basis expansion with data dr…
The relationship between a time-dependent covariate and survival times is usually evaluated via the Cox model. Time-dependent covariates are generally available as longitudinal data collected regularly during the course of the study. A frequent problem, however, is the occurence of missing covariate data. A recent approach to estimation in the Cox model in this case jointly models survival and the longitudinal covariate. However, theoretical justification of this approach is still lacking. In this paper we prove existence and consistency of the maximum likelihood estimators in a joint model. T…
Measurement error in the covariate of main interest (e.g. the exposure variable, or the risk factor) is common in epidemiologic and health studies. It can effect the relative risk estimator or other types of coefficients derived from the fitted regression model. In order to perform a measurement error analysis, one needs information about the error structure. Two sources of validation data are an internal subset of the main data, and external or independent study. For the both sources, the true covariate is measured (that is, without error), or alternatively, its surrogate, which is error-pron…
Functional covariates are common in many medical, biodemographic, and neuroimaging studies. The aim of this paper is to study functional Cox models with right-censored data in the presence of both functional and scalar covariates. We study the asymptotic properties of the maximum partial likelihood estimator and establish the asymptotic normality and efficiency of the estimator of the finite-dimensional estimator. Under the framework of reproducing kernel Hilbert space, the estimator of the coefficient function for a functional covariate achieves the minimax optimal rate of convergence under a…
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 conditions under which our confidence intervals are asymptotically valid, are supported by extensive numerical experimen…
We study problems with multiple missing covariates and partially observed responses. We develop a new framework to handle complex missing covariate scenarios via inverse probability weighting, regression adjustment, and a multiply-robust procedure. We apply our framework to three classical problems: the Cox model from survival analysis, missing response, and binary treatment from causal inference. We also discuss how to handle missing covariates in these scenarios, and develop associated identifying theories and asymptotic theories. We apply our procedure to simulations and an Alzheimer's dise…
The change-plane Cox model is a popular tool for the subgroup analysis of survival data. Despite the rich literature on this model, there has been limited investigation into the asymptotic properties of the estimators of the finite-dimensional parameter. Particularly, the convergence rate, not to mention the asymptotic distribution, has not been fully characterized for the general model where classification is based on multiple covariates. To bridge this theoretical gap, this study proposes a maximum smoothed partial likelihood estimator and establishes the following asymptotic properties. Fir…
Counting processes often written $N=(N_t)_{t\in\mathbb{R}^+}$ are used in several applications of biostatistics, notably for the study of chronic diseases. In the case of respiratory illness it is natural to suppose that the count of the visits of a patient can be described by such a process which intensity depends on environmental covariates. Cox processes (also called doubly stochastic Poisson processes) allows to model such situations. The random intensity then writes $λ(t)=θ(t,Z_t)$ where $θ$ is a non-random function, $t\in\mathbb{R}^+$ is the time variable and $(Z_t)_{t\in\mathbb{R}^+}$ i…
Efficient Poisson Subsampling for the Partially Linear Additive Cox Model
Nankai University（南开大学）；Academy of Mathematics and Systems Science, Chinese Academy of Sciences（中国科学院数学与系统科学研究院）；University of Chinese Academy of Sciences（中国科学院大学）；Changchun University of Technology（长春工业大学）；Liaoning University（辽宁大学）；University of Connecticut（康涅狄格大学）；Tianjin University（天津大学）
The additive hazards model specifies the effect of covariates on the hazard in an additive way, in contrast to the popular Cox model, in which it is multiplicative. As non-parametric model, it offers a very flexible way of modeling time-varying covariate effects. It is most commonly estimated by ordinary least squares. In this paper we consider the case where covariates are bounded, and derive the maximum likelihood estimator under the constraint that the hazard is non-negative for all covariate values in their domain. We describe an efficient algorithm to find the maximum likelihood estimator…
In real supervised learning scenarios, it is not uncommon that the training and test sample follow different probability distributions, thus rendering the necessity to correct the sampling bias. Focusing on a particular covariate shift problem, we derive high probability confidence bounds for the kernel mean matching (KMM) estimator, whose convergence rate turns out to depend on some regularity measure of the regression function and also on some capacity measure of the kernel. By comparing KMM with the natural plug-in estimator, we establish the superiority of the former hence provide concrete…
Box-Cox power transformation is a commonly used methodology to transform the distribution of a non-normal data into a normal one. Estimation of the transformation parameter is crucial in this methodology. In this study, the estimation process is hold via a searching algorithm and is integrated into well-known seven goodness of fit tests for normal distribution. An artificial covariate method is also included for comparative purposes. Simulation studies are implemented to compare the effectiveness of the proposed methods. The methods are also illustrated on two different real life data applicat…
In a functional setting, we propose two test statistics to highlight the Poisson nature of a Cox process when n copies of the process are available. Our approach involves a comparison of the empirical mean and the empirical variance of the functional data and can be seen as an extended version of a classical overdispersion test for counting data. The limiting distributions of our statistics are derived using a functional central limit theorem for c`adl`ag martingales. We also study the asymptotic power of our tests under some local alternatives. Our procedure is easily implementable and does n…
In the analysis of time-to-event data with multiple causes using a competing risks Cox model, often the cause of failure is unknown for some of the cases. The probability of a missing cause is typically assumed to be independent of the cause given the time of the event and covariates measured before the event occurred. In practice, however, the underlying missing-at-random assumption does not necessarily hold. Motivated by colorectal cancer subtype analysis, we develop semiparametric methods to conduct valid analysis, first when additional auxiliary variables are available for cases only. We c…
The use of massive survival data has become common in survival analysis. In this study, a subsampling algorithm is proposed for the Cox proportional hazards model with time-dependent covariates when the sample is extraordinarily large but computing resources are relatively limited. A subsample estimator is developed by maximizing the weighted partial likelihood; it is shown to have consistency and asymptotic normality. By minimizing the asymptotic mean squared error of the subsample estimator, the optimal subsampling probabilities are formulated with explicit expressions. Simulation studies sh…
We review recent advances in modal regression studies using kernel density estimation. Modal regression is an alternative approach for investigating relationship between a response variable and its covariates. Specifically, modal regression summarizes the interactions between the response variable and covariates using the conditional mode or local modes. We first describe the underlying model of modal regression and its estimators based on kernel density estimation. We then review the asymptotic properties of the estimators and strategies for choosing the smoothing bandwidth. We also discuss u…
We consider two isotonic smooth estimators for a monotone baseline hazard in the Cox model, a maximum smooth likelihood estimator and a Grenander-type estimator based on the smoothed Breslow estimator for the cumulative baseline hazard. We show that they are both asymptotically normal at rate $n^{m/(2m+1)}$, where $m\geq 2$ denotes the level of smoothness considered, and we relate their limit behavior to kernel smoothed isotonic estimators studied in Lopuhaä and Musta (2016). It turns out that the Grenander-type estimator is asymptotically equivalent to the kernel smoothed isotonic estimators,…
The Cox regression model is a popular model for analyzing the relationship between a covariate and a survival endpoint. The standard Cox model assumes a constant covariate effect across the entire covariate domain. However, in many epidemiological and other applications, the covariate of main interest is subject to a threshold effect: a change in the slope at a certain point within the covariate domain. Often, the covariate of interest is subject to some degree of measurement error. In this paper, we study measurement error correction in the case where the threshold is known. Several bias corr…
The main purpose is to estimate the regression function of a real random variable with functional explanatory variable by using a recursive nonparametric kernel approach. The mean square error and the almost sure convergence of a family of recursive kernel estimates of the regression function are derived. These results are established with rates and precise evaluation of the constant terms. Also, a central limit theorem for this class of estimators is established. The method is evaluated on simulations and real data set studies.
The purpose of this article is to provide an adaptive estimator of the baseline function in the Cox model with high-dimensional covariates. We consider a two-step procedure : first, we estimate the regression parameter of the Cox model via a Lasso procedure based on the partial log-likelihood, secondly, we plug this Lasso estimator into a least-squares type criterion and then perform a model selection procedure to obtain an adaptive penalized contrast estimator of the baseline function. Using non-asymptotic estimation results stated for the Lasso estimator of the regression parameter, we estab…
We develop a unified theory of designs for controlled experiments that balance baseline covariates a priori (before treatment and before randomization) using the framework of minimax variance and a new method called kernel allocation. We show that any notion of a priori balance must go hand in hand with a notion of structure, since with no structure on the dependence of outcomes on baseline covariates complete randomization (no special covariate balance) is always minimax optimal. Restricting the structure of dependence, either parametrically or non-parametrically, gives rise to certain covari…
Continuous time network data have been successfully modeled by multivariate counting processes, in which the intensity function is characterized by covariate information. However, degree heterogeneity has not been incorporated into the model which may lead to large biases for the estimation of homophily effects. In this paper, we propose a degree-corrected Cox network model to simultaneously analyze the dynamic degree heterogeneity and homophily effects for continuous time directed network data. Since each node has individual-specific in- and out-degree effects in the model, the dimension of t…
Combining patient-level data from clinical trials can connect rare phenomena with clinical endpoints, but statistical techniques applied to a single trial may become problematical when trials are pooled. Estimating the hazard of a binary variable unevenly distributed across trials showcases a common pooled database issue. We studied how an unevenly distributed binary variable can compromise the integrity of fixed and random effects Cox proportional hazards models. We compared fixed effect and random effects Cox proportional hazards models on a set of simulated datasets inspired by a 17-trial p…
The standard Cox model in survival analysis assumes that the covariate effect is constant across the entire covariate domain. However, in many applications, there is interest in considering the possibility that the covariate of main interest is subject to a threshold effect: a change in the slope at a certain point within the covariate domain. Often, the value of this threshold is unknown and need to be estimated. In addition, often, the covariate of interest is not measured exactly, but rather is subject to some degree of measurement error. In this paper, we discuss estimation of the model pa…
The case-cohort study design bypasses resource constraints by collecting certain expensive covariates for only a small subset of the full cohort. Weighted Cox regression is the most widely used approach for analysing case-cohort data within the Cox model, but is inefficient. Alternative approaches based on multiple imputation and nonparametric maximum likelihood suffer from incompatibility and computational issues respectively. We introduce a novel Bayesian framework for case-cohort Cox regression that avoids the aforementioned problems. Users can include auxiliary variables to help predict th…
In the spatial point process context, kernel intensity estimation has been mainly restricted to exploratory analysis due to its lack of consistency. Different methods have been analysed to overcome this problem, and the inclusion of covariates resulted to be one possible solution. In this paper we focus on de\-fi\-ning a theoretical framework to derive a consistent kernel intensity estimator using covariates, as well as a consistent smooth bootstrap procedure. We define two new data-driven bandwidth selectors specifically designed for our estimator: a rule-of-thumb and a plug-in bandwidth base…
A prevalent feature of high-dimensional data is the dependence among covariates, and model selection is known to be challenging when covariates are highly correlated. To perform model selection for the high-dimensional Cox proportional hazards model in presence of correlated covariates with factor structure, we propose a new model, Factor-Augmented Regularized Model for Hazard Regression (FarmHazard), which builds upon latent factors that drive covariate dependence and extends Cox's model. This new model generates procedures that operate in two steps by learning factors and idiosyncratic compo…
Classical penalized likelihood regression problems deal with the case that the independent variables data are known exactly. In practice, however, it is common to observe data with incomplete covariate information. We are concerned with a fundamentally important case where some of the observations do not represent the exact covariate information, but only a probability distribution. In this case, the maximum penalized likelihood method can be still applied to estimating the regression function. We first show that the maximum penalized likelihood estimate exists under a mild condition. In the c…
Fulfilling the promise of precision medicine requires accurately and precisely classifying disease states. For cancer, this includes prediction of survival time from a surfeit of covariates. Such data presents an opportunity for improved prediction, but also a challenge due to high dimensionality. Furthermore, disease populations can be heterogeneous. Integrative modeling is sensible, as the underlying hypothesis is that joint analysis of multiple covariates provides greater explanatory power than separate analyses. We propose an integrative latent variable model that combines factor analysis …
The analysis of randomized trials with time-to-event endpoints is nearly always plagued by the problem of censoring. As the censoring mechanism is usually unknown, analyses typically employ the assumption of non-informative censoring. While this assumption usually becomes more plausible as more baseline covariates are being adjusted for, such adjustment also raises concerns. Pre-specification of which covariates will be adjusted for (and how) is difficult, thus prompting the use of data-driven variable selection procedures, which may impede valid inferences to be drawn. The adjustment for cova…
Statistical inference after variable selection in Cox models: A simulation study
Mathematical Statistics and Artificial Intelligence in Medicine, University of Augsburg（医学中的数学统计与人工智能，乌尔姆大学）；Center for Advanced Analytics and Predictive Sciences (CAAPS), University of Augsburg（高级分析与预测科学中心（CAAPS），乌尔姆大学）
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 simply too large to fit in memory. Many current implementations for time-to-event analysis are ill-suited for these problem…
Stanford University（斯坦福大学）；Université Paris 1 Panthéon-Sorbonne（巴黎第一大学先贤祠-索邦大学）；University of Toronto（多伦多大学）；Northwestern University（西北大学）
The Cox proportional hazards model is a canonical method in survival analysis for prediction of the life expectancy of a patient given clinical or genetic covariates -- it is a linear model in its original form. In recent years, several methods have been proposed to generalize the Cox model to neural networks, but none of these are both numerically correct and computationally efficient. We propose FastCPH, a new method that runs in linear time and supports both the standard Breslow and Efron methods for tied events. We also demonstrate the performance of FastCPH combined with LassoNet, a neura…
Survival data with time-varying covariates are common in practice. If relevant, they can improve on the estimation of survival function. However, the traditional survival forests - conditional inference forest, relative risk forest and random survival forest - have accommodated only time-invariant covariates. We generalize the conditional inference and relative risk forests to allow time-varying covariates. We also propose a general framework for estimation of a survival function in the presence of time-varying covariates. We compare their performance with that of the Cox model and transformat…
Doubly stochastic Poisson processes, also known as the Cox processes, frequently occur in various scientific fields. In this article, motivated primarily by analyzing Cox process data in biophysics, we propose a nonparametric kernel-based inference method. We conduct a detailed study, including an asymptotic analysis, of the proposed method, and provide guidelines for its practical use, introducing a fast and stable regression method for bandwidth selection. We apply our method to real photon arrival data from recent single-molecule biophysical experiments, investigating proteins' conformation…
In the absence of unobserved confounders, matching and weighting methods are widely used to estimate causal quantities including the Average Treatment Effect on the Treated (ATT). Unfortunately, these methods do not necessarily achieve their goal of making the multivariate distribution of covariates for the control group identical to that of the treated, leaving some (potentially multivariate) functions of the covariates with different means between the two groups. When these "imbalanced" functions influence the non-treatment potential outcome, the conditioning on observed covariates fails, an…
