Maximum likelihood estimation has been extensively used in the joint analysis of repeated measurements and survival time. However, there is a lack of theoretical justification of the asymptotic properties for the maximum likelihood estimators. This paper intends to fill this gap. Specifically, we prove the consistency of the maximum likelihood estimators and derive their asymptotic distributions. The maximum likelihood estimators are shown to be semiparametrically efficient.
In this work we present a simple estimation procedure for a general frailty model for analysis of prospective correlated failure times. Earlier work showed this method to perform well in a simulation study. Here we provide rigorous large-sample theory for the proposed estimators of both the regression coefficient vector and the dependence parameter, including consistent variance estimators.
This work studies the statistical properties of the maximum penalized likelihood approach in a semi-parametric framework. We recall the penalized likelihood approach for estimating a function and review some asymptotic results. We investigate the properties of two estimators of the variance of maximum penalized likelihood estimators: sandwich estimator and a Bayesian estimator. The coverage rates of confidence intervals based on these estimators are studied through a simulation study of survival data. In a first simulation the coverage rates for the survival function and the hazard function ar…
For discrete-time survival data, conditional likelihood inference in Cox's hazard odds model is theoretically desirable but exact calculation is numerical intractable with a moderate to large number of tied events. Unconditional maximum likelihood estimation over both regression coefficients and baseline hazard probabilities can be problematic with a large number of time intervals. We develop new methods and theory using numerically simple estimating functions, along with model-based and model-robust variance estimation, in hazard probability and odds models. For the probability hazard model, …
There is a difficulty in finding an estimate of variance of the profile likelihood estimator in the joint model of longitudinal and survival data. We solve the difficulty by introducing the ``statistical generalized derivative''. The derivative is used to show the asymptotic normality of the estimator without assuming the second derivative of the density function in the model exists.
Non-parametric maximum likelihood estimation encompasses a group of classic methods to estimate distribution-associated functions from potentially censored and truncated data, with extensive applications in survival analysis. These methods, including the Kaplan-Meier estimator and Turnbull's method, often result in overfitting, especially when the sample size is small. We propose an improvement to these methods by applying kernel smoothing to their raw estimates, based on a BIC-type loss function that balances the trade-off between optimizing model fit and controlling model complexity. In the …
In studies involving lifetimes, observed survival times are frequently censored and possibly subject to biased sampling. In this paper, we model survival times under biased sampling (a.k.a., biased survival data) by a semi-parametric model, in which the selection function $w(t)$ (that leads to the biased sampling) is specified up to an unknown finite dimensional parameter $θ$, while the density function $f(t)$ of the survival times is assumed only to be smooth. Under this model, two estimators are derived to estimate the density function $f$, and a pseudo maximum likelihood estimation procedur…
This paper considers the nonparametric maximum likelihood estimator (MLE) for the joint distribution function of an interval censored survival time and a continuous mark variable. We provide a new explicit formula for the MLE in this problem. We use this formula and the mark specific cumulative hazard function of Huang and Louis (1998) to obtain the almost sure limit of the MLE. This result leads to necessary and sufficient conditions for consistency of the MLE which imply that the MLE is inconsistent in general. We show that the inconsistency can be repaired by discretizing the marks. Our the…
We propose an adjusted likelihood ratio test of two-factor separability (Kronecker product structure) for unbalanced multivariate repeated measures data. Here we address the particular case where the within subject correlation is believed to decrease exponentially in both dimensions (e.g., temporal and spatial dimensions). However, the test can be easily generalized to factor specific matrices of any structure. A simulation study is conducted to assess the inference accuracy of the proposed test. Longitudinal medical imaging data concerning schizophrenia and caudate morphology illustrates the …
The coefficient of determination, known as $R^2$, is commonly used as a goodness-of-fit criterion for fitting linear models. $R^2$ is somewhat controversial when fitting nonlinear models, although it may be generalised on a case-by-case basis to deal with specific models such as the logistic model. Assume we are fitting a parametric distribution to a data set using, say, the maximum likelihood estimation method. A general approach to measure the goodness-of-fit of the fitted parameters, which is advocated herein, is to use a nonparametric measure for comparison between the empirical distributi…
This paper considers a wide family of semiparametric repeated measures regression models, in which the main interest is on estimating population-level quantities such as mean, variance, probabilities etc. Examples of our framework include generalized linear models for clustered/longitudinal data, among many others. We derive plug-in kernel-based estimators of the population level quantities and derive their asymptotic distribution. An example involving estimation of the survival function of hemoglobin measures in the Kenya hemoglobin study data is presented to demonstrate our methodology.
This paper investigates the (in)-consistency of various bootstrap methods for making inference on a change-point in time in the Cox model with right censored survival data. A criterion is established for the consistency of any bootstrap method. It is shown that the usual nonparametric bootstrap is inconsistent for the maximum partial likelihood estimation of the change-point. A new model-based bootstrap approach is proposed and its consistency established. Simulation studies are carried out to assess the performance of various bootstrap schemes.
In this paper we introduce a multilevel specification with stochastic volatility for repeated cross-sectional data. Modelling the time dynamics in repeated cross sections requires a suitable adaptation of the multilevel framework where the individuals/items are modelled at the first level whereas the time component appears at the second level. We perform maximum likelihood estimation by means of a nonlinear state space approach combined with Gauss-Legendre quadrature methods to approximate the likelihood function. We apply the model to the first database of tribal art items sold in the most im…
Motivated by the classical Susceptible-Infected-Recovered (SIR) epidemic models proposed by Kermack and Mckendrick, we consider a class of stochastic compartmental dynamical systems with a notion of partial ordering among the compartments. We call such systems unidirectional Mass Transfer Models (MTMs). We show that there is a natural way of interpreting a uni-directional MTM as a Survival Dynamical System (SDS) that is described in terms of survival functions instead of population counts. This SDS interpretation allows us to employ tools from survival analysis to address various issues with d…
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…
Probabilistic survival predictions from models trained with Maximum Likelihood Estimation (MLE) can have high, and sometimes unacceptably high variance. The field of meteorology, where the paradigm of maximizing sharpness subject to calibration is popular, has addressed this problem by using scoring rules beyond MLE, such as the Continuous Ranked Probability Score (CRPS). In this paper we present the \emph{Survival-CRPS}, a generalization of the CRPS to the survival prediction setting, with right-censored and interval-censored variants. We evaluate our ideas on the mortality prediction task us…
In this work we provide a simple estimation procedure for a general frailty model for analysis of prospective correlated failure times. Rigorous large-sample theory for the proposed estimators of both the regression coefficient vector and the dependence parameter is given, including consistent variance estimators. In a simulation study under the widely used gamma frailty model, our proposed approach was found to have essentially the same efficiency as the EM-based estimator considered by other authors, with negligible difference between the standard errors of the two estimators. The proposed a…
We consider mark-recapture-recovery (MRR) data of animals where the model parameters are a function of individual time-varying continuous covariates. For such covariates, the covariate value is unobserved if the corresponding individual is unobserved, in which case the survival probability cannot be evaluated. For continuous-valued covariates, the corresponding likelihood can only be expressed in the form of an integral that is analytically intractable and, to date, no maximum likelihood approach that uses all the information in the data has been developed. Assuming a first-order Markov proces…
There is a constant need for many healthcare programs to timely address problems with infection prevention and control (IP&C). For example, pathogens can be transmitted among patients with cystic fibrosis (CF) in both the inpatient and outpatient settings within the healthcare system even with the existing recommended IP&C practices, and these pathogens are often associated with negative clinical outcomes. Because of limited and delayed data sharing, CF programs need a reliable method to track infection rates. There are three complex structures in CF registry data: recurrent infections, missin…
Temporal Point Processes (TPP) with partial likelihoods involving a latent structure often entail an intractable marginalization, thus making inference hard. We propose a novel approach to Maximum Likelihood Estimation (MLE) involving approximate inference over the latent variables by minimizing a tight upper bound on the approximation gap. Given a discrete latent variable $Z$, the proposed approximation reduces inference complexity from $O(|Z|^c)$ to $O(|Z|)$. We use convex conjugates to determine this upper bound in a closed form and show that its addition to the optimization objective resul…
This paper considers one-step targeted maximum likelihood estimation method for general competing risks and survival analysis settings where event times take place on the positive real line R+ and are subject to right-censoring. Our interest is overall in the effects of baseline treatment decisions, static, dynamic or stochastic, possibly confounded by pre-treatment covariates. We point out two overall contributions of our work. First, our method can be used to obtain simultaneous inference across all absolute risks in competing risks settings. Second, we present a practical result for achievi…
Cure models have been developed as an alternative modelling approach to conventional survival analysis in order to account for the presence of cured subjects that will never experience the event of interest. Mixture cure models, which model separately the cure probability and the survival of uncured subjects depending on a set of covariates, are particularly useful for distinguishing curative from life-prolonging effects. In practice, it is common to assume a parametric model for the cure probability and a semiparametric model for the survival of the susceptibles. Because of the latent cure st…
In this work we deal with correlated failure time (age at onset) data arising from population-based case-control studies, where case and control probands are selected by population-based sampling and an array of risk factor measures is collected for both cases and controls and their relatives. Parameters of interest are effects of risk factors on the hazard function of failure times and within-family dependencies of failure times after adjusting for the risk factors. Due to the retrospective nature of sampling, a large sample theory for existing methods has not been established. We develop a n…
Targeted maximum likelihood estimation is a general methodology combining flexible ensemble learning and semiparametric efficiency theory in a two-step procedure for estimation of causal parameters. Proposed targeted maximum likelihood procedures for survival and competing risks analysis have so far focused on events taken values in discrete time. We here present a targeted maximum likelihood estimation procedure for event times that take values in R+. We focuson the estimation of intervention-specific mean outcomes with stochastic interventions on a time-fixed treatment. For data-adaptive est…
Analysis of 2 by 2 tables and two-sample survival data has been widely used. Exact calculation is computational intractable for conditional likelihood inference in odds ratio models with large marginals in 2 by 2 tables, or partial likelihood inference in Cox's proportional hazards models with considerable tied event times. Approximate methods are often employed, but their statistical properties have not been formally studied while taking into account the approximation involved. We develop new methods and theory by constructing suitable estimating functions while leveraging knowledge from cond…
There is a surge in medical follow-up studies that include longitudinal covariates in the modeling of survival data. So far, the focus has been largely on right-censored survival data. We consider survival data that are subject to both left truncation and right censoring. Left truncation is well known to produce biased sample. The sampling bias issue has been resolved in the literature for the case which involves baseline or time-varying covariates that are observable. The problem remains open, however, for the important case where longitudinal covariates are present in survival models. A join…
The approximate Bernstein polynomial model, a mixture of beta distributions, is applied to obtain maximum likelihood estimates of the regression coefficients, and the baseline density and survival functions in an accelerated failure time model based on interval censored data including current status data. The rate of convergence of the proposed estimates are given under some conditions for uncensored and interval censored data. Simulation shows that the proposed method is better than its competitors. The proposed method is illustrated by fitting the Breast Cosmetic Data using the accelerated f…
Shape-Preserving Covariate Adjustment via Empirical Likelihood in Randomized Experiment
Zhejiang University of Finance and Economics（浙江财经大学）；University of Wisconsin, Madison（威斯康星大学麦迪逊分校）；University of Washington（华盛顿大学）；Eli Lilly and Company（礼来公司）
In making inference on the relation between failure and exposure histories in the Cox semiparametric model, the maximum partial likelihood estimator (MPLE) of the finite dimensional odds parameter, and the Breslow estimator of the baseline survival function, are known to achieve full efficiency when data is available for all time on all cohort members, even when the covariates are time dependent. When cohort sizes become too large for the collection of complete data, sampling schemes such as nested case control sampling must be used and, under various models, there exist estimators based on th…
We discuss the role of misspecification and censoring on Bayesian model selection in the contexts of right-censored survival and concave log-likelihood regression. Misspecification includes wrongly assuming the censoring mechanism to be non-informative. Emphasis is placed on additive accelerated failure time, Cox proportional hazards and probit models. We offer a theoretical treatment that includes local and non-local priors, and a general non-linear effect decomposition to improve power-sparsity trade-offs. We discuss a fundamental question: what solution can one hope to obtain when (inevitab…
This paper introduces an Ordinary Differential Equation (ODE) notion for survival analysis. The ODE notion not only provides a unified modeling framework, but more importantly, also enables the development of a widely applicable, scalable, and easy-to-implement procedure for estimation and inference. Specifically, the ODE modeling framework unifies many existing survival models, such as the proportional hazards model, the linear transformation model, the accelerated failure time model, and the time-varying coefficient model as special cases. The generality of the proposed framework serves as t…
Robust Survival Estimation under Interval Censoring: Expectation-Maximization and Bayesian Accelerated Failure Time Assessment via Simulation and Application
School of Engineering, Computing and Mathematics（工程、计算与数学学院）；Oxford Brookes University（牛津布鲁克斯大学）
The notion of belief likelihood function of repeated trials is introduced, whenever the uncertainty for individual trials is encoded by a belief measure (a finite random set). This generalises the traditional likelihood function, and provides a natural setting for belief inference from statistical data. Factorisation results are proven for the case in which conjunctive or disjunctive combination are employed, leading to analytical expressions for the lower and upper likelihoods of `sharp' samples in the case of Bernoulli trials, and to the formulation of a generalised logistic regression frame…
