Shape Constrained Non‐parametric Estimators of the Baseline Distribution in Cox Proportional Hazards Model

Abstract. We investigate non‐parametric estimation of a monotone baseline hazard and a decreasing baseline density within the Cox model. Two estimators of a non‐decreasing baseline hazard function are proposed. We derive the non‐parametric maximum likelihood estimator and consider a Grenander type estimator, defined as the left‐hand slope of the greatest convex minorant of the Breslow estimator. We demonstrate that the two estimators are strongly consistent and asymptotically equivalent and derive their common limit distribution at a fixed point. Both estimators of a non‐increasing baseline hazard and their asymptotic properties are obtained in a similar manner. Furthermore, we introduce a Grenander type estimator for a non‐increasing baseline density, defined as the left‐hand slope of the least concave majorant of an estimator of the baseline cumulative distribution function, derived from the Breslow estimator. We show that this estimator is strongly consistent and derive its asymptotic distribution at a fixed point.     

HAZARD RATE ESTIMATION FOR CENSORED DATA BY WAVELET METHODS

ABSTRACT

We study the estimation of a hazard rate function based on censored data by non-linear wavelet method. We provide an asymptotic formula for the mean integrated squared error (MISE) of nonlinear wavelet-based hazard rate estimators under randomly censored data. We show this MISE formula, when the underlying hazard rate function and censoring distribution function are only piecewise smooth, has the same expansion as analogous kernel estimators, a feature not available for the kernel estimators. In addition, we establish an asymptotic normality of the nonlinear wavelet estimator.     

An Additive–Multiplicative Cox–Aalen Regression Model

We propose an additive–multiplicative intensity model that extends the Cox regression model as well as the additive Aalen model. Instead of having a simple baseline intensity the extended model uses an additive Aalen model as its covariate dependent baseline. Approximate maximum likelihood estimators of the baseline intensity functions and the relative risk parameters of the Cox model are suggested by solving the score equations. The derived estimator is efficient. We establish the large sample properties of the estimator. The model provides a simple pragmatic way of including time-varying covariate effects.     

Non parametric regression analysis for longitudinal data with time-depending autoregressive error process

This paper considers a non parametric longitudinal model, where the within-subject correlation structure is represented by a time-depending autoregressive error process. An initial estimator without taking into account the within-subject correlation is obtained to fit the time-depending autoregressive error process. With the initial estimator, we construct a two-stage local linear estimator of the mean function. According to the asymptotic normality of the initial and two-stage estimators, it is discovered that the two-stage estimator has a smaller asymptotic variance. The simulation results show us that the two-stage estimation has some good properties. The analysis of a data set demonstrates its application.     

Boundary and Bias Correction in Kernel Hazard Estimation

A new class of local linear hazard estimators based on weighted least square kernel estimation is considered. The class includes the kernel hazard estimator of Ramlau-Hansen (1983), which has the same boundary correction property as the local linear regression estimator (see Fan & Gijbels, 1996). It is shown that all the local linear estimators in the class have the same pointwise asymptotic properties. We derive the multiplicative bias correction of the local linear estimator. In addition we propose a new bias correction technique based on bootstrap estimation of additive bias. This latter method has excellent theoretical properties. Based on an extensive simulation study where we compare the performance of competing estimators, we also recommend the use of the additive bias correction in applied work.     

A Non-stationary Cox Model

The purpose of this paper is to consider the problem of statistical inference about a hazard rate function that is specified as the product of a parametric regression part and a non-parametric baseline hazard. Unlike Cox's proportional hazard model, the baseline hazard not only depends on the duration variable, but also on the starting date of the phenomenon of interest. We propose a new estimator of the regression parameter which allows for non-stationarity in the hazard rate. We show that it is asymptotically normal at root- n and that its asymptotic variance attains the information bound for estimation of the regression coefficient. We also consider an estimator of the integrated baseline hazard, and determine its asymptotic properties. The finite sample performance of our estimators are studied.     

A note on the asymptotic relative efficiency of estimators from the additive hazards model

In this note, the asymptotic variance formulas are explicitly derived and compared between the parametric and semiparametric estimators of a regression parameter and survival probability under the additive hazards model. To obtain explicit formulas, it is assumed that the covariate term including a regression coefficient follows a gamma distribution and the baseline hazard function is constant. The results show that the semiparametric estimator of the regression coefficient parameter is fully efficient relative to the parametric counterpart when the survival time and a covariate are independent, as in the proportional hazards model. Relative to a more realistic case of the parametric additive hazards model with a Weibull baseline, the loss of efficiency of the semiparametric estimator of survival probability is moderate.     

Understanding Estimators of Treatment Effects in Regression Discontinuity Designs

In this paper, we propose two new estimators of treatment effects in regression discontinuity designs. These estimators can aid understanding of the existing estimators such as the local polynomial estimator and the partially linear estimator. The first estimator is the partially polynomial estimator which extends the partially linear estimator by further incorporating derivative differences of the conditional mean of the outcome on the two sides of the discontinuity point. This estimator is related to the local polynomial estimator by a relocalization effect. Unlike the partially linear estimator, this estimator can achieve the optimal rate of convergence even under broader regularity conditions. The second estimator is an instrumental variable estimator in the fuzzy design. This estimator will reduce to the local polynomial estimator if higher order endogeneities are neglected. We study the asymptotic properties of these two estimators and conduct simulation studies to confirm the theoretical analysis.     

Isotonic Window Estimators of the Baseline Hazard Function in Cox's Regression Model Under Order Restriction

The regression model suggested by Cox (1972) has been widely used in survival analysis with censored observations. We propose isotonic window estimators for a monotone baseline hazard function in the Cox regression model. We prove that these estimators are asymptotically normal. The simulati on results presented in the article suggest that the proposed estimator performs better than several existing estimators in the literature     

Smoothing for discrete-valued time series

We deal with smoothed estimators for conditional probability functions of discrete-valued time series { Y_t } under two different settings. When the conditional distribution of Y_t given its lagged values falls in a parametric family and depends on exogenous random variables, a smoothed maximum (partial) likelihood estimator for the unknown parameter is proposed. While there is no prior information on the distribution, various nonparametric estimation methods have been compared and the adjusted Nadaraya–Watson estimator stands out as it shares the advantages of both Nadaraya–Watson and local linear regression estimators. The asymptotic normality of the estimators proposed has been established in the manner of sparse asymptotics, which shows that the smoothed methods proposed outperform their conventional, unsmoothed, parametric counterparts under very mild conditions. Simulation results lend further support to this assertion. Finally, the new method is illustrated via a real data set concerning the relationship between the number of daily hospital admissions and the levels of pollutants in Hong Kong in 1994–1995. An ad hoc model selection procedure based on a local Akaike information criterion is proposed to select the significant pollutant indices.     

Smoothed Isotonic Estimators of a Monotone Baseline Hazard in the Cox Model

We consider the smoothed maximum likelihood estimator and the smoothed Grenander‐type estimator for a monotone baseline hazard rate λ ₀ in the Cox model. We analyze their asymptotic behaviour and show that they are asymptotically normal at rate n ^{m /(2m +1)}, when λ ₀ is m ≥2 times continuously differentiable, and that both estimators are asymptotically equivalent. Finally, we present numerical results on pointwise confidence intervals that illustrate the comparable behaviour of the two methods.     

Model selection and post estimation based on a pretest for logistic regression models

ABSTRACT

This article addresses the problem of parameter estimation of the logistic regression model under subspace information via linear shrinkage, pretest, and shrinkage pretest estimators along with the traditional unrestricted maximum likelihood estimator and restricted estimator. We developed an asymptotic theory for the linear shrinkage and pretest estimators and compared their relative performance using the notion of asymptotic distributional bias and asymptotic quadratic risk. The analytical results demonstrated that the proposed estimation strategies outperformed the classical estimation strategies in a meaningful parameter space. Detailed Monte-Carlo simulation studies were conducted for different combinations and the performance of each estimation method was evaluated in terms of simulated relative efficiency. The results of the simulation study were in strong agreement with the asymptotic analytical findings. Two real-data examples are also given to appraise the performance of the estimators.     

Effects of model misspecification on tests of no randomized treatment effect arising from Cox's proportional hazards model

We examine the asymptotic and small sample properties of model-based and robust tests of the null hypothesis of no randomized treatment effect based on the partial likelihood arising from an arbitrarily misspecified Cox proportional hazards model. When the distribution of the censoring variable is either conditionally independent of the treatment group given covariates or conditionally independent of covariates given the treatment group, the numerators of the partial likelihood treatment score and Wald tests have asymptotic mean equal to 0 under the null hypothesis, regardless of whether or how the Cox model is misspecified. We show that the model-based variance estimators used in the calculation of the model-based tests are not, in general, consistent under model misspecification, yet using analytic considerations and simulations we show that their true sizes can be as close to the nominal value as tests calculated with robust variance estimators. As a special case, we show that the model-based log-rank test is asymptotically valid. When the Cox model is misspecified and the distribution of censoring depends on both treatment group and covariates, the asymptotic distributions of the resulting partial likelihood treatment score statistic and maximum partial likelihood estimator do not, in general, have a zero mean under the null hypothesis. Here neither the fully model-based tests, including the log-rank test, nor the robust tests will be asymptotically valid, and we show through simulations that the distortion to test size can be substantial.     

Nonparametric hazard rate estimation by orthogonal wavelet methods

We propose linear and nonlinear wavelet-based hazard rate estimators where the linear estimator is equivalent to a generalized kernel estimator. An asymptotic formula for the mean integrated squared error (MISE) of the nonlinear wavelet-based hazard rate estimator is provided. It is shown that the MISE formula for the nonlinear estimator is available for hazard rates which are smooth only in a piecewise sense, a feature not available for the kernel estimators.     

Estimating the First- and Second-Order Parameters of a Heavy-Tailed Distribution

This paper suggests censored maximum likelihood estimators for the first‐ and second‐order parameters of a heavy‐tailed distribution by incorporating the second‐order regular variation into the censored likelihood function. This approach is different from the bias‐reduced maximum likelihood method proposed by Feuerverger and Hall in 1999. The paper derives the joint asymptotic limit for the first‐ and second‐order parameters under a weaker assumption. The paper also demonstrates through a simulation study that the suggested estimator for the first‐order parameter is better than the estimator proposed by Feuerverger and Hall although these two estimators have the same asymptotic variances.     

Hazard-based nonparametric survivor function estimation

Summary.  A representation is developed that expresses the bivariate survivor function as a function of the hazard function for truncated failure time variables. This leads to a class of nonparametric survivor function estimators that avoid negative mass. The transformation from hazard function to survivor function is weakly continuous and compact differentiable, so that such properties as strong consistency, weak convergence to a Gaussian process and bootstrap applicability for a hazard function estimator are inherited by the corresponding survivor function estimator. The set of point mass assignments for a survivor function estimator is readily obtained by using a simple matrix calculation on the set of hazard rate estimators. Special cases arise from a simple empirical hazard rate estimator, and from an empirical hazard rate estimator following the redistribution of singly censored observations within strips. The latter is shown to equal van der Laan's repaired nonparametric maximum likelihood estimator, for which a Greenwood-like variance estimator is given. Simulation studies are presented to compare the moderate sample performance of various nonparametric survivor function estimators.     

Marginal hazard regression for correlated failure time data with auxiliary covariates

In many biomedical studies, it is common that due to budget constraints, the primary covariate is only collected in a randomly selected subset from the full study cohort. Often, there is an inexpensive auxiliary covariate for the primary exposure variable that is readily available for all the cohort subjects. Valid statistical methods that make use of the auxiliary information to improve study efficiency need to be developed. To this end, we develop an estimated partial likelihood approach for correlated failure time data with auxiliary information. We assume a marginal hazard model with common baseline hazard function. The asymptotic properties for the proposed estimators are developed. The proof of the asymptotic results for the proposed estimators is nontrivial since the moments used in estimating equation are not martingale-based and the classical martingale theory is not sufficient. Instead, our proofs rely on modern empirical process theory. The proposed estimator is evaluated through simulation studies and is shown to have increased efficiency compared to existing methods. The proposed method is illustrated with a data set from the Framingham study.     

Cox regression with missing covariate data using a modified partial likelihood method

Missing covariate values is a common problem in survival analysis. In this paper we propose a novel method for the Cox regression model that is close to maximum likelihood but avoids the use of the EM-algorithm. It exploits that the observed hazard function is multiplicative in the baseline hazard function with the idea being to profile out this function before carrying out the estimation of the parameter of interest. In this step one uses a Breslow type estimator to estimate the cumulative baseline hazard function. We focus on the situation where the observed covariates are categorical which allows us to calculate estimators without having to assume anything about the distribution of the covariates. We show that the proposed estimator is consistent and asymptotically normal, and derive a consistent estimator of the variance–covariance matrix that does not involve any choice of a perturbation parameter. Moderate sample size performance of the estimators is investigated via simulation and by application to a real data example.     

Preliminary test and Bayes Estimation of a Location Parameter Under Blinex Loss

In this article, the preliminary test estimator is considered under the BLINEX loss function. The problem under consideration is the estimation of the location parameter from a normal distribution. The risk under the null hypothesis for the preliminary test estimator, the exact risk function for restricted maximum likelihood and approximated risk function for the unrestricted maximum likelihood estimator, are derived under BLINEX loss and the different risk structures are compared to one another both analytically and computationally. As a motivation on the use of BLINEX rather than LINEX, the risk for the preliminary test estimator under BLINEX loss is compared to the risk of the preliminary test estimator under LINEX loss and it is shown that the LINEX expected loss is higher than BLINEX expected loss. Furthermore, two feasible Bayes estimators are derived under BLINEX loss, and a feasible Bayes preliminary test estimator is defined and compared to the classical preliminary test estimator.     

Focused information criterion and model averaging based on weighted composite quantile regression

We study the focused information criterion and frequentist model averaging and their application to post‐model‐selection inference for weighted composite quantile regression (WCQR) in the context of the additive partial linear models. With the non‐parametric functions approximated by polynomial splines, we show that, under certain conditions, the asymptotic distribution of the frequentist model averaging WCQR‐estimator of a focused parameter is a non‐linear mixture of normal distributions. This asymptotic distribution is used to construct confidence intervals that achieve the nominal coverage probability. With properly chosen weights, the focused information criterion based WCQR estimators are not only robust to outliers and non‐normal residuals but also can achieve efficiency close to the maximum likelihood estimator, without assuming the true error distribution. Simulation studies and a real data analysis are used to illustrate the effectiveness of the proposed procedure.