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.     

On Local Polynomial Modelling of the Additive Risk Model

The additive risk model provides an alternative modelling technique for failure time data to the proportional hazards model. In this article, we consider the additive risk model with a nonparametric risk effect. We study estimation of the risk function and its derivatives with a parametric and an unspecified baseline hazard function respectively. The resulting estimators are the local likelihood and the local score estimators. We establish the asymptotic normality of the estimators and show that both methods have the same formula for asymptotic bias but different formula for variance. It is found that, in some special cases, the local score estimator is of the same efficiency as the local likelihood estimator though it does not use the information about the baseline hazard function. Another advantage of the local score estimator is that it has a closed form and is easy to implement. Some simulation studies are conducted to evaluate and compare the performance of the two estimators. A numerical example is used for illustration.     

A Spline‐Based Semiparametric Maximum Likelihood Estimation Method for the Cox Model with Interval‐Censored Data

Abstract. We propose a spline‐based semiparametric maximum likelihood approach to analysing the Cox model with interval‐censored data. With this approach, the baseline cumulative hazard function is approximated by a monotone B‐spline function. We extend the generalized Rosen algorithm to compute the maximum likelihood estimate. We show that the estimator of the regression parameter is asymptotically normal and semiparametrically efficient, although the estimator of the baseline cumulative hazard function converges at a rate slower than root‐n. We also develop an easy‐to‐implement method for consistently estimating the standard error of the estimated regression parameter, which facilitates the proposed inference procedure for the Cox model with interval‐censored data. The proposed method is evaluated by simulation studies regarding its finite sample performance and is illustrated using data from a breast cosmesis study.     

An Asymptotic Linear Representation for the Breslow Estimator

We provide an asymptotic linear representation for the Breslow estimator of the baseline cumulative hazard function in the Cox model. Our representation consists of an average of independent random variables and a term involving the difference between the maximum partial likelihood estimator and the underlying regression parameter. The order of the remainder term is arbitrarily close to n ^?1.     

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.     

A Wald-type test statistic based on robust modified median estimator in logistic regression models

In this paper a new robust estimator, modified median estimator, is introduced and studied for the logistic regression model. This estimator is based on the median estimator considered in Hobza et al. [Robust median estimator in logistic regression. J Stat Plan Inference. 2008;138:3822–3840]. Its asymptotic distribution is obtained. Using the modified median estimator, we also consider a Wald-type test statistic for testing linear hypotheses in the logistic regression model and we obtain its asymptotic distribution under the assumption of random regressors. An extensive simulation study is presented in order to analyse the efficiency as well as the robustness of the modified median estimator and Wald-type test based on it.     

Local linear kernel estimation for discontinuous nonparametric regression functions

In this paper, we consider using a local linear (LL) smoothing method to estimate a class of discontinuous regression functions. We establish the asymptotic normality of the integrated square error (ISE) of a LL-type estimator and show that the ISE has an asymptotic rate of convergence as good as for smooth functions, and the asymptotic rate of convergence of the ISE of the LL estimator is better than that of the Nadaraya-Watson (NW) and the Gasser-Miiller (GM) estimators.     

On maximum likelihood estimation of the semi-parametric Cox model with time-varying covariates

Including time-varying covariates is a popular extension to the Cox model and a suitable approach for dealing with non-proportional hazards. However, partial likelihood (PL) estimation of this model has three shortcomings: (i) estimated regression coefficients can be less accurate in small samples with heavy censoring; (ii) the baseline hazard is not directly estimated and (iii) a covariance matrix for both the regression coefficients and the baseline hazard is not easily produced.We address these by developing a maximum likelihood (ML) approach to jointly estimate regression coefficients and baseline hazard using a constrained optimisation ensuring the latter''s non-negativity. We demonstrate asymptotic properties of these estimates and show via simulation their increased accuracy compared to PL estimates in small samples and show our method produces smoother baseline hazard estimates than the Breslow estimator.Finally, we apply our method to two examples, including an important real-world financial example to estimate time to default for retail home loans. We demonstrate using our ML estimate for the baseline hazard can give much clearer corroboratory evidence of the ‘humped hazard’, whereby the risk of loan default rises to a peak and then later falls.     

Bootstrapping quantiles in a fixed design regression model with censored data

We consider the problem of estimating the quantiles of a distribution function in a fixed design regression model in which the observations are subject to random right censoring. The quantile estimator is defined via a conditional Kaplan-Meier type estimator for the distribution at a given design point. We establish an a.s. asymptotic representation for this quantile estimator, from which we obtain its asymptotic normality. Because a complicated estimation procedure is necessary for estimating the asymptotic bias and variance, we use a resampling procedure, which provides us, via an asymptotic representation for the bootstrapped estimator, with an alternative for the normal approximation.     

Inference for proportional hazard model with propensity score

Since the publication of the seminal paper by Cox (1972), proportional hazard model has become very popular in regression analysis for right censored data. In observational studies, treatment assignment may depend on observed covariates. If these confounding variables are not accounted for properly, the inference based on the Cox proportional hazard model may perform poorly. As shown in Rosenbaum and Rubin (1983), under the strongly ignorable treatment assignment assumption, conditioning on the propensity score yields valid causal effect estimates. Therefore we incorporate the propensity score into the Cox model for causal inference with survival data. We derive the asymptotic property of the maximum partial likelihood estimator when the model is correctly specified. Simulation results show that our method performs quite well for observational data. The approach is applied to a real dataset on the time of readmission of trauma patients. We also derive the asymptotic property of the maximum partial likelihood estimator with a robust variance estimator, when the model is incorrectly specified.     

Testing Monotonicity of Regression Functions – An Empirical Process Approach

We propose several new tests for monotonicity of regression functions based on different empirical processes of residuals and pseudo‐residuals. The residuals are obtained from an unconstrained kernel regression estimator whereas the pseudo‐residuals are obtained from an increasing regression estimator. Here, in particular, we consider a recently developed simple kernel‐based estimator for increasing regression functions based on increasing rearrangements of unconstrained non‐parametric estimators. The test statistics are estimated distance measures between the regression function and its increasing rearrangement. We discuss the asymptotic distributions, consistency and small sample performances of the tests.     

Generation of pseudo random numbers and estimation under Cox models with time-dependent covariates

ABSTRACT

We study the method for generating pseudo random numbers under various special cases of the Cox model with time-dependent covariates when the baseline hazard function may not be constant and the random variable may equal infinity with a positive probability. During our simulation studies in computing the partial likelihood estimates, in between 3% and 20% of the time with a moderate sample size, it happens that the partial likelihood estimate of the regression coefficient is ∞ for the data from the Cox model. We propose a semi-parametric estimator as a modification for such a case. We present simulation results on the asymptotic properties of the semi-parametric estimator.     

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.     

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.     

On variable bandwidth selection in local polynomial regression

The performances of data-driven bandwidth selection procedures in local polynomial regression are investigated by using asymptotic methods and simulation. The bandwidth selection procedures considered are based on minimizing 'prelimit' approximations to the (conditional) mean-squared error (MSE) when the MSE is considered as a function of the bandwidth h . We first consider approximations to the MSE that are based on Taylor expansions around h=0 of the bias part of the MSE. These approximations lead to estimators of the MSE that are accurate only for small bandwidths h . We also consider a bias estimator which instead of using small h approximations to bias naïvely estimates bias as the difference of two local polynomial estimators of different order and we show that this estimator performs well only for moderate to large h . We next define a hybrid bias estimator which equals the Taylor-expansion-based estimator for small h and the difference estimator for moderate to large h . We find that the MSE estimator based on this hybrid bias estimator leads to a bandwidth selection procedure with good asymptotic and, for our Monte Carlo examples, finite sample properties.     

On the Breslow estimator

In his discussion of Cox’s (1972) paper on proportional hazards regression, Breslow (1972) provided the maximum likelihood estimator for the cumulative baseline hazard function. This estimator is commonly used in practice. The estimator has also been highly valuable in the further development of Cox regression and semiparametric inference with censored data. The present paper describes the Breslow estimator and its tremendous impact on the theory and practice of survival analysis.     

Tests for Coefficients in High‐dimensional Additive Hazard Models

We consider hypothesis testing problems for low‐dimensional coefficients in a high dimensional additive hazard model. A variance reduced partial profiling estimator (VRPPE) is proposed and its asymptotic normality is established, which enables us to test the significance of each single coefficient when the data dimension is much larger than the sample size. Based on the p‐values obtained from the proposed test statistics, we then apply a multiple testing procedure to identify significant coefficients and show that the false discovery rate can be controlled at the desired level. The proposed method is also extended to testing a low‐dimensional sub‐vector of coefficients. The finite sample performance of the proposed testing procedure is evaluated by simulation studies. We also apply it to two real data sets, with one focusing on testing low‐dimensional coefficients and the other focusing on identifying significant coefficients through the proposed multiple testing procedure.     

Estimation of the cumulative baseline hazard function for dependently right-censored failure time data

In this paper, we study the properties of a special class of frailty models when the frailty is common to several failure times. The models are closely linked to Archimedean copula models. We establish a useful formula for cumulative baseline hazard functions and develop a new estimator for cumulative baseline hazard functions in bivariate frailty regression models. Based on our proposed estimator, we present a graphical model checking procedure. We fit a leukemia data set using our model and end our paper with some discussions.     

Asymptotic expansion for nonparametric M-estimator in a nonlinear regression model with long-memory errors

We consider asymptotic expansion of the nonparametric M-estimator in a fixed-design nonlinear regression model when the errors are generated by long-memory linear processes. Under mild conditions, we show that the nonparametric M-estimator is first-order equivalent to the Nadaraya-Watson (NW) estimator, which implies that the nonparametric M-estimator has the same asymptotic distribution as that of the NW estimator. Furthermore, we study the second-order asymptotic expansion of the nonparametric M-estimator and show that the difference between the nonparametric M-estimator and the NW estimator has a limiting distribution after suitable standardization. The nature of the limiting distribution depends on the range of long-memory parameter α. We also compare the finite sample behavior of the two estimators through a numerical example when the errors are long-memory.