Efficient distribution estimation for data with unobserved sub-population identifiers

We recently proposed a representation of the bivariate survivor function as a mapping of the hazard function for truncated failure time variates. The representation led to a class of estimators that includes van der Laan's repaired nonparametric maximum likelihood estimator (NPMLE) as an important special case. We proposed a Greenwood-like variance estimator for the repaired NPMLE but found somewhat poor agreement between the empirical variance estimates and these analytic estimates for the sample sizes and bandwidths considered in our simulation study. The simulation results also confirmed those of others in showing slightly inferior performance for the repaired NPMLE compared to other competing estimators as well as a sensitivity to bandwidth choice in moderate sized samples. Despite its attractive asymptotic properties, the repaired NPMLE has drawbacks that hinder its practical application. This paper presents a modification of the repaired NPMLE that improves its performance in moderate sized samples and renders it less sensitive to the choice of bandwidth. Along with this modified estimator, more extensive simulation studies of the repaired NPMLE and Greenwood-like variance estimates are presented. The methods are then applied to a real data example.

The nonparametric maximum likelihood estimation (NPMLE) of the distribution function from the interval censored (IC) data has been extensively studied in the extant literature. The NPMLE was also developed for the subdistribution functions in an IC competing risks model and in an illness-death model under various interval-censoring scenarios. But the important problem of estimation of the cumulative intensities (CIs) in the interval-censored models has not been considered previously. We develop the NPMLE of the CI in a simple alive/dead model and of the CIs in a competing risks model. Assuming that data are generated by a discrete and finite mixed case interval censoring mechanism we provide a discussion and the simulation study of the asymptotic properties of the NPMLEs of the CIs. In particular we show that they are asymptotically unbiased; in contrast the ad hoc estimators presented in extant literature are substantially biased. We illustrate our methods with the data from a prospective cohort study on the longevity of dental veneers.

We show that under reasonable conditions the nonparametric maximum likelihood estimate (NPMLE) of the distribution function from left-truncated and case 1 interval-censored data is inconsistent, in contrast to the consistency properties of the NPMLE from only left-truncated data or only interval-censored data. However, the conditional NPMLE is shown to be consistent. Numerical examples are provided to illustrate their finite sample properties.

A receiver operating characteristic (ROC) curve plots the true positive rate of a classier against its false positive rate, both of which are accuracy measures of the classier. The ROC curve has several interesting geometrical properties, including concavity which is a neces- sary condition for a classier to be optimal. In this paper, we study the nonparametric maximum likelihood estimator (NPMLE) of a con- cave ROC curve and its modication to reduce bias. We characterize the NPMLE as a solution to a geometric programming, a special type of a mathematical optimization problem. Wend that the NPMLE is close to the convex hull of the empirical ROC curve and, thus, has smaller variance but positive bias at a given false positive rate. To reduce the bias, we propose a modication of the NPMLE which minimizes the L1 distance from the empirical ROC curve. We numerically compare the �nite sample performance of three estimators, the empirical ROC curve, the NMPLE, and the modied NPMLE. Finally, we apply the estimators to estimating the optimal ROC curve of the variance-thresho classier to segment a low depth ofeld image and tonding a diagnostic tool with multiple tests for detection of hemophilia A carrier.

We develop the non-parametric maximum likelihood estimator (MLE) of the full Mbh capture-recapture model which utilizes both initial capture and recapture data and permits both heterogeneity (h) between animals and behavioural (b) response to capture. Our MLE procedure utilizes non-parametric maximum likelihood estimation of mixture distributions (Lindsay, 1983; Lindsay and Roeder, 1992) and the EM algorithm (Dempsteret al., 1977). Our MLE estimate provides the first non-parametric estimate of the bivariate capture-recapture distribution. Since non-parametric maximum likelihood estimation exists for submodels Mh (allowing heterogeneity only), Mb (allowing behavioural response only) and M0 (allowing no changes), we develop maximum likelihood-based model selection, specifically the Akaike information criterion (AIC) (Akaike, 1973). The AIC procedure does well in detecting behavioural response but has difficulty in detecting heterogeneity.

Consider independent observations $$(X_i,R_i)$$ with random or fixed ranks $$R_i$$, while conditional on $$R_i$$, the random variable $$X_i$$ has the same distribution as the $$R_i$$-th order statistic within a random sample of size k from an unknown distribution function F. Such observation schemes are well known from ranked set sampling and judgment post-stratification. Within a general, not necessarily balanced setting we derive and compare the asymptotic distributions of three different estimators of the distribution function F: a stratified estimator, a nonparametric maximum-likelihood estimator and a moment-based estimator. Our functional central limit theorems generalize and refine previous asymptotic analyses. In addition, we discuss briefly pointwise and simultaneous confidence intervals for the distribution function with guaranteed coverage probability for finite sample sizes. The methods are illustrated with a real data example, and the potential impact of imperfect rankings is investigated in a small simulation experiment.

The events of interest in any survival analysis study are regularly subject to censoring. There are various censoring schemes, including right or left censoring, and interval censoring. The most frequent censoring scheme is the right censoring, where subjects might drop out of the study or simply because not all events of interest occur before the end of the study. Moreover, for each subject, additional information referred to as covariates is registered at the beginning or throughout the study, such as age, sex, undergoing treatment, etc. The classical model to study the distribution of the events of interest, while accounting for additional information, is the Cox model. The Cox model expresses the hazard function of a subject given a set of covariates in terms of a baseline hazard, for which all covariates are zero, and an exponential function of the covariates and corresponding regression parameters. The baseline hazard can be left completely unspecified while estimating the regression parameters. Nonetheless, in practice, there are numerous studies in which the baseline hazard appears to be monotone. Time to death or to the onset of a disease are observed to have a nondecreasing baseline hazard, while the survival or recovery time after a successful medical treatment usually exhibit a nonincreasing baseline hazard. The aim of this thesis is to study the behavior of nonparametric baseline hazard and baseline density estimators in the Cox model under monotonicity constraints. The event times are assumed to be right censored and the censoring mechanism is assumed to be independent of the event of interest and non-informative. The covariates are assumed to be time-independent, usually recorded at the beginning of the study. In addition to point estimates, interval estimates of a monotone baseline hazard will be provided, based on a likelihood ratio method, along with testing at a fixed point. Furthermore, kernel smoothed estimates of a monotone baseline hazard will be defined and their behavior will be investigated. In Chapter 2, we propose several nonparametric monotone estimators of a baseline hazard or a baseline density within the Cox model. We derive the nonparametric maximum likelihood estimator of a nondecreasing baseline hazard and we consider a Grenander-type estimator, defined as the left-hand slope of the greatest convex minorant of the Breslow estimator. The two estimators are then shown to be strongly consistent and asymptotically equivalent. Moreover, we derive their common limit distribution at a fixed point. The two equivalent estimators of a nonincreasing baseline hazard and their asymptotic properties are acquired similarly. Furthermore, we introduce a Grenander-type estimator of a nonincreasing 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. This estimator is proven to be strongly consistent and its asymptotic distribution at a fixed point is derived. Chapter 3 provides an asymptotic linear representation of the Breslow estimator of the baseline cumulative hazard function in the Cox model. This representation can be used to derive the asymptotic distribution of the Grenander type estimator of a monotone baseline hazard estimator. The 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. Chapter 4 focuses on interval estimation and on testing whether a monotone baseline hazard function in the Cox model has a particular value at a fixed point, via a likelihood ratio method. Nonparametric maximum likelihood estimators under the null hypothesis are defined for both nondecreasing and nonincreasing baseline hazard functions. These characterizations, along with those of the monotone nonparametric maximum likelihood estimators provide the asymptotic distribution of the likelihood ratio test. This asymptotic distribution enables, via inversion, the construction of pointwise confidence intervals. This method of constructing confidence intervals avoids the issue of estimating the nuisance parameters, as in the case of confidence intervals based on the asymptotic distribution of the estimators. Simulations indicate that the two methods yield confidence intervals with comparable coverage probabilities. Nonetheless, the confidence intervals based on the likelihood ratio are smaller, on average. Finally, in chapter 5 we consider smooth baseline hazard estimators. The estimators are obtained by kernel smoothing the maximum likelihood and Grenander-type estimators of a monotone baseline hazard function. Three different estimators are proposed for a nondecreasing baseline hazard, which are provided by the interchange of the smoothing and isotonization step. With this respect, we define a smoothed maximum likelihood estimator (SMLE), as well as a smoothed Grenander type (SG) estimator and a Grenander type smoothed (GS) estimator. All estimators are shown to be strongly pointwise or uniformly consistent.

To the Editor: Familial combined hyperlipidemia (FCHL), associated with premature cardiovascular disease, is the most common genetic hyperlipidemia with an estimated prevalence of 1%.1 The complex genetic background of FCHL is slowly being dissected through genome screens and positional candidate association studies.2–6 However, it has also been argued that although numerous studies have been conducted and reported, there are many conflicting results and a true understanding of the genetics remains largely unknown.7 Previously in this journal, we reported 4 quantitative trait loci (QTL) for apolipoprotein B (apoB), cholesterol, and triglycerides with P <0.001 in 22 FCHL pedigrees from Maastricht, in The Netherlands.8 The original QTL study was based on the premise that because FCHL is defined by increased serum levels of cholesterol, apoB, and triglycerides in families, QTL analyses of these quantitative traits in FCHL families might identify important genetic loci for this disorder. This letter reports QTL analyses of 5-year follow-up data in the same individuals. Longitudinal studies show that the lipid …

Doubly truncated data consist of samples whose observed values fall between the right- and left- truncation limits. With such samples, the distribution function of interest is estimated using the nonparametric maximum likelihood estimator (NPMLE) that is obtained through a self-consistency algorithm. Owing to the complicated asymptotic distribution of the NPMLE, the bootstrap method has been suggested for statistical inference. This paper proposes a closed-form estimator for the asymptotic covariance function of the NPMLE, which is computationally attractive alternative to bootstrapping. Furthermore, we develop various statistical inference procedures, such as confidence interval, goodness-of-fit tests, and confidence bands to demonstrate the usefulness of the proposed covariance estimator. Simulations are performed to compare the proposed method with both the bootstrap and jackknife methods. The methods are illustrated using the childhood cancer dataset.

Abstract. This paper studies the representation and large‐sample consistency for non‐parametric maximum likelihood estimators (NPMLEs) of an unknown baseline continuous cumulative‐hazard‐type function and parameter of group survival difference, based on right‐censored two‐sample survival data with marginal survival function assumed to follow a transformation model, a slight generalization of the class of frailty survival regression models. The paper's main theoretical results are existence and unique a.s. limit, characterized variationally, for large data samples of the NPMLE of baseline nuisance function in an appropriately defined neighbourhood of the true function when the group difference parameter is fixed, leading to consistency of the NPMLE when the difference parameter is fixed at a consistent estimator of its true value. The joint NPMLE is also shown to be consistent. An algorithm for computing it numerically, based directly on likelihood equations in place of the expectation‐maximization (EM) algorithm, is illustrated with real data.

SUMMARY A great deal of recent attention has focused on the estimation of survival distributions based on current status data, an extreme form of interval censored data. This particular data structure arises in a wide variety of applications where cross-sectional observation either naturally occurs or is preferred to more traditional forms of follow-up. Here we consider current status data in the context of competing risks. We briefly consider simple parametric models as a backdrop to nonparametric procedures. We make some brief comparisons and remarks regarding the nonparametric maximum likelihood estimator. The ideas are illustrated on the data of Krailo & Pike (1983) which considers estimation of the age distribution at both natural and operative menopause. We also consider the case where there is exact observation of failure times due to one of the competing risks when failure occurs prior to the monitoring time. Basic techniques of survival analysis focus on estimation of the survival distribution based on various forms of censored data. An extreme form of censoring arises where the only information on studied individuals is their survival status at a single monitoring time. This particular data structure is known as current status data. Nonparametric estimation of the survival function and semiparametric techniques for related regression models, based on current status data, have been much studied of late. Here, we consider estimation of sub-survival functions based on current status observations in the presence of competing risks. For simplicity, we describe only two competing risks, but the ideas are easily extended when there are more than two possible causes of failure. Let )j denote the cause-specific hazard function for cause j = 1, 2 (Kalbfleisch & Prentice, 2002, p. 252). If T and J are the random variables that measure time to failure and cause of failure, respectively, the two sub-distribution functions of interest are

Multivariate, heteroscedastic errors complicate statistical inference in many large-scale denoizing problems. Empirical Bayes is attractive in such settings, but standard parametric approaches rest on assumptions about the form of the prior distribution which can be hard to justify and which introduce unnecessary tuning parameters. We extend the nonparametric maximum-likelihood estimator (NPMLE) for Gaussian location mixture densities to allow for multivariate, heteroscedastic errors. NPMLEs estimate an arbitrary prior by solving an infinite-dimensional, convex optimization problem; we show that this convex optimization problem can be tractably approximated by a finite-dimensional version. The empirical Bayes posterior means based on an NPMLE have low regret, meaning they closely target the oracle posterior means one would compute with the true prior in hand. We prove an oracle inequality implying that the empirical Bayes estimator performs at nearly the optimal level (up to logarithmic factors) for denoizing without prior knowledge. We provide finite-sample bounds on the average Hellinger accuracy of an NPMLE for estimating the marginal densities of the observations. We also demonstrate the adaptive and nearly optimal properties of NPMLEs for deconvolution. We apply our method to two denoizing problems in astronomy and to two hierarchical linear modelling problems in social science and biology.

We study the nonparametric maximum likelihood estimator (NPMLE) for a concave distribution function $F$ and its decreasing density $f$ based on right-censored data. Without the concavity constraint, the NPMLE of $F$ is the product-limit estimator proposed by Kaplan and Meier. If there is no censoring, the NPMLE of $f$, derived by Grenander, is the left derivative of the least concave majorant of the empirical distribution function, and its local and global behavior was investigated, respectively, by Prakasa Rao and Groeneboom. In this paper, we present a necessary and sufficient condition, a self-consistency equation and an analytic solution for the NPMLE, and we extend Prakasa Rao's result to the censored model.

The frailty model is a generalization of Cox's proportional hazard model, where a shared unobserved quantity in the intensity induces a positive correlation among the survival times. Murphy showed consistency and asymptotic normality of the nonparametric maximum likelihood estimator (NPMLE) for the shared gamma-frailty model without covariates. In this paper we extend this result to the correlated gamma-frailty model, and we allow for covariates. We discuss the definition of the nonparametric likelihood function in terms of a classical proof of consistency for the maximum likelihood estimator, which goes back to Wald. Our proof of the consistency for the NPMLE is essentially the same as the classical proof for the maximum likelihood estimator. A new central limit theorem for processes of bounded variation is given. Furthermore, we prove that a consistent estimator for the asymptotic variance of the NPMLE is given by the inverse of a discrete observed information matrix.

Thirty-nine chromosome segment substitution lines (CSSLs) population derived from a Koshihikari / Kasalath cross was used for quantitative trait locus (QTL) analysis of plant type in rice (Oryza sativa L.). Putative rough QTLs (26.2∼60.3cM of Kasalath chromosomal segments) for culm length, plant height, panicle number, chlorophyll content of flag leaf blade at heading and specific leaf weight, were mapped on the several chromosomal segments based on the comparison of CSSLs with Koshihikari in the field experiment for 3 years. In order to verify and narrow QTLs detected in CSSLs, we conducted QTL analyses using F2 populations derived from a cross between Koshihikari and target CSSL holding a putative rough QTL. The qPN-2, QTL for panicle number was mapped on chromosome 2. In traits of flag leaf, the qCHL-4-1 and qCHL-4-2 for chlorophyll content was mapped on chromosome 4, and the qSLW-7 for specific leaf weight on chromosome 7. All QTLs were detected in narrow marker intervals, compared with rough QTLs in CSSLs. The qPN-2, qCHL-4-1 and qCHL-4-2 had only additive effect. On the other hand, the qSLW-7 showed over-dominance. It could be emphasized that QTL analysis in the present study with the combination of CSSLs and backcross progeny F2 population can not only verify the rough QTLs detected in CSSLs but also estimate allelic effects on the QTL.