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Checking the Cox Proportional Hazards Model with Interval-Censored Data

区间删失数据下 Cox 比例风险模型的检验

This article presents a general framework for checking the adequacy of the Cox proportional hazards model with interval-censored data, which arise when the event of interest is known only to occur over a random time interval. Specifically, we construct certain stochastic processes that are informative about various aspects of the model, that is, the functional forms of covariates, the exponential link function and the proportional hazards assumption. We establish their weak…

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Semiparametric Regression Analysis of Interval-Censored Multi-State Data with An Absorbing State

含吸收态的区间删失多状态数据半参数回归分析

In studies of chronic diseases, the health status of a subject can often be characterized by a finite number of transient disease states and an absorbing state, such as death. The times of transitions among the transient states are ascertained through periodic examinations and thus interval-censored. The time of reaching the absorbing state is known or right-censored, with the transient state at the previous instant being unobserved. In this paper, we provide a general…

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Semiparametric latent-class models for multivariate longitudinal and survival data

多变量纵向与生存数据的半参数潜在类别模型

In long-term follow-up studies, data are often collected on repeated measures of multivariate response variables as well as on time to the occurrence of a certain event. To jointly analyze such longitudinal data and survival time, we propose a general class of semiparametric latent-class models that accommodates a heterogeneous study population with flexible dependence structures between the longitudinal and survival outcomes. We combine nonparametric maximum likelihood…

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Robust Score Tests With Missing Data in Genomics Studies

基因组研究中含缺失数据的稳健得分检验

Analysis of genomic data is often complicated by the presence of missing values, which may arise due to cost or other reasons. The prevailing approach of single imputation is generally invalid if the imputation model is misspecified. In this paper, we propose a robust score statistic based on imputed data for testing the association between a phenotype and a genomic variable with (partially) missing values. We fit a semiparametric regression model for the genomic variable…

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Semiparametric Regression Analysis of Multiple Right- and Interval-Censored Events

多个右删失与区间删失事件的半参数回归分析

Health sciences research often involves both right- and interval-censored events because the occurrence of a symptomatic disease can only be observed up to the end of follow-up, while the occurrence of an asymptomatic disease can only be detected through periodic examinations. We formulate the effects of potentially time-dependent covariates on the joint distribution of multiple right- and interval-censored events through semiparametric proportional hazards models with…

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Efficient Estimation for Semiparametric Structural Equation Models With Censored Data

含删失数据的半参数结构方程模型高效估计

Structural equation modeling is commonly used to capture complex structures of relationships among multiple variables, both latent and observed. We propose a general class of structural equation models with a semiparametric component for potentially censored survival times. We consider nonparametric maximum likelihood estimation and devise a combined Expectation-Maximization and Newton-Raphson algorithm for its implementation. We establish conditions for model…

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Maximum likelihood estimation for semiparametric regression models with multivariate interval-censored data

多元区间删失数据半参数回归模型的最大似然估计

Interval-censored multivariate failure time data arise when there are multiple types of failure or there is clustering of study subjects and each failure time is known only to lie in a certain interval. We investigate the effects of possibly time-dependent covariates on multivariate failure times by considering a broad class of semiparametric transformation models with random effects, and we study nonparametric maximum likelihood estimation under general interval-censoring…

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Efficient Estimation of Semiparametric Transformation Models for the Cumulative Incidence of Competing Risks

竞争风险累积发生率半参数变换模型的有效估计

Summary The cumulative incidence is the probability of failure from the cause of interest over a certain time period in the presence of other risks. A semiparametric regression model proposed by Fine and Gray has become the method of choice for formulating the effects of covariates on the cumulative incidence. Its estimation, however, requires modelling of the censoring distribution and is not statistically efficient. We present a broad class of semiparametric transformation…

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Maximum likelihood estimation for semiparametric transformation models with interval-censored data

区间删失数据半参数变换模型的最大似然估计

Interval censoring arises frequently in clinical, epidemiological, financial and sociological studies, where the event or failure of interest is known only to occur within an interval induced by periodic monitoring. We formulate the effects of potentially time-dependent covariates on the interval-censored failure time through a broad class of semiparametric transformation models that encompasses proportional hazards and proportional odds models. We consider nonparametric…

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On random-effects meta-analysis

随机效应元分析

Meta-analysis is widely used to compare and combine the results of multiple independent studies. To account for between-study heterogeneity, investigators often employ random-effects models, under which the effect sizes of interest are assumed to follow a normal distribution. It is common to estimate the mean effect size by a weighted linear combination of study-specific estimators, with the weight for each study being inversely proportional to the sum of the variance of the…

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A Likelihood-Based Framework for Association Analysis of Allele-Specific Copy Numbers

等位基因特异性拷贝数关联分析的似然框架

Copy number variants (CNVs) and single nucleotide polymorphisms (SNPs) co-exist throughout the human genome and jointly contribute to phenotypic variations. Thus, it is desirable to consider both types of variants, as characterized by allele-specific copy numbers (ASCNs), in association studies of complex human diseases. Current SNP genotyping technologies capture the CNV and SNP information simultaneously via fluorescent intensity measurements. The common practice of…

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Efficient Estimation of Semiparametric Transformation Models for Two-Phase Cohort Studies

两阶段队列研究中半参数变换模型的有效估计

Under two-phase cohort designs, such as case-cohort and nested case-control sampling, information on observed event times, event indicators, and inexpensive covariates is collected in the first phase, and the first-phase information is used to select subjects for measurements of expensive covariates in the second phase; inexpensive covariates are also used in the data analysis to control for confounding and to evaluate interactions. This paper provides efficient estimation…

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Predictive accuracy of covariates for event times

协变量对事件发生时间的预测准确性

We propose a graphical measure, the generalized negative predictive function, to quantify the predictive accuracy of covariates for survival time or recurrent event times. This new measure characterizes the event-free probabilities over time conditional on a thresholded linear combination of covariates and has direct clinical utility. We show that this function is maximized at the set of covariates truly related to event times and thus can be used to compare the predictive…

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Correcting for Population Stratification in Genomewide Association Studies

全基因组关联研究中的群体分层校正

Genomewide association studies have become the primary tool for discovering the genetic basis of complex human diseases. Such studies are susceptible to the confounding effects of population stratification, in that the combination of allele-frequency heterogeneity with disease-risk heterogeneity among different ancestral subpopulations can induce spurious associations between genetic variants and disease. This article provides a statistically rigorous and computationally…

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Attributable fraction functions for censored event times

删失事件时间的归因分数函数

Attributable fractions are commonly used to measure the impact of risk factors on disease incidence in the population. These static measures can be extended to functions of time when the time to disease occurrence or event time is of interest. The present paper deals with nonparametric and semiparametric estimation of attributable fraction functions for cohort studies with potentially censored event time data. The semiparametric models include the familiar proportional…

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On the relative efficiency of using summary statistics versus individual-level data in meta-analysis

元分析中汇总统计量与个体数据的相对效率

Meta-analysis is widely used to synthesize the results of multiple studies. Although meta-analysis is traditionally carried out by combining the summary statistics of relevant studies, advances in technologies and communications have made it increasingly feasible to access the original data on individual participants. In the present paper, we investigate the relative efficiency of analyzing original data versus combining summary statistics. We show that, for all commonly…

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Maximum Likelihood Estimation in Semiparametric Regression Models with Censored Data

删失数据半参数回归模型中的极大似然估计

Summary Semiparametric regression models play a central role in formulating the effects of covariates on potentially censored failure times and in the joint modelling of incomplete repeated measures and failure times in longitudinal studies. The presence of infinite dimensional parameters poses considerable theoretical and computational challenges in the statistical analysis of such models. We present several classes of semiparametric regression models, which extend the…

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Efficient estimation of semiparametric transformation models for counting processes

计数过程半参数变换模型的有效估计

A class of semiparametric transformation models is proposed to characterise the effects of possibly time-varying covariates on the intensity functions of counting processes. The class includes the proportional intensity model and linear transformation models as special cases. Nonparametric maximum likelihood estimators are developed for the regression parameters and cumulative intensity functions of these models based on censored data. The estimators are shown to be…

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On least-squares regression with censored data

删失数据的最小二乘回归

The semiparametric accelerated failure time model relates the logarithm of the failure time linearly to the covariates while leaving the error distribution unspecified. The present paper describes simple and reliable inference procedures based on the least-squares principle for this model with right-censored data. The proposed estimator of the vector-valued regression parameter is an iterative solution to the Buckley–James estimating equation with a preliminary consistent…

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Semiparametric Regression for the Mean and Rate Functions of Recurrent Events

重复事件均值函数与发生率函数的半参数回归

Summary The counting process with the Cox-type intensity function has been commonly used to analyse recurrent event data. This model essentially assumes that the underlying counting process is a time-transformed Poisson process and that the covariates have multiplicative effects on the mean and rate function of the counting process. Recently, Pepe and Cai, and Lawless and co-workers have proposed semiparametric procedures for making inferences about the mean and rate…

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Additive Hazards Regression with Covariate Measurement Error

协变量存在测量误差时的加性风险回归

The additive hazards model specifies that the hazard function conditional on a set of covariates is the sum of an arbitrary baseline hazard function and a regression function of covariates. This article deals with the analysis of this semiparametric regression model with censored failure time data when covariates are subject to measurement error. We assume that the true covariate is measured on a randomly chosen validation set, whereas a Surrogate covariate (i.e., an…

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Parametric Regression Models for Continuous Time Removal and Recapture Studies

连续时间移除与再捕获研究的参数回归模型

Summary We use a class of parametric counting process regression models that are commonly employed in the analysis of failure time data to formulate the subject-specific capture probabilities for removal and recapture studies conducted in continuous time. We estimate the regression parameters by modifying the conventional likelihood score function for left-truncated and right-censored data to accommodate an unknown population size and missing covariates on uncaptured…

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A General Theory on Stochastic Curtailment for Censored Survival Data

删失生存数据随机提前终止的一般理论

Stochastic curtailment is a valuable tool in monitoring long-term medical studies. Under this approach, one calculates the conditional power, which is the probability of rejecting the null hypothesis at the scheduled end of the study given the existing data at the interim analysis, along with certain speculation about the future data. The conditional power may be used to aid the decision to terminate a study prematurely or to extend a study beyond its originally planned…

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A General Theory on Stochastic Curtailment for Censored Survival Data

删失生存数据随机提前终止的一般理论

Stochastic curtailment is a valuable tool in monitoring long-term medical studies. Under this approach, one calculates the conditional power, which is the probability of rejecting the null hypothesis at the scheduled end of the study given the existing data at the interim analysis, along with certain speculation about the future data. The conditional power may be used to aid the decision to terminate a study prematurely or to extend a study beyond its originally planned…

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