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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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Doubly robust learning for estimating individualized treatment with censored data

删失数据下个体化治疗规则估计的双重稳健学习

Individualized treatment rules recommend treatments based on individual patient characteristics in order to maximize clinical benefit. When the clinical outcome of interest is survival time, estimation is often complicated by censoring. We develop nonparametric methods for estimating an optimal individualized treatment rule in the presence of censored data. To adjust for censoring, we propose a doubly robust estimator which requires correct specification of either 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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Variable selection in semiparametric transformation models for right-censored data

右删失数据半参数变换模型中的变量选择

We study variable selection in general transformation models for right-censored data. The models studied can incorporate external time-varying covariates, and they include the proportional hazards model and the proportional odds model as special cases. We propose an estimation method that involves minimizing a weighted negative partial loglikelihood function plus an adaptive lasso penalty, with the initial values obtained from nonparametric maximum likelihood estimation. The…

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Estimating time-varying effects for overdispersed recurrent events data with treatment switching

治疗转换下过度离散复发事件的时变效应估计

In the analysis of multivariate event times, frailty models assuming time-independent regression coefficients are often considered, mainly due to their mathematical convenience. In practice, regression coefficients are often time dependent and the temporal effects are of clinical interest. Motivated by a phase III clinical trial in multiple sclerosis, we develop a semiparametric frailty modelling approach to estimate time-varying effects for overdispersed recurrent events…

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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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Estimating treatment effects with treatment switching via semicompeting risks models: an application to a colorectal cancer study

利用半竞争风险模型估计治疗转换下的治疗效应:结直肠癌研究应用

Treatment switching is a frequent occurrence in clinical trials, where, during the course of the trial, patients who fail on the control treatment may change to the experimental treatment. Analysing the data without accounting for switching yields highly biased and inefficient estimates of the treatment effect. In this paper, we propose a novel class of semiparametric semicompeting risks transition survival models to accommodate treatment switches. Theoretical properties of…

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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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A semiparametric additive rate model for recurrent events with an informative terminal event

存在信息性终止事件的重复事件半参数加性率模型

We propose a semiparametric additive rate model for modelling recurrent events in the presence of a terminal event. The dependence between recurrent events and terminal event is nonparametric. A general transformation model is used to model the terminal event. We construct an estimating equation for parameter estimation and derive the asymptotic distributions of the proposed estimators. Simulation studies demonstrate that the proposed inference procedure performs well in…

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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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Gamma frailty transformation models for multivariate survival times

多元生存时间的 Gamma 脆弱性变换模型

We propose a class of transformation models for multivariate failure times. The class of transformation models generalize the usual gamma frailty model and yields a marginally linear transformation model for each failure time. Nonparametric maximum likelihood estimation is used for inference. The maximum likelihood estimators for the regression coefficients are shown to be consistent and asymptotically normal, and their asymptotic variances attain the semiparametric…

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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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