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An Alternative to Pooling Kaplan-Meier Curves in Time-to-Event Meta-Analysis 时间-事件元分析中Kaplan-Meier曲线池化的替代方法
IF 1.2 4区 数学 Pub Date : 2011-03-30 DOI: 10.2202/1557-4679.1289
D. Rubin
A meta-analysis that uses individual-level data instead of study-level data is widely considered to be a gold standard approach, in part because it allows a time-to-event analysis. Unfortunately, with the common practice of presenting Kaplan-Meier survival curves after pooling subjects across randomized trials, using individual-level data can actually be a step backwards; a Simpson's paradox can occur in which pooling incorrectly reverses the direction of an association. We introduce a nonparametric procedure for synthesizing survival curves across studies that is designed to avoid this difficulty and preserve the integrity of randomization. The technique is based on a counterfactual formulation in which we ask what pooled survival curves would look like if all subjects in all studies had been assigned treatment, or if all subjects had been assigned to control arms. The method is related to a Kaplan-Meier adjustment proposed in 2005 by Xie and Liu to correct for confounding in nonrandomized studies, but is formulated for the meta-analysis setting. The procedure is discussed in the context of examining rosiglitazone and cardiovascular adverse events.
使用个人层面数据而不是研究层面数据的元分析被广泛认为是一种黄金标准方法,部分原因是它允许对事件进行时间分析。不幸的是,在随机试验汇集受试者后呈现Kaplan-Meier生存曲线的普遍做法是,使用个人水平的数据实际上是一种倒退;辛普森悖论可能发生在汇集错误地扭转了一个联系的方向。我们引入了一种非参数程序来综合研究中的生存曲线,旨在避免这一困难并保持随机化的完整性。这项技术是基于一个反事实的公式,在这个公式中,我们问如果所有研究中的所有受试者都被分配治疗,或者如果所有受试者都被分配到对照组,那么合并生存曲线会是什么样子。该方法与Xie和Liu在2005年提出的Kaplan-Meier调整有关,该调整旨在纠正非随机研究中的混淆,但该方法是为meta分析设置而制定的。在检查罗格列酮和心血管不良事件的背景下讨论该程序。
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引用次数: 2
Marginal Models for Censored Longitudinal Cost Data: Appropriate Working Variance Matrices in Inverse-Probability-Weighted GEEs Can Improve Precision 删减纵向成本数据的边际模型:在反概率加权GEEs中适当的工作方差矩阵可以提高精度
IF 1.2 4区 数学 Pub Date : 2011-02-07 DOI: 10.2202/1557-4679.1170
E. Pullenayegum, A. Willan
When cost data are collected in a clinical study, interest centers on the between-treatment difference in mean cost. When censoring is present, the resulting loss of information can be limited by collecting cost data for several pre-specified time intervals, leading to censored longitudinal cost data. Most models for marginal costs stratify by time interval. However, in few other areas of biostatistics would we stratify by default. We argue that there are benefits to considering more general models: for example, in some settings, pooling regression coefficients across intervals can improve the precision of the estimated between-treatment difference in mean cost. Previous work has used inverse-probability-weighted GEEs coupled with an independent working variance to estimate parameters from these more general models. We show that the greatest precision benefits of non-stratified models are achieved by using more sophisticated working variance matrices.
当在临床研究中收集成本数据时,兴趣集中在平均成本的治疗间差异上。当存在审查时,可以通过收集几个预先指定的时间间隔的成本数据来限制所导致的信息丢失,从而导致审查的纵向成本数据。大多数边际成本模型按时间间隔分层。然而,在生物统计学的其他领域,我们不会默认分层。我们认为,考虑更一般的模型是有好处的:例如,在某些情况下,跨区间的回归系数池化可以提高估计平均成本的处理间差异的精度。以前的工作使用了逆概率加权的GEEs,再加上一个独立的工作方差,从这些更一般的模型中估计参数。我们表明,非分层模型的最大精度效益是通过使用更复杂的工作方差矩阵来实现的。
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引用次数: 1
HingeBoost: ROC-Based Boost for Classification and Variable Selection HingeBoost:基于roc的分类和变量选择Boost
IF 1.2 4区 数学 Pub Date : 2011-02-04 DOI: 10.2202/1557-4679.1304
Zhuo Wang
In disease classification, a traditional technique is the receiver operative characteristic (ROC) curve and the area under the curve (AUC). With high-dimensional data, the ROC techniques are needed to conduct classification and variable selection. The current ROC methods do not explicitly incorporate unequal misclassification costs or do not have a theoretical grounding for optimizing the AUC. Empirical studies in the literature have demonstrated that optimizing the hinge loss can maximize the AUC approximately. In theory, minimizing the hinge rank loss is equivalent to minimizing the AUC in the asymptotic limit. In this article, we propose a novel nonparametric method HingeBoost to optimize a weighted hinge loss incorporating misclassification costs. HingeBoost can be used to construct linear and nonlinear classifiers. The estimation and variable selection for the hinge loss are addressed by a new boosting algorithm. Furthermore, the proposed twin HingeBoost can select more sparse predictors. Some properties of HingeBoost are studied as well. To compare HingeBoost with existing classification methods, we present empirical study results using data from simulations and a prostate cancer study with mass spectrometry-based proteomics.
在疾病分类中,传统的方法是根据受试者的工作特征(ROC)曲线和曲线下面积(AUC)进行分类。对于高维数据,需要使用ROC技术进行分类和变量选择。目前的ROC方法没有明确地纳入不等错分类成本,也没有优化AUC的理论基础。已有文献的实证研究表明,优化铰链损耗可以近似地使AUC最大化。理论上,最小化铰阶损失相当于最小化渐近极限下的AUC。在本文中,我们提出了一种新的非参数方法HingeBoost来优化包含误分类成本的加权铰链损失。HingeBoost可以用来构造线性和非线性分类器。提出了一种新的增强算法,解决了铰链损耗的估计和变量选择问题。此外,提出的孪生HingeBoost可以选择更多的稀疏预测器。研究了HingeBoost的一些特性。为了将HingeBoost与现有的分类方法进行比较,我们利用模拟数据和基于质谱的蛋白质组学的前列腺癌研究结果进行了实证研究。
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引用次数: 30
Targeting the Optimal Design in Randomized Clinical Trials with Binary Outcomes and No Covariate: Simulation Study 二元结果无协变量随机临床试验的优化设计目标:模拟研究
IF 1.2 4区 数学 Pub Date : 2011-01-24 DOI: 10.2202/1557-4679.1310
A. Chambaz, M. J. van der Laan
We undertake here a comprehensive simulation study of the theoretical properties that we derive in a companion article devoted to the asymptotic study of adaptive group sequential designs in the case of randomized clinical trials (RCTs) with binary treatment, binary outcome and no covariate. By adaptive design, we mean in this setting a RCT design that allows the investigator to dynamically modify its course through data-driven adjustment of the randomization probability based on data accrued so far without negatively impacting on the statistical integrity of the trial. By adaptive group sequential design, we refer to the fact that group sequential testing methods can be equally well applied on top of adaptive designs. The simulation study validates the theory. It notably shows in the estimation framework that the confidence intervals we obtain achieve the desired coverage even for moderate sample sizes. In addition, it shows in the testing framework that type I error control at the prescribed level is guaranteed and that all sampling procedures only suffer from a very slight increase of the type II error. A three-sentence take-home message is “Adaptive designs do learn the targeted optimal design and inference and testing can be carried out under adaptive sampling as they would under the targeted optimal randomization probability iid sampling. In particular, adaptive designs achieve the same efficiency as the fixed oracle design. This is confirmed by a simulation study, at least for moderate or large sample sizes, across a large collection of targeted randomization probabilities.”
我们在这里进行了一项全面的模拟研究,该研究是我们在一篇同伴文章中得出的,该文章致力于在随机临床试验(rct)中采用二元治疗、二元结果和无协变量的情况下,对自适应组序列设计进行渐近研究。通过自适应设计,我们的意思是在这种情况下,RCT设计允许研究者根据迄今为止累积的数据,通过数据驱动的随机化概率调整来动态修改其过程,而不会对试验的统计完整性产生负面影响。通过自适应组序列设计,我们指的是组序列测试方法可以同样很好地应用于自适应设计之上。仿真研究验证了理论的正确性。值得注意的是,在估计框架中,即使对于中等样本量,我们获得的置信区间也达到了期望的覆盖率。此外,在测试框架中,可以保证在规定的水平上控制第一类误差,并且所有采样过程只会受到第二类误差的非常轻微的增加。一个三句话的关键信息是“自适应设计确实学习目标最佳设计,并且在自适应抽样下可以进行推理和测试,就像在目标最佳随机化概率抽样下一样。”特别是,自适应设计可以达到与固定oracle设计相同的效率。模拟研究证实了这一点,至少对于中等或较大的样本量,在大量目标随机化概率的集合中。”
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引用次数: 30
Relative Risk Estimation in Randomized Controlled Trials: A Comparison of Methods for Independent Observations 随机对照试验的相对风险估计:独立观察方法的比较
IF 1.2 4区 数学 Pub Date : 2011-01-06 DOI: 10.2202/1557-4679.1278
L. Yelland, A. Salter, Philip Ryan
The relative risk is a clinically important measure of the effect of treatment on binary outcomes in randomized controlled trials (RCTs). An adjusted relative risk can be estimated using log binomial regression; however, convergence problems are common with this model. While alternative methods have been proposed for estimating relative risks, comparisons between methods have been limited, particularly in the context of RCTs. We compare ten different methods for estimating relative risks under a variety of scenarios relevant to RCTs with independent observations. Results of a large simulation study show that some methods may fail to overcome the convergence problems of log binomial regression, while others may substantially overestimate the treatment effect or produce inaccurate confidence intervals. Further, conclusions about the effectiveness of treatment may differ depending on the method used. We give recommendations for choosing a method for estimating relative risks in the context of RCTs with independent observations.
在随机对照试验(rct)中,相对危险度是衡量治疗对二元结局影响的重要临床指标。调整后的相对风险可用对数二项回归估计;然而,该模型的收敛性问题是常见的。虽然已经提出了估算相对风险的替代方法,但方法之间的比较有限,特别是在随机对照试验的背景下。我们比较了十种不同的方法来估计相对风险在各种情况下与独立观察的随机对照试验相关。一项大型模拟研究的结果表明,一些方法可能无法克服对数二项回归的收敛问题,而另一些方法可能严重高估处理效果或产生不准确的置信区间。此外,关于治疗有效性的结论可能因使用的方法而异。我们建议在独立观察的随机对照试验中选择一种估计相对风险的方法。
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引用次数: 38
Classification of Stationary Signals with Mixed Spectrum 混合频谱平稳信号的分类
IF 1.2 4区 数学 Pub Date : 2011-01-06 DOI: 10.2202/1557-4679.1288
P. Saavedra, A. Santana-del-Pino, C. N. Hernández-Flores, J. Artiles-Romero, J. J. González-Henríquez
This paper deals with the problem of discrimination between two sets of complex signals generated by stationary processes with both random effects and mixed spectral distributions. The presence of outlier signals and their influence on the classification process is also considered. As an initial input, a feature vector obtained from estimations of the spectral distribution is proposed and used with two different learning machines, namely a single artificial neural network and the LogitBoost classifier. Performance of both methods is evaluated on five simulation studies as well as on a set of actual data of electroencephalogram (EEG) records obtained from both normal subjects and others having experienced epileptic seizures. Of the different classification methods, Logitboost is shown to be more robust to the presence of outlier signals.
本文研究了具有随机效应和混合谱分布的平稳过程产生的两组复信号的判别问题。还考虑了异常信号的存在及其对分类过程的影响。作为初始输入,提出了由谱分布估计得到的特征向量,并将其用于两种不同的学习机,即单个人工神经网络和LogitBoost分类器。这两种方法的性能通过五个模拟研究以及从正常受试者和其他经历过癫痫发作的人获得的脑电图(EEG)记录的一组实际数据进行了评估。在不同的分类方法中,Logitboost对异常信号的存在表现出更强的鲁棒性。
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引用次数: 0
An Improved Bland-Altman Method for Concordance Assessment 一种改进的Bland-Altman一致性评价方法
IF 1.2 4区 数学 Pub Date : 2011-01-06 DOI: 10.2202/1557-4679.1295
Jason J. Z. Liao, R. Capen
It is often necessary to compare two measurement methods in medicine and other experimental sciences. This problem covers a broad range of data with applications arising from many different fields. The Bland-Altman method has been a favorite method for concordance assessment. However, the Bland-Altman approach creates a problem of interpretation for many applications when a mixture of fixed bias, proportional bias and/or proportional error occurs. In this paper, an improved Bland-Altman method is proposed to handle more complicated scenarios in practice. This new approach includes Bland-Altman's approach as its special case. We evaluate concordance by defining an agreement interval for each individual paired observation and assessing the overall concordance. The proposed interval approach is very informative and offers many advantages over existing approaches. Data sets are used to demonstrate the advantages of the new method.
在医学和其他实验科学中,经常需要比较两种测量方法。这个问题涉及的数据范围很广,应用程序来自许多不同的领域。Bland-Altman方法一直是一致性评估的常用方法。然而,当固定偏差、比例偏差和/或比例误差混合出现时,Bland-Altman方法在许多应用中产生了解释问题。本文提出了一种改进的Bland-Altman方法来处理实际中更复杂的场景。这种新方法将布兰德-奥特曼的方法作为特例。我们通过定义每个个体配对观察的一致间隔和评估整体一致性来评估一致性。所提出的区间方法信息量很大,与现有方法相比具有许多优点。数据集被用来证明新方法的优点。
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引用次数: 10
A Dunnett-Type Procedure for Multiple Endpoints 多端点的dunnett型过程
IF 1.2 4区 数学 Pub Date : 2011-01-06 DOI: 10.2202/1557-4679.1258
M. Hasler, L. Hothorn
This paper describes a method for comparisons of several treatments with a control, simultaneously for multiple endpoints. These endpoints are assumed to be normally distributed with different scales and variances. An approximate multivariate t-distribution is used to obtain quantiles for test decisions, multiplicity-adjusted p-values, and simultaneous confidence intervals. Simulation results show that this approach controls the family-wise error type I over both the comparisons and the endpoints in an admissible range. The approach will be applied to a randomized clinical trial comparing two new sets of extracorporeal circulations with a standard for three primary endpoints. A related R package is available.
本文描述了一种同时对多个终点进行几种处理与对照比较的方法。假设这些端点是正态分布,具有不同的尺度和方差。近似的多变量t分布用于获得测试决策的分位数,多重调整的p值和同时置信区间。仿真结果表明,该方法在可接受的范围内控制了比较点和端点的类误差。该方法将应用于一项随机临床试验,比较两组新的体外循环与三个主要终点的标准。相关的R包是可用的。
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引用次数: 26
Rejoinder to Nancy Cook's Comment on "Measures to Summarize and Compare the Predictive Capacity of Markers" 对Nancy Cook关于“总结和比较标记预测能力的措施”的回答
IF 1.2 4区 数学 Pub Date : 2010-07-29 DOI: 10.2202/1557-4679.1280
M. Pepe
This is a response to Nancy Cook's Readers' Reaction to "Measures to Summarize and Compare the Predictive Capacity of Markers."
这是对Nancy Cook的读者对“总结和比较标记预测能力的措施”的反应的回应。
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引用次数: 2
Dynamic Regime Marginal Structural Mean Models for Estimation of Optimal Dynamic Treatment Regimes, Part I: Main Content 动态状态边缘结构均值模型估计最优动态处理状态,第一部分:主要内容
IF 1.2 4区 数学 Pub Date : 2010-03-03 DOI: 10.2202/1557-4679.1200
Liliana Orellana, A. Rotnitzky, J. Robins
Dynamic treatment regimes are set rules for sequential decision making based on patient covariate history. Observational studies are well suited for the investigation of the effects of dynamic treatment regimes because of the variability in treatment decisions found in them. This variability exists because different physicians make different decisions in the face of similar patient histories. In this article we describe an approach to estimate the optimal dynamic treatment regime among a set of enforceable regimes. This set is comprised by regimes defined by simple rules based on a subset of past information. The regimes in the set are indexed by a Euclidean vector. The optimal regime is the one that maximizes the expected counterfactual utility over all regimes in the set. We discuss assumptions under which it is possible to identify the optimal regime from observational longitudinal data. Murphy et al. (2001) developed efficient augmented inverse probability weighted estimators of the expected utility of one fixed regime. Our methods are based on an extension of the marginal structural mean model of Robins (1998, 1999) which incorporate the estimation ideas of Murphy et al. (2001). Our models, which we call dynamic regime marginal structural mean models, are specially suitable for estimating the optimal treatment regime in a moderately small class of enforceable regimes of interest. We consider both parametric and semiparametric dynamic regime marginal structural models. We discuss locally efficient, double-robust estimation of the model parameters and of the index of the optimal treatment regime in the set. In a companion paper in this issue of the journal we provide proofs of the main results.
动态治疗方案是根据患者协变量历史为顺序决策制定规则。观察性研究非常适合调查动态治疗方案的效果,因为在这些研究中发现的治疗决策的可变性。这种差异的存在是因为不同的医生在面对相似的病人病史时会做出不同的决定。在这篇文章中,我们描述了一种在一组可执行的制度中估计最优动态处理制度的方法。该集合由基于过去信息子集的简单规则定义的制度组成。集合中的区域由欧几里德向量表示。最优制度是在集合中所有制度中使预期反事实效用最大化的制度。我们讨论了一些假设,在这些假设下,可以从观测的纵向数据中确定最佳状态。Murphy等人(2001)开发了一个固定制度预期效用的有效增广逆概率加权估计器。我们的方法是基于罗宾斯(1998,1999)的边际结构平均模型的扩展,该模型结合了墨菲等人(2001)的估计思想。我们的模型,我们称之为动态制度边际结构平均模型,特别适合于估计中等规模的可执行的利益制度的最佳处理制度。我们考虑了参数和半参数动力体系边缘结构模型。我们讨论了模型参数的局部有效、双鲁棒估计和集合中最优处理方案的指标估计。在本期杂志的一篇配套论文中,我们提供了主要结果的证明。
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引用次数: 201
期刊
International Journal of Biostatistics
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