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On High-Dimensional Covariate Adjustment for Estimating Causal Effects in Randomized Trials with Survival Outcomes. 关于在有生存结果的随机试验中估算因果效应的高维变量调整。
IF 1 Q2 Mathematics Pub Date : 2023-04-01 Epub Date: 2022-09-25 DOI: 10.1007/s12561-022-09358-2
Ran Dai, Cheng Zheng, Mei-Jie Zhang

The purpose of this work is to improve the efficiency in estimating the average causal effect (ACE) on the survival scale where right-censoring exists and high-dimensional covariate information is available. We propose new estimators using regularized survival regression and survival Random Forest (RF) to adjust for the high-dimensional covariate to improve efficiency. We study the behavior of the adjusted estimators under mild assumptions and show theoretical guarantees that the proposed estimators are more efficient than the unadjusted ones asymptotically when using RF for the adjustment. In addition, these adjusted estimators are n - consistent and asymptotically normally distributed. The finite sample behavior of our methods is studied by simulation. The simulation results are in agreement with the theoretical results. We also illustrate our methods by analyzing the real data from transplant research to identify the relative effectiveness of identical sibling donors compared to unrelated donors with the adjustment of cytogenetic abnormalities.

这项工作的目的是在存在右删减和高维协变量信息的情况下,提高生存尺度上平均因果效应(ACE)的估算效率。我们提出了使用正则化生存回归和生存随机森林(RF)来调整高维协变量以提高效率的新估计方法。我们研究了经调整的估计器在温和假设下的行为,并从理论上证明了当使用 RF 进行调整时,所提出的估计器在渐近上比未经调整的估计器更有效。此外,这些调整后的估计值具有 n 一致性和渐近正态分布。我们通过模拟研究了我们方法的有限样本行为。模拟结果与理论结果一致。我们还通过分析移植研究的真实数据来说明我们的方法,以确定同胞捐献者与非亲属捐献者在细胞遗传学异常调整后的相对有效性。
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引用次数: 0
A functional model for studying common trends across trial time in eye tracking experiments. 用于研究眼动跟踪实验中跨试验时间的共同趋势的功能模型。
IF 1 Q2 Mathematics Pub Date : 2023-04-01 Epub Date: 2022-09-05 DOI: 10.1007/s12561-022-09354-6
Mingfei Dong, Donatello Telesca, Catherine Sugar, Frederick Shic, Adam Naples, Scott P Johnson, Beibin Li, Adham Atyabi, Minhang Xie, Sara J Webb, Shafali Jeste, Susan Faja, April R Levin, Geraldine Dawson, James C McPartland, Damla Şentürk

Eye tracking (ET) experiments commonly record the continuous trajectory of a subject's gaze on a two-dimensional screen throughout repeated presentations of stimuli (referred to as trials). Even though the continuous path of gaze is recorded during each trial, commonly derived outcomes for analysis collapse the data into simple summaries, such as looking times in regions of interest, latency to looking at stimuli, number of stimuli viewed, number of fixations or fixation length. In order to retain information in trial time, we utilize functional data analysis (FDA) for the first time in literature in the analysis of ET data. More specifically, novel functional outcomes for ET data, referred to as viewing profiles, are introduced that capture the common gazing trends across trial time which are lost in traditional data summaries. Mean and variation of the proposed functional outcomes across subjects are then modeled using functional principal components analysis. Applications to data from a visual exploration paradigm conducted by the Autism Biomarkers Consortium for Clinical Trials showcase the novel insights gained from the proposed FDA approach, including significant group differences between children diagnosed with autism and their typically developing peers in their consistency of looking at faces early on in trial time.

眼动追踪(ET)实验通常记录受试者在二维屏幕上重复呈现刺激物(称为试验)时的连续注视轨迹。尽管在每次试验中都记录了连续的注视轨迹,但通常得出的分析结果会将数据折叠成简单的摘要,如在感兴趣区域的注视时间、注视刺激物的潜伏期、注视刺激物的数量、固定次数或固定长度。为了保留试验时间的信息,我们首次在文献中利用功能数据分析(FDA)来分析 ET 数据。更具体地说,我们为 ET 数据引入了新的功能结果,即 "注视轮廓",它能捕捉整个试验时间内的共同注视趋势,而这些趋势在传统的数据总结中会丢失。然后使用功能主成分分析法对所提出的功能结果在不同受试者之间的平均值和变化进行建模。自闭症生物标记物临床试验联盟(Autism Biomarkers Consortium for Clinical Trials)进行的视觉探索范式的数据应用,展示了从拟议的 FDA 方法中获得的新见解,包括被诊断患有自闭症的儿童与发育正常的同龄人在试验时间早期注视人脸的一致性方面存在的显著群体差异。
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引用次数: 0
Using Controlled Feeding Study for Biomarker Development in Regression Calibration for Disease Association Estimation. 疾病关联估计回归校准中生物标志物发展的控制饲养研究。
IF 1 Q2 Mathematics Pub Date : 2023-04-01 DOI: 10.1007/s12561-022-09349-3
Cheng Zheng, Yiwen Zhang, Ying Huang, Ross Prentice

Correction for systematic measurement error in self-reported data is an important challenge in association studies of dietary intake and chronic disease risk. The regression calibration method has been used for this purpose when an objectively measured biomarker is available. However, a big limitation of the regression calibration method is that biomarkers have only been developed for a few dietary components. We propose new methods to use controlled feeding studies to develop valid biomarkers for many more dietary components and to estimate the diet disease associations. Asymptotic distribution theory for the proposed estimators is derived. Extensive simulation is performed to study the finite sample performance of the proposed estimators. We applied our method to examine the associations between the sodium/potassium intake ratio and cardiovascular disease incidence using the Women's Health Initiative cohort data. We discovered positive associations between sodium/potassium ratio and the risks of coronary heart disease, nonfatal myocardial infarction, coronary death, ischemic stroke, and total cardiovascular disease.

在膳食摄入与慢性疾病风险相关性研究中,对自我报告数据中的系统测量误差进行校正是一项重要挑战。当客观测量的生物标志物可用时,回归校准方法已用于此目的。然而,回归校准方法的一个很大的局限性是,生物标志物只针对少数饮食成分开发。我们提出了新的方法,利用控制喂养研究来开发更多膳食成分的有效生物标志物,并估计饮食疾病的相关性。给出了所提估计量的渐近分布理论。通过广泛的仿真研究了所提估计器的有限样本性能。我们利用妇女健康倡议队列数据,应用我们的方法来检验钠/钾摄入比例与心血管疾病发病率之间的关系。我们发现钠钾比与冠心病、非致死性心肌梗死、冠状动脉死亡、缺血性中风和总心血管疾病的风险呈正相关。
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引用次数: 2
Causal Inference with Secondary Outcomes 与次要结果的因果推断
IF 1 Q2 Mathematics Pub Date : 2023-03-20 DOI: 10.1007/s12561-023-09363-z
Ying Zhou
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引用次数: 0
Introduction 介绍
IF 1 Q2 Mathematics Pub Date : 2023-01-17 DOI: 10.1007/s12561-018-9218-3
Benjamin Gillespie
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引用次数: 0
Impact of the Error Structure on the Design and Analysis of Enzyme Kinetic Models. 误差结构对设计和分析酶动力学模型的影响。
IF 1 Q2 Mathematics Pub Date : 2023-01-01 Epub Date: 2022-06-09 DOI: 10.1007/s12561-022-09347-5
Elham Yousefi, Werner G Müller

The statistical analysis of enzyme kinetic reactions usually involves models of the response functions which are well defined on the basis of Michaelis-Menten type equations. The error structure, however, is often without good reason assumed as additive Gaussian noise. This simple assumption may lead to undesired properties of the analysis, particularly when simulations are involved and consequently negative simulated reaction rates may occur. In this study, we investigate the effect of assuming multiplicative log normal errors instead. While there is typically little impact on the estimates, the experimental designs and their efficiencies are decisively affected, particularly when it comes to model discrimination problems.

酶促反应的统计分析通常涉及反应函数模型,这些模型在 Michaelis-Menten 类型方程的基础上定义明确。然而,误差结构往往被无理假定为加性高斯噪声。这种简单的假设可能会导致分析结果出现不理想的性质,尤其是在涉及模拟的情况下,因此可能会出现负的模拟反应速率。在本研究中,我们研究了假设对数正态误差的影响。虽然对估计值的影响通常不大,但实验设计及其效率却会受到决定性的影响,尤其是在涉及模型判别问题时。
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引用次数: 0
On the Methodological Aspects of the Clinical Trials for COVID-19 Conducted in the First Year of the Pandemic: A Descriptive Analysis. 新冠肺炎疫情第一年临床试验的方法论方面:描述性分析。
IF 1 Q2 Mathematics Pub Date : 2023-01-01 Epub Date: 2023-03-16 DOI: 10.1007/s12561-023-09366-w
Eleni Georgiadi, Athanasios Sachlas

In 2020, the whole planet was plagued by the extremely deadly COVID-19 pandemic. More than 83 million people had been infected with COVID-19 while more than 1.9 million people around the planet had died from this virus in the first year of the pandemic. From the first moment, the medical community started working to deal with this pandemic. For this reason, many clinical trials have been and continue to be conducted to find a safe and efficient cure for the virus. In this paper, we review the 96 clinical trials, registered in the ClinicalTrials.gov database, that had been completed by the end of the first year of the pandemic. Although the clinical trials contained significant heterogeneity in the main methodological features (enrollment, duration, allocation, intervention model, and masking) they seemed to be conducted based on an appropriate methodological basis.

2020年,整个地球都受到极其致命的新冠肺炎大流行的困扰。在大流行的第一年,超过8300万人感染了新冠肺炎,而全球超过190万人死于这种病毒。从第一刻起,医学界就开始努力应对这一流行病。出于这个原因,许多临床试验已经并将继续进行,以找到一种安全有效的病毒治疗方法。在这篇论文中,我们回顾了在ClinicalTrials.gov数据库中注册的96项临床试验,这些试验在大流行的第一年结束时已经完成。尽管临床试验在主要方法学特征(入组、持续时间、分配、干预模型和掩蔽)方面存在显著的异质性,但它们似乎是基于适当的方法学基础进行的。
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引用次数: 0
New Confidence Intervals for Relative Risk of Two Correlated Proportions. 两个相关比例相对风险的新置信区间。
IF 0.8 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2023-01-01 Epub Date: 2022-05-20 DOI: 10.1007/s12561-022-09345-7
Natalie DelRocco, Yipeng Wang, Dongyuan Wu, Yuting Yang, Guogen Shan

Biomedical studies, such as clinical trials, often require the comparison of measurements from two correlated tests in which each unit of observation is associated with a binary outcome of interest via relative risk. The associated confidence interval is crucial because it provides an appreciation of the spectrum of possible values, allowing for a more robust interpretation of relative risk. Of the available confidence interval methods for relative risk, the asymptotic score interval is the most widely recommended for practical use. We propose a modified score interval for relative risk and we also extend an existing nonparametric U-statistic-based confidence interval to relative risk. In addition, we theoretically prove that the original asymptotic score interval is equivalent to the constrained maximum likelihood-based interval proposed by Nam and Blackwelder. Two clinically relevant oncology trials are used to demonstrate the real-world performance of our methods. The finite sample properties of the new approaches, the current standard of practice, and other alternatives are studied via extensive simulation studies. We show that, as the strength of correlation increases, when the sample size is not too large the new score-based intervals outperform the existing intervals in terms of coverage probability. Moreover, our results indicate that the new nonparametric interval provides the coverage that most consistently meets or exceeds the nominal coverage probability.

生物医学研究(如临床试验)通常需要对两个相关测试的测量结果进行比较,其中每个观察单位通过相对风险与感兴趣的二元结果相关联。相关的置信区间至关重要,因为它提供了对可能值范围的了解,从而可以对相对风险做出更稳健的解释。在现有的相对风险置信区间方法中,渐近分数置信区间是实际应用中最广泛推荐的方法。我们提出了一种改进的相对风险评分区间,并将现有的基于 U 统计量的非参数置信区间扩展到相对风险。此外,我们还从理论上证明,原始的渐近评分区间等同于 Nam 和 Blackwelder 提出的基于最大似然法的约束区间。我们使用了两项临床相关的肿瘤试验来证明我们的方法在现实世界中的表现。通过大量的模拟研究,对新方法、现行实践标准和其他替代方法的有限样本特性进行了研究。我们的研究表明,随着相关性强度的增加,当样本量不太大时,基于评分的新区间在覆盖概率方面优于现有区间。此外,我们的结果表明,新的非参数区间提供的覆盖率最稳定地达到或超过了名义覆盖概率。
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引用次数: 0
Simultaneous Confidence Band Approach for Comparison of COVID-19 Case Counts. 新冠肺炎病例数比较的同时置信带方法。
IF 1 Q2 Mathematics Pub Date : 2023-01-01 Epub Date: 2023-03-07 DOI: 10.1007/s12561-023-09364-y
Q Shao

The outbreak of the novel coronavirus (COVID-19) was declared to be a global emergency in January of 2020, and everyday life throughout the world was disrupted. Among many questions about COVID-19 that remain unanswered, it is of interest for society to identify whether there is any significant difference in daily case counts between males and females. The daily case count sequences are correlated due to the nature of a contagious disease, and contain a nonlinear trend owing to several unexpected events, such as vaccinations and the appearance of the delta variant. It is possible that these unexpected events have changed the dynamical system that generates data. The classic t-test is not appropriate to analyze such correlated data with a nonconstant trend. This study applies a simultaneous confidence band approach in an attempt to overcome these difficulties; that is, a simultaneous confidence band for the trend of an autoregressive moving-average time series is constructed using B-spline estimation. The proposed method is applied to the daily case count data of seniors of both genders (at least 60 years old) in the State of Ohio from April 1, 2020 to March 31, 2022, and the result shows that there is a significant difference at the 95% confidence level between the two gender case counts adjusted for the population sizes.

2020年1月,新型冠状病毒(新冠肺炎)的爆发被宣布为全球紧急事件,世界各地的日常生活受到干扰。在许多关于新冠肺炎的问题中,社会有兴趣确定男性和女性的每日病例数是否存在显著差异。由于传染病的性质,每日病例数序列是相关的,并且由于一些意外事件,如疫苗接种和德尔塔变异株的出现,包含非线性趋势。这些意外事件可能改变了生成数据的动力系统。经典的t检验不适合分析这种具有非恒定趋势的相关数据。本研究采用同时置信带方法试图克服这些困难;即,使用B样条估计构建自回归移动平均时间序列趋势的同时置信带。将所提出的方法应用于2020年4月1日至2022年3月31日俄亥俄州男女老年人(至少60岁)的每日病例数数据,结果显示,根据人口规模调整后的男女病例数在95%置信水平上存在显著差异。
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引用次数: 1
Irregular Shaped Small Nodule Detection Using a Robust Scan Statistic. 基于鲁棒扫描统计量的不规则小结节检测。
IF 1 Q2 Mathematics Pub Date : 2023-01-01 DOI: 10.1007/s12561-022-09353-7
Ali Abolhassani, Marcos O Prates, Safieh Mahmoodi

The spatial scan statistics based on the Poisson and binomial models are the most common methods to detect spatial clusters in disease surveillance. These models rely on Monte-Carlo simulation which are time consuming. Moreover, frequently, datasets present over-dispersion which cannot be handled by them. Thus, we have the following goals. First, we propose irregularly shaped spatial scan for the Bell, Poisson, and binomial. The Bell distribution has just one parameter but it is capable of handling over-dispersed datasets. Second, we apply these scan statistics to big maps. A fast version, without Monte-Carlo simulation, for the proposed Poisson and binomial scans is introduced. Intensive simulation studies are carried out to assess the quality of the proposals. In addition, we show the time improvement of the fast scan versions over their traditional ones. Finally, we end the paper with an application on the detection of irregular shape small nodules in a medical image.

Supplementary information: The online version contains supplementary material available at 10.1007/s12561-022-09353-7.

基于泊松模型和二项模型的空间扫描统计是疾病监测中最常用的空间聚类检测方法。这些模型依赖于蒙特卡罗模拟,耗时较长。此外,数据集经常出现过度分散,这是它们无法处理的。因此,我们有以下目标。首先,我们提出了不规则形状的空间扫描贝尔,泊松和二项。贝尔分布只有一个参数,但它能够处理过度分散的数据集。其次,我们将这些扫描统计数据应用于大地图。一个快速版本,没有蒙特卡罗模拟,提出了泊松和二项扫描。进行了密集的模拟研究,以评估建议的质量。此外,我们还展示了快速扫描版本比传统版本在时间上的改进。最后,我们以一个在医学图像中不规则形状小结节检测中的应用作为本文的结束语。补充信息:在线版本包含补充资料,下载地址为10.1007/s12561-022-09353-7。
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引用次数: 1
期刊
Statistics in Biosciences
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