{"title":"τ $\\tau$ -Inflated Beta Regression Model for Estimating τ $\\tau$ -Restricted Means and Event-Free Probabilities for Censored Time-to-Event Data.","authors":"Yizhuo Wang, Susan Murray","doi":"10.1002/bimj.70009","DOIUrl":null,"url":null,"abstract":"<p>In this research, we propose analysis of <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-restricted censored time-to-event data via a <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-inflated beta regression (<span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-IBR) model. The outcome of interest is <span></span><math>\n <semantics>\n <mrow>\n <mi>min</mi>\n <mo>(</mo>\n <mi>τ</mi>\n <mo>,</mo>\n <mi>T</mi>\n <mo>)</mo>\n </mrow>\n <annotation>${\\rm min}(\\tau,T)$</annotation>\n </semantics></math>, where <span></span><math>\n <semantics>\n <mi>T</mi>\n <annotation>$T$</annotation>\n </semantics></math> and <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math> are the time-to-event and follow-up duration, respectively. Our analysis goals include estimation and inference related to <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-restricted mean survival time (<span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-RMST) values and event-free probabilities at <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math> that address the censored nature of the data. In this setting, it is common to observe many individuals with <span></span><math>\n <semantics>\n <mrow>\n <mi>min</mi>\n <mo>(</mo>\n <mi>τ</mi>\n <mo>,</mo>\n <mi>T</mi>\n <mo>)</mo>\n <mo>=</mo>\n <mi>τ</mi>\n </mrow>\n <annotation>${\\rm min}(\\tau,T)=\\tau$</annotation>\n </semantics></math>, a point mass that is typically overlooked in <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-restricted event-time analyses. Our proposed <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-IBR model is based on a decomposition of <span></span><math>\n <semantics>\n <mrow>\n <mi>min</mi>\n <mo>(</mo>\n <mi>τ</mi>\n <mo>,</mo>\n <mi>T</mi>\n <mo>)</mo>\n </mrow>\n <annotation>${\\rm min}(\\tau,T)$</annotation>\n </semantics></math> into <span></span><math>\n <semantics>\n <mrow>\n <mi>τ</mi>\n <mo>[</mo>\n <mi>I</mi>\n <mo>(</mo>\n <mi>T</mi>\n <mo>≥</mo>\n <mi>τ</mi>\n <mo>)</mo>\n <mo>+</mo>\n <mo>(</mo>\n <mi>T</mi>\n <mo>/</mo>\n <mi>τ</mi>\n <mo>)</mo>\n <mi>I</mi>\n <mo>(</mo>\n <mi>T</mi>\n <mo><</mo>\n <mi>τ</mi>\n <mo>)</mo>\n <mo>]</mo>\n </mrow>\n <annotation>$\\tau [I(T \\ge \\tau) +(T/\\tau) I(T &lt;\\tau)]$</annotation>\n </semantics></math>. We model the mean of this latter expression using joint logistic and beta regression models that are fit using an expectation-maximization algorithm. An alternative multiple imputation (MI) algorithm for fitting the <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-IBR model has the additional advantage of producing uncensored datasets for analysis. Simulations indicate excellent performance of the <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-IBR model(s), and corresponding <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-RMST estimates, in independent and dependent censoring settings. We apply our method to the Azithromycin for Prevention of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Trial. In addition to <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-IBR model results providing a nuanced understanding of the treatment effect, visually appealing heatmaps of the <span></span><math>\n <semantics>\n <mi>τ</mi>\n <annotation>$\\tau$</annotation>\n </semantics></math>-restricted event times based on our MI datasets are given, a visualization not typically available for censored time-to-event data.</p>","PeriodicalId":55360,"journal":{"name":"Biometrical Journal","volume":"66 8","pages":""},"PeriodicalIF":1.3000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bimj.70009","citationCount":"0","resultStr":"{\"title\":\"τ\\n $\\\\tau$\\n -Inflated Beta Regression Model for Estimating \\n \\n τ\\n $\\\\tau$\\n -Restricted Means and Event-Free Probabilities for Censored Time-to-Event Data\",\"authors\":\"Yizhuo Wang, Susan Murray\",\"doi\":\"10.1002/bimj.70009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>In this research, we propose analysis of <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-restricted censored time-to-event data via a <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-inflated beta regression (<span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-IBR) model. The outcome of interest is <span></span><math>\\n <semantics>\\n <mrow>\\n <mi>min</mi>\\n <mo>(</mo>\\n <mi>τ</mi>\\n <mo>,</mo>\\n <mi>T</mi>\\n <mo>)</mo>\\n </mrow>\\n <annotation>${\\\\rm min}(\\\\tau,T)$</annotation>\\n </semantics></math>, where <span></span><math>\\n <semantics>\\n <mi>T</mi>\\n <annotation>$T$</annotation>\\n </semantics></math> and <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math> are the time-to-event and follow-up duration, respectively. Our analysis goals include estimation and inference related to <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-restricted mean survival time (<span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-RMST) values and event-free probabilities at <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math> that address the censored nature of the data. In this setting, it is common to observe many individuals with <span></span><math>\\n <semantics>\\n <mrow>\\n <mi>min</mi>\\n <mo>(</mo>\\n <mi>τ</mi>\\n <mo>,</mo>\\n <mi>T</mi>\\n <mo>)</mo>\\n <mo>=</mo>\\n <mi>τ</mi>\\n </mrow>\\n <annotation>${\\\\rm min}(\\\\tau,T)=\\\\tau$</annotation>\\n </semantics></math>, a point mass that is typically overlooked in <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-restricted event-time analyses. Our proposed <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-IBR model is based on a decomposition of <span></span><math>\\n <semantics>\\n <mrow>\\n <mi>min</mi>\\n <mo>(</mo>\\n <mi>τ</mi>\\n <mo>,</mo>\\n <mi>T</mi>\\n <mo>)</mo>\\n </mrow>\\n <annotation>${\\\\rm min}(\\\\tau,T)$</annotation>\\n </semantics></math> into <span></span><math>\\n <semantics>\\n <mrow>\\n <mi>τ</mi>\\n <mo>[</mo>\\n <mi>I</mi>\\n <mo>(</mo>\\n <mi>T</mi>\\n <mo>≥</mo>\\n <mi>τ</mi>\\n <mo>)</mo>\\n <mo>+</mo>\\n <mo>(</mo>\\n <mi>T</mi>\\n <mo>/</mo>\\n <mi>τ</mi>\\n <mo>)</mo>\\n <mi>I</mi>\\n <mo>(</mo>\\n <mi>T</mi>\\n <mo><</mo>\\n <mi>τ</mi>\\n <mo>)</mo>\\n <mo>]</mo>\\n </mrow>\\n <annotation>$\\\\tau [I(T \\\\ge \\\\tau) +(T/\\\\tau) I(T &lt;\\\\tau)]$</annotation>\\n </semantics></math>. We model the mean of this latter expression using joint logistic and beta regression models that are fit using an expectation-maximization algorithm. An alternative multiple imputation (MI) algorithm for fitting the <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-IBR model has the additional advantage of producing uncensored datasets for analysis. Simulations indicate excellent performance of the <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-IBR model(s), and corresponding <span></span><math>\\n <semantics>\\n <mi>τ</mi>\\n <annotation>$\\\\tau$</annotation>\\n </semantics></math>-RMST estimates, in independent and dependent censoring settings. We apply our method to the Azithromycin for Prevention of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Trial. 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引用次数: 0
摘要
在这项研究中,我们提出通过τ $\tau$ -膨胀贝塔回归(τ $\tau$ -IBR)模型来分析τ $\tau$ -限制删减的时间到事件数据。我们感兴趣的结果是 min ( τ , T ) ${rm min}(\tau,T)$,其中 T $T$ 和 τ $\tau$ 分别是事件发生时间和随访持续时间。我们的分析目标包括与τ $\tau$ -限制平均生存时间(τ $\tau$ -RMST)值和τ $\tau$ 处的无事件概率相关的估计和推断,以解决数据的删减性质。在这种情况下,通常会观察到许多个体的 min ( τ , T ) = τ ${rm min}(\tau,T)=\tau$,这是在 τ $\tau$ 限制的事件时间分析中通常会忽略的点质量。我们提出的 τ $\tau$ -IBR 模型基于将 min ( τ , T ) ${rm min}(\tau,T)$分解为 τ [ I ( T ≥ τ ) + ( T / τ ) I ( T τ ) ] $\tau [I(T \ge \tau) +(T/\tau) I(T <\tau)]$ 。我们使用联合逻辑和贝塔回归模型对后一个表达式的均值进行建模,并使用期望最大化算法进行拟合。用于拟合 τ $\tau$ -IBR 模型的另一种多重归因(MI)算法的另一个优点是可以生成用于分析的无删减数据集。模拟结果表明,在独立和从属删失设置中,τ $\tau$ -IBR模型和相应的τ $\tau$ -RMST估计值都具有出色的性能。我们将我们的方法应用于阿奇霉素预防慢性阻塞性肺病(COPD)恶化试验。除了τ $\tau$ -IBR模型结果提供了对治疗效果的细微理解外,我们还给出了基于我们的MI数据集的τ $\tau$ -限制事件时间的直观热图,这种可视化方式通常无法用于删减时间到事件数据。
τ
$\tau$
-Inflated Beta Regression Model for Estimating
τ
$\tau$
-Restricted Means and Event-Free Probabilities for Censored Time-to-Event Data
In this research, we propose analysis of -restricted censored time-to-event data via a -inflated beta regression (-IBR) model. The outcome of interest is , where and are the time-to-event and follow-up duration, respectively. Our analysis goals include estimation and inference related to -restricted mean survival time (-RMST) values and event-free probabilities at that address the censored nature of the data. In this setting, it is common to observe many individuals with , a point mass that is typically overlooked in -restricted event-time analyses. Our proposed -IBR model is based on a decomposition of into . We model the mean of this latter expression using joint logistic and beta regression models that are fit using an expectation-maximization algorithm. An alternative multiple imputation (MI) algorithm for fitting the -IBR model has the additional advantage of producing uncensored datasets for analysis. Simulations indicate excellent performance of the -IBR model(s), and corresponding -RMST estimates, in independent and dependent censoring settings. We apply our method to the Azithromycin for Prevention of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Trial. In addition to -IBR model results providing a nuanced understanding of the treatment effect, visually appealing heatmaps of the -restricted event times based on our MI datasets are given, a visualization not typically available for censored time-to-event data.
期刊介绍:
Biometrical Journal publishes papers on statistical methods and their applications in life sciences including medicine, environmental sciences and agriculture. Methodological developments should be motivated by an interesting and relevant problem from these areas. Ideally the manuscript should include a description of the problem and a section detailing the application of the new methodology to the problem. Case studies, review articles and letters to the editors are also welcome. Papers containing only extensive mathematical theory are not suitable for publication in Biometrical Journal.