Pub Date : 2024-05-01Epub Date: 2024-03-20DOI: 10.1177/09622802241239008
Marta Bofill Roig, Ekkehard Glimm, Tobias Mielke, Martin Posch
Platform trials are randomized clinical trials that allow simultaneous comparison of multiple interventions, usually against a common control. Arms to test experimental interventions may enter and leave the platform over time. This implies that the number of experimental intervention arms in the trial may change as the trial progresses. Determining optimal allocation rates to allocate patients to the treatment and control arms in platform trials is challenging because the optimal allocation depends on the number of arms in the platform and the latter typically varies over time. In addition, the optimal allocation depends on the analysis strategy used and the optimality criteria considered. In this article, we derive optimal treatment allocation rates for platform trials with shared controls, assuming that a stratified estimation and a testing procedure based on a regression model are used to adjust for time trends. We consider both, analysis using concurrent controls only as well as analysis methods using concurrent and non-concurrent controls and assume that the total sample size is fixed. The objective function to be minimized is the maximum of the variances of the effect estimators. We show that the optimal solution depends on the entry time of the arms in the trial and, in general, does not correspond to the square root of allocation rule used in classical multi-arm trials. We illustrate the optimal allocation and evaluate the power and type 1 error rate compared to trials using one-to-one and square root of allocations by means of a case study.
平台试验是一种随机临床试验，可同时比较多种干预措施，通常是与一种共同对照进行比较。测试实验干预措施的臂可能会随着时间的推移进入或离开平台。这意味着试验中实验干预臂的数量可能会随着试验的进展而发生变化。在平台试验中，确定将患者分配到治疗臂和对照臂的最佳分配率具有挑战性，因为最佳分配率取决于平台中的臂数，而后者通常会随着时间的推移而变化。此外，最佳分配率还取决于所使用的分析策略和所考虑的优化标准。在本文中，我们假定使用分层估计和基于回归模型的测试程序来调整时间趋势，从而推导出共享对照的平台试验的最佳治疗分配率。我们既考虑了仅使用同期对照的分析方法，也考虑了使用同期和非同期对照的分析方法，并假设总样本量是固定的。需要最小化的目标函数是效应估计值方差的最大值。我们的研究表明，最优解取决于试验中各臂的进入时间，一般来说，最优解与经典多臂试验中使用的 k 的平方根分配规则并不一致。我们通过案例研究说明了最优分配，并评估了与使用一对一和 k 的平方根分配的试验相比的功率和 1 类错误率。
{"title":"Optimal allocation strategies in platform trials with continuous endpoints.","authors":"Marta Bofill Roig, Ekkehard Glimm, Tobias Mielke, Martin Posch","doi":"10.1177/09622802241239008","DOIUrl":"10.1177/09622802241239008","url":null,"abstract":"<p><p>Platform trials are randomized clinical trials that allow simultaneous comparison of multiple interventions, usually against a common control. Arms to test experimental interventions may enter and leave the platform over time. This implies that the number of experimental intervention arms in the trial may change as the trial progresses. Determining optimal allocation rates to allocate patients to the treatment and control arms in platform trials is challenging because the optimal allocation depends on the number of arms in the platform and the latter typically varies over time. In addition, the optimal allocation depends on the analysis strategy used and the optimality criteria considered. In this article, we derive optimal treatment allocation rates for platform trials with shared controls, assuming that a stratified estimation and a testing procedure based on a regression model are used to adjust for time trends. We consider both, analysis using concurrent controls only as well as analysis methods using concurrent and non-concurrent controls and assume that the total sample size is fixed. The objective function to be minimized is the maximum of the variances of the effect estimators. We show that the optimal solution depends on the entry time of the arms in the trial and, in general, does not correspond to the square root of <math><mi>k</mi></math> allocation rule used in classical multi-arm trials. We illustrate the optimal allocation and evaluate the power and type 1 error rate compared to trials using one-to-one and square root of <math><mi>k</mi></math> allocations by means of a case study.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"858-874"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11041082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This article proposes a Bayesian approach for jointly estimating marginal conditional quantiles of multi-response longitudinal data with multivariate mixed effects model. The multivariate asymmetric Laplace distribution is employed to construct the working likelihood of the considered model. Penalization priors on regression parameters are incorporated into the working likelihood to conduct Bayesian high-dimensional inference. Markov chain Monte Carlo algorithm is used to obtain the fully conditional posterior distributions of all parameters and latent variables. Monte Carlo simulations are conducted to evaluate the sample performance of the proposed joint quantile regression approach. Finally, we analyze a longitudinal medical dataset of the primary biliary cirrhosis sequential cohort study to illustrate the real application of the proposed modeling method.
{"title":"Bayesian analysis of joint quantile regression for multi-response longitudinal data with application to primary biliary cirrhosis sequential cohort study","authors":"Yu-Zhu Tian, Man-Lai Tang, Catherine Wong, Mao-Zai Tian","doi":"10.1177/09622802241247725","DOIUrl":"https://doi.org/10.1177/09622802241247725","url":null,"abstract":"This article proposes a Bayesian approach for jointly estimating marginal conditional quantiles of multi-response longitudinal data with multivariate mixed effects model. The multivariate asymmetric Laplace distribution is employed to construct the working likelihood of the considered model. Penalization priors on regression parameters are incorporated into the working likelihood to conduct Bayesian high-dimensional inference. Markov chain Monte Carlo algorithm is used to obtain the fully conditional posterior distributions of all parameters and latent variables. Monte Carlo simulations are conducted to evaluate the sample performance of the proposed joint quantile regression approach. Finally, we analyze a longitudinal medical dataset of the primary biliary cirrhosis sequential cohort study to illustrate the real application of the proposed modeling method.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"53 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-27DOI: 10.1177/09622802241247728
Mayu Hiraishi, Ke Wan, Kensuke Tanioka, Hiroshi Yadohisa, Toshio Shimokawa
We propose a novel framework based on the RuleFit method to estimate heterogeneous treatment effect in randomized clinical trials. The proposed method estimates a rule ensemble comprising a set of prognostic rules, a set of prescriptive rules, as well as the linear effects of the original predictor variables. The prescriptive rules provide an interpretable description of the heterogeneous treatment effect. By including a prognostic term in the proposed model, the selected rule is represented as an heterogeneous treatment effect that excludes other effects. We confirmed that the performance of the proposed method was equivalent to that of other ensemble learning methods through numerical simulations and demonstrated the interpretation of the proposed method using a real data application.
{"title":"Causal rule ensemble method for estimating heterogeneous treatment effect with consideration of prognostic effects","authors":"Mayu Hiraishi, Ke Wan, Kensuke Tanioka, Hiroshi Yadohisa, Toshio Shimokawa","doi":"10.1177/09622802241247728","DOIUrl":"https://doi.org/10.1177/09622802241247728","url":null,"abstract":"We propose a novel framework based on the RuleFit method to estimate heterogeneous treatment effect in randomized clinical trials. The proposed method estimates a rule ensemble comprising a set of prognostic rules, a set of prescriptive rules, as well as the linear effects of the original predictor variables. The prescriptive rules provide an interpretable description of the heterogeneous treatment effect. By including a prognostic term in the proposed model, the selected rule is represented as an heterogeneous treatment effect that excludes other effects. We confirmed that the performance of the proposed method was equivalent to that of other ensemble learning methods through numerical simulations and demonstrated the interpretation of the proposed method using a real data application.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"43 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1177/09622802241244608
Lucy D’Agostino McGowan, Sarah C Lotspeich, Staci A Hepler
Missing data is a common challenge when analyzing epidemiological data, and imputation is often used to address this issue. Here, we investigate the scenario where a covariate used in an analysis has missingness and will be imputed. There are recommendations to include the outcome from the analysis model in the imputation model for missing covariates, but it is not necessarily clear if this recommendation always holds and why this is sometimes true. We examine deterministic imputation (i.e. single imputation with fixed values) and stochastic imputation (i.e. single or multiple imputation with random values) methods and their implications for estimating the relationship between the imputed covariate and the outcome. We mathematically demonstrate that including the outcome variable in imputation models is not just a recommendation but a requirement to achieve unbiased results when using stochastic imputation methods. Moreover, we dispel common misconceptions about deterministic imputation models and demonstrate why the outcome should not be included in these models. This article aims to bridge the gap between imputation in theory and in practice, providing mathematical derivations to explain common statistical recommendations. We offer a better understanding of the considerations involved in imputing missing covariates and emphasize when it is necessary to include the outcome variable in the imputation model.
{"title":"The “Why” behind including “Y” in your imputation model","authors":"Lucy D’Agostino McGowan, Sarah C Lotspeich, Staci A Hepler","doi":"10.1177/09622802241244608","DOIUrl":"https://doi.org/10.1177/09622802241244608","url":null,"abstract":"Missing data is a common challenge when analyzing epidemiological data, and imputation is often used to address this issue. Here, we investigate the scenario where a covariate used in an analysis has missingness and will be imputed. There are recommendations to include the outcome from the analysis model in the imputation model for missing covariates, but it is not necessarily clear if this recommendation always holds and why this is sometimes true. We examine deterministic imputation (i.e. single imputation with fixed values) and stochastic imputation (i.e. single or multiple imputation with random values) methods and their implications for estimating the relationship between the imputed covariate and the outcome. We mathematically demonstrate that including the outcome variable in imputation models is not just a recommendation but a requirement to achieve unbiased results when using stochastic imputation methods. Moreover, we dispel common misconceptions about deterministic imputation models and demonstrate why the outcome should not be included in these models. This article aims to bridge the gap between imputation in theory and in practice, providing mathematical derivations to explain common statistical recommendations. We offer a better understanding of the considerations involved in imputing missing covariates and emphasize when it is necessary to include the outcome variable in the imputation model.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"219 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1177/09622802241236934
Jiren Sun, Thomas Cook
Many non-fatal events can be considered recurrent in that they can occur repeatedly over time, and some researchers may be interested in the trajectory and relative risk of non-fatal events. With the competing risk of death, the treatment effect on the mean number of recurrent events is non-identifiable since the observed mean is a function of both the recurrent event and terminal event processes. In this paper, we assume independence between the non-fatal and the terminal event process, conditional on the shared frailty, to fit a parametric model that recovers the trajectory of, and identifies the effect of treatment on, the non-fatal event process in the presence of the competing risk of death. Simulation studies are conducted to verify the reliability of our estimators. We illustrate the method and perform model diagnostics using the Carvedilol Prospective Randomized Cumulative Survival trial which involves heart-failure events.
{"title":"A simple and robust parametric shared frailty model for recurrent events with the competing risk of death: An application to the Carvedilol Prospective Randomized Cumulative Survival trial","authors":"Jiren Sun, Thomas Cook","doi":"10.1177/09622802241236934","DOIUrl":"https://doi.org/10.1177/09622802241236934","url":null,"abstract":"Many non-fatal events can be considered recurrent in that they can occur repeatedly over time, and some researchers may be interested in the trajectory and relative risk of non-fatal events. With the competing risk of death, the treatment effect on the mean number of recurrent events is non-identifiable since the observed mean is a function of both the recurrent event and terminal event processes. In this paper, we assume independence between the non-fatal and the terminal event process, conditional on the shared frailty, to fit a parametric model that recovers the trajectory of, and identifies the effect of treatment on, the non-fatal event process in the presence of the competing risk of death. Simulation studies are conducted to verify the reliability of our estimators. We illustrate the method and perform model diagnostics using the Carvedilol Prospective Randomized Cumulative Survival trial which involves heart-failure events.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"70 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1177/09622802241242313
Cong Jiang, Mary Thompson, Michael Wallace
The focus of precision medicine is on decision support, often in the form of dynamic treatment regimes, which are sequences of decision rules. At each decision point, the decision rules determine the next treatment according to the patient’s baseline characteristics, the information on treatments and responses accrued by that point, and the patient’s current health status, including symptom severity and other measures. However, dynamic treatment regime estimation with ordinal outcomes is rarely studied, and rarer still in the context of interference – where one patient’s treatment may affect another’s outcome. In this paper, we introduce the weighted proportional odds model: a regression based, approximate doubly-robust approach to single-stage dynamic treatment regime estimation for ordinal outcomes. This method also accounts for the possibility of interference between individuals sharing a household through the use of covariate balancing weights derived from joint propensity scores. Examining different types of balancing weights, we verify the approximate double robustness of weighted proportional odds model with our adjusted weights via simulation studies. We further extend weighted proportional odds model to multi-stage dynamic treatment regime estimation with household interference, namely dynamic weighted proportional odds model. Lastly, we demonstrate our proposed methodology in the analysis of longitudinal survey data from the Population Assessment of Tobacco and Health study, which motivates this work. Furthermore, considering interference, we provide optimal treatment strategies for households to achieve smoking cessation of the pair in the household.
{"title":"Estimating dynamic treatment regimes for ordinal outcomes with household interference: Application in household smoking cessation","authors":"Cong Jiang, Mary Thompson, Michael Wallace","doi":"10.1177/09622802241242313","DOIUrl":"https://doi.org/10.1177/09622802241242313","url":null,"abstract":"The focus of precision medicine is on decision support, often in the form of dynamic treatment regimes, which are sequences of decision rules. At each decision point, the decision rules determine the next treatment according to the patient’s baseline characteristics, the information on treatments and responses accrued by that point, and the patient’s current health status, including symptom severity and other measures. However, dynamic treatment regime estimation with ordinal outcomes is rarely studied, and rarer still in the context of interference – where one patient’s treatment may affect another’s outcome. In this paper, we introduce the weighted proportional odds model: a regression based, approximate doubly-robust approach to single-stage dynamic treatment regime estimation for ordinal outcomes. This method also accounts for the possibility of interference between individuals sharing a household through the use of covariate balancing weights derived from joint propensity scores. Examining different types of balancing weights, we verify the approximate double robustness of weighted proportional odds model with our adjusted weights via simulation studies. We further extend weighted proportional odds model to multi-stage dynamic treatment regime estimation with household interference, namely dynamic weighted proportional odds model. Lastly, we demonstrate our proposed methodology in the analysis of longitudinal survey data from the Population Assessment of Tobacco and Health study, which motivates this work. Furthermore, considering interference, we provide optimal treatment strategies for households to achieve smoking cessation of the pair in the household.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"4 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-10DOI: 10.1177/09622802241244613
Esmail Abdul-Fattah, Elias Krainski, Janet Van Niekerk, Håvard Rue
This paper aims to extend the Besag model, a widely used Bayesian spatial model in disease mapping, to a non-stationary spatial model for irregular lattice-type data. The goal is to improve the model’s ability to capture complex spatial dependence patterns and increase interpretability. The proposed model uses multiple precision parameters, accounting for different intensities of spatial dependence in different sub-regions. We derive a joint penalized complexity prior to the flexible local precision parameters to prevent overfitting and ensure contraction to the stationary model at a user-defined rate. The proposed methodology can be used as a basis for the development of various other non-stationary effects over other domains such as time. An accompanying R package fbesag equips the reader with the necessary tools for immediate use and application. We illustrate the novelty of the proposal by modeling the risk of dengue in Brazil, where the stationary spatial assumption fails and interesting risk profiles are estimated when accounting for spatial non-stationary. Additionally, we model different causes of death in Brazil, where we use the new model to investigate the spatial stationarity of these causes.
本文旨在将疾病绘图中广泛使用的贝叶斯空间模型 Besag 模型扩展为不规则网格型数据的非稳态空间模型。目的是提高模型捕捉复杂空间依赖模式的能力，增加可解释性。建议的模型使用多个精确参数，以反映不同子区域的不同空间依赖强度。我们为灵活的局部精度参数推导了一个联合惩罚复杂性先验，以防止过拟合，并确保以用户定义的速率收缩到静态模型。所提出的方法可作为开发其他领域（如时间）各种非稳态效应的基础。随附的 R 软件包 fbesag 为读者提供了立即使用和应用的必要工具。我们通过对巴西登革热风险的建模来说明该建议的新颖性，在巴西，静态空间假设失效，在考虑空间非静态因素时，可以估算出有趣的风险概况。此外，我们还对巴西的不同死因进行了建模，并利用新模型对这些死因的空间静止性进行了研究。
{"title":"Non-stationary Bayesian spatial model for disease mapping based on sub-regions","authors":"Esmail Abdul-Fattah, Elias Krainski, Janet Van Niekerk, Håvard Rue","doi":"10.1177/09622802241244613","DOIUrl":"https://doi.org/10.1177/09622802241244613","url":null,"abstract":"This paper aims to extend the Besag model, a widely used Bayesian spatial model in disease mapping, to a non-stationary spatial model for irregular lattice-type data. The goal is to improve the model’s ability to capture complex spatial dependence patterns and increase interpretability. The proposed model uses multiple precision parameters, accounting for different intensities of spatial dependence in different sub-regions. We derive a joint penalized complexity prior to the flexible local precision parameters to prevent overfitting and ensure contraction to the stationary model at a user-defined rate. The proposed methodology can be used as a basis for the development of various other non-stationary effects over other domains such as time. An accompanying R package fbesag equips the reader with the necessary tools for immediate use and application. We illustrate the novelty of the proposal by modeling the risk of dengue in Brazil, where the stationary spatial assumption fails and interesting risk profiles are estimated when accounting for spatial non-stationary. Additionally, we model different causes of death in Brazil, where we use the new model to investigate the spatial stationarity of these causes.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"31 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Fellegi-Sunter model is a latent class model widely used in probabilistic linkage to identify records that belong to the same entity. Record linkage practitioners typically employ all available matching fields in the model with the premise that more fields convey greater information about the true match status and hence result in improved match performance. In the context of model-based clustering, it is well known that such a premise is incorrect and the inclusion of noisy variables could compromise the clustering. Variable selection procedures have therefore been developed to remove noisy variables. Although these procedures have the potential to improve record matching, they cannot be applied directly due to the ubiquity of the missing data in record linkage applications. In this paper, we modify the stepwise variable selection procedure proposed by Fop, Smart, and Murphy and extend it to account for missing data common in record linkage. Through simulation studies, our proposed method is shown to select the correct set of matching fields across various settings, leading to better-performing algorithms. The improved match performance is also seen in a real-world application. We therefore recommend the use of our proposed selection procedure to identify informative matching fields for probabilistic record linkage algorithms.
{"title":"Variable selection for latent class analysis in the presence of missing data with application to record linkage","authors":"Huiping Xu, Xiaochun Li, Zuoyi Zhang, Shaun Grannis","doi":"10.1177/09622802241242317","DOIUrl":"https://doi.org/10.1177/09622802241242317","url":null,"abstract":"The Fellegi-Sunter model is a latent class model widely used in probabilistic linkage to identify records that belong to the same entity. Record linkage practitioners typically employ all available matching fields in the model with the premise that more fields convey greater information about the true match status and hence result in improved match performance. In the context of model-based clustering, it is well known that such a premise is incorrect and the inclusion of noisy variables could compromise the clustering. Variable selection procedures have therefore been developed to remove noisy variables. Although these procedures have the potential to improve record matching, they cannot be applied directly due to the ubiquity of the missing data in record linkage applications. In this paper, we modify the stepwise variable selection procedure proposed by Fop, Smart, and Murphy and extend it to account for missing data common in record linkage. Through simulation studies, our proposed method is shown to select the correct set of matching fields across various settings, leading to better-performing algorithms. The improved match performance is also seen in a real-world application. We therefore recommend the use of our proposed selection procedure to identify informative matching fields for probabilistic record linkage algorithms.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"62 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-09DOI: 10.1177/09622802241242325
Maximilian Bardo, Cynthia Huber, Norbert Benda, Jonas Brugger, Tobias Fellinger, Vaidotas Galaune, Judith Heinz, Harald Heinzl, Andrew C Hooker, Florian Klinglmüller, Franz König, Tim Mathes, Martina Mittlböck, Martin Posch, Robin Ristl, Tim Friede
For the analysis of time-to-event data, frequently used methods such as the log-rank test or the Cox proportional hazards model are based on the proportional hazards assumption, which is often debatable. Although a wide range of parametric and non-parametric methods for non-proportional hazards has been proposed, there is no consensus on the best approaches. To close this gap, we conducted a systematic literature search to identify statistical methods and software appropriate under non-proportional hazard. Our literature search identified 907 abstracts, out of which we included 211 articles, mostly methodological ones. Review articles and applications were less frequently identified. The articles discuss effect measures, effect estimation and regression approaches, hypothesis tests, and sample size calculation approaches, which are often tailored to specific non-proportional hazard situations. Using a unified notation, we provide an overview of methods available. Furthermore, we derive some guidance from the identified articles.
{"title":"Methods for non-proportional hazards in clinical trials: A systematic review","authors":"Maximilian Bardo, Cynthia Huber, Norbert Benda, Jonas Brugger, Tobias Fellinger, Vaidotas Galaune, Judith Heinz, Harald Heinzl, Andrew C Hooker, Florian Klinglmüller, Franz König, Tim Mathes, Martina Mittlböck, Martin Posch, Robin Ristl, Tim Friede","doi":"10.1177/09622802241242325","DOIUrl":"https://doi.org/10.1177/09622802241242325","url":null,"abstract":"For the analysis of time-to-event data, frequently used methods such as the log-rank test or the Cox proportional hazards model are based on the proportional hazards assumption, which is often debatable. Although a wide range of parametric and non-parametric methods for non-proportional hazards has been proposed, there is no consensus on the best approaches. To close this gap, we conducted a systematic literature search to identify statistical methods and software appropriate under non-proportional hazard. Our literature search identified 907 abstracts, out of which we included 211 articles, mostly methodological ones. Review articles and applications were less frequently identified. The articles discuss effect measures, effect estimation and regression approaches, hypothesis tests, and sample size calculation approaches, which are often tailored to specific non-proportional hazard situations. Using a unified notation, we provide an overview of methods available. Furthermore, we derive some guidance from the identified articles.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"46 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1177/09622802241236951
Yang Li, Wanzhu Tu
Designed clinical studies often assess outcomes at pre-planned time points. In most situations, standard statistical models, such as generalized linear mixed models and generalized additive models, are sufficient to depict the temporal trends of the outcome and produce valid inference. Complicating factors, however, do exist in practical data analyses. One complication arises when the outcome and observational processes are interdependent, that is, the observational process is informative; another challenge is patient characteristics may influence the longitudinally observed outcomes in non-additive ways, for example, by multiplicative factors. In this research, we extend the standard longitudinal models to accommodate informative observation through a more flexible modeling structure—one with additive-multiplicative components that do not require explicit specification of the dependency structure between the outcome and observation processes. Along this vein, we provide the essential theory for inference in such models. Simulation studies showed the proposed method performs well for finite-sample scenarios, and the method was applied to analyze a motivating example from an alcohol-associated hepatitis observational study.
{"title":"An additive-multiplicative model for longitudinal data with informative observation times","authors":"Yang Li, Wanzhu Tu","doi":"10.1177/09622802241236951","DOIUrl":"https://doi.org/10.1177/09622802241236951","url":null,"abstract":"Designed clinical studies often assess outcomes at pre-planned time points. In most situations, standard statistical models, such as generalized linear mixed models and generalized additive models, are sufficient to depict the temporal trends of the outcome and produce valid inference. Complicating factors, however, do exist in practical data analyses. One complication arises when the outcome and observational processes are interdependent, that is, the observational process is informative; another challenge is patient characteristics may influence the longitudinally observed outcomes in non-additive ways, for example, by multiplicative factors. In this research, we extend the standard longitudinal models to accommodate informative observation through a more flexible modeling structure—one with additive-multiplicative components that do not require explicit specification of the dependency structure between the outcome and observation processes. Along this vein, we provide the essential theory for inference in such models. Simulation studies showed the proposed method performs well for finite-sample scenarios, and the method was applied to analyze a motivating example from an alcohol-associated hepatitis observational study.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"51 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号