Abstract In phase II and/or III clinical trial study, there are several competing treatments, the goal is to assess the performances of the treatments at the end of the study, the trial design aims to minimize risks to the patients in the trial, according to some given allocation optimality criterion. Recently, a new type of clinical trial, the staggered-start trial has been proposed in some studies, in which different treatments enter the same trial at different times. Some basic questions for this trial are whether optimality can still be kept? under what conditions? and if so how to allocate the the coming patients to treatments to achieve such optimality? Here we propose and study a class of adaptive designs of staggered-start clinical trials, in which for given optimality criterion object, we show that as long as the initial sizes at the beginning of the successive trials are not too large relative to the total sample size, the proposed design can still achieve optimality criterion asymptotically for the allocation proportions as the ordinary trials; if these initial sample sizes have about the same magnitude as the total sample size, full optimality cannot be achieved. The proposed method is simple to use and is illustrated with several examples and a simulation study.
{"title":"Adaptive Design for Staggered-Start Clinical Trial","authors":"A. Yuan, Qizhai Li, Ming Xiong, M. Tan","doi":"10.1515/ijb-2015-0011","DOIUrl":"https://doi.org/10.1515/ijb-2015-0011","url":null,"abstract":"Abstract In phase II and/or III clinical trial study, there are several competing treatments, the goal is to assess the performances of the treatments at the end of the study, the trial design aims to minimize risks to the patients in the trial, according to some given allocation optimality criterion. Recently, a new type of clinical trial, the staggered-start trial has been proposed in some studies, in which different treatments enter the same trial at different times. Some basic questions for this trial are whether optimality can still be kept? under what conditions? and if so how to allocate the the coming patients to treatments to achieve such optimality? Here we propose and study a class of adaptive designs of staggered-start clinical trials, in which for given optimality criterion object, we show that as long as the initial sizes at the beginning of the successive trials are not too large relative to the total sample size, the proposed design can still achieve optimality criterion asymptotically for the allocation proportions as the ordinary trials; if these initial sample sizes have about the same magnitude as the total sample size, full optimality cannot be achieved. The proposed method is simple to use and is illustrated with several examples and a simulation study.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"12 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/ijb-2015-0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66987633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asanao Shimokawa, Y. Narita, S. Shibui, E. Miyaoka
Abstract In many scenarios, a patient in medical research is treated as a statistical unit. However, in some scenarios, we are interested in treating aggregate data as a statistical unit. In such situations, each set of aggregated data is considered to be a concept in a symbolic representation, and each concept has a hyperrectangle or multiple points in the variable space. To construct a tree-structured model from these aggregate survival data, we propose a new approach, where a datum can be included in several terminal nodes in a tree. By constructing a model under this condition, we expect to obtain a more flexible model while retaining the interpretive ease of a hierarchical structure. In this approach, the survival function of concepts that are partially included in a node is constructed using the Kaplan-Meier method, where the number of events and risks at each time point is replaced by the expectation value of the number of individual descriptions of concepts. We present an application of this proposed model using primary brain tumor patient data. As a result, we obtained a new interpretation of the data in comparison to the classical survival tree modeling methods.
{"title":"Tree Based Method for Aggregate Survival Data Modeling","authors":"Asanao Shimokawa, Y. Narita, S. Shibui, E. Miyaoka","doi":"10.1515/ijb-2015-0071","DOIUrl":"https://doi.org/10.1515/ijb-2015-0071","url":null,"abstract":"Abstract In many scenarios, a patient in medical research is treated as a statistical unit. However, in some scenarios, we are interested in treating aggregate data as a statistical unit. In such situations, each set of aggregated data is considered to be a concept in a symbolic representation, and each concept has a hyperrectangle or multiple points in the variable space. To construct a tree-structured model from these aggregate survival data, we propose a new approach, where a datum can be included in several terminal nodes in a tree. By constructing a model under this condition, we expect to obtain a more flexible model while retaining the interpretive ease of a hierarchical structure. In this approach, the survival function of concepts that are partially included in a node is constructed using the Kaplan-Meier method, where the number of events and risks at each time point is replaced by the expectation value of the number of individual descriptions of concepts. We present an application of this proposed model using primary brain tumor patient data. As a result, we obtained a new interpretation of the data in comparison to the classical survival tree modeling methods.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"39 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/ijb-2015-0071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66987991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Understanding treatment heterogeneity is essential to the development of precision medicine, which seeks to tailor medical treatments to subgroups of patients with similar characteristics. One of the challenges of achieving this goal is that we usually do not have a priori knowledge of the grouping information of patients with respect to treatment effect. To address this problem, we consider a heterogeneous regression model which allows the coefficients for treatment variables to be subject-dependent with unknown grouping information. We develop a concave fusion penalized method for estimating the grouping structure and the subgroup-specific treatment effects, and derive an alternating direction method of multipliers algorithm for its implementation. We also study the theoretical properties of the proposed method and show that under suitable conditions there exists a local minimizer that equals the oracle least squares estimator based on a priori knowledge of the true grouping information with high probability. This provides theoretical support for making statistical inference about the subgroup-specific treatment effects using the proposed method. The proposed method is illustrated in simulation studies and illustrated with real data from an AIDS Clinical Trials Group Study.
{"title":"Exploration of Heterogeneous Treatment Effects via Concave Fusion","authors":"Shujie Ma, Jian Huang, Zhiwei Zhang, Mingming Liu","doi":"10.1515/ijb-2018-0026","DOIUrl":"https://doi.org/10.1515/ijb-2018-0026","url":null,"abstract":"Abstract Understanding treatment heterogeneity is essential to the development of precision medicine, which seeks to tailor medical treatments to subgroups of patients with similar characteristics. One of the challenges of achieving this goal is that we usually do not have a priori knowledge of the grouping information of patients with respect to treatment effect. To address this problem, we consider a heterogeneous regression model which allows the coefficients for treatment variables to be subject-dependent with unknown grouping information. We develop a concave fusion penalized method for estimating the grouping structure and the subgroup-specific treatment effects, and derive an alternating direction method of multipliers algorithm for its implementation. We also study the theoretical properties of the proposed method and show that under suitable conditions there exists a local minimizer that equals the oracle least squares estimator based on a priori knowledge of the true grouping information with high probability. This provides theoretical support for making statistical inference about the subgroup-specific treatment effects using the proposed method. The proposed method is illustrated in simulation studies and illustrated with real data from an AIDS Clinical Trials Group Study.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"16 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2016-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/ijb-2018-0026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66988175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Linn, Bilwaj Gaonkar, J. Doshi, C. Davatzikos, R. Shinohara
Abstract Understanding structural changes in the brain that are caused by a particular disease is a major goal of neuroimaging research. Multivariate pattern analysis (MVPA) comprises a collection of tools that can be used to understand complex disease efxcfects across the brain. We discuss several important issues that must be considered when analyzing data from neuroimaging studies using MVPA. In particular, we focus on the consequences of confounding by non-imaging variables such as age and sex on the results of MVPA. After reviewing current practice to address confounding in neuroimaging studies, we propose an alternative approach based on inverse probability weighting. Although the proposed method is motivated by neuroimaging applications, it is broadly applicable to many problems in machine learning and predictive modeling. We demonstrate the advantages of our approach on simulated and real data examples.
{"title":"Addressing Confounding in Predictive Models with an Application to Neuroimaging","authors":"K. Linn, Bilwaj Gaonkar, J. Doshi, C. Davatzikos, R. Shinohara","doi":"10.1515/ijb-2015-0030","DOIUrl":"https://doi.org/10.1515/ijb-2015-0030","url":null,"abstract":"Abstract Understanding structural changes in the brain that are caused by a particular disease is a major goal of neuroimaging research. Multivariate pattern analysis (MVPA) comprises a collection of tools that can be used to understand complex disease efxcfects across the brain. We discuss several important issues that must be considered when analyzing data from neuroimaging studies using MVPA. In particular, we focus on the consequences of confounding by non-imaging variables such as age and sex on the results of MVPA. After reviewing current practice to address confounding in neuroimaging studies, we propose an alternative approach based on inverse probability weighting. Although the proposed method is motivated by neuroimaging applications, it is broadly applicable to many problems in machine learning and predictive modeling. We demonstrate the advantages of our approach on simulated and real data examples.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"12 1","pages":"31 - 44"},"PeriodicalIF":1.2,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/ijb-2015-0030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66987699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Goldstein, E. Polley, F. Briggs, M. J. van der Laan, A. Hubbard
Abstract Comparing the relative fit of competing models can be used to address many different scientific questions. In classical statistics one can, if appropriate, use likelihood ratio tests and information based criterion, whereas clinical medicine has tended to rely on comparisons of fit metrics like C-statistics. However, for many data adaptive modelling procedures such approaches are not suitable. In these cases, statisticians have used cross-validation, which can make inference challenging. In this paper we propose a general approach that focuses on the “conditional” risk difference (conditional on the model fits being fixed) for the improvement in prediction risk. Specifically, we derive a Wald-type test statistic and associated confidence intervals for cross-validated test sets utilizing the independent validation within cross-validation in conjunction with a test for multiple comparisons. We show that this test maintains proper Type I Error under the null fit, and can be used as a general test of relative fit for any semi-parametric model alternative. We apply the test to a candidate gene study to test for the association of a set of genes in a genetic pathway.
{"title":"Testing the Relative Performance of Data Adaptive Prediction Algorithms: A Generalized Test of Conditional Risk Differences","authors":"B. Goldstein, E. Polley, F. Briggs, M. J. van der Laan, A. Hubbard","doi":"10.1515/ijb-2015-0014","DOIUrl":"https://doi.org/10.1515/ijb-2015-0014","url":null,"abstract":"Abstract Comparing the relative fit of competing models can be used to address many different scientific questions. In classical statistics one can, if appropriate, use likelihood ratio tests and information based criterion, whereas clinical medicine has tended to rely on comparisons of fit metrics like C-statistics. However, for many data adaptive modelling procedures such approaches are not suitable. In these cases, statisticians have used cross-validation, which can make inference challenging. In this paper we propose a general approach that focuses on the “conditional” risk difference (conditional on the model fits being fixed) for the improvement in prediction risk. Specifically, we derive a Wald-type test statistic and associated confidence intervals for cross-validated test sets utilizing the independent validation within cross-validation in conjunction with a test for multiple comparisons. We show that this test maintains proper Type I Error under the null fit, and can be used as a general test of relative fit for any semi-parametric model alternative. We apply the test to a candidate gene study to test for the association of a set of genes in a genetic pathway.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"12 1","pages":"117 - 129"},"PeriodicalIF":1.2,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/ijb-2015-0014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66987670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Often the biological and/or clinical experiments result in longitudinal data from multiple related groups. The analysis of such data is quite challenging due to the fact that groups might have shared information on the mean and/or covariance functions. In this article, we consider a Bayesian semiparametric approach of modeling the mean trajectories for longitudinal response coming from multiple related groups. We consider matrix stick-breaking process priors on the group mean parameters which allows information sharing on the mean trajectories across the groups. Simulation studies are performed to demonstrate the effectiveness of the proposed approach compared to the more traditional approaches. We analyze data from a one-year follow-up of nutrition education for hypercholesterolemic children with three different treatments where the children are from different age-groups. Our analysis provides more clinically useful information than the previous analysis of the same dataset. The proposed approach will be a very powerful tool for analyzing data from clinical trials and other medical experiments.
{"title":"A Semiparametric Bayesian Approach for Analyzing Longitudinal Data from Multiple Related Groups","authors":"Kiranmoy Das, Prince Afriyie, Lauren Spirko","doi":"10.1515/ijb-2015-0002","DOIUrl":"https://doi.org/10.1515/ijb-2015-0002","url":null,"abstract":"Abstract Often the biological and/or clinical experiments result in longitudinal data from multiple related groups. The analysis of such data is quite challenging due to the fact that groups might have shared information on the mean and/or covariance functions. In this article, we consider a Bayesian semiparametric approach of modeling the mean trajectories for longitudinal response coming from multiple related groups. We consider matrix stick-breaking process priors on the group mean parameters which allows information sharing on the mean trajectories across the groups. Simulation studies are performed to demonstrate the effectiveness of the proposed approach compared to the more traditional approaches. We analyze data from a one-year follow-up of nutrition education for hypercholesterolemic children with three different treatments where the children are from different age-groups. Our analysis provides more clinically useful information than the previous analysis of the same dataset. The proposed approach will be a very powerful tool for analyzing data from clinical trials and other medical experiments.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"30 1","pages":"273 - 284"},"PeriodicalIF":1.2,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/ijb-2015-0002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66987590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract We construct an optimal design to simultaneously estimate three common interesting features in a dose-finding trial with possibly different emphasis on each feature. These features are (1) the shape of the dose-response curve, (2) the median effective dose and (3) the minimum effective dose level. A main difficulty of this task is that an optimal design for a single objective may not perform well for other objectives. There are optimal designs for dual objectives in the literature but we were unable to find optimal designs for 3 or more objectives to date with a concrete application. A reason for this is that the approach for finding a dual-objective optimal design does not work well for a 3 or more multiple-objective design problem. We propose a method for finding multiple-objective optimal designs that estimate the three features with user-specified higher efficiencies for the more important objectives. We use the flexible 4-parameter logistic model to illustrate the methodology but our approach is applicable to find multiple-objective optimal designs for other types of objectives and models. We also investigate robustness properties of multiple-objective optimal designs to mis-specification in the nominal parameter values and to a variation in the optimality criterion. We also provide computer code for generating tailor made multiple-objective optimal designs.
{"title":"Multiple-Objective Optimal Designs for Studying the Dose Response Function and Interesting Dose Levels","authors":"Seung Won Hyun, W. Wong","doi":"10.1515/ijb-2015-0044","DOIUrl":"https://doi.org/10.1515/ijb-2015-0044","url":null,"abstract":"Abstract We construct an optimal design to simultaneously estimate three common interesting features in a dose-finding trial with possibly different emphasis on each feature. These features are (1) the shape of the dose-response curve, (2) the median effective dose and (3) the minimum effective dose level. A main difficulty of this task is that an optimal design for a single objective may not perform well for other objectives. There are optimal designs for dual objectives in the literature but we were unable to find optimal designs for 3 or more objectives to date with a concrete application. A reason for this is that the approach for finding a dual-objective optimal design does not work well for a 3 or more multiple-objective design problem. We propose a method for finding multiple-objective optimal designs that estimate the three features with user-specified higher efficiencies for the more important objectives. We use the flexible 4-parameter logistic model to illustrate the methodology but our approach is applicable to find multiple-objective optimal designs for other types of objectives and models. We also investigate robustness properties of multiple-objective optimal designs to mis-specification in the nominal parameter values and to a variation in the optimality criterion. We also provide computer code for generating tailor made multiple-objective optimal designs.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"11 1","pages":"253 - 271"},"PeriodicalIF":1.2,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/ijb-2015-0044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66988220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract We study the problem of multiple hypothesis testing for correlated clustered data. As the existing multiple comparison procedures based on maximum likelihood estimation could be computationally intensive, we propose to construct multiple comparison procedures based on composite likelihood method. The new test statistics account for the correlation structure within the clusters and are computationally convenient to compute. Simulation studies show that the composite likelihood based procedures maintain good control of the familywise type I error rate in the presence of intra-cluster correlation, whereas ignoring the correlation leads to erratic performance.
{"title":"Multiple Comparisons Using Composite Likelihood in Clustered Data","authors":"M. Azadbakhsh, Xin Gao, H. Jankowski","doi":"10.1515/ijb-2016-0004","DOIUrl":"https://doi.org/10.1515/ijb-2016-0004","url":null,"abstract":"Abstract We study the problem of multiple hypothesis testing for correlated clustered data. As the existing multiple comparison procedures based on maximum likelihood estimation could be computationally intensive, we propose to construct multiple comparison procedures based on composite likelihood method. The new test statistics account for the correlation structure within the clusters and are computationally convenient to compute. Simulation studies show that the composite likelihood based procedures maintain good control of the familywise type I error rate in the presence of intra-cluster correlation, whereas ignoring the correlation leads to erratic performance.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"12 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2014-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/ijb-2016-0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66988085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Motivated by modeling and analysis of mass-spectrometry data, a semi- and nonparametric model is proposed that consists of linear parametric components for individual location and scale and a nonparametric regression function for the common shape. A multi-step approach is developed that simultaneously estimates the parametric components and the nonparametric function. Under certain regularity conditions, it is shown that the resulting estimators is consistent and asymptotic normal for the parametric part and achieve the optimal rate of convergence for the nonparametric part when the bandwidth is suitably chosen. Simulation results are presented to demonstrate the effectiveness and finite-sample performance of the method. The method is also applied to a SELDI-TOF mass spectrometry data set from a study of liver cancer patients.
{"title":"Functional and Parametric Estimation in a Semi- and Nonparametric Model with Application to Mass-Spectrometry Data","authors":"Weiping Ma, Yang Feng, Kani Chen, Z. Ying","doi":"10.1515/ijb-2014-0066","DOIUrl":"https://doi.org/10.1515/ijb-2014-0066","url":null,"abstract":"Abstract Motivated by modeling and analysis of mass-spectrometry data, a semi- and nonparametric model is proposed that consists of linear parametric components for individual location and scale and a nonparametric regression function for the common shape. A multi-step approach is developed that simultaneously estimates the parametric components and the nonparametric function. Under certain regularity conditions, it is shown that the resulting estimators is consistent and asymptotic normal for the parametric part and achieve the optimal rate of convergence for the nonparametric part when the bandwidth is suitably chosen. Simulation results are presented to demonstrate the effectiveness and finite-sample performance of the method. The method is also applied to a SELDI-TOF mass spectrometry data set from a study of liver cancer patients.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"11 1","pages":"285 - 303"},"PeriodicalIF":1.2,"publicationDate":"2013-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/ijb-2014-0066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66987582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Relative risks have become a popular measure of treatment effect for binary outcomes in randomized controlled trials (RCTs). Relative risks can be estimated directly using log binomial regression but the model may fail to converge. Alternative methods are available for estimating relative risks but these have generally only been evaluated for independent data. As some of these methods are now being applied in cluster RCTs, investigation of their performance in this context is needed. We compare log binomial regression and three alternative methods (expanded logistic regression, log Poisson regression and log normal regression) for estimating relative risks in cluster RCTs. Clustering is taken into account using generalized estimating equations (GEEs) with an independence or exchangeable working correlation structure. The results of our large simulation study show that the log binomial GEE generally performs well for clustered data but suffers from convergence problems, as expected. Both the log Poisson GEE and log normal GEE have advantages in certain settings in terms of type I error, bias and coverage. The expanded logistic GEE can perform poorly and is sensitive to the chosen working correlation structure. Conclusions about the effectiveness of treatment often differ depending on the method used, highlighting the need to pre-specify an analysis approach. We recommend pre-specifying that either the log Poisson GEE or log normal GEE will be used in the event that the log binomial GEE fails to converge.
{"title":"Relative Risk Estimation in Cluster Randomized Trials: A Comparison of Generalized Estimating Equation Methods","authors":"L. Yelland, A. Salter, Philip Ryan","doi":"10.2202/1557-4679.1323","DOIUrl":"https://doi.org/10.2202/1557-4679.1323","url":null,"abstract":"Relative risks have become a popular measure of treatment effect for binary outcomes in randomized controlled trials (RCTs). Relative risks can be estimated directly using log binomial regression but the model may fail to converge. Alternative methods are available for estimating relative risks but these have generally only been evaluated for independent data. As some of these methods are now being applied in cluster RCTs, investigation of their performance in this context is needed. We compare log binomial regression and three alternative methods (expanded logistic regression, log Poisson regression and log normal regression) for estimating relative risks in cluster RCTs. Clustering is taken into account using generalized estimating equations (GEEs) with an independence or exchangeable working correlation structure. The results of our large simulation study show that the log binomial GEE generally performs well for clustered data but suffers from convergence problems, as expected. Both the log Poisson GEE and log normal GEE have advantages in certain settings in terms of type I error, bias and coverage. The expanded logistic GEE can perform poorly and is sensitive to the chosen working correlation structure. Conclusions about the effectiveness of treatment often differ depending on the method used, highlighting the need to pre-specify an analysis approach. We recommend pre-specifying that either the log Poisson GEE or log normal GEE will be used in the event that the log binomial GEE fails to converge.","PeriodicalId":50333,"journal":{"name":"International Journal of Biostatistics","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2011-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2202/1557-4679.1323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68718384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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