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Articles 31 - 45 of 45
Full-Text Articles in Statistical Theory
Analyzing Direct Effects In Randomized Trials With Secondary Interventions , Michael Rosenblum, Nicholas P. Jewell, Mark J. Van Der Laan, Stephen Shiboski, Ariane Van Der Straten, Nancy Padian
Analyzing Direct Effects In Randomized Trials With Secondary Interventions , Michael Rosenblum, Nicholas P. Jewell, Mark J. Van Der Laan, Stephen Shiboski, Ariane Van Der Straten, Nancy Padian
U.C. Berkeley Division of Biostatistics Working Paper Series
The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the active treatment arm or not. Additionally, all subjects in both arms received intensive condom counselling and provision, the "gold standard" HIV prevention barrier method. There was much lower reported condom use in the intervention arm than in the control arm, making it difficult to answer important public health questions based solely on the intention-to-treat analysis. We adapt an analysis …
Bayesian Hidden Markov Modeling Of Array Cgh Data, Subharup Guha, Yi Li, Donna Neuberg
Bayesian Hidden Markov Modeling Of Array Cgh Data, Subharup Guha, Yi Li, Donna Neuberg
Harvard University Biostatistics Working Paper Series
Genomic alterations have been linked to the development and progression of cancer. The technique of Comparative Genomic Hybridization (CGH) yields data consisting of fluorescence intensity ratios of test and reference DNA samples. The intensity ratios provide information about the number of copies in DNA. Practical issues such as the contamination of tumor cells in tissue specimens and normalization errors necessitate the use of statistics for learning about the genomic alterations from array-CGH data. As increasing amounts of array CGH data become available, there is a growing need for automated algorithms for characterizing genomic profiles. Specifically, there is a need for …
Estimating A Treatment Effect With Repeated Measurements Accounting For Varying Effectiveness Duration, Ying Qing Chen, Jingrong Yang, Su-Chun Cheng
Estimating A Treatment Effect With Repeated Measurements Accounting For Varying Effectiveness Duration, Ying Qing Chen, Jingrong Yang, Su-Chun Cheng
UW Biostatistics Working Paper Series
To assess treatment efficacy in clinical trials, certain clinical outcomes are repeatedly measured for same subject over time. They can be regarded as function of time. The difference in their mean functions between the treatment arms usually characterises a treatment effect. Due to the potential existence of subject-specific treatment effectiveness lag and saturation times, erosion of treatment effect in the difference may occur during the observation period of time. Instead of using ad hoc parametric or purely nonparametric time-varying coefficients in statistical modeling, we first propose to model the treatment effectiveness durations, which are the varying time intervals between the …
Semiparametric Estimation In General Repeated Measures Problems, Xihong Lin, Raymond J. Carroll
Semiparametric Estimation In General Repeated Measures Problems, Xihong Lin, Raymond J. Carroll
Harvard University Biostatistics Working Paper Series
This paper considers a wide class of semiparametric problems with a parametric part for some covariate effects and repeated evaluations of a nonparametric function. Special cases in our approach include marginal models for longitudinal/clustered data, conditional logistic regression for matched case-control studies, multivariate measurement error models, generalized linear mixed models with a semiparametric component, and many others. We propose profile-kernel and backfitting estimation methods for these problems, derive their asymptotic distributions, and show that in likelihood problems the methods are semiparametric efficient. While generally not true, with our methods profiling and backfitting are asymptotically equivalent. We also consider pseudolikelihood methods …
Direct Effect Models, Mark J. Van Der Laan, Maya L. Petersen
Direct Effect Models, Mark J. Van Der Laan, Maya L. Petersen
U.C. Berkeley Division of Biostatistics Working Paper Series
The causal effect of a treatment on an outcome is generally mediated by several intermediate variables. Estimation of the component of the causal effect of a treatment that is mediated by a given intermediate variable (the indirect effect of the treatment), and the component that is not mediated by that intermediate variable (the direct effect of the treatment) is often relevant to mechanistic understanding and to the design of clinical and public health interventions. Under the assumption of no-unmeasured confounders for treatment and the intermediate variable, Robins & Greenland (1992) define an individual direct effect as the counterfactual effect of …
Causal Inference In Longitudinal Studies With History-Restricted Marginal Structural Models, Romain Neugebauer, Mark J. Van Der Laan, Ira B. Tager
Causal Inference In Longitudinal Studies With History-Restricted Marginal Structural Models, Romain Neugebauer, Mark J. Van Der Laan, Ira B. Tager
U.C. Berkeley Division of Biostatistics Working Paper Series
Causal Inference based on Marginal Structural Models (MSMs) is particularly attractive to subject-matter investigators because MSM parameters provide explicit representations of causal effects. We introduce History-Restricted Marginal Structural Models (HRMSMs) for longitudinal data for the purpose of defining causal parameters which may often be better suited for Public Health research. This new class of MSMs allows investigators to analyze the causal effect of a treatment on an outcome based on a fixed, shorter and user-specified history of exposure compared to MSMs. By default, the latter represents the treatment causal effect of interest based on a treatment history defined by the …
A Bayesian Mixture Model Relating Dose To Critical Organs And Functional Complication In 3d Conformal Radiation Therapy, Tim Johnson, Jeremy Taylor, Randall K. Ten Haken, Avraham Eisbruch
A Bayesian Mixture Model Relating Dose To Critical Organs And Functional Complication In 3d Conformal Radiation Therapy, Tim Johnson, Jeremy Taylor, Randall K. Ten Haken, Avraham Eisbruch
The University of Michigan Department of Biostatistics Working Paper Series
A goal of radiation therapy is to deliver maximum dose to the target tumor while minimizing complications due to irradiation of critical organs. Technological advances in 3D conformal radiation therapy has allowed great strides in realizing this goal, however complications may still arise. Critical organs may be adjacent to tumors or in the path of the radiation beam. Several mathematical models have been proposed that describe a relationship between dose and observed functional complication, however only a few published studies have successfully fit these models to data using modern statistical methods which make efficient use of the data. One complication …
Cholesky Residuals For Assessing Normal Errors In A Linear Model With Correlated Outcomes: Technical Report, E. Andres Houseman, Louise Ryan, Brent Coull
Cholesky Residuals For Assessing Normal Errors In A Linear Model With Correlated Outcomes: Technical Report, E. Andres Houseman, Louise Ryan, Brent Coull
Harvard University Biostatistics Working Paper Series
Despite the widespread popularity of linear models for correlated outcomes (e.g. linear mixed models and time series models), distribution diagnostic methodology remains relatively underdeveloped in this context. In this paper we present an easy-to-implement approach that lends itself to graphical displays of model fit. Our approach involves multiplying the estimated margional residual vector by the Cholesky decomposition of the inverse of the estimated margional variance matrix. The resulting "rotated" residuals are used to construct an empirical cumulative distribution function and pointwise standard errors. The theoretical framework, including conditions and asymptotic properties, involves technical details that are motivated by Lange and …
Estimation Of Direct And Indirect Causal Effects In Longitudinal Studies, Mark J. Van Der Laan, Maya L. Petersen
Estimation Of Direct And Indirect Causal Effects In Longitudinal Studies, Mark J. Van Der Laan, Maya L. Petersen
U.C. Berkeley Division of Biostatistics Working Paper Series
The causal effect of a treatment on an outcome is generally mediated by several intermediate variables. Estimation of the component of the causal effect of a treatment that is mediated by a given intermediate variable (the indirect effect of the treatment), and the component that is not mediated by that intermediate variable (the direct effect of the treatment) is often relevant to mechanistic understanding and to the design of clinical and public health interventions. Under the assumption of no-unmeasured confounders, Robins & Greenland (1992) and Pearl (2000), develop two identifiability results for direct and indirect causal effects. They define an …
Efficient Semiparametric Marginal Estimation For Longitudinal/Clustered Data, Naisyin Wang, Raymond J. Carroll, Xihong Lin
Efficient Semiparametric Marginal Estimation For Longitudinal/Clustered Data, Naisyin Wang, Raymond J. Carroll, Xihong Lin
The University of Michigan Department of Biostatistics Working Paper Series
We consider marginal generalized semiparametric partially linear models for clustered data. Lin and Carroll (2001a) derived the semiparametric efficinet score funtion for this problem in the mulitvariate Gaussian case, but they were unable to contruct a semiparametric efficient estimator that actually achieved the semiparametric information bound. We propose such an estimator here and generalize the work to marginal generalized partially liner models. Asymptotic relative efficincies of the estimation or throughout are investigated. The finite sample performance of these estimators is evaluated through simulations and illustrated using a longtiudinal CD4 count data set. Both theoretical and numerical results indicate that properly …
Equivalent Kernels Of Smoothing Splines In Nonparametric Regression For Clustered/Longitudinal Data, Xihong Lin, Naisyin Wang, Alan H. Welsh, Raymond J. Carroll
Equivalent Kernels Of Smoothing Splines In Nonparametric Regression For Clustered/Longitudinal Data, Xihong Lin, Naisyin Wang, Alan H. Welsh, Raymond J. Carroll
The University of Michigan Department of Biostatistics Working Paper Series
We compare spline and kernel methods for clustered/longitudinal data. For independent data, it is well known that kernel methods and spline methods are essentially asymptotically equivalent (Silverman, 1984). However, the recent work of Welsh, et al. (2002) shows that the same is not true for clustered/longitudinal data. First, conventional kernel methods fail to account for the within- cluster correlation, while spline methods are able to account for this correlation. Second, kernel methods and spline methods were found to have different local behavior, with conventional kernels being local and splines being non-local. To resolve these differences, we show that a smoothing …
Locally Efficient Estimation Of Nonparametric Causal Effects On Mean Outcomes In Longitudinal Studies, Romain Neugebauer, Mark J. Van Der Laan
Locally Efficient Estimation Of Nonparametric Causal Effects On Mean Outcomes In Longitudinal Studies, Romain Neugebauer, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
Marginal Structural Models (MSM) have been introduced by Robins (1998a) as a powerful tool for causal inference as they directly model causal curves of interest, i.e. mean treatment-specific outcomes possibly adjusted for baseline covariates. Two estimators of the corresponding MSM parameters of interest have been proposed, see van der Laan and Robins (2002): the Inverse Probability of Treatment Weighted (IPTW) and the Double Robust (DR) estimators. A parametric MSM approach to causal inference has been favored since the introduction of MSM. It relies on correct specification of a parametric MSM to consistently estimate the parameter of interest using the IPTW …
Double Robust Estimation In Longitudinal Marginal Structural Models, Zhuo Yu, Mark J. Van Der Laan
Double Robust Estimation In Longitudinal Marginal Structural Models, Zhuo Yu, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
Consider estimation of causal parameters in a marginal structural model for the discrete intensity of the treatment specific counting process (e.g. hazard of a treatment specific survival time) based on longitudinal observational data on treatment, covariates and survival. We assume the sequential randomization assumption (SRA) on the treatment assignment mechanism and the so called experimental treatment assignment assumption which is needed to identify the causal parameters from the observed data distribution. Under SRA, the likelihood of the observed data structure factorizes in the auxiliary treatment mechanism and the partial likelihood consisting of the product over time of conditional distributions of …
Construction Of Counterfactuals And The G-Computation Formula, Zhuo Yu, Mark J. Van Der Laan
Construction Of Counterfactuals And The G-Computation Formula, Zhuo Yu, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
Robins' causal inference theory assumes existence of treatment specific counterfactual variables so that the observed data augmented by the counterfactual data will satisfy a consistency and a randomization assumption. Gill and Robins [2001] show that the consistency and randomization assumptions do not add any restrictions to the observed data distribution. In particular, they provide a construction of counterfactuals as a function of the observed data distribution. In this paper we provide a construction of counterfactuals as a function of the observed data itself. Our construction provides a new statistical tool for estimation of counterfactual distributions. Robins [1987b] shows that the …
Semiparametric Regression Analysis On Longitudinal Pattern Of Recurrent Gap Times, Ying Qing Chen, Mei-Cheng Wang, Yijian Huang
Semiparametric Regression Analysis On Longitudinal Pattern Of Recurrent Gap Times, Ying Qing Chen, Mei-Cheng Wang, Yijian Huang
U.C. Berkeley Division of Biostatistics Working Paper Series
In longitudinal studies, individual subjects may experience recurrent events of the same type over a relatively long period of time. The longitudinal pattern of the gaps between the successive recurrent events is often of great research interest. In this article, the probability structure of the recurrent gap times is first explored in the presence of censoring. According to the discovered structure, we introduce the proportional reverse-time hazards models with unspecified baseline functions to accommodate heterogeneous individual underlying distributions, when the ongitudinal pattern parameter is of main interest. Inference procedures are proposed and studied by way of proper riskset construction. The …