Survival Analysis Commons^™

Piecewise Constant Cross-Ratio Estimation For Association In Bivariate Survival Data With Application To Studying Markers Of Menopausal Transition, Bin Nan, Xihong Lin, Lynda D. Lisabet, Sioban Harlow

The University of Michigan Department of Biostatistics Working Paper Series

A question of significant interest in female reproductive aging is to identify bleeding criteria for the menopausal transition. Although various bleeding criteria, or markers, have been proposed for the menopausal transition, their validity has not been adequately examined. The Tremin Trust data are collected from a long-term cohort study that followed a group of women throughout their whole reproductive life, and provide a unique opportunity for assessing the association between age at onset of a bleeding marker and age onset of menopause. Formal statistical analysis of this dependence is challenging give the fact that both the marker event and menopause …

Individual Prediction In Prostate Cancer Studies Using A Joint Longitudinal-Survival-Cure Model, Menggang Yu, Jeremy Taylor, Howard M. Sandler

The University of Michigan Department of Biostatistics Working Paper Series

For monitoring patients treated for prostate cancer, Prostate Specific Antigen (PSA) is measured periodically after they receive treatment. Increases in PSA are suggestive of recurrence of the cancer and are used in making decisions about possible new treatments. The data from studies of such patients typically consist of longitudinal PSA measurements, censored event times and baseline covariates. Methods for the combined analysis of both longitudinal and survival data have been developed in recent years, with the main emphasis being on modeling and estimation. We analyze data from a prostate cancer study that has been extended by adding a mixture structure …

Survival Model Predictive Accuracy And Roc Curves, Patrick Heagerty, Yingye Zheng

UW Biostatistics Working Paper Series

The predictive accuracy of a survival model can be summarized using extensions of the proportion of variation explained by the model, or R^2, commonly used for continuous response models, or using extensions of sensitivity and specificity which are commonly used for binary response models.

In this manuscript we propose new time-dependent accuracy summaries based on time-specific versions of sensitivity and specificity calculated over risk sets. We connect the accuracy summaries to a previously proposed global concordance measure which is a variant of Kendall's tau. In addition, we show how standard Cox regression output can be used to obtain estimates of …

Partly Conditional Survival Models For Longitudinal Data, Yingye Zheng, Patrick Heagerty

UW Biostatistics Working Paper Series

It is common in longitudinal studies to collect information on the time until a key clinical event, such as death, and to measure markers of patient health at multiple follow-up times. One approach to the joint analysis of survival and repeated measures data adopts a time-varying covariate regression model for the event time hazard. Using this standard approach the instantaneous risk of death at time t is specified as a possibly semi-parametric function of covariate information that has accrued through time t. In this manuscript we decouple the time scale for modeling the hazard from the time scale for accrual …

Semiparametric Estimation Of Time-Dependent: Roc Curves For Longitudinal Marker Data, Yingye Zheng, Patrick Heagerty

UW Biostatistics Working Paper Series

One approach to evaluating the strength of association between a longitudinal marker process and a key clinical event time is through predictive regression methods such as a time-dependent covariate hazard model. For example, a time-varying covariate Cox model specifies the instantaneous risk of the event as a function of the time-varying marker and additional covariates. In this manuscript we explore a second complementary approach which characterizes the distribution of the marker as a function of both the measurement time and the ultimate event time. Our goal is to flexibly extend the standard diagnostic accuracy concepts of sensitivity and specificity to …

Loss-Based Estimation With Cross-Validation: Applications To Microarray Data Analysis And Motif Finding, Sandrine Dudoit, Mark J. Van Der Laan, Sunduz Keles, Annette M. Molinaro, Sandra E. Sinisi, Siew Leng Teng

U.C. Berkeley Division of Biostatistics Working Paper Series

Current statistical inference problems in genomic data analysis involve parameter estimation for high-dimensional multivariate distributions, with typically unknown and intricate correlation patterns among variables. Addressing these inference questions satisfactorily requires: (i) an intensive and thorough search of the parameter space to generate good candidate estimators, (ii) an approach for selecting an optimal estimator among these candidates, and (iii) a method for reliably assessing the performance of the resulting estimator. We propose a unified loss-based methodology for estimator construction, selection, and performance assessment with cross-validation. In this approach, the parameter of interest is defined as the risk minimizer for a suitable …

Kernel Estimation Of Rate Function For Recurrent Event Data, Chin-Tsang Chiang, Mei-Cheng Wang, Chiung-Yu Huang

Johns Hopkins University, Dept. of Biostatistics Working Papers

Recurrent event data are largely characterized by the rate function but smoothing techniques for estimating the rate function have never been rigorously developed or studied in statistical literature. This paper considers the moment and least squares methods for estimating the rate function from recurrent event data. With an independent censoring assumption on the recurrent event process, we study statistical properties of the proposed estimators and propose bootstrap procedures for the bandwidth selection and for the approximation of confidence intervals in the estimation of the occurrence rate function. It is identified that the moment method without resmoothing via a smaller bandwidth …

Unified Cross-Validation Methodology For Selection Among Estimators And A General Cross-Validated Adaptive Epsilon-Net Estimator: Finite Sample Oracle Inequalities And Examples, Mark J. Van Der Laan, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

In Part I of this article we propose a general cross-validation criterian for selecting among a collection of estimators of a particular parameter of interest based on n i.i.d. observations. It is assumed that the parameter of interest minimizes the expectation (w.r.t. to the distribution of the observed data structure) of a particular loss function of a candidate parameter value and the observed data structure, possibly indexed by a nuisance parameter. The proposed cross-validation criterian is defined as the empirical mean over the validation sample of the loss function at the parameter estimate based on the training sample, averaged over …

Estimating Predictors For Long- Or Short-Term Survivors, Lu Tian, Wei Wang, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Corrected Pseudo-Score Approach For Additive Hazards Model With Longitudinal Covariates Measured With Error, Xiao Song, Yijian Huang

UW Biostatistics Working Paper Series

In medical studies, it is often of interest to characterize the relationship between a time-to-event and covariates, not only time-independent but also time-dependent. Time-dependent covariates are generally measured intermittently and with error. Recent interests focus on the proportional hazards framework, with longitudinal data jointly modeled through a mixed effects model. However, approaches under this framework depend on the normality assumption of the error, and might encounter intractable numerical difficulties in practice. This motivates us to consider an alternative framework, that is, the additive hazards model, under which little has been done when time-dependent covariates are measured with error. We propose …

A Nonparametric Comparison Of Conditional Distributions With Nonnegligible Cure Fractions, Yi Li, Jin Feng

Harvard University Biostatistics Working Paper Series

No abstract provided.

Survival Analysis With Heterogeneous Covariate Measurement Error, Yi Li, Louise Ryan

Harvard University Biostatistics Working Paper Series

No abstract provided.

Statistical Inference For Infinite Dimensional Parameters Via Asymptotically Pivotal Estimating Functions, Meredith A. Goldwasser, Lu Tian, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Joint Modeling And Estimation For Recurrent Event Processes And Failure Time Data, Chiung-Yu Huang, Mei-Cheng Wang

Johns Hopkins University, Dept. of Biostatistics Working Papers

Recurrent event data are commonly encountered in longitudinal follow-up studies related to biomedical science, econometrics, reliability, and demography. In many studies, recurrent events serve as important measurements for evaluating disease progression, health deterioration, or insurance risk. When analyzing recurrent event data, an independent censoring condition is typically required for the construction of statistical methods. Nevertheless, in some situations, the terminating time for observing recurrent events could be correlated with the recurrent event process and, as a result, the assumption of independent censoring is violated. In this paper, we consider joint modeling of a recurrent event process and a failure time …

Semi-Parametric Box-Cox Power Transformation Models For Censored Survival Observations, Tianxi Cai, Lu Tian, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Statistical Inferences Based On Non-Smooth Estimating Functions, Lu Tian, Jun S. Liu, Mary Zhao, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

On The Cox Model With Time-Varying Regression Coefficients, Lu Tian, David Zucker, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Maximum Likelihood Estimation Of Ordered Multinomial Parameters , Nicholas P. Jewell, Jack Kalbfleisch

The University of Michigan Department of Biostatistics Working Paper Series

The pool-adjacent violator-algorithm (Ayer et al., 1955) has long been known to give the maximum likelihood estimator of a series of ordered binomial parameters, based on an independent observation from each distribution (see, Barlow et al., 1972). This result has immediate application to estimation of a survival distribution based on current survival status at a set of monitoring times. This paper considers an extended problem of maximum likelihood estimation of a series of ‘ordered’ multinomial parameters pi = (p1i, p2i, . . . , pmi) for 1 < = I < = k, where ordered means that pj1 < = pj2 < = .. . < = pjk for each j with 1 < = j < = m-1. The data consist of k independent observations X1, . . . ,Xk where Xi has a multinomial distribution with probability parameter pi and known index ni > = 1. By making use of variants of the pool adjacent violator algorithm, …

Nonparametric Estimation Of The Bivariate Recurrence Time Distribution, Chiung-Yu Huang, Mei-Cheng Wang

Johns Hopkins University, Dept. of Biostatistics Working Papers

This paper considers statistical models in which two different types of events, such as the diagnosis of a disease and the remission of the disease, occur alternately over time and are observed subject to right censoring. We propose nonparametric estimators for the joint distribution of bivariate recurrence times and the marginal distribution of the first recurrence time. In general, the marginal distribution of the second recurrence time cannot be estimated due to an identifiability problem, but a conditional distribution of the second recurrence time can be estimated non-parametrically. In literature, statistical methods have been developed to estimate the joint distribution …

A Varying-Coefficient Cox Model For The Effect Of Age At A Marker Event On Age At Menopause, Bin Nan, Xihong Lin, Lynda D. Lisabeth, Sioban D. Harlow

The University of Michigan Department of Biostatistics Working Paper Series

. It is of recent interest in reproductive health research to investigate the validity of a marker event for the onset of menopausal transition and to estimate age at menopause using age at the marker event. We propose a varying coefficient Cox model to investigate the association between age at a marker event, denned as a specific bleeding pattern change, and age at menopause, where both events are subject to censoring and their association varies with age at the marker event. Estimation proceeds using the regression spline method. The proposed method is applied to the Tremin Trust Data to evaluate …

Asymptotically Optimal Model Selection Method With Right Censored Outcomes, Sunduz Keles, Mark J. Van Der Laan, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

Over the last two decades, non-parametric and semi-parametric approaches that adapt well known techniques such as regression methods to the analysis of right censored data, e.g. right censored survival data, became popular in the statistics literature. However, the problem of choosing the best model (predictor) among a set of proposed models (predictors) in the right censored data setting have not gained much attention. In this paper, we develop a new cross-validation based model selection method to select among predictors of right censored outcomes such as survival times. The proposed method considers the risk of a given predictor based on the …

Tree-Based Multivariate Regression And Density Estimation With Right-Censored Data , Annette M. Molinaro, Sandrine Dudoit, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a unified strategy for estimator construction, selection, and performance assessment in the presence of censoring. This approach is entirely driven by the choice of a loss function for the full (uncensored) data structure and can be stated in terms of the following three main steps. (1) Define the parameter of interest as the minimizer of the expected loss, or risk, for a full data loss function chosen to represent the desired measure of performance. Map the full data loss function into an observed (censored) data loss function having the same expected value and leading to an efficient estimator …

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 …

The Effect Of Ultrasonics On Fibroblast Cells, Sheila A. Harris

Loma Linda University Electronic Theses, Dissertations & Projects

The field of dentistry uses the debriding properties of ultrasonic vibration. It is unknown if this property is detrimental to the periodontal ligament (PDL) of an avulsed tooth. This information is important when a clinician is faced with a debris-covered avulsed tooth following a traumatic event. The purpose of this study was to determine the effect that ultrasonic vibration has on those PDL cells most numerous and most vital to a successful tooth replantation, namely, the fibroblasts.

Several fibroblast cell sources were exposed to varying ultrasonic times. These included a commercially available cell line of human foreskin fibroblast (HFF), a …

Bootstrap Confidence Intervals For Medical Costs With Censored Observations, Hongyu Jiang, Xiao-Hua Zhou

UW Biostatistics Working Paper Series

Medical costs data with administratively censored observations often arise in cost-effectiveness studies of treatments for life threatening diseases. Mean of medical costs incurred from the start of a treatment till death or certain timepoint after the implementation of treatment is frequently of interest. In many situations, due to the skewed nature of the cost distribution and non-uniform rate of cost accumulation over time, the currently available normal approximation confidence interval has poor coverage accuracy. In this paper, we proposed a bootstrap confidence interval for the mean of medical costs with censored observations. In simulation studies, we showed that the proposed …

A Semiparametric Model Selection Criterion With Applications To The Marginal Structural Model, M. Alan Brookhart, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Estimators for the parameter of interest in semiparametric models often depend on a guessed model for the nuisance parameter. The choice of the model for the nuisance parameter can affect both the finite sample bias and efficiency of the resulting estimator of the parameter of interest. In this paper we propose a finite sample criterion based on cross validation that can be used to select a nuisance parameter model from a list of candidate models. We show that expected value of this criterion is minimized by the nuisance parameter model that yields the estimator of the parameter of interest with …

Recurrent Events Analysis In The Presence Of Time Dependent Covariates And Dependent Censoring, Maja Miloslavsky, Sunduz Keles, Mark J. Van Der Laan, Steve Butler

U.C. Berkeley Division of Biostatistics Working Paper Series

Recurrent events models have lately received a lot of attention in the literature. The majority of approaches discussed show the consistency of parameter estimates under the assumption that censoring is independent of the recurrent events process of interest conditional on the covariates included into the model. We provide an overview of available recurrent events analysis methods, and present an inverse probability of censoring weighted estimator for the regression parameters in the Andersen-Gill model that is commonly used for recurrent event analysis. This estimator remains consistent under informative censoring if the censoring mechanism is estimated consistently, and generally improves on the …

Analysis Of Longitudinal Marginal Structural Models , Jennifer F. Bryan, Zhuo Yu, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In this article we construct and study estimators of the causal effect of a time-dependent treatment on survival in longitudinal studies. We employ a particular marginal structural model (MSM), and follow a general methodology for constructing estimating functions in censored data models. The inverse probability of treatment weighted (IPTW) estimator is used as an initial estimator and the corresponding treatment-orthogonalized, one-step estimator is consistent and asymptotically linear when the treatment mechanism is consistently estimated. We extend these methods to handle informative censoring. A simulation study demonstrates that the the treatment-orthogonalized, one-step estimator is superior to the IPTW estimator in terms …

Locally Efficient Estimation With Bivariate Right Censored Data , Christopher M. Quale, Mark J. Van Der Laan, James M. Robins

U.C. Berkeley Division of Biostatistics Working Paper Series

Estimation for bivariate right censored data is a problem that has had much study over the past 15 years. In this paper we propose a new class of estimators for the bivariate survivor function based on locally efficient estimation. The locally efficient estimator takes bivariate estimators Fn and Gn of the distributions of the time variables T1,T2 and the censoring variables C1,C2, respectively, and maps them to the resulting estimator. If Fn and Gn are consistent estimators of F and G, respectively, then the resulting estimator will be nonparametrically efficient (thus the term ``locally efficient''). However, if either Fn or …

Accelerated Hazards Model: Method, Theory And Applications, Ying Qing Chen, Nicholas P. Jewell, Jingrong Yang

U.C. Berkeley Division of Biostatistics Working Paper Series

In an accelerated hazards model, the hazard functions of a failure time are related through the time scale-change, which is often a function of covariates and associated parameters. When the hazard functions have special properties, such as monotonicity in time, the parameters may be clinically meaningful in measuring a treatment effect. This paper reviews methodological and theoretical development of this model. Applications of the accelerated hazards model including sample size calculation in clinical trials, are also explored.