Survival Analysis Commons^™

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.

Locally Efficient Estimation Of Regression Parameters Using Current Status Data, Chris Andrews, Mark J. Van Der Laan, James M. Robins

U.C. Berkeley Division of Biostatistics Working Paper Series

In biostatistics applications interest often focuses on the estimation of the distribution of a time-variable T. If one only observes whether or not T exceeds an observed monitoring time C, then the data structure is called current status data, also known as interval censored data, case I. We consider this data structure extended to allow the presence of both time-independent covariates and time-dependent covariate processes that are observed until the monitoring time. We assume that the monitoring process satisfies coarsening at random.

Our goal is to estimate the regression parameter beta of the regression model T = Z*beta+epsilon where the …

Case-Control Current Status Data, Nicholas P. Jewell, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Current status observation on survival times has recently been widely studied. An extreme form of interval censoring, this data structure refers to situations where the only available information on a survival random variable, T, is whether or not T exceeds a random independent monitoring time C, a binary random variable, Y. To date, nonparametric analyses of current status data have assumed the availability of i.i.d. random samples of the random variable (Y, C), or a similar random sample at each of a set of fixed monitoring times. In many situations, it is useful to consider a case-control sampling scheme. Here, …

Why Prefer Double Robust Estimates? Illustration With Causal Point Treatment Studies, Romain Neugebauer, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In point treatment marginal structural models with treatment A, outcome Y and covariates W, causal parameters can be estimated under the assumption of no unobserved confounders. Three estimates can be used: the G-computation, Inverse Probability of Treatment Weighted (IPTW) or Double Robust (DR) estimates. The properties of the IPTW and DR estimates are known under an assumption on the treatment mechanism that we name "Experimental Treatment Assignment" (ETA) assumption. We show that the DR estimating function is unbiased when the ETA assumption is violated if the model used to regress Y on A and W is correctly specified. The practical …

Bivariate Current Status Data, Mark J. Van Der Laan, Nicholas P. Jewell

U.C. Berkeley Division of Biostatistics Working Paper Series

In many applications, it is often of interest to estimate a bivariate distribution of two survival random variables. Complete observation of such random variables is often incomplete. If one only observes whether or not each of the individual survival times exceeds a common observed monitoring time C, then the data structure is referred to as bivariate current status data (Wang and Ding, 2000). For such data, we show that the identifiable part of the joint distribution is represented by three univariate cumulative distribution functions, namely the two marginal cumulative distribution functions, and the bivariate cumulative distribution function evaluated on the …

Current Status Data: Review, Recent Developments And Open Problems, Nicholas P. Jewell, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Researchers working with survival data are by now adept at handling issues associated with incomplete data, particular those associated with various forms of censoring. An extreme form of interval censoring, known as current status observation, refers to situations where the only available information on a survival random variable T is whether or not T exceeds a random independent monitoring time C. This article contains a brief review of the extensive literature on the analysis of current status data, discussing the implications of response-based sampling on these methods. The majority of the paper introduces some recent extensions of these ideas to …

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 …

Estimation Of The Bivariate Survival Function With Generalized Bivariate Right Censored Data Structures, Sunduz Keles, Mark J. Van Der Laan, James M. Robins

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a bivariate survival function estimator for a general right censored data structure that includes a time dependent covariate process. Firstly, an initial estimator that generalizes Dabrowska's (1988) estimator is introduced. We obtain this estimator by a general methodology of constructing estimating functions in censored data models. The initial estimator is guaranteed to improve on Dabrowska's estimator and remains consistent and asymptotically linear under informative censoring schemes if the censoring mechanism is estimated consistently. We then construct an orthogonalized estimating function which results in a more robust and efficient estimator than our initial estimator. A simulation study demonstrates the …

Inference For Proportional Mean Residual Life Model In The Presence Of Censoring, Ying Q. Chen, Nicholas P. Jewell

U.C. Berkeley Division of Biostatistics Working Paper Series

As a function of time t, mean residual life is defined as remaining life expectancy of a subject given its survival to t. It plays an important role in many research areas to characterise stochastic behavior of survival over time. Similar to the Cox proportional hazard model, the proportional mean residual life model were proposed in statistical literature to study association between the mean residual life and individual subject's explanatory covariates. In this article, we will study this model and develop appropriate inference procedures in presence of censoring. Numerical studies including simulation and real data analysis are presented as well.

Regression Analysis Of Recurrent Gap Times With Time-Dependent Covariates, Ying Qing Chen, Mei-Cheng Wang, Yijian Huang

U.C. Berkeley Division of Biostatistics Working Paper Series

Individual subjects may experience recurrent events of same type over a relatively long period of time in a longitudinal study. Researchers are often interested in the distributional pattern of gaps between the successive recurrent events and their association with certain concomitant covariates as well. In this article, their probability structure is investigated in presence of censoring. According to the identified structure, we introduce the proportional reverse-time hazards models that allow arbitrary baseline function for every individual in the study, when the time-dependent covariates effect is of main interest. Appropriate inference procedures are proposed and studied to estimate the parameters of …

Marginal Regression Of Gaps Between Recurrent Events, Yijian Huang, Ying Qing Chen

U.C. Berkeley Division of Biostatistics Working Paper Series

Recurrent event data typically exhibit the phenomenon of intra-individual correlation, owing to not only observed covariates but also random effects. In many applications, the population can be reasonably postulated as a heterogeneous mixture of individual renewal processes, and the inference of interest is the effect of individual-level covariates. In this article, we suggest and investigate a marginal proportional hazards model for gaps between recurrent events. A connection is established between observed gap times and clustered survival data, however, with informative cluster size. We then derive a novel and general inference procedure for the latter, based on a functional formulation of …

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

U.C. Berkeley Division 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. By making use of variants of the pool adjacent violator algorithm, we obtain a simple algorithm to compute the maximum likelihood estimator and demonstrate …

Mixture Hazards Models With Additive Random Effects Accounting For Treatment Effectiveness Lag Time, Ying Qing Chen, C. A. Rohde, M.-C. Wang

U.C. Berkeley Division of Biostatistics Working Paper Series

In many clinical trials to evaluate treatment efficacy, it is believed that there may exist latent treatment effectiveness lag times after which medical treatment procedure or chemical compound would be in full effect. In this article, semiparametric regression models are proposed and studied for estimating the treatment effect accounting for such latent lag times. The new models take advantage of the invariance property of the additive hazards model in marginalising over an additive latent variable; parameters in the models are thus easily estimated and interpreted, while the flexibility of not having to specify the baseline hazard function is preserved. Monte …

A Class Of Semiparametric Scale-Change Hazards Regression Models And Its Adequacy For Censored Survival Data, Ying Qing Chen

U.C. Berkeley Division of Biostatistics Working Paper Series

A class of semiparametric hazards regression models called the accelerated hazards models was introduced to identify the covariate effect characterized by the scale-change between hazard functions. In this article, we compare the accelerated hazards models with several other popular classes of regression models in statistical literature for censored survival data. We also propose and study some test statistics to assess the models' adequacy. Simulation studies are conducted to evaluate the performance of the test statistics. Actual clinical trials data are analyzed to demonstrate the proposed models and test statistics.

Estimation Of The Captive-Carry Survival Function For The Advanced Medium Range Air-To-Air Missile (Amraam), David R. Denhard

Theses and Dissertations

This thesis considers the problem of estimating the survival function of an item (probability that the item functions for a time greater than a given time t) from sampling data subject to partial right censoring (a portion of the items in the sampling data have not yet been observed to fail). Specifically the thesis describes several parametric and non-parametric statistical models that can be used when the sampling data is subject to partial right censoring. These models are applied to the case of estimating the captive-carry survival function of the AIM-120A Advanced Medium Range Air-to-Air Missile (AMRAAM).

Reducing Carcase Rejection : A Comparison Of Carcase Rejection Rates In Sheep Delivered Either Direct From Farm To Abattoir Or Via The Saleyard System, C L. Mcdonald

Journal of the Department of Agriculture, Western Australia, Series 4

No abstract provided.

Cell Mediated Immunity By Cytotoxicity Assay And The Effect Of Corynebacterium Parvum And Radiation On Mice Bearing Herpes-Induced Tumors, Robert B. Stagg

Loma Linda University Electronic Theses, Dissertations & Projects

Cell mediated immune (CMI) cytotoxic reactivity of Balb/c mice against H238 cells, a Herpes simplex virus (HSV) Type 2 - induced sarcoma, was measured by the ¹²⁵IUdR release assay. The Balb/c mouse response to the growing HSV-induced tumor, treated with radiation and , was measured by survival rate, tumor growth and immune cytotoxicity of spleen and peritoneal exudate cells (PEC) as determined by ¹²⁵IUdR release assay. Subcutaneous (s.c.) inoculation of 1 x 10⁶ H238 cells (high dose) produced progressive tumor growth while s.c. inoculation of 1 x 10⁴ H238 cells (low dose) produced no tumors. A …

Published On Sw July First, Sid Twentythree

Sid Twentythree

Concurrent Infections Of Schistosoma Mansoni And Trypanosoma Equiperdum In Mice, Venus Ee-Siriporn

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this investigation was to determine factors which may influence the survival time of mice infected with Trypanosoma equiperdum and the effects of T. equiperdum on mice infected with Schistosoma mansoni.

In order to maintain experimentally obtained standard hours of survival (88 hrs) in mice inoculated intraperitoneally with 150,000 T. equiperdum, it was found that trypanosomes removed from the donor rat should be kept at 25 C and all counts, dilutions of the organisms, and injection should be completed within 1 hour after removal from the donor host. Survival time of mice is increased as the …

The Fecal Shedding Of Listeria Monocytogenes By Conventional And "Germ Free" Mice, Margaret Joyce Ramsay

Loma Linda University Electronic Theses, Dissertations & Projects

A series of experiments involving Listeria monocytogenes was undertaken to study first the fecal shedding of Listeria by conventional mice challenged intraperitoneally with Listeria and second the fecal shedding and ability to survive of germ free mice with similar challenge. In addition, mites infesting Listeria infected mice were cultured for their possible contamination by Listeria.

Conventional mice were challenged intraperitoneally with a single near LD₅₀ dose of Listeria. Fecal Listeria were detected by collecting specimens from each mouse daily for the first 4 days and every second day thereafter. The feces was held at 7°C for 14 …

Morbidity, Growth And Development Of Prematurely-Born Twins In Early Childhood, Lynelle King

Loma Linda University Electronic Theses, Dissertations & Projects

This study was concerned with the problem of determining the effect of twinship on the prematurely-born twin's growth and physical and emotional morbidity during early childhood. The immediate purposes of the study were to compare prematurely-born twins with prematurely-born singletons regarding their incidence and types of physical and emotional morbidity, and their growth during early childhood. It was hypothesized that prematurely-born twins have slower growth and more physical and emotional morbidity than prematurely born singletons. The descriptive survey method was used. From children cared for at a selected premature clinic, nineteen twins were matched with nineteen singletons for: race, sex, …