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In some cross-sectional studies of chronic disease, data consist of the age at examination, whether the disease was present at the exam, and recall of the age at first diagnosis. This article describes a flexible parametric approach for combining current status and age at first diagnosis data. We assume that the log odds of onset by a given age and of detection by a given age conditional on onset by that age are nondecreasing functions of time plus linear combinations of covariates. Piecewise linear models are used to characterize changes across time in the baseline odds. Methods are described for accommodating informatively missing current status data and inferences based on the age-specific incidence of disease prior to a landmark event (e.g., puberty, menopause). Our formulation enables straightforward maximum likelihood estimation without requiring restrictive parametric or Markov assumptions. The methods are applied to data from a study of uterine fibroids. 相似文献
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The coarse data model of Heitjan and Rubin (1991) generalizes the missing data model of Rubin (1976) to cover other forms of incompleteness such as censoring and grouping. The model has 2 components: an ideal data model describing the distribution of the quantity of interest and a coarsening mechanism that describes a distribution over degrees of coarsening given the ideal data. The coarsening mechanism is said to be nonignorable when the degree of coarsening depends on an incompletely observed ideal outcome, in which case failure to properly account for it can spoil inferences. A theme in recent research is to measure sensitivity to nonignorability by evaluating the effect of a small departure from ignorability on the maximum likelihood estimate (MLE) of a parameter of the ideal data model. One such construct is the "index of local sensitivity to nonignorability" (ISNI) (Troxel and others, 2004), which is the derivative of the MLE with respect to a nonignorability parameter evaluated at the ignorable model. In this paper, we adapt ISNI to Bayesian modeling by instead defining it as the derivative of the posterior expectation. We propose the application of ISNI as a first step in judging the robustness of a Bayesian analysis to nonignorable coarsening. We derive formulas for a range of models and apply the method to evaluate sensitivity to nonignorable coarsening in 2 real data examples, one involving missing CD4 counts in an HIV trial and the other involving potentially informatively censored relapse times in a leukemia trial. 相似文献
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Liang H 《Biometrical journal. Biometrische Zeitschrift》2005,47(3):358-368
To analyze responses of solid tumors to treatment with antitumor therapy, we applied nonparametric mixed-effects models to investigate tumor volumes measured over a fixed. The population and individual response functions were approximated by penalized splines. Linear mixed-effects modeling was applied in the implementation of the estimation. We applied the approach to an analysis of a real xenograft study of a new antitumor agent, temozolomide, combined with irinotecan. The model fitted the data very well. We conducted a sensitivity analysis to determine the effect of informative dropout. We also propose an intuitive approach to a comparison of the antitumor effects of two different treatments. Biological interpretations and clinical implications are discussed. 相似文献
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Xingqiu Zhao Li Liu Yanyan Liu Wei Xu 《Biometrical journal. Biometrische Zeitschrift》2012,54(5):585-599
Multivariate recurrent event data are usually encountered in many clinical and longitudinal studies in which each study subject may experience multiple recurrent events. For the analysis of such data, most existing approaches have been proposed under the assumption that the censoring times are noninformative, which may not be true especially when the observation of recurrent events is terminated by a failure event. In this article, we consider regression analysis of multivariate recurrent event data with both time‐dependent and time‐independent covariates where the censoring times and the recurrent event process are allowed to be correlated via a frailty. The proposed joint model is flexible where both the distributions of censoring and frailty variables are left unspecified. We propose a pairwise pseudolikelihood approach and an estimating equation‐based approach for estimating coefficients of time‐dependent and time‐independent covariates, respectively. The large sample properties of the proposed estimates are established, while the finite‐sample properties are demonstrated by simulation studies. The proposed methods are applied to the analysis of a set of bivariate recurrent event data from a study of platelet transfusion reactions. 相似文献
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Chyong‐Mei Chen Tai‐Fang C. Lu Man‐Hua Chen Chao‐Min Hsu 《Biometrical journal. Biometrische Zeitschrift》2012,54(5):641-656
Current status data arise due to only one feasible examination such that the failure time of interest occurs before or after the examination time. If the examination time is intrinsically related to the failure time of interest, the examination time is referred to as an informative censoring time. Such data may occur in many fields, for example, epidemiological surveys and animal carcinogenicity experiments. To avoid severely misleading inferences resulted from ignoring informative censoring, we propose a class of semiparametric transformation models with log‐normal frailty for current status data with informative censoring. A shared frailty is used to account for the correlation between the failure time and censoring time. The expectation‐maximization (EM) algorithm combining a sieve method for approximating an infinite‐dimensional parameter is employed to estimate all parameters. To investigate finite sample properties of the proposed method, simulation studies are conducted, and a data set from a rodent tumorigenicity experiment is analyzed for illustrative purposes. 相似文献
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Summary Increasingly, estimations of health care costs are used to evaluate competing treatments or to assess the expected expenditures associated with certain diseases. In health policy and economics, the primary focus of these estimations has been on the mean cost, because the total cost can be derived directly from the mean cost, and because information about total resources utilized is highly relevant for policymakers. Yet, the median cost also could be important, both as an intuitive measure of central tendency in cost distribution and as a subject of interest to payers and consumers. In many prospective studies, cost data collection is sometimes incomplete for some subjects due to right censoring, which typically is caused by loss to follow-up or by limited study duration. Censoring poses a unique challenge for cost data analysis because of so-called induced informative censoring, in that traditional methods suited for survival data generally are invalid in censored cost estimation. In this article, we propose methods for estimating the median cost and its confidence interval (CI) when data are subject to right censoring. We also consider the estimation of the ratio and difference of two median costs and their CIs. These methods can be extended to the estimation of other quantiles and other informatively censored data. We conduct simulation and real data analysis in order to examine the performance of the proposed methods. 相似文献
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Siannis F 《Biometrics》2004,60(3):704-714
In this article, we explore the use of a parametric model (for analyzing survival data) which is defined to allow sensitivity analysis for the presence of informative censoring. The dependence between the failure and the censoring processes is expressed through a parameter delta and a general bias function B(t, theta). We calculate the expectation of the potential bias due to informative censoring, which is an overall measure of how misleading our results might be if censoring is actually nonignorable. Bounds are also calculated for quantities of interest, e.g., parameter of the distribution of the failure process, which do not depend on the choice of the bias function for fixed delta. An application that relates to systematic lupus erythematosus data illustrates how additional information can result in reducing the uncertainty on estimates of the location parameter. Sensitivity analysis on a relative risk parameter is also explored. 相似文献
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We discuss how to apply the conditional informative missing model of Wu and Bailey (1989, Biometrics 45, 939-955) to the setting where the probability of missing a visit depends on the random effects of the primary response in a time-dependent fashion. This includes the case where the probability of missing a visit depends on the true value of the primary response. Summary measures for missingness that are weighted sums of the indicators of missed visits are derived for these situations. These summary measures are then incorporated as covariates in a random effects model for the primary response. This approach is illustrated by analyzing data collected from a trial of heroin addicts where missed visits are informative about drug test results. Simulations of realistic experiments indicate that these time-dependent summary measures also work well under a variety of informative censoring models. These summary measures can achieve large reductions in estimation bias and mean squared errors relative to those obtained by using other summary measures. 相似文献
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Ghosh D 《Biometrics》2003,59(3):721-726
In tumorigenicity experiments, a complication is that the time to event is generally not observed, so that the time to tumor is subject to interval censoring. One of the goals in these studies is to properly model the effect of dose on risk. Thus, it is important to have goodness of fit procedures available for assessing the model fit. While several estimation procedures have been developed for current-status data, relatively little work has been done on model-checking techniques. In this article, we propose numerical and graphical methods for the analysis of current-status data using the additive-risk model, primarily focusing on the situation where the monitoring times are dependent. The finite-sample properties of the proposed methodology are examined through numerical studies. The methods are then illustrated with data from a tumorigenicity experiment. 相似文献
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We develop an approach, based on multiple imputation, to using auxiliary variables to recover information from censored observations in survival analysis. We apply the approach to data from an AIDS clinical trial comparing ZDV and placebo, in which CD4 count is the time-dependent auxiliary variable. To facilitate imputation, a joint model is developed for the data, which includes a hierarchical change-point model for CD4 counts and a time-dependent proportional hazards model for the time to AIDS. Markov chain Monte Carlo methods are used to multiply impute event times for censored cases. The augmented data are then analyzed and the results combined using standard multiple-imputation techniques. A comparison of our multiple-imputation approach to simply analyzing the observed data indicates that multiple imputation leads to a small change in the estimated effect of ZDV and smaller estimated standard errors. A sensitivity analysis suggests that the qualitative findings are reproducible under a variety of imputation models. A simulation study indicates that improved efficiency over standard analyses and partial corrections for dependent censoring can result. An issue that arises with our approach, however, is whether the analysis of primary interest and the imputation model are compatible. 相似文献
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Joint models for a time-to-event (e.g., survival) and a longitudinal response have generated considerable recent interest. The longitudinal data are assumed to follow a mixed effects model, and a proportional hazards model depending on the longitudinal random effects and other covariates is assumed for the survival endpoint. Interest may focus on inference on the longitudinal data process, which is informatively censored, or on the hazard relationship. Several methods for fitting such models have been proposed, most requiring a parametric distributional assumption (normality) on the random effects. A natural concern is sensitivity to violation of this assumption; moreover, a restrictive distributional assumption may obscure key features in the data. We investigate these issues through our proposal of a likelihood-based approach that requires only the assumption that the random effects have a smooth density. Implementation via the EM algorithm is described, and performance and the benefits for uncovering noteworthy features are illustrated by application to data from an HIV clinical trial and by simulation. 相似文献
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In cancer drug development, demonstrating activity in xenograft models, where mice are grafted with human cancer cells, is an important step in bringing a promising compound to humans. A key outcome variable is the tumor volume measured in a given period of time for groups of mice given different doses of a single or combination anticancer regimen. However, a mouse may die before the end of a study or may be sacrificed when its tumor volume quadruples, and its tumor may be suppressed for some time and then grow back. Thus, incomplete repeated measurements arise. The incompleteness or missingness is also caused by drastic tumor shrinkage (<0.01 cm3) or random truncation. Because of the small sample sizes in these models, asymptotic inferences are usually not appropriate. We propose two parametric test procedures based on the EM algorithm and the Bayesian method to compare treatment effects among different groups while accounting for informative censoring. A real xenograft study on a new antitumor agent, temozolomide, combined with irinotecan is analyzed using the proposed methods. 相似文献
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Chang SH 《Biometrics》2000,56(1):183-189
A longitudinal study is conducted to compare the process of particular disease between two groups. The process of the disease is monitored according to which of several ordered events occur. In the paper, the sojourn time between two successive events is considered as the outcome of interest. The group effects on the sojourn times of the multiple events are parameterized by scale changes in a semiparametric accelerated failure time model where the dependence structure among the multivariate sojourn times is unspecified. Suppose that the sojourn times are subject to dependent censoring and the censoring times are observed for all subjects. A log-rank-type estimating approach by rescaling the sojourn times and the dependent censoring times into the same distribution is constructed to estimate the group effects and the corresponding estimators are consistent and asymptotically normal. Without the dependent censoring, the independent censoring times in general are not available for the uncensored data. In order to complete the censoring information, pseudo-censoring times are generated from the corresponding nonparametrically estimated survival function in each group, and we can still obtained unbiased estimating functions for the group effects. A real application and a simulation study are conducted to illustrate the proposed methods. 相似文献