Browsing by Subject "Nonparametric"

Now showing 1 - 3 of 3
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    Modeling longitudinal data with interval censored anchoring events
    (2018-03-01) Chu, Chenghao; Zhang, Ying; Tu, Wanzhu
    In many longitudinal studies, the time scales upon which we assess the primary outcomes are anchored by pre-specified events. However, these anchoring events are often not observable and they are randomly distributed with unknown distribution. Without direct observations of the anchoring events, the time scale used for analysis are not available, and analysts will not be able to use the traditional longitudinal models to describe the temporal changes as desired. Existing methods often make either ad hoc or strong assumptions on the anchoring events, which are unveri able and prone to biased estimation and invalid inference. Although not able to directly observe, researchers can often ascertain an interval that includes the unobserved anchoring events, i.e., the anchoring events are interval censored. In this research, we proposed a two-stage method to fit commonly used longitudinal models with interval censored anchoring events. In the first stage, we obtain an estimate of the anchoring events distribution by nonparametric method using the interval censored data; in the second stage, we obtain the parameter estimates as stochastic functionals of the estimated distribution. The construction of the stochastic functional depends on model settings. In this research, we considered two types of models. The first model was a distribution-free model, in which no parametric assumption was made on the distribution of the error term. The second model was likelihood based, which extended the classic mixed-effects models to the situation that the origin of the time scale for analysis was interval censored. For the purpose of large-sample statistical inference in both models, we studied the asymptotic properties of the proposed functional estimator using empirical process theory. Theoretically, our method provided a general approach to study semiparametric maximum pseudo-likelihood estimators in similar data situations. Finite sample performance of the proposed method were examined through simulation study. Algorithmically eff- cient algorithms for computing the parameter estimates were provided. We applied the proposed method to a real data analysis and obtained new findings that were incapable using traditional mixed-effects models.
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    Nonparametric Analysis of Semi-Competing Risks Data
    (2020-04) Li, Jing; Bakoyannis, Giorgos; Zhang, Ying; Gao, Sujuan; Song, Yiqing; Zhang, Chi
    It is generally of interest to explore if the risk of death would be modified by medical conditions (e.g., illness) that have occurred prior. This situation gives rise to semicompeting risks data, which are a mixture of competing risks and progressive state data. This type of data occurs when a non-terminal event can be censored by a well-defined terminal event, but not vice versa. In the first part of this dissertation, the shared gamma-frailty conditional Markov model (GFCMM) is adopted because it bridges the copula models and illness-death models. Maximum likelihood estimation methodology has been proposed in the literature. However, we found through numerical experiments that the unrestricted model sometimes yields nonparametric biased estimation. Hence a practical guideline is provided for using the GFCMM that includes (i) a score test to assess whether the restricted model, which does not exhibit estimation problems, is reasonable under a proportional hazards assumption, and (ii) a graphical illustration to evaluate whether the unrestricted model yields nonparametric estimation with substantial bias for cases where the test provides a statistical significant result against the restricted model. However, the scientific question of interest that whether the status of non-terminal event alters the risk to terminal event can only be partially addressed based on the aforementioned approach. Therefore in the second part of this dissertation, we adopt a Markov illness-death model, whose transition intensities are essentially equivalent to the marginal hazards defined in GFCMM, but with different interpretations; we develop three nonparametric tests, including a linear test, a Kolmogorov-Smirnov-type test, and a L2-distance-type test, to directly compare the two transition intensities under consideration. The asymptotic properties of the proposed test statistics are established using empirical process theory. The performance of these tests in nite samples is numerically evaluated through extensive simulation studies. All three tests provide similar power levels with non-crossing curves of cumulative transition intensities, while the linear test is suboptimal when the curves cross. Eventually, the proposed tests successfully address the scientific question of interest. This research is applied to Indianapolis-Ibadan Dementia Project (IIDP) to explore whether dementia occurrence changes mortality risk.
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    Statistical methods to study heterogeneity of treatment effects
    (2015-09-25) Taft, Lin H.; Shen, Changyu; Li, Xiaochun; Chen, Peng-Sheng; Wessel, Jennifer
    Randomized studies are designed to estimate the average treatment effect (ATE) of an intervention. Individuals may derive quantitatively, or even qualitatively, different effects from the ATE, which is called the heterogeneity of treatment effect. It is important to detect the existence of heterogeneity in the treatment responses, and identify the different sub-populations. Two corresponding statistical methods will be discussed in this talk: a hypothesis testing procedure and a mixture-model based approach. The hypothesis testing procedure was constructed to test for the existence of a treatment effect in sub-populations. The test is nonparametric, and can be applied to all types of outcome measures. A key innovation of this test is to build stochastic search into the test statistic to detect signals that may not be linearly related to the multiple covariates. Simulations were performed to compare the proposed test with existing methods. Power calculation strategy was also developed for the proposed test at the design stage. The mixture-model based approach was developed to identify and study the sub-populations with different treatment effects from an intervention. A latent binary variable was used to indicate whether or not a subject was in a sub-population with average treatment benefit. The mixture-model combines a logistic formulation of the latent variable with proportional hazards models. The parameters in the mixture-model were estimated by the EM algorithm. The properties of the estimators were then studied by the simulations. Finally, all above methods were applied to a real randomized study in a low ejection fraction population that compared the Implantable Cardioverter Defibrillator (ICD) with conventional medical therapy in reducing total mortality.