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Register a new userSemiparametric Sieve Maximum Likelihood Estimation Under Cure Model with Partly Interval Censored and Left Truncated Data for Application to Spontaneous Abortion Data
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Yuan Wu
Publication date
2017
fields
Mathematical Statistics
and research's language is
English
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This work was motivated by observational studies in pregnancy with spontaneous abortion (SAB) as outcome. Clearly some women experience the SAB event but the rest do not. In addition, the data are left truncated due to the way pregnant women are recruited into these studies. For those women who do experience SAB, their exact event times are sometimes unknown. Finally, a small percentage of the women are lost to follow-up during their pregnancy. All these give rise to data that are left truncated, partly interval and right-censored, and with a clearly defined cured portion. We consider the non-mixture Cox regression cure rate model and adopt the semiparametric spline-based sieve maximum likelihood approach to analyze such data. Using modern empirical process theory we show that both the parametric and the nonparametric parts of the sieve estimator are consistent, and we establish the asymptotic normality for both parts. Simulation studies are conducted to establish the finite sample performance. Finally, we apply our method to a database of observational studies on spontaneous abortion.
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The mixture cure rate model is the most commonly used cure rate model in the literature. In the context of mixture cure rate model, the standard approach to model the effect of covariates on the cured or uncured probability is to use a logistic function. This readily implies that the boundary classifying the cured and uncured subjects is linear. In this paper, we propose a new mixture cure rate model based on interval censored data that uses the support vector machine (SVM) to model the effect of covariates on the uncured or the cured probability (i.e., on the incidence part of the model). Our proposed model inherits the features of the SVM and provides flexibility to capture classification boundaries that are non-linear and more complex. Furthermore, the new model can be used to model the effect of covariates on the incidence part when the dimension of covariates is high. The latency part is modeled by a proportional hazards structure. We develop an estimation procedure based on the expectation maximization (EM) algorithm to estimate the cured/uncured probability and the latency model parameters. Our simulation study results show that the proposed model performs better in capturing complex classification boundaries when compared to the existing logistic regression based mixture cure rate model. We also show that our models ability to capture complex classification boundaries improve the estimation results corresponding to the latency parameters. For illustrative purpose, we present our analysis by applying the proposed methodology to an interval censored data on smoking cessation.
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A maximum likelihood methodology for a general class of models is presented, using an approximate Bayesian computation (ABC) approach. The typical target of ABC methods are models with intractable likelihoods, and we combine an ABC-MCMC sampler with so-called data cloning for maximum likelihood estimation. Accuracy of ABC methods relies on the use of a small threshold value for comparing simulations from the model and observed data. The proposed methodology shows how to use large threshold values, while the number of data-clones is increased to ease convergence towards an approximate maximum likelihood estimate. We show how to exploit the methodology to reduce the number of iterations of a standard ABC-MCMC algorithm and therefore reduce the computational effort, while obtaining reasonable point estimates. Simulation studies show the good performance of our approach on models with intractable likelihoods such as g-and-k distributions, stochastic differential equations and state-space models.
Partially observed cured data occur in the analysis of spontaneous abortion (SAB) in observational studies in pregnancy. In contrast to the traditional cured data, such data has an observable `cured portion as women who do not abort spontaneously. The data is also subject to left truncate in addition to right-censoring because women may enter or withdraw from a study any time during their pregnancy. Left truncation in particular causes unique bias in the presence of a cured portion. In this paper, we study a cure rate model and develop a conditional nonparametric maximum likelihood approach. To tackle the computational challenge we adopt an EM algorithm making use of ghost copies of the data, and a closed form variance estimator is derived. Under suitable assumptions, we prove the consistency of the resulting estimator involving an unbounded cumulative baseline hazard function, as well as the asymptotic normality. Simulation results are carried out to evaluate the finite sample performance. We present the analysis of the motivating SAB study to illustrate the power of our model addressing both occurrence and timing of SAB, as compared to existing approaches in practice.
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