Kullback-leibler information approach to the optimum measurement point for bayesian estimation

When an appropriate parametric model and a prior distribution of its parameters are given to describe clinical time courses of a dynamic biological process, Bayesian approaches allow us to estimate the entire profiles from a few or even a single observation per subject. The goodness of the estimation depends on the measurement points at which the observations were made. The number of measurement points per subject is generally limited to one or two. The limited measurement points have to be selected carefully. This paper proposes an approach to the selection of the optimum measurement point for Bayesian estimations of clinical time courses. The selection is made among given candidates, based on the goodness of estimation evaluated by the Kullback-Leibler information. This information measures the discrepancy of an estimated time course from the true one specified by a given appropriate model. The proposed approach is applied to a pharmacokinetic analysis, which is a typical clinical example where the selection is required. The results of the present study strongly suggest that the proposed approach is applicable to pharmacokinetic data and has a wide range of clinical applications.     

A Method for Simulating Multivariate Non Normal Distributions with Specified Standardized Cumulants and Intraclass Correlation Coefficients

Intraclass correlation coefficients (ICCs) are commonly used indices in subject areas such as biometrics, longitudinal data analysis, measurement theory, quality control, and survey research. The properties of the ICCs most often used are derived under the assumption of normality. However, real-world data often violate the normality assumption. In view of this, a computationally efficient procedure is developed for simulating multivariate non normal continuous distributions with specified (a) standardized cumulants, (b) Pearson intercorrelations, and (c) ICCs. The linear model specified is a two-factor design with either fixed or random effects. A numerical example is worked and the results of a Monte Carlo simulation are provided to demonstrate and confirm the methodology.     

Multivariate Birnbaum–Saunders distribution: properties and associated inference

The univariate fatigue life distribution proposed by Birnbaum and Saunders [A new family of life distributions. J Appl Probab. 1969;6:319–327] has been used quite effectively to model times to failure for materials subject to fatigue and for modelling lifetime data and reliability problems. In this article, we introduce a Birnbaum–Saunders (BS) distribution in the multivariate setting. The new multivariate model arises in the context of conditionally specified distributions. The proposed multivariate model is an absolutely continuous distribution whose marginals are univariate BS distributions. General properties of the multivariate BS distribution are derived and the estimation of the unknown parameters by maximum likelihood is discussed. Further, the Fisher's information matrix is determined. Applications to real data of the proposed multivariate distribution are provided for illustrative purposes.     

A Bayesian semiparametric method for analyzing length-biased data

Survival data obtained from prevalent cohort study designs are often subject to length-biased sampling. Frequentist methods including estimating equation approaches, as well as full likelihood methods, are available for assessing covariate effects on survival from such data. Bayesian methods allow a perspective of probability interpretation for the parameters of interest, and may easily provide the predictive distribution for future observations while incorporating weak prior knowledge on the baseline hazard function. There is lack of Bayesian methods for analyzing length-biased data. In this paper, we propose Bayesian methods for analyzing length-biased data under a proportional hazards model. The prior distribution for the cumulative hazard function is specified semiparametrically using I-Splines. Bayesian conditional and full likelihood approaches are developed for analyzing simulated and real data.     

THE ANALYSIS OF DISCRETE CHOICE EXPERIMENTS WITH CORRELATED ERROR STRUCTURE

In a stated preference discrete choice experiment each subject is typically presented with several choice sets, and each choice set contains a number of alternatives. The alternatives are defined in terms of their name (brand) and their attributes at specified levels. The task for the subject is to choose from each choice set the alternative with highest utility for them. The multinomial is an appropriate distribution for the responses to each choice set since each subject chooses one alternative, and the multinomial logit is a common model. If the responses to the several choice sets are independent, the likelihood function is simply the product of multinomials. The most common and generally preferred method of estimating the parameters of the model is maximum likelihood (that is, selecting as estimates those values that maximize the likelihood function). If the assumption of within-subject independence to successive choice tasks is violated (it is almost surely violated), the likelihood function is incorrect and maximum likelihood estimation is inappropriate. The most serious errors involve the estimation of the variance-covariance matrix of the model parameter estimates, and the corresponding variances of market shares and changes in market shares.

In this paper we present an alternative method of estimation of the model parameter coefficients that incorporates a first-order within-subject covariance structure. The method involves the familiar log-odds transformation and application of the multivariate delta method. Estimation of the model coefficients after the transformation is a straightforward generalized least squares regression, and the corresponding improved estimate of the variance-covariance matrix is in closed form. Estimates of market share (and change in market share) follow from a second application of the multivariate delta method. The method and comparison with maximum likelihood estimation are illustrated with several simulated and actual data examples.

Advantages of the proposed method are: 1) it incorporates the within-subject covariance structure; 2) it is completely data driven; 3) it requires no additional model assumptions; 4) assuming asymptotic normality, it provides a simple procedure for computing confidence regions on market shares and changes in market shares; and 5) it produces results that are asymptotically equivalent to those produced by maximum likelihood when the data are independent.     

OPTIMAL DESIGNS FOR FITTING A PROPORTIONAL HAZARDS REGRESSION MODEL TO DATA SUBJECT TO CENSORING

Suppose the probability model for failure time data, subject to censoring, is specified by the hazard function λ(t)exp(β_T x), where x is a vector of covariates. Analytical difficulties involved in finding the optimal design are avoided by assuming that λ is completely specified and by using D-optimality based on the information matrix for β Optimal designs are found to depend on β, but some results of practical consequence are obtained. It is found that censoring does not affect the choice of design appreciably when β^T x ≥ 0 for all points of the feasible region, but may have an appreciable effect when β_ix_i 0, for all i and all points in the feasible experimental region. The nature of the effect is discussed in detail for the cases of one and two parameters. It is argued that in practical biomedical situations the optimal design is almost always the same as for uncensored data.     

Generalized monotonic functional mixed models with application to modelling normal tissue complications

Summary.  Normal tissue complications are a common side effect of radiation therapy. They are the consequence of the dose of radiation that is received by the normal tissue surrounding the site of the tumour. Within a specified organ each voxel receives a certain dose of radiation, leading to a distribution of doses over the organ. It is often not known what aspect of the dose distribution drives the presence and severity of the complications. A summary measure of the dose distribution can be obtained by integrating a weighting function of dose ( w ( d )) over the density of dose. For biological reasons the weight function should be monotonic. We propose a generalized monotonic functional mixed model to study the dose effect on a clinical outcome by estimating this weight function non-parametrically by using splines and subject to the monotonicity constraint, while allowing for overdispersion and correlation of multiple obervations within the same subject. We illustrate our method with data from a head and neck cancer study in which the irradiation of the parotid gland results in loss of saliva flow.     

Bias from the use of generalized estimating equations to analyze incomplete longitudinal binary data

Patient dropout is a common problem in studies that collect repeated binary measurements. Generalized estimating equations (GEE) are often used to analyze such data. The dropout mechanism may be plausibly missing at random (MAR), i.e. unrelated to future measurements given covariates and past measurements. In this case, various authors have recommended weighted GEE with weights based on an assumed dropout model, or an imputation approach, or a doubly robust approach based on weighting and imputation. These approaches provide asymptotically unbiased inference, provided the dropout or imputation model (as appropriate) is correctly specified. Other authors have suggested that, provided the working correlation structure is correctly specified, GEE using an improved estimator of the correlation parameters (‘modified GEE’) show minimal bias. These modified GEE have not been thoroughly examined. In this paper, we study the asymptotic bias under MAR dropout of these modified GEE, the standard GEE, and also GEE using the true correlation. We demonstrate that all three methods are biased in general. The modified GEE may be preferred to the standard GEE and are subject to only minimal bias in many MAR scenarios but in others are substantially biased. Hence, we recommend the modified GEE be used with caution.     

Maximum likelihood estimation in generalized broken‐line regression

The author examines the existence, uniqueness, and identifiability of estimators produced by maximum likelihood for a model where the canonical parameter of an exponential family gradually begins to drift from its initial value at an unknown change point. He illustrates these properties with theoretical examples and applies his results to global warming data and failure data for emergency diesel generators.     

A Semi‐parametric Transformation Frailty Model for Semi‐competing Risks Survival Data

In the analysis of semi‐competing risks data interest lies in estimation and inference with respect to a so‐called non‐terminal event, the observation of which is subject to a terminal event. Multi‐state models are commonly used to analyse such data, with covariate effects on the transition/intensity functions typically specified via the Cox model and dependence between the non‐terminal and terminal events specified, in part, by a unit‐specific shared frailty term. To ensure identifiability, the frailties are typically assumed to arise from a parametric distribution, specifically a Gamma distribution with mean 1.0 and variance, say, σ². When the frailty distribution is misspecified, however, the resulting estimator is not guaranteed to be consistent, with the extent of asymptotic bias depending on the discrepancy between the assumed and true frailty distributions. In this paper, we propose a novel class of transformation models for semi‐competing risks analysis that permit the non‐parametric specification of the frailty distribution. To ensure identifiability, the class restricts to parametric specifications of the transformation and the error distribution; the latter are flexible, however, and cover a broad range of possible specifications. We also derive the semi‐parametric efficient score under the complete data setting and propose a non‐parametric score imputation method to handle right censoring; consistency and asymptotic normality of the resulting estimators is derived and small‐sample operating characteristics evaluated via simulation. Although the proposed semi‐parametric transformation model and non‐parametric score imputation method are motivated by the analysis of semi‐competing risks data, they are broadly applicable to any analysis of multivariate time‐to‐event outcomes in which a unit‐specific shared frailty is used to account for correlation. Finally, the proposed model and estimation procedures are applied to a study of hospital readmission among patients diagnosed with pancreatic cancer.     

Bayesian Analysis of an Unobserved-Component Time Series Model of GDP With Markov-Switching and Time-Varying Growths

We propose an unobserved-component time series model of gross domestic product that includes Markov switching as an unobserved component. In addition to a trend component, the model has two time-varying drift components. One drift represents the expected rate of growth during recession; the other drift represents the expected rate during expansion. Estimates indicate a substantial decline in the latter annual rate for the United States from 6.4% in 1950 to 3.6% by 1990. We have employed weak priors based on prewar data. The estimation makes use of the Gibbs sampler and the Metropolis algorithm.     

Bayesian inference of the fully specified subdistribution model for survival data with competing risks

Competing risks data are routinely encountered in various medical applications due to the fact that patients may die from different causes. Recently, several models have been proposed for fitting such survival data. In this paper, we develop a fully specified subdistribution model for survival data in the presence of competing risks via a subdistribution model for the primary cause of death and conditional distributions for other causes of death. Various properties of this fully specified subdistribution model have been examined. An efficient Gibbs sampling algorithm via latent variables is developed to carry out posterior computations. Deviance information criterion (DIC) and logarithm of the pseudomarginal likelihood (LPML) are used for model comparison. An extensive simulation study is carried out to examine the performance of DIC and LPML in comparing the cause-specific hazards model, the mixture model, and the fully specified subdistribution model. The proposed methodology is applied to analyze a real dataset from a prostate cancer study in detail.     

The Augmented Semi-Markov System in Continuous Time

This article proposes a continuous time semi-Markov hierarchical manpower planning model that incorporates the need of the employees to attend seminars, so as to enhance their prospects, as well as the organizations' intention to avoid situations concerning unavailability in skilled personnel when needed. At large, we study a hierarchical system where the workforce demand at each time period can be met via internal mobility and two streams of recruitment; one from the outside environment and another from a supplementary auxiliary system. For the suggested model, namely the Continuous Time Augmented Semi-Markov System, we examine initially its dynamic behavior by deriving the equations reflecting the expected number of persons in each grade. In the sequel, we probe its limiting population structure and it is found that under a set of conditions this structure exists and is specified. Finally, we present a real case which demonstrates the practical motivation of the subject under study.     

Nonparametric likelihood and doubly robust estimating equations for marginal and nested structural models

This article considers Robins's marginal and nested structural models in the cross‐sectional setting and develops likelihood and regression estimators. First, a nonparametric likelihood method is proposed by retaining a finite subset of all inherent and modelling constraints on the joint distributions of potential outcomes and covariates under a correctly specified propensity score model. A profile likelihood is derived by maximizing the nonparametric likelihood over these joint distributions subject to the retained constraints. The maximum likelihood estimator is intrinsically efficient based on the retained constraints and weakly locally efficient. Second, two regression estimators, named hat and tilde, are derived as first‐order approximations to the likelihood estimator under the propensity score model. The tilde regression estimator is intrinsically and weakly locally efficient and doubly robust. The methods are illustrated by data analysis for an observational study on right heart catheterization. The Canadian Journal of Statistics 38: 609–632; 2010 © 2010 Statistical Society of Canada     

Nonparametric estimation of the limiting availability

The point availability of a repairable system is the probability that the system is operating at a specified time. As time increases, the point availability converges to a positive constant called the limiting availability. Baxter and Li (1994a) developed a technique for constructing nonparametric confidence intervals for the point availability. However, nonparametric estimators of the limiting availability have not previously been studied in the literature. In this paper, we consider two separate cases: (1) the data are complete and (2) the data are subject to right censorship. For each case, a nonparametric confidence interval for the limiting availability is derived. Applications and simulation studies are presented.deceased after the paper was accepted     

Several nonparametric and semiparametric approaches to linear mixed model regression

Mixed models are powerful tools for the analysis of clustered data and many extensions of the classical linear mixed model with normally distributed response have been established. As with all parametric (P) models, correctness of the assumed model is critical for the validity of the ensuing inference. An incorrectly specified P means model may be improved by using a local, or nonparametric (NP), model. Two local models are proposed by a pointwise weighting of the marginal and conditional variance–covariance matrices. However, NP models tend to fit to irregularities in the data and may provide fits with high variance. Model robust regression techniques estimate mean response as a convex combination of a P and a NP model fit to the data. It is a semiparametric method by which incomplete or incorrectly specified P models can be improved by adding an appropriate amount of the NP fit. We compare the approximate integrated mean square error of the P, NP, and mixed model robust methods via a simulation study and apply these methods to two real data sets: the monthly wind speed data from countries in Ireland and the engine speed data.     

A model for extreme wind gusts

Estimates of the largest wind gust that will occur at a given location over a specified period are required by civil engineers. Estimation is usually based on models which are derived from the limiting distributions of maxima of stationary time series and which are fitted to data on extreme gusts. In this paper we develop a model for maximum gusts which also incorporates data on hourly mean speeds through a distributional relationship between maxima and means. This joint model is closely linked to the physical processes which generate the most extreme values and thus provides a mechanism by which data on means can augment those on gusts. It is argued that this increases the credibility of extrapolation in estimates of long period return gusts. The model is shown to provide a good fit to data obtained at a location in northern England and is compared with a more traditional modelling approach, which also performs well for this site.     

在经济数据中寻找混沌

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Robust quasi-randomization-based estimation with ensemble learning for missing data

Missing data analysis requires assumptions about an outcome model or a response probability model to adjust for potential bias due to nonresponse. Doubly robust (DR) estimators are consistent if at least one of the models is correctly specified. Multiply robust (MR) estimators extend DR estimators by allowing for multiple models for both the outcome and/or response probability models and are consistent if at least one of the multiple models is correctly specified. We propose a robust quasi-randomization-based model approach to bring more protection against model misspecification than the existing DR and MR estimators, where any multiple semiparametric, nonparametric or machine learning models can be used for the outcome variable. The proposed estimator achieves unbiasedness by using a subsampling Rao–Blackwell method, given cell-homogenous response, regardless of any working models for the outcome. An unbiased variance estimation formula is proposed, which does not use any replicate jackknife or bootstrap methods. A simulation study shows that our proposed method outperforms the existing multiply robust estimators.     

Multiple robustness estimation in causal inference

Abstract

Estimation of average treatment effect is crucial in causal inference for evaluation of treatments or interventions in biostatistics, epidemiology, econometrics, sociology. However, existing estimators require either a propensity score model, an outcome vector model, or both is correctly specified, which is difficult to verify in practice. In this paper, we allow multiple models for both the propensity score models and the outcome models, and then construct a weighting estimator based on observed data by using two-sample empirical likelihood. The resulting estimator is consistent if any one of those multiple models is correctly specified, and thus provides multiple protection on consistency. Moreover, the proposed estimator can attain the semiparametric efficiency bound when one propensity score model and one outcome vector model are correctly specified, without requiring knowledge of which models are correct. Simulations are performed to evaluate the finite sample performance of the proposed estimators. As an application, we analyze the data collected from the AIDS Clinical Trials Group Protocol 175.