Semiparametric analysis for case-control studies: a partial smoothing spline approach

Case-control data are often used in medical-related applications, and most studies have applied parametric logistic regression to analyze such data. In this study, we investigated a semiparametric model for the analysis of case-control data by relaxing the linearity assumption of risk factors by using a partial smoothing spline model. A faster computation method for the model by extending the lower-dimensional approximation approach of Gu and Kim 4 Gu, C. and Kim, Y.-J. 2002. Penalized likelihood regression: General formulation and efficient approximation. Canad. J. Statist., 30: 619–628. [Crossref], [Web of Science ®] [Google Scholar] developed in penalized likelihood regression is considered to apply to case-control studies. Simulations were conducted to evaluate the performance of the method with selected smoothing parameters and to compare the method with existing methods. The method was applied to Korean gastric cancer case-control data to estimate the nonparametric probability function of age and regression parameters for other categorical risk factors simultaneously. The method could be used in preliminary studies to identify whether there is a flexible function form of risk factors in the semiparametric logistic regression analysis involving a large data set.     

Some characteristics on the selection of spline smoothing parameter

The smoothing spline method is used to fit a curve to a noisy data set, where selection of the smoothing parameter is essential. An adaptive C_p criterion (Chen and Huang 2011 Chen, C. S., and H. C. Huang. 2011. An improved C_p criterion for spline smoothing. Journal of Statistical Planning and Inference 141:445–52.[Crossref], [Web of Science ®] , [Google Scholar]) based on the Stein’s unbiased risk estimate has been proposed to select the smoothing parameter, which not only considers the usual effective degrees of freedom but also takes into account the selection variability. The resulting fitted curve has been shown to be superior and more stable than commonly used selection criteria and possesses the same asymptotic optimality as C_p. In this paper, we further discuss some characteristics on the selection of smoothing parameter, especially for the selection variability.     

Grkpack fitting smoothing spline anova models for exponential families

Wahba, Wang, Gu, Klein and Klein introduced Smoothing Spline ANalysis of VAriance (SS ANOVA) method for data from exponential families. Based on RKPACK, which fits SS ANOVA models to Gaussian data, we introduce GRKPACK a collection of Fortran subroutines for binary, binomial, Poisson and Gamma data. We also show how to calculate Bayesian confidence intervals for SS ANOVA estimates.     

A cubic smoothing spline based lack of fit test for nonlinear regression models

The use of a statistic based on cubic spline smoothing is considered for testing nonlinear regression models for lack of fit. The statistic is defined to be the Euclidean squared norm of the smoothed residual vector obtained from fitting the nonlinear model, The asymptotic distribution of the statistic is derived under suitable smooth local alternatives and a numerical example is presented.     

Inference in smoothing spline analysis of variance

Summary. Smoothing spline analysis of variance decomposes a multivariate function into additive components. This decomposition not only provides an efficient way to model a multivariate function but also leads to meaningful inference by testing whether a certain component equals 0. No formal procedure is yet available to test such a hypothesis. We propose an asymptotic method based on the likelihood ratio to test whether a functional component is 0. This test allows us to choose an optimal model and to compare groups of curves. We first develop the general theory by exploiting the connection between mixed effects models and smoothing splines. We then apply this to compare two groups of curves and to select an optimal model in a two-dimensional problem. A small simulation is used to assess the finite sample performance of the likelihood ratio test.     

Boundary corrected cubic smoothing splines

Smoothing splines are known to exhibit a type of boundary bias that can reduce their estimation efficiency. In this paper, a boundary corrected cubic smoothing spline is developed in a way that produces a uniformly fourth order estimator. The resulting estimator can be calculated efficiently using an O(n) algorithm that is designed for the computation of fitted values and associated smoothing parameter selection criteria. A simulation study shows that use of the boundary corrected estimator can improve estimation efficiency in finite samples. Applications to the construction of asymptotically valid pointwise confidence intervals are also investigated .     

Adaptive modelling of dose–response relationships using smoothing splines

We consider the use of smoothing splines for the adaptive modelling of dose–response relationships. A smoothing spline is a nonparametric estimator of a function that is a compromise between the fit to the data and the degree of smoothness and thus provides a flexible way of modelling dose–response data. In conjunction with decision rules for which doses to continue with after an interim analysis, it can be used to give an adaptive way of modelling the relationship between dose and response. We fit smoothing splines using the generalized cross‐validation criterion for deciding on the degree of smoothness and we use estimated bootstrap percentiles of the predicted values for each dose to decide upon which doses to continue with after an interim analysis. We compare this approach with a corresponding adaptive analysis of variance approach based upon new simulations of the scenarios previously used by the PhRMA Working Group on Adaptive Dose‐Ranging Studies. The results obtained for the adaptive modelling of dose–response data using smoothing splines are mostly comparable with those previously obtained by the PhRMA Working Group for the Bayesian Normal Dynamic Linear model (GADA) procedure. These methods may be useful for carrying out adaptations, detecting dose–response relationships and identifying clinically relevant doses. Copyright © 2009 John Wiley & Sons, Ltd.     

Estimating a frequency distribution when the sampling is biased

A simple random sample on a random variable A allows its density to be consistently estimated, by a histogram or preferably a kernel density estimate. When the sampling is biased towards certain x-values these methods instead estimate a weighted version of the density function. This article proposes a method for estimating both the density and the sampling bias simultaneously. The technique requires two independent samples and utilises ideas from mark-recapture experiments. An estimator of the size of the sampled population also follows simply from this density estimate.     

A method for choosing the smoothing parameter in a semi-parametric model for detecting change-points in blood flow

In a smoothing spline model with unknown change-points, the choice of the smoothing parameter strongly influences the estimation of the change-point locations and the function at the change-points. In a tumor biology example, where change-points in blood flow in response to treatment were of interest, choosing the smoothing parameter based on minimizing generalized cross-validation (GCV) gave unsatisfactory estimates of the change-points. We propose a new method, aGCV, that re-weights the residual sum of squares and generalized degrees of freedom terms from GCV. The weight is chosen to maximize the decrease in the generalized degrees of freedom as a function of the weight value, while simultaneously minimizing aGCV as a function of the smoothing parameter and the change-points. Compared with GCV, simulation studies suggest that the aGCV method yields improved estimates of the change-point and the value of the function at the change-point.     

A nonparametric estimator of the number of classes based on a stratified random sample

Under stratified random sampling, we develop a k^th-order bootstrap bias-corrected estimator of the number of classes θ which exist in a study region. This research extends Smith and van Belle’s (1984) first-order bootstrap bias-corrected estimator under simple random sampling. Our estimator has applicability for many settings including: estimating the number of animals when there are stratified capture periods, estimating the number of species based on stratified random sampling of subunits (say, quadrats) from the region, and estimating the number of errors/defects in a product based on observations from two or more types of inspectors. When the differences between the strata are large, utilizing stratified random sampling and our estimator often results in superior performance versus the use of simple random sampling and its bootstrap or jackknife [Burnham and Overton (1978)] estimator. The superior performance is often associated with more observed classes, and we provide insights into optimal designation of the strata and optimal allocation of sample sectors to strata.     

A stepwise approach for the purely periodic interaction spline model

The basic idea of an interaction spline model was presented in Barry (1983). The general interaction spline models were proposed by Wahba (1986). The purely periodic spline model, a special case of the general interaction spline models, is considered in this paper. A stepwise approach using generalized cross validation (GCV) for fitting the model is proposed. Based on the nice orthogonality properties of the purely periodic functions, the stepwise approach is a promising method for the interaction spline model. The approach can also be generalized to the non-purely-periodic spline models. But this is no done here.     

Likelihood-based cross-validation score for selecting the smoothing parameter in maximum penalized likelihood estimation

Maximum penalized likelihood estimation is applied in non(semi)-para-metric regression problems, and enables us exploratory identification and diagnostics of nonlinear regression relationships. The smoothing parameter A controls trade-off between the smoothness and the goodness-of-fit of a function. The method of cross-validation is used for selecting A, but the generalized cross-validation, which is based on the squared error criterion, shows bad be¬havior in non-normal distribution and can not often select reasonable A. The purpose of this study is to propose a method which gives more suitable A and to evaluate the performance of it.

A method of simple calculation for the delete-one estimates in the likeli¬hood-based cross-validation (LCV) score is described. A score of similar form to the Akaike information criterion (AIC) is also derived. The proposed scores are compared with the ones of standard procedures by using data sets in liter¬atures. Simulations are performed to compare the patterns of selecting A and overall goodness-of-fit and to evaluate the effects of some factors. The LCV-scores by the simple calculation provide good approximation to the exact one if λ is not extremeiy smaii Furthermore the LCV scores by the simple size it possible to select X adaptively They have the effect, of reducing the bias of estimates and provide better performance in the sense of overall goodness-of fit. These scores are useful especially in the case of small sample size and in the case of binary logistic regression.     

Improved point estimation for the Kumaraswamy distribution

We develop nearly unbiased estimators for the Kumaraswamy distribution proposed by Kumaraswamy [Generalized probability density-function for double-bounded random-processes, J. Hydrol. 46 (1980), pp. 79–88], which has considerable attention in hydrology and related areas. We derive modified maximum-likelihood estimators that are bias-free to second order. As an alternative to the analytically bias-corrected estimators discussed, we consider a bias correction mechanism based on the parametric bootstrap. We conduct Monte Carlo simulations in order to investigate the performance of the corrected estimators. The numerical results show that the bias correction scheme yields nearly unbiased estimates.     

On the shrinkage of local linear curve estimators

Local linear curve estimators are typically constructed using a compactly supported kernel, which minimizes edge effects and (in the case of the Epanechnikov kernel) optimizes asymptotic performance in a mean square sense. The use of compactly supported kernels can produce numerical problems, however. A common remedy is ridging, which may be viewed as shrinkage of the local linear estimator towards the origin. In this paper we propose a general form of shrinkage, and suggest that, in practice, shrinkage be towards a proper curve estimator. For the latter we propose a local linear estimator based on an infinitely supported kernel. This approach is resistant against selection of too large a shrinkage parameter, which can impair performance when shrinkage is towards the origin. It also removes problems of numerical instability resulting from using a compactly supported kernel, and enjoys very good mean squared error properties.     

Selection of the splined variables and convergence rates in a partial spline model

A method based on the principle of unbiased risk estimation is used to select the splined variables in an exploratory partial spline model proposed by Wahba (1985). The probability of correct selection based on the proposed procedure is discussed under regularity conditions. Furthermore, the resulting estimate of the regression function achieves the optimal rates of convergence over a general class of smooth regression functions (Stone 1982) when its underlying smoothness condition is not known.     

A New Kernel Distribution Function Estimator Based on a Non-parametric Transformation of the Data

Abstract.  A new kernel distribution function (df) estimator based on a non-parametric transformation of the data is proposed. It is shown that the asymptotic bias and mean squared error of the estimator are considerably smaller than that of the standard kernel df estimator. For the practical implementation of the new estimator a data-based choice of the bandwidth is proposed. Two possible areas of application are the non-parametric smoothed bootstrap and survival analysis. In the latter case new estimators for the survival function and the mean residual life function are derived.     

Hypothesis test for paired samples in the presence of missing data

Missing data are present in almost all statistical analysis. In simple paired design tests, when some subject has one of the involved variables missing in the so-called partially overlapping samples scheme, it is usually discarded for the analysis. The lack of consistency between the information reported in the univariate and multivariate analysis is, perhaps, the main consequence. Although the randomness on the missing mechanism (missingness completely at random) is an usual and needed assumption for this particular situation, missing data presence could lead to serious inconsistencies on the reported conclusions. In this paper, the authors develop a simple and direct procedure which allows using the whole available information in order to perform paired tests. In particular, the proposed methodology is applied to check the equality among the means from two paired samples. In addition, the use of two different resampling techniques is also explored. Finally, real-world data are analysed.     

Asymptotically Unbiased Estimation of the Coefficient of Tail Dependence

Abstract. We introduce and study a class of weighted functional estimators for the coefficient of tail dependence in bivariate extreme value statistics. Asymptotic normality of these estimators is established under a second‐order condition on the joint tail behaviour, some conditions on the weight function and for appropriately chosen sequences of intermediate order statistics. Asymptotically unbiased estimators are constructed by judiciously chosen linear combinations of weighted functional estimators, and variance optimality within this class of asymptotically unbiased estimators is discussed. The finite sample performance of some specific examples from our class of estimators and some alternatives from the recent literature are evaluated with a small simulation experiment.     

A monte carlo comparison of the smoothing,scoring and em algorithms for dispersion matrix estimation with incomplete growth curve data

Incomplete growth curve data often result from missing or mistimed observations in a repeated measures design. Virtually all methods of analysis rely on the dispersion matrix estimates. A Monte Carlo simulation was used to compare three methods of estimation of dispersion matrices for incomplete growth curve data. The three methods were: 1) maximum likelihood estimation with a smoothing algorithm, which finds the closest positive semidefinite estimate of the pairwise estimated dispersion matrix; 2) a mixed effects model using the EM (estimation maximization) algorithm; and 3) a mixed effects model with the scoring algorithm. The simulation included 5 dispersion structures, 20 or 40 subjects with 4 or 8 observations per subject and 10 or 30% missing data. In all the simulations, the smoothing algorithm was the poorest estimator of the dispersion matrix. In most cases, there were no significant differences between the scoring and EM algorithms. The EM algorithm tended to be better than the scoring algorithm when the variances of the random effects were close to zero, especially for the simulations with 4 observations per subject and two random effects.     

Conditional design of the CUSUM median chart for the process position when process parameters are unknown

In practice, different practitioners will use different Phase I samples to estimate the process parameters, which will lead to different Phase II control chart's performance. Researches refer to this variability as between-practitioners-variability of control charts. Since between-practitioners-variability is important in the design of the CUSUM median chart with estimated process parameters, the standard deviation of average run length (SDARL) will be used to study its properties. It is shown that the CUSUM median chart requires a larger amount of Phase I samples to sufficiently reduce the variation in the in-control ARL of the CUSUM median chart. Considering the limitation of the amount of the Phase I samples, a bootstrap approach is also used here to adjust the control limits of the CUSUM median chart. Comparisons are made for the CUSUM and Shewhart median charts with estimated parameters when using the adjusted- and unadjusted control limits and some conclusions are made.