The use of restricted cubic splines to approximate complex hazard functions in the analysis of time-to-event data: a simulation study

If interest lies in reporting absolute measures of risk from time-to-event data then obtaining an appropriate approximation to the shape of the underlying hazard function is vital. It has previously been shown that restricted cubic splines can be used to approximate complex hazard functions in the context of time-to-event data. The degree of complexity for the spline functions is dictated by the number of knots that are defined. We highlight through the use of a motivating example that complex hazard function shapes are often required when analysing time-to-event data. Through the use of simulation, we show that provided a sufficient number of knots are used, the approximated hazard functions given by restricted cubic splines fit closely to the true function for a range of complex hazard shapes. The simulation results also highlight the insensitivity of the estimated relative effects (hazard ratios) to the correct specification of the baseline hazard.     

The Analysis of Designed Experiments and Longitudinal Data by Using Smoothing Splines

In designed experiments and in particular longitudinal studies, the aim may be to assess the effect of a quantitative variable such as time on treatment effects. Modelling treatment effects can be complex in the presence of other sources of variation. Three examples are presented to illustrate an approach to analysis in such cases. The first example is a longitudinal experiment on the growth of cows under a factorial treatment structure where serial correlation and variance heterogeneity complicate the analysis. The second example involves the calibration of optical density and the concentration of a protein DNase in the presence of sampling variation and variance heterogeneity. The final example is a multienvironment agricultural field experiment in which a yield–seeding rate relationship is required for several varieties of lupins. Spatial variation within environments, heterogeneity between environments and variation between varieties all need to be incorporated in the analysis. In this paper, the cubic smoothing spline is used in conjunction with fixed and random effects, random coefficients and variance modelling to provide simultaneous modelling of trends and covariance structure. The key result that allows coherent and flexible empirical model building in complex situations is the linear mixed model representation of the cubic smoothing spline. An extension is proposed in which trend is partitioned into smooth and non-smooth components. Estimation and inference, the analysis of the three examples and a discussion of extensions and unresolved issues are also presented.     

Computation aspects of the parameter estimates of linear mixed effects model in multivariate repeated measures set-up

The number of parameters mushrooms in a linear mixed effects (LME) model in the case of multivariate repeated measures data. Computation of these parameters is a real problem with the increase in the number of response variables or with the increase in the number of time points. The problem becomes more intricate and involved with the addition of additional random effects. A multivariate analysis is not possible in a small sample setting. We propose a method to estimate these many parameters in bits and pieces from baby models, by taking a subset of response variables at a time, and finally using these bits and pieces at the end to get the parameter estimates for the mother model, with all variables taken together. Applying this method one can calculate the fixed effects, the best linear unbiased predictions (BLUPs) for the random effects in the model, and also the BLUPs at each time of observation for each response variable, to monitor the effectiveness of the treatment for each subject. The proposed method is illustrated with an example of multiple response variables measured over multiple time points arising from a clinical trial in osteoporosis.     

Testing Treatment-Covariate Interaction in a Nonparametric Analysis of Covariance Model

We consider a recently introduced nonparametric model for Analysis of Covariance and derive an asymptotic test for interaction between covariate and treatment. Furthermore, we suggest data depth techniques to obtain joint confidence regions for the covariate effects in this model.

The finite sample behavior of the asymptotic method is evaluated in simulations. Application of the procedures is illustrated using an epileptic seizures and chemotherapy data set.     

The impact of dichotomization in longitudinal data analysis: a simulation study

In this paper, a simulation study is conducted to systematically investigate the impact of dichotomizing longitudinal continuous outcome variables under various types of missing data mechanisms. Generalized linear models (GLM) with standard generalized estimating equations (GEE) are widely used for longitudinal outcome analysis, but these semi‐parametric approaches are only valid under missing data completely at random (MCAR). Alternatively, weighted GEE (WGEE) and multiple imputation GEE (MI‐GEE) were developed to ensure validity under missing at random (MAR). Using a simulation study, the performance of standard GEE, WGEE and MI‐GEE on incomplete longitudinal dichotomized outcome analysis is evaluated. For comparisons, likelihood‐based linear mixed effects models (LMM) are used for incomplete longitudinal original continuous outcome analysis. Focusing on dichotomized outcome analysis, MI‐GEE with original continuous missing data imputation procedure provides well controlled test sizes and more stable power estimates compared with any other GEE‐based approaches. It is also shown that dichotomizing longitudinal continuous outcome will result in substantial loss of power compared with LMM. Copyright © 2009 John Wiley & Sons, Ltd.     

General linear estimators under the prediction error sum of squares criterion in a linear regression model

In this paper, the notion of the general linear estimator and its modified version are introduced using the singular value decomposition theorem in the linear regression model y=X β+e to improve some classical linear estimators. The optimal selections of the biasing parameters involved are theoretically given under the prediction error sum of squares criterion. A numerical example and a simulation study are finally conducted to illustrate the superiority of the proposed estimators.     

Theoretical evaluation of prediction error in linear regression with a bivariate response variable containing missing data

Methods for linear regression with multivariate response variables are well described in statistical literature. In this study we conduct a theoretical evaluation of the expected squared prediction error in bivariate linear regression where one of the response variables contains missing data. We make the assumption of known covariance structure for the error terms. On this basis, we evaluate three well-known estimators: standard ordinary least squares, generalized least squares, and a James–Stein inspired estimator. Theoretical risk functions are worked out for all three estimators to evaluate under which circumstances it is advantageous to take the error covariance structure into account.     

制造业效率区域差异及其影响因素分析——基于中国省级面板数据的研究

制造业的发展关系到第二产业乃至整个国民经济的发展,制造业的增长是中国工业经济增长的主导力量。本文运用数据包络分析法,测度了制造业各行业及中国各省制造业效率情况,然后利用中国省级制造业效率指标以及专利申请、地区经济发展水平等制造业效率影响因素的外延数据构成面板数据（Panel Data）建立模型。通过实证分析得出：地区经济的发展有利于制造业效率的提升。专利申请与制造业效率呈负相关。     

Optimal Prediction in Stochastic Regression Models with Application to the Analysis of Repeated Surveys

Several results relating to the optimal prediction of regression coefficients and random variables under a general linear model with stochastic coefficients are presented. These results are then applied to the analysis of repeated sample surveys over time. In particular, if the finite population can be modelled by a superpopulation model, a fully efficient method for the analysis of repeated surveys is proposed.     

Sampling a finite population in the presence of trend and correlation: Estimation of total 305-day lactation production in cattle

This paper studies the estimation of a finite population total in the presence of trend. A practical problem of dairy science is to estimate a cow's total 305-day milk production given a number of test-day records. We analyze this problem as one of estimating the total of a discrete population when the population values are correlated and exhibit a trend over time. Linear prediction estimators that are BLUE for known covariance and trend function linear in unknown parameters were applied to the estimation of the milk yield total. An empirical study compares BLUE with the expansion estimator and the procedure currently used by the Canadian Record of Performance for Dairy Cattle.     

Permutation Methods for Comparing the Accuracy of Nested Prediction Models in Survival Analysis

When making patient-specific prediction, it is important to compare prediction models to evaluate the gain in prediction accuracy for including additional covariates. We propose two statistical testing methods, the complete data permutation (CDP) and the permutation cross-validation (PCV) for comparing prediction models. We simulate clinical trial settings extensively and show that both methods are robust and achieve almost correct test sizes; the methods have comparable power in moderate to large sample situations, while the CDP is more efficient in computation. The methods are also applied to ovarian cancer clinical trial data.     

On the effect of the number of quadrature points in a logistic random effects model: an example

Although generalized linear mixed models are recognized to be of major practical importance, it is also known that they can be computationally demanding. The problem is the evaluation of the integral in calculating the marginalized likelihood. The straightforward method is based on the Gauss–Hermite technique, based on Gaussian quadrature points. Another approach is provided by the class of penalized quasi-likelihood methods. It is commonly believed that the Gauss–Hermite method works relatively well in simple situations but fails in more complicated structures. However, we present here a strikingly simple example of a logistic random-intercepts model in the context of a longitudinal clinical trial where the method gives valid results only for a high number of quadrature points ( Q ). As a consequence, this result warns the practitioner to examine routinely the dependence of the results on Q . The adaptive Gaussian quadrature, as implemented in the new SAS procedure NLMIXED, offered the solution to our problem. However, even the adaptive version of Gaussian quadrature needs careful handling to ensure convergence.     

Analysis of functional status transitions by using a semi-Markov process model in the presence of left-censored spells

Summary.  To analyse functional status transitions in the older population better, we fit a semi-Markov process model to data from the 1992–2002 Medicare Current Beneficiary Survey. We used an analogue of the stochastic EM algorithm to address the problem of left censoring of spells in longitudinal data. The iterative algorithm converged robustly under various initial values for the unobserved elapsed durations of spells in progress at base-line. Results on life expectancy and recovery from functional limitations based on the semi-Markov process model differ from those based on the traditional multistate life-table method. The proposed treatment of left-censored spells has the potential to expand the modelling capability that is available to researchers in fields where left censoring is a concern.