Restricted minimax robust designs for misspecified regression models

The authors propose and explore new regression designs. Within a particular parametric class, these designs are minimax robust against bias caused by model misspecification while attaining reasonable levels of efficiency as well. The introduction of this restricted class of designs is motivated by a desire to avoid the mathematical and numerical intractability found in the unrestricted minimax theory. Robustness is provided against a family of model departures sufficiently broad that the minimax design measures are necessarily absolutely continuous. Examples of implementation involve approximate polynomial and second order multiple regression.     

Designing and integrating composite networks for monitoring multivariate gaussian pollution fields

Networks of ambient monitoring stations are used to monitor environmental pollution fields such as those for acid rain and air pollution. Such stations provide regular measurements of pollutant concentrations. The networks are established for a variety of purposes at various times so often several stations measuring different subsets of pollutant concentrations can be found in compact geographical regions. The problem of statistically combining these disparate information sources into a single 'network' then arises. Capitalizing on the efficiencies so achieved can then lead to the secondary problem of extending this network. The subject of this paper is a set of 31 air pollution monitoring stations in southern Ontario. Each of these regularly measures a particular subset of ionic sulphate, sulphite, nitrite and ozone. However, this subset varies from station to station. For example only two stations measure all four. Some measure just one. We describe a Bayesian framework for integrating the measurements of these stations to yield a spatial predictive distribution for unmonitored sites and unmeasured concentrations at existing stations. Furthermore we show how this network can be extended by using an entropy maximization criterion. The methods assume that the multivariate response field being measured has a joint Gaussian distribution conditional on its mean and covariance function. A conjugate prior is used for these parameters, some of its hyperparameters being fitted empirically.     

Diagnostic checks for discrete data regression models using posterior predictive simulations

Model checking with discrete data regressions can be difficult because the usual methods such as residual plots have complicated reference distributions that depend on the parameters in the model. Posterior predictive checks have been proposed as a Bayesian way to average the results of goodness-of-fit tests in the presence of uncertainty in estimation of the parameters. We try this approach using a variety of discrepancy variables for generalized linear models fitted to a historical data set on behavioural learning. We then discuss the general applicability of our findings in the context of a recent applied example on which we have worked. We find that the following discrepancy variables work well, in the sense of being easy to interpret and sensitive to important model failures: structured displays of the entire data set, general discrepancy variables based on plots of binned or smoothed residuals versus predictors and specific discrepancy variables created on the basis of the particular concerns arising in an application. Plots of binned residuals are especially easy to use because their predictive distributions under the model are sufficiently simple that model checks can often be made implicitly. The following discrepancy variables did not work well: scatterplots of latent residuals defined from an underlying continuous model and quantile–quantile plots of these residuals.     

Adaptive Estimation of the Integral of Squared Regression Derivatives

A problem of estimating the integral of a squared regression function and of its squared derivatives has been addressed in a number of papers. For the case of a heteroscedastic model where smoothness of the underlying regression function, the design density, and the variance of errors are known, the asymptotically sharp minimax lower bound and a sharp estimator were found in Pastuchova & Khasminski (1989). However, there are apparently no results on the either rate optimal or sharp optimal adaptive, or data-driven, estimation when neither the degree of regression function smoothness nor design density, scale function and distribution of errors are known. After a brief review of main developments in non-parametric estimation of non-linear functionals, we suggest a simple adaptive estimator for the integral of a squared regression function and its derivatives and prove that it is sharp-optimal whenever the estimated derivative is sufficiently smooth.     

Maximum entropy sampling and optimal Bayesian experimental design

When Shannon entropy is used as a criterion in the optimal design of experiments, advantage can be taken of the classical identity representing the joint entropy of parameters and observations as the sum of the marginal entropy of the observations and the preposterior conditional entropy of the parameters. Following previous work in which this idea was used in spatial sampling, the method is applied to standard parameterized Bayesian optimal experimental design. Under suitable conditions, which include non-linear as well as linear regression models, it is shown in a few steps that maximizing the marginal entropy of the sample is equivalent to minimizing the preposterior entropy, the usual Bayesian criterion, thus avoiding the use of conditional distributions. It is shown using this marginal formulation that under normality assumptions every standard model which has a two-point prior distribution on the parameters gives an optimal design supported on a single point. Other results include a new asymptotic formula which applies as the error variance is large and bounds on support size.     

MUX級联网络的組合設計

利用MUX级联网络实现多变量逻辑函数时,为求得最简的级联系统,本文提出了利用剩余函数立方图求取变量划分的快速方法。该法无需借助卡诺图,也不需要进行复杂的运算。结果表明,该法行之有效而且十分方便。     

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to be stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase II and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail.     

Models for the analysis of C-reactive protein in statin trials

Elevation in C-reactive protein (CRP) is an independent risk factor for cardiovascular disease progression and levels are reduced by treatment with statins. However, on-treatment CRP, given baseline CRP and treatment, is not normally distributed and outliers exist even when transformations are applied. Although classical non-parametric tests address some of these issues, they do not enable straightforward inclusion of covariate information. The aims of this study were to produce a model that improved efficiency and accuracy of analysis of CRP data. Estimation of treatment effects and identification of outliers were addressed using controlled trials of rosuvastatin. The robust statistical technique of MM-estimation was used to fit models to data in the presence of outliers and was compared with least-squares estimation. To develop the model, appropriate transformations of the response and baseline variables were selected. The model was used to investigate how on-treatment CRP related to baseline CRP and estimated treatment effects with rosuvastatin. On comparing least-squares and MM-estimation, MM-estimation was superior to least-squares estimation in that parameter estimates were more efficient and outliers were clearly identified. Relative reductions in CRP were higher at higher baseline CRP levels. There was also evidence of a dose-response relationship between CRP reductions from baseline and rosuvastatin. Several large outliers were identified, although there did not appear to be any relationships between the incidence of outliers and treatments. In conclusion, using robust estimation to model CRP data is superior to least-squares estimation and non-parametric tests in terms of efficiency, outlier identification and the ability to include covariate information.     

Missing item imputation for quality-of-life instruments with application to asthma quality-of-life questionnaires

There has been increasing use of quality-of-life (QoL) instruments in drug development. Missing item values often occur in QoL data. A common approach to solve this problem is to impute the missing values before scoring. Several imputation procedures, such as imputing with the most correlated item and imputing with a row/column model or an item response model, have been proposed. We examine these procedures using data from two clinical trials, in which the original asthma quality-of-life questionnaire (AQLQ) and the miniAQLQ were used. We propose two modifications to existing procedures: truncating the imputed values to eliminate outliers and using the proportional odds model as the item response model for imputation. We also propose a novel imputation method based on a semi-parametric beta regression so that the imputed value is always in the correct range and illustrate how this approach can easily be implemented in commonly used statistical software. To compare these approaches, we deleted 5% of item values in the data according to three different missingness mechanisms, imputed them using these approaches and compared the imputed values with the true values. Our comparison showed that the row/column-model-based imputation with truncation generally performed better, whereas our new approach had better performance under a number scenarios.