Robust testing with generalized partial linear models for longitudinal data

By approximating the nonparametric component using a regression spline in generalized partial linear models (GPLM), robust generalized estimating equations (GEE), involving bounded score function and leverage-based weighting function, can be used to estimate the regression parameters in GPLM robustly for longitudinal data or clustered data. In this paper, score test statistics are proposed for testing the regression parameters with robustness, and their asymptotic distributions under the null hypothesis and a class of local alternative hypotheses are studied. The proposed score tests reply on the estimation of a smaller model without the testing parameters involved, and perform well in the simulation studies and real data analysis conducted in this paper.     

A modified random-effect procedure for combining risk difference in sets of 2×2 tables from clinical trials

Summary Meta-analyses of sets of clinical trials often combine risk differences from several 2×2 tables according to a random-effects model. The DerSimonian-Laird random-effects procedure, widely used for estimating the populaton mean risk difference, weights the risk difference from each primary study inversely proportional to an estimate of its variance (the sum of the between-study variance and the conditional within-study variance). Because those weights are not independent of the risk differences, however, the procedure sometimes exhibits bias and unnatural behavior. The present paper proposes a modified weighting scheme that uses the unconditional within-study variance to avoid this source of bias. The modified procedure has variance closer to that available from weighting by ideal weights when such weights are known. We studied the modified procedure in extensive simulation experiments using situations whose parameters resemble those of actual studies in medical research. For comparison we also included two unbiased procedures, the unweighted mean and a sample-size-weighted mean; their relative variability depends on the extent of heterogeneity among the primary studies. An example illustrates the application of the procedures to actual data and the differences among the results. This research was supported by Grant HS 05936 from the Agency for Health Care Policy and Research to Harvard University.     

LENGTH-BIASING, CHARACTERIZATIONS OF LAWS AND THE MOMENT PROBLEM

A positive random variable X with a finite mean has an induced length-biased law represented by Y, and Y is stochastically larger than X. An independent uniform random contraction of Y, UY, has the same law as X if and only if the latter is exponential. This property is extended to non-uniform contractions and a more general notion of length-biasing. The distributional equality of X and W leads to a functional equation for the moment function of X, which has either Infinitely many solutions or none. When U is constant, X can have a log-normal law, but it can also have laws with the same moment sequence as this log-nod law. The case where U has a certain beta, or generalized beta, law give t3 characterizations of generalized gamma laws, or to products of independent copies of them. This occurs even when these laws are not determined by their moment sequences.     

Bayesian updating of atmospheric dispersion after a nuclear accident

Summary.  We consider a Bayesian forecasting system to predict the dispersal of contamination on a large scale grid in the event of an accidental release of radioactivity. The statistical model is built on a physical model for atmospheric dispersion and transport called MATCH. Our spatiotemporal model is a dynamic linear model where the state parameters are the (essentially, deterministic) predictions of MATCH; the distributions of these are updated sequentially in the light of monitoring data. One of the distinguishing features of the model is that the number of these parameters is very large (typically several hundreds of thousands) and we discuss practical issues arising in its implementation as a realtime model. Our procedures have been checked against a variational approach which is used widely in the atmospheric sciences. The results of the model are applied to test data from a tracer experiment.     

Residual analysis for spatial point processes (with discussion)

Summary.  We define residuals for point process models fitted to spatial point pattern data, and we propose diagnostic plots based on them. The residuals apply to any point process model that has a conditional intensity; the model may exhibit spatial heterogeneity, interpoint interaction and dependence on spatial covariates. Some existing ad hoc methods for model checking (quadrat counts, scan statistic, kernel smoothed intensity and Berman's diagnostic) are recovered as special cases. Diagnostic tools are developed systematically, by using an analogy between our spatial residuals and the usual residuals for (non-spatial) generalized linear models. The conditional intensity λ plays the role of the mean response. This makes it possible to adapt existing knowledge about model validation for generalized linear models to the spatial point process context, giving recommendations for diagnostic plots. A plot of smoothed residuals against spatial location, or against a spatial covariate, is effective in diagnosing spatial trend or co-variate effects. Q – Q -plots of the residuals are effective in diagnosing interpoint interaction.     

ON THE INDEPENDENCE OF THE SAMPLE MEAN AND TRANSLATION-INVARIANT STATISTICS FOR MATRIX NORMAL DISTRIBUTIONS

We present an explicit characterization of the joint dependency structure of an n×p matrix normal random matrix such that the p-dimensional sample mean vector is independent of all translation invariant statistics.     

A partial score test for difference among heterogeneous populations

In event time data analysis, comparisons between distributions are made by the logrank test. When the data appear to contain crossing hazards phenomena, nonparametric weighted logrank statistics are usually suggested to accommodate different-weighted functions to increase the power. However, the gain in power by imposing different weights has its limits since differences before and after the crossing point may balance each other out. In contrast to the weighted logrank tests, we propose a score-type statistic based on the semiparametric-, heteroscedastic-hazards regression model of Hsieh [2001. On heteroscedastic hazards regression models: theory and application. J. Roy. Statist. Soc. Ser. B 63, 63–79.], by which the nonproportionality is explicitly modeled. Our score test is based on estimating functions derived from partial likelihood under the heteroscedastic model considered herein. Simulation results show the benefit of modeling the heteroscedasticity and power of the proposed test to two classes of weighted logrank tests (including Fleming–Harrington's test and Moreau's locally most powerful test), a Renyi-type test, and the Breslow's test for acceleration. We also demonstrate the application of this test by analyzing actual data in clinical trials.     

Bootstrap Estimation of Benchmark Doses and Confidence Limits with Clustered Quantal Data

The benchmark dose (BMD) is an exposure level that would induce a small risk increase (BMR level) above the background. The BMD approach to deriving a reference dose for risk assessment of noncancer effects is advantageous in that the estimate of BMD is not restricted to experimental doses and utilizes most available dose-response information. To quantify statistical uncertainty of a BMD estimate, we often calculate and report its lower confidence limit (i.e., BMDL), and may even consider it as a more conservative alternative to BMD itself. Computation of BMDL may involve normal confidence limits to BMD in conjunction with the delta method. Therefore, factors, such as small sample size and nonlinearity in model parameters, can affect the performance of the delta method BMDL, and alternative methods are useful. In this article, we propose a bootstrap method to estimate BMDL utilizing a scheme that consists of a resampling of residuals after model fitting and a one-step formula for parameter estimation. We illustrate the method with clustered binary data from developmental toxicity experiments. Our analysis shows that with moderately elevated dose-response data, the distribution of BMD estimator tends to be left-skewed and bootstrap BMDL s are smaller than the delta method BMDL s on average, hence quantifying risk more conservatively. Statistically, the bootstrap BMDL quantifies the uncertainty of the true BMD more honestly than the delta method BMDL as its coverage probability is closer to the nominal level than that of delta method BMDL. We find that BMD and BMDL estimates are generally insensitive to model choices provided that the models fit the data comparably well near the region of BMD. Our analysis also suggests that, in the presence of a significant and moderately strong dose-response relationship, the developmental toxicity experiments under the standard protocol support dose-response assessment at 5% BMR for BMD and 95% confidence level for BMDL.     

A Numerical Solution to the Nonhomogeneous Two-Stage MVK Model of Cancer

In this article, we describe a straightforward method for solving the probability of at least one malignant cell by time t, and the associated hazard function, in the general (i.e., nonhomogeneous) two-stage Moolgavkar-Venzon-Knudson (MVK) model of cancer. The method consists of solving four coupled ordinary differential equations derived from the Kolmogorov backward equations for this process. The relationship of this method to previously proposed solutions is discussed.     

Semiparametric linear transformation models for current status data

Current status data arise when the death of every subject in a study cannot be determined precisely, but is known only to have occurred before or after a random monitoring time. The authors discuss the analysis of such data under semiparametric linear transformation models for which they propose a general inference procedure based on estimating functions. They determine the properties of the estimates they propose for the regression parameters of the model and illustrate their technique using tumorigenicity data.