On pseudo-values for regression analysis in competing risks models

For regression on state and transition probabilities in multi-state models Andersen et al. (Biometrika 90:15–27, 2003) propose a technique based on jackknife pseudo-values. In this article we analyze the pseudo-values suggested for competing risks models and prove some conjectures regarding their asymptotics (Klein and Andersen, Biometrics 61:223–229, 2005). The key is a second order von Mises expansion of the Aalen-Johansen estimator which yields an appropriate representation of the pseudo-values. The method is illustrated with data from a clinical study on total joint replacement. In the application we consider for comparison the estimates obtained with the Fine and Gray approach (J Am Stat Assoc 94:496–509, 1999) and also time-dependent solutions of pseudo-value regression equations.     

THE USE OF AGGREGATE DATA TO ESTIMATE GOMPERTZ‐TYPE OLD‐AGE MORTALITY IN HETEROGENEOUS POPULATIONS

We consider two related aspects of the study of old‐age mortality. One is the estimation of a parameterized hazard function from grouped data, and the other is its possible deceleration at extreme old age owing to heterogeneity described by a mixture of distinct sub‐populations. The first is treated by half of a logistic transform, which is known to be free of discretization bias at older ages, and also preserves the increasing slope of the log hazard in the Gompertz case. It is assumed that data are available in the form published by official statistical agencies, that is, as aggregated frequencies in discrete time. Local polynomial modelling and weighted least squares are applied to cause‐of‐death mortality counts. The second, related, problem is to discover what conditions are necessary for population mortality to exhibit deceleration for a mixture of Gompertz sub‐populations. The general problem remains open but, in the case of three groups, we demonstrate that heterogeneity may be such that it is possible for a population to show decelerating mortality and then return to a Gompertz‐like increase at a later age. This implies that there are situations, depending on the extent of heterogeneity, in which there is at least one age interval in which the hazard function decreases before increasing again.     

VARIATIONAL BAYESIAN ANALYSIS FOR HIDDEN MARKOV MODELS

The variational approach to Bayesian inference enables simultaneous estimation of model parameters and model complexity. An interesting feature of this approach is that it also leads to an automatic choice of model complexity. Empirical results from the analysis of hidden Markov models with Gaussian observation densities illustrate this. If the variational algorithm is initialized with a large number of hidden states, redundant states are eliminated as the method converges to a solution, thereby leading to a selection of the number of hidden states. In addition, through the use of a variational approximation, the deviance information criterion for Bayesian model selection can be extended to the hidden Markov model framework. Calculation of the deviance information criterion provides a further tool for model selection, which can be used in conjunction with the variational approach.     

Shrinkage inverse regression estimation for model-free variable selection

Summary.  The family of inverse regression estimators that was recently proposed by Cook and Ni has proven effective in dimension reduction by transforming the high dimensional predictor vector to its low dimensional projections. We propose a general shrinkage estimation strategy for the entire inverse regression estimation family that is capable of simultaneous dimension reduction and variable selection. We demonstrate that the new estimators achieve consistency in variable selection without requiring any traditional model, meanwhile retaining the root n estimation consistency of the dimension reduction basis. We also show the effectiveness of the new estimators through both simulation and real data analysis.     

A likelihood based estimator for vector autoregressive processes

A onestep estimator, which is an approximation to the unconditional maximum likelihood estimator (MLE) of the coefficient matrices of a Gaussian vector autoregressive process is presented. The onestep estimator is easy to compute and can be computed using standard software. Unlike the computation of the unconditional MLE, the computation of the onestep estimator does not require any iterative optimization and the computation is numerically stable. In finite samples the onestep estimator generally has smaller mean square error than the ordinary least squares estimator. In a simple model, where the unconditional MLE can be computed, numerical investigation shows that the onestep estimator is slightly worse than the unconditional MLE in terms of mean square error but superior to the ordinary least squares estimator. The limiting distribution of the onestep estimator for processes with some unit roots is derived.     

On the Assessment of Monte Carlo Error in Simulation-Based Statistical Analyses

Statistical experiments, more commonly referred to as Monte Carlo or simulation studies, are used to study the behavior of statistical methods and measures under controlled situations. Whereas recent computing and methodological advances have permitted increased efficiency in the simulation process, known as variance reduction, such experiments remain limited by their finite nature and hence are subject to uncertainty; when a simulation is run more than once, different results are obtained. However, virtually no emphasis has been placed on reporting the uncertainty, referred to here as Monte Carlo error, associated with simulation results in the published literature, or on justifying the number of replications used. These deserve broader consideration. Here we present a series of simple and practical methods for estimating Monte Carlo error as well as determining the number of replications required to achieve a desired level of accuracy. The issues and methods are demonstrated with two simple examples, one evaluating operating characteristics of the maximum likelihood estimator for the parameters in logistic regression and the other in the context of using the bootstrap to obtain 95% confidence intervals. The results suggest that in many settings, Monte Carlo error may be more substantial than traditionally thought.     

Parametric non-mixture cure models for schedule finding of therapeutic agents

We propose a phase I clinical trial design that seeks to determine the cumulative safety of a series of administrations of a fixed dose of an investigational agent. In contrast with traditional phase I trials that are designed solely to find the maximum tolerated dose of the agent, our design instead identifies a maximum tolerated schedule that includes a maximum tolerated dose as well as a vector of recommended administration times. Our model is based on a non-mixture cure model that constrains the probability of dose limiting toxicity for all patients to increase monotonically with both dose and the number of administrations received. We assume a specific parametric hazard function for each administration and compute the total hazard of dose limiting toxicity for a schedule as a sum of individual administration hazards. Throughout a variety of settings motivated by an actual study in allogeneic bone marrow transplant recipients, we demonstrate that our approach has excellent operating characteristics and performs as well as the only other currently published design for schedule finding studies. We also present arguments for the preference of our non-mixture cure model over the existing model.     

Reports of Conferences,Institutes, and Seminars

This installment of "Serials Spoken Here" covers events that transpired between late September and late October 2008. Reported herein are two Webinars, one on ONIX for Serials, the other on SUSHI, and two conferences: the eighty-fourth annual Meeting of the Potomac Technical Processing Librarians and the New England Library Association's Annual Conference.     

Hypotheses testing: Poisson versus stress-release

We consider the problem of hypotheses testing with the basic simple hypothesis: observed sequence of points corresponds to stationary Poisson process with known intensity against a composite one-sided parametric alternative that this is a stress-release point process. The underlying family of measures is locally asymptotically quadratic and we describe the behavior of score-function, likelihood ratio and Wald tests in the asymptotics of large samples. The results of numerical simulations are presented.     

Order statistics from trivariate normal and -distributions in terms of generalized skew-normal and skew- distributions

We consider here a generalization of the skew-normal distribution, GSN(λ₁,λ₂,ρ), defined through a standard bivariate normal distribution with correlation ρ, which is a special case of the unified multivariate skew-normal distribution studied recently by Arellano-Valle and Azzalini [2006. On the unification of families of skew-normal distributions. Scand. J. Statist. 33, 561–574]. We then present some simple and useful properties of this distribution and also derive its moment generating function in an explicit form. Next, we show that distributions of order statistics from the trivariate normal distribution are mixtures of these generalized skew-normal distributions; thence, using the established properties of the generalized skew-normal distribution, we derive the moment generating functions of order statistics, and also present expressions for means and variances of these order statistics.Next, we introduce a generalized skew-t_ν distribution, which is a special case of the unified multivariate skew-elliptical distribution presented by Arellano-Valle and Azzalini [2006. On the unification of families of skew-normal distributions. Scand. J. Statist. 33, 561–574] and is in fact a three-parameter generalization of Azzalini and Capitanio's [2003. Distributions generated by perturbation of symmetry with emphasis on a multivariate skew t distribution. J. Roy. Statist. Soc. Ser. B 65, 367–389] univariate skew-t_ν form. We then use the relationship between the generalized skew-normal and skew-t_ν distributions to discuss some properties of generalized skew-t_ν as well as distributions of order statistics from bivariate and trivariate t_ν distributions. We show that these distributions of order statistics are indeed mixtures of generalized skew-t_ν distributions, and then use this property to derive explicit expressions for means and variances of these order statistics.