The residual effect of a growth-decay mechanism and the distributions of covariance structures

The product of two independent or dependent scalar normal variables, sums of products, sample covariances, and general bilinear forms are considered. Their distributions are shown to belong to a class called generalized Laplacian. A growth-decay mechanism is also shown to produce such a generalized Laplacian. Sets of necessary and sufficient conditions are derived for bilinear forms to belong to this class. As a generalization, the distributions of rectangular matrices associated with multivariate normal random vectors are also discussed.     

Nonparametric smoothing in the analysis of air pollution and respiratory illness

While most of epidemiology is observational, rather than experimental, the culture of epidemiology is still derived from agricultural experiments, rather than other observational fields, such as astronomy or economics. The mismatch is made greater as focus has turned to continue risk factors, multifactorial outcomes, and outcomes with large variation unexplainable by available risk factors. The analysis of such data is often viewed as hypothesis testing with statistical control replacing randomization. However, such approaches often test restricted forms of the hypothesis being investigated, such as the hypothesis of a linear association, when there is no prior empirical or theoretical reason to believe that if an association exists, it is linear. In combination with the large nonstochastic sources of error in such observational studies, this suggests the more flexible alternative of exploring the association. Conclusions on the possible causal nature of any discovered association will rest on the coherence and consistency of multiple studies. Nonparametric smoothing in general, and generalized additive models in particular, represent an attractive approach to such problems. This is illustrated using data examining the relationship between particulate air pollution and daily mortality in Birmingham, Alabama; between particulate air pollution, ozone, and SO₂ and daily hospital admissions for respiratory illness in Philadelphia; and between ozone and particulate air pollution and coughing episodes in children in six eastern U.S. cities. The results indicate that airborne particles and ozone are associated with adverse health outcomes at very low concentrations, and that there are likely no thresholds for these relationships.     

On random variate generation for the generalized hyperbolic secant distributions

We give random variate generators for the generalized hyperbolic secant distribution and related families such as Morris's skewed generalized hyperbolic secant family and a family introduced by Laha and Lukacs. The rejection method generators are uniformly fast over the parameter space and are based upon a complex function representation of the distributions due to Harkness and HarknessThe author's research was sponsored by NSERC Grant A3456 and FCAR Grant 90-ER-0291.     

Limit theorems for a general weighted process under random censoring

Necessary and sufficient conditions for weak and strong convergence are derived for the weighted version of a general process under random censoring. To be more explicit, this means that for this process complete analogues are obtained of the Chibisov-O'Reilly theorem, the Lai-Wellner Glivenko-Cantelli theorem, and the James law of the iterated logarithm for the empirical process. The process contains as special cases the so-called basic martingale, the empirical cumulative hazard process, and the product-limit process. As a tool we derive a Kiefer-process-type approximation of our process, which may be of independent interest.     

The generalized exponential cure rate model with covariates

In this article, we consider a parametric survival model that is appropriate when the population of interest contains long-term survivors or immunes. The model referred to as the cure rate model was introduced by Boag 1 Boag, J. W. 1949. Maximum likelihood estimates of the proportion of patients cured by cancer therapy. J. R. Stat. Soc. Ser. B, 11: 15–53.  [Google Scholar] in terms of a mixture model that included a component representing the proportion of immunes and a distribution representing the life times of the susceptible population. We propose a cure rate model based on the generalized exponential distribution that incorporates the effects of risk factors or covariates on the probability of an individual being a long-time survivor. Maximum likelihood estimators of the model parameters are obtained using the the expectation-maximisation (EM) algorithm. A graphical method is also provided for assessing the goodness-of-fit of the model. We present an example to illustrate the fit of this model to data that examines the effects of different risk factors on relapse time for drug addicts.     

A spatial Bayesian semiparametric mixture model for positive definite matrices with applications in diffusion tensor imaging

Studies on diffusion tensor imaging (DTI) quantify the diffusion of water molecules in a brain voxel using an estimated 3 × 3 symmetric positive definite (p.d.) diffusion tensor matrix. Due to the challenges associated with modelling matrix‐variate responses, the voxel‐level DTI data are usually summarized by univariate quantities, such as fractional anisotropy. This approach leads to evident loss of information. Furthermore, DTI analyses often ignore the spatial association among neighbouring voxels, leading to imprecise estimates. Although the spatial modelling literature is rich, modelling spatially dependent p.d. matrices is challenging. To mitigate these issues, we propose a matrix‐variate Bayesian semiparametric mixture model, where the p.d. matrices are distributed as a mixture of inverse Wishart distributions, with the spatial dependence captured by a Markov model for the mixture component labels. Related Bayesian computing is facilitated by conjugacy results and use of the double Metropolis–Hastings algorithm. Our simulation study shows that the proposed method is more powerful than competing non‐spatial methods. We also apply our method to investigate the effect of cocaine use on brain microstructure. By extending spatial statistics to matrix‐variate data, we contribute to providing a novel and computationally tractable inferential tool for DTI analysis.     

A pragmatic adaptive enrichment design for selecting the right target population for cancer immunotherapies

One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more prespecified biomarker subpopulations at an interim analysis have been proposed in this setting but practical case studies of AEDs are still relatively rare. We present the design of an AED with a binary endpoint in the highly dynamic setting of cancer immunotherapy. The trial was initiated as a conventional trial in early triple-negative breast cancer but amended to an AED based on emerging data external to the trial suggesting that PD-L1 status could be a predictive biomarker. Operating characteristics are discussed including the concept of a minimal detectable difference, that is, the smallest observed treatment effect that would lead to a statistically significant result in at least one of the target populations at the interim or the final analysis, respectively, in the setting of AED.     

Irregular Identification,Support Conditions,and Inverse Weight Estimation

In weighted moment condition models, we show a subtle link between identification and estimability that limits the practical usefulness of estimators based on these models. In particular, if it is necessary for (point) identification that the weights take arbitrarily large values, then the parameter of interest, though point identified, cannot be estimated at the regular (parametric) rate and is said to be irregularly identified. This rate depends on relative tail conditions and can be as slow in some examples as n^−1/4. This nonstandard rate of convergence can lead to numerical instability and/or large standard errors. We examine two weighted model examples: (i) the binary response model under mean restriction introduced by Lewbel (1997) and further generalized to cover endogeneity and selection, where the estimator in this class of models is weighted by the density of a special regressor, and (ii) the treatment effect model under exogenous selection (Rosenbaum and Rubin (1983)), where the resulting estimator of the average treatment effect is one that is weighted by a variant of the propensity score. Without strong relative support conditions, these models, similar to well known “identified at infinity” models, lead to estimators that converge at slower than parametric rate, since essentially, to ensure point identification, one requires some variables to take values on sets with arbitrarily small probabilities, or thin sets. For the two models above, we derive some rates of convergence and propose that one conducts inference using rate adaptive procedures that are analogous to Andrews and Schafgans (1998) for the sample selection model.     

Discriminating between generalized exponential,geometric extreme exponential and Weibull distributions

Generalized exponential, geometric extreme exponential and Weibull distributions are three non-negative skewed distributions that are suitable for analysing lifetime data. We present diagnostic tools based on the likelihood ratio test (LRT) and the minimum Kolmogorov distance (KD) method to discriminate between these models. Probability of correct selection has been calculated for each model and for several combinations of shape parameters and sample sizes using Monte Carlo simulation. Application of LRT and KD discrimination methods to some real data sets has also been studied.     

Confidence interval estimation for negative binomial group distribution

Negative binomial group distribution was proposed in the literature which was motivated by inverse sampling when considering group inspection: products are inspected group by group, and the number of non-conforming items of a group is recorded only until the inspection of the whole group is finished. The non-conforming probability p of the population is thus the parameter of interest. In this paper, the confidence interval construction for this parameter is investigated. The common normal approximation and exact method are applied. To overcome the drawbacks of these commonly used methods, a composite method that is based on the confidence intervals of the negative binomial distribution is proposed, which benefits from the relationship between negative binomial distribution and negative binomial group distribution. Simulation studies are carried out to examine the performances of our methods. A real data example is also presented to illustrate the application of our method.