Bayes shrinkage estimator for consistency assessment of treatment effects in multi-regional clinical trials

The primary objective of a multi-regional clinical trial is to investigate the overall efficacy of the drug across regions and evaluate the possibility of applying the overall trial result to some specific region. A challenge arises when there is not enough regional sample size. We focus on the problem of evaluating applicability of a drug to a specific region of interest under the criterion of preserving a certain proportion of the overall treatment effect in the region. We propose a variant of James-Stein shrinkage estimator in the empirical Bayes context for the region-specific treatment effect. The estimator has the features of accommodating the between-region variation and finiteness correction of bias. We also propose a truncated version of the proposed shrinkage estimator to further protect risk in the presence of extreme value of regional treatment effect. Based on the proposed estimator, we provide the consistency assessment criterion and sample size calculation for the region of interest. Simulations are conducted to demonstrate the performance of the proposed estimators in comparison with some existing methods. A hypothetical example is presented to illustrate the application of the proposed method.     

Bias correction for parameter estimates of spatial point process models

When a spatial point process model is fitted to spatial point pattern data using standard software, the parameter estimates are typically biased. Contrary to folklore, the bias does not reflect weaknesses of the underlying mathematical methods, but is mainly due to the effects of discretization of the spatial domain. We investigate two approaches to correcting the bias: a Newton–Raphson-type correction and Richardson extrapolation. In simulation experiments, Richardson extrapolation performs best.     

Percentage points of the statistics for testing hypotheses on mean vectors of multivariate normal distributions with missing observations

A problem of testing of hypotheses on the mean vector of a multivariate normal distribution with unknown and positive definite covariance matrix is considered when a sample with a special, though not unusual, pattern of missing observations from that population is available. The approximate percentage points of the test statistic are obtained and their accuracy has been checked by comparing them with some exact percentage points which are calculated for complete samples and some special incomplete samples. The approximate percentage points are in good agreement with exact percentage points. The above work is extended to the problem of testing the hypothesis of equality of two mean vectors of two multivariate normal distributions with the same, unknown covariance matrix     

On an asymptotic relative efficiency concept based on expected volumes of confidence regions

ABSTRACT

The paper deals with an asymptotic relative efficiency concept for confidence regions of multidimensional parameters that is based on the expected volumes of the confidence regions. Under standard conditions the asymptotic relative efficiencies of confidence regions are seen to be certain powers of the ratio of the limits of the expected volumes. These limits are explicitly derived for confidence regions associated with certain plugin estimators, likelihood ratio tests and Wald tests. Under regularity conditions, the asymptotic relative efficiency of each of these procedures with respect to each one of its competitors is equal to 1. The results are applied to multivariate normal distributions and multinomial distributions in a fairly general setting.     

Modified likelihood ratio tests in heteroskedastic multivariate regression models with measurement error

In this paper, we develop modified versions of the likelihood ratio test for multivariate heteroskedastic errors-in-variables regression models. The error terms are allowed to follow a multivariate distribution in the elliptical class of distributions, which has the normal distribution as a special case. We derive the Skovgaard-adjusted likelihood ratio statistics, which follow a chi-squared distribution with a high degree of accuracy. We conduct a simulation study and show that the proposed tests display superior finite sample behaviour as compared to the standard likelihood ratio test. We illustrate the usefulness of our results in applied settings using a data set from the WHO MONICA Project on cardiovascular disease.     

A pool-adjacent-violators-algorithm approach to detect infinite parameter estimates in one-regressor dose–response models with asymptotes

Binary response models are often applied in dose–response settings where the number of dose levels is limited. Commonly, one can find cases where the maximum likelihood estimation process for these models produces infinite values for at least one of the parameters, often corresponding to the ‘separated data’ issue. Algorithms for detecting such data have been proposed, but are usually incorporated directly into in the parameter estimation. Additionally, they do not consider the use of asymptotes in the model formulation. In order to study this phenomenon in greater detail, we define the class of specifiably degenerate functions where this can occur (including the popular logistic and Weibull models) that allows for asymptotes in the dose–response specification. We demonstrate for this class that the well-known pool-adjacent-violators algorithm can efficiently pre-screen for non-estimable data. A simulation study demonstrates the frequency with which this problem can occur for various response models and conditions.     

Modern likelihood inference for the maximum/minimum of a bivariate normal vector

ABSTRACT

We consider the use of modern likelihood asymptotics in the construction of confidence intervals for the parameter which determines the skewness of the distribution of the maximum/minimum of an exchangeable bivariate normal random vector. Simulation studies were conducted to investigate the accuracy of the proposed methods and to compare them to available alternatives. Accuracy is evaluated in terms of both coverage probability and expected length of the interval. We furthermore illustrate the suitability of our proposals by means of two data sets, consisting of, respectively, measurements taken on the brains of 10 mono-zygotic twins and measurements of mineral content of bones in the dominant and non-dominant arms for 25 elderly women.     

Implementing particle swarm optimization algorithm to estimate the mixture of two Weibull parameters with censored data

We present the maximum likelihood estimation (MLE) via particle swarm optimization (PSO) algorithm to estimate the mixture of two Weibull parameters with complete and multiple censored data. A simulation study is conducted to assess the performance of the MLE via PSO algorithm, quasi-Newton method and expectation-maximization (EM) algorithm for different parameter settings and sample sizes in both uncensored and censored cases. The simulation results showed that the PSO algorithm outperforms the quasi-Newton method and the EM algorithm in most cases regarding bias and root mean square errors. Two numerical examples are used to demonstrate the performance of our proposed method.     

Comparing diagnostic tests: test of hypothesis for likelihood ratios

Likelihood ratios (LRs) are used to characterize the efficiency of diagnostic tests. In this paper, we use the classical weighted least squares (CWLS) test procedure, which was originally used for testing the homogeneity of relative risks, for comparing the LRs of two or more binary diagnostic tests. We compare the performance of this method with the relative diagnostic likelihood ratio (rDLR) method and the diagnostic likelihood ratio regression (DLRReg) approach in terms of size and power, and we observe that the performances of CWLS and rDLR are the same when used to compare two diagnostic tests, while DLRReg method has higher type I error rates and powers. We also examine the performances of the CWLS and DLRReg methods for comparing three diagnostic tests in various sample size and prevalence combinations. On the basis of Monte Carlo simulations, we conclude that all of the tests are generally conservative and have low power, especially in settings of small sample size and low prevalence.