Cost-cautious designs for confirmatory bioassay

Confirmatory bioassay experiments take place in late stages of the drug discovery process when a small number of compounds have to be compared with respect to their properties. As the cost of the observations may differ considerably, the design problem is well specified by the cost of compound used rather than by the number of observations. We show that cost-efficient designs can be constructed using useful properties of the minimum support designs. These designs are particularly suited for studies where the parameters of the model to be estimated are known with high accuracy prior to the experiment, although they prove to be robust against typical inaccuracies of these values. When the parameters of the model can only be specified with ranges of values or by a probability distribution, we use a Bayesian criterion of optimality to construct the required designs. Typically, the number of their support points depends on the prior knowledge for the model parameters. In all cases we recommend identifying a set of designs with good statistical properties but different potential costs to choose from.     

Optimal block designs for three treatments when observations are correlated

E$E$-optimal designs for comparing three treatments in blocks of size three are identified, where intrablock observations are correlated according to a first order autoregressive error process with parameter ρ∈(0,1)$\rho \in (0,1)$. For number of blocks b   of the form b=3n+1$b=3n+1$, there are two distinct optimal designs depending on the value of ρ$\rho$, with the best design being unequally replicated for large ρ$\rho$. For other values of b$b$, binary, equireplicate designs with specified within-block assignment patterns are best. In many cases, the stronger majorization optimality is established.     

An optimality criterion for supersaturated designs with quantitative factors

A supersaturated design (SSD) is a factorial design in which the degrees of freedom for all its main effects exceed the total number of distinct factorial level-combinations (runs) of the design. Designs with quantitative factors, in which level permutation within one or more factors could result in different geometrical structures, are very different from designs with nominal ones which have been treated as traditional designs. In this paper, a new criterion is proposed for SSDs with quantitative factors. Comparison and analysis for this new criterion are made. It is shown that the proposed criterion has a high efficiency in discriminating geometrically nonisomorphic designs and an advantage in computation.     

Optimal designs for both model discrimination and parameter estimation

The KL-optimality criterion has been recently proposed to discriminate between any two statistical models. However, designs which are optimal for model discrimination may be inadequate for parameter estimation. In this paper, the DKL-optimality criterion is proposed which is useful for the dual problem of model discrimination and parameter estimation. An equivalence theorem and a stopping rule for the corresponding iterative algorithms are provided. A pharmacokinetics application and a bioassay example are given to show the good properties of a DKL-optimum design.     

D-optimal designs for logistic models with three and four parameters

Logistic functions are used in different applications, including biological growth studies and assay data analysis. Locally D-optimal designs for logistic models with three and four parameters are investigated. It is shown that these designs are minimally supported. Efficiencies are computed for equally spaced and uniform designs.     

Defining equations for two-level factorial designs

Defining equations are introduced in the context of two-level factorial designs and they are shown to provide a concise specification of both regular and nonregular designs. The equations are used to find orthogonal arrays of high strength and some optimal designs. The latter optimal designs are formed in a new way by augmenting notional orthogonal arrays which are allowed to have some runs with a negative number of replicates before augmentation. Defining equations are also shown to be useful when the factorial design is blocked.     

Negative dependence and the Simes inequality

It is shown that the Simes inequality is reversed for a broad class of negatively dependent distributions.     

Predictability of designs which adjust for imbalances in prognostic factors

Minimisation is a method often used in clinical trials to balance the treatment groups with respect to some prognostic factors. In the case of two treatments, the predictability of this method is calculated for different numbers of factors, different numbers of levels of each factor and for different proportions of the population at each level. It is shown that if we know nothing about the previous patients except the last treatment allocation, the next treatment can be correctly guessed more than 60% of the time if no biased coin is used. If the two previous assignments are known to have been the same, the next treatment can be guessed correctly around 80% of the time. Therefore, it is suggested that a biased coin should always be used with minimisation. Different choices of biased coin are investigated in terms of the reduction in predictability and the increase in imbalance that they produce. An alternative design to minimisation which makes use of optimum design theory is also investigated, by means of simulation, and does not appear to have any clear advantages over minimisation with a biased coin.     

Selecting and checking a binomial response generalized linear model using phi-divergences

This work introduces specific tools based on phi-divergences to select and check generalized linear models with binary data. A backward selection criterion that helps to reduce the number of explanatory variables is considered. Diagnostic methods based on divergence measures such as a new measure to detect leverage points and two indicators to detect influential points are introduced. As an illustration, the diagnostics are applied to human psychology data.     

A constrained optimum experimental design problem for model discrimination with a continuously varying factor

We present the theoretical background and the numerical procedure for calculating optimum experimental designs for non-linear model discrimination in the presence of constraints. The design support points consist of two kinds of factors: a continuous function of time and discrete levels of other quantitative factors. That is, some of the experimental conditions are allowed to continually vary during the experimental run. We implement the theory in a chemical kinetic model discrimination problem.     

Prediction intervals for general balanced linear random models

The main interest of prediction intervals lies in the results of a future sample from a previously sampled population. In this article, we develop procedures for the prediction intervals which contain all of a fixed number of future observations for general balanced linear random models. Two methods based on the concept of a generalized pivotal quantity (GPQ) and one based on ANOVA estimators are presented. A simulation study using the balanced one-way random model is conducted to evaluate the proposed methods. It is shown that one of the two GPQ-based and the ANOVA-based methods are computationally more efficient and they also successfully maintain the simulated coverage probabilities close to the nominal confidence level. Hence, they are recommended for practical use. In addition, one example is given to illustrate the applicability of the recommended methods.     

Addition of runs to an s-level supersaturated design

The purpose of the present work is to extend the work of Gupta et al. (2010) to s  -level column balanced supersaturated designs. Addition of runs to an existing E(χ²)-optimal$E({\chi }^2)\mathrm{-}\mathrm{optimal}$ supersaturated design and to study the optimality of the resulting design is an important issue. This paper considers the study of the optimality of the resulting design. A lower bound to E(χ²)$E({\chi }^2)$ has been obtained for the extended supersaturated designs. Some examples and a small catalogue of E(χ²)-optimal$E({\chi }^2)\mathrm{-}\mathrm{optimal}$ supersaturated designs are also presented.     

Using pilot study information to increase efficiency in clinical trials

It is often necessary to conduct a pilot study to determine the sample size required for a clinical trial. Due to differences in sampling environments, the pilot data are usually discarded after sample size calculation. This paper tries to use the pilot information to modify the subsequent testing procedure when a two-sided t$t$-test or a regression model is used to compare two treatments. The new test maintains the required significance level regardless of the dissimilarity between the pilot and the target populations, but increases the power when the two are similar. The test is constructed based on the posterior distribution of the parameters given the pilot study information, but its properties are investigated from a frequentist's viewpoint. Due to the small likelihood of an irrelevant pilot population, the new approach is a viable alternative to the current practice.     

On the distributions of multivariate sample skewness

In this paper, we consider the multivariate normality test based on measure of multivariate sample skewness defined by Srivastava (1984). Srivastava derived asymptotic expectation up to the order N⁻¹ for the multivariate sample skewness and approximate χ²${\chi }^2$ test statistic, where N   is sample size. Under normality, we derive another expectation and variance for Srivastava's multivariate sample skewness in order to obtain a better test statistic. From this result, improved approximate χ²${\chi }^2$ test statistic using the multivariate sample skewness is also given for assessing multivariate normality. Finally, the numerical result by Monte Carlo simulation is shown in order to evaluate accuracy of the obtained expectation, variance and improved approximate χ²${\chi }^2$ test statistic. Furthermore, upper and lower percentiles of χ²${\chi }^2$ test statistic derived in this paper are compared with those of χ²${\chi }^2$ test statistic derived by Mardia (1974) which is used multivariate sample skewness defined by Mardia (1970).     

On batch queueing systems: A combinatorial approach

We consider batch queueing systems M/M^H/1$M/M^H/1$ and M^H/M/1$M^H/M/1$ with catastrophes. The transient probability functions of these queueing systems are obtained by a Lattice Path Combinatorics approach that utilizes randomization and dual processes. Steady state distributions are also determined. Generalization to systems having batches of different sizes are discussed.     

Statistical analysis for rounded data

When random variables do not take discrete values, observed data are often the rounded values of continuous random variables. Errors caused by rounding of data are often neglected by classical statistical theories. While some pioneers have identified and made suggestions to rectify the problem, few suitable approaches were proposed. In this paper, we propose an approximate MLE (AMLE) procedure to estimate the parameters and discuss the consistency and asymptotic normality of the estimates. For our illustration, we shall consider the estimates of the parameters in AR(p)$\mathit{AR}(p)$ and MA(q)$\mathit{MA}(q)$ models for rounded data.     

ANOVA-like analysis of matched series of studies with a common structure

It is shown how to condense the information contained in a series of studies, each constituted by an objects by variables matrix and a pair of weight matrices, into a structure vector and a sum of sums of squares of residuals. Based on this condensation we propose to carry out ANOVA-like inference for matched series of studies associated with the level combinations of some factors. It is shown how to validate the assumptions underlying the inference. An application to the results of local elections in Portugal is given.     

Kernel density estimators for random fields satisfying an interlaced mixing condition

For a sequence of strictly stationary random fields that are uniformly ρ′-mixing$\rho \prime \mathrm{-}\mathrm{mixing}$ and satisfy a Lindeberg condition, a central limit theorem is obtained for sequences of “rectangular” sums from the given random fields. The “Lindeberg CLT” is then used to prove a CLT for some kernel estimators of probability density for some strictly stationary random fields satisfying ρ′-mixing$\rho \prime \mathrm{-}\mathrm{mixing}$, and whose probability density and joint densities are absolutely continuous.