Locally optimal designs for some dose–response models with continuous endpoints

We consider the problem of constructing static (or non sequential), approximate optimal designs for a class of dose–response models with continuous outcomes. We obtain conditions for a design being D-optimal or c-optimal. The designs are locally optimal in that they depend on the model parameters. The efficiency studies show that these designs have high efficiency when the mis-specification of the initial values of model parameters is not severe. A case study indicates that using an optimal design may result in a significant saving of resources.     

Multiplicative algorithms for computing optimum designs

We study a new approach to determine optimal designs, exact or approximate, both for the uncorrelated case and when the responses may be correlated. A simple version of this method is based on transforming design points on a finite interval to proportions of the interval. Methods for determining optimal design weights can therefore be used to determine optimal values of these proportions. We explore the potential of this method in a range of examples encompassing linear and non-linear models, some assuming a correlation structure and some with more than one design variable.     

Bayes A-optimal designs for comparing test treatments with a control

The problem of comparing v test treatments simultaneously with a control treatment when k, v ⩾ 3 is considered. Following the work of Majumdar (1992), we use exact design theory to derive Bayes A-optimal block designs and optimal Г-minimax designs for a more general prior assumption for the one-way elimination of heterogeneity model. Examples of robust optimal designs, highly efficient designs, and the comparisons of the approximate optimal designs that are derived by our methods and by some other existing rounding-off schemes when using Owen's procedure are also provided.     

Optimal statistical designs with circular string property

This paper develops an approximate theory for D- and A-optlmal statistical designs with a circular string property. It is shown how the problems of deriving optimal designs can be reduced to non-linear programming problems involving small numbers of decision variables. The results are seen to be helpful in dealing with the exact design problem with a finite number of obser vations.     

Optimal designs for exponential regression

This paper is concerned with the optimal design problem for the particular case of non-linear parametrisation:the parameters to be estimated are included in exponents.Some properties of locally optimal designs as functions of estimated parameters are investigated and a table of such designs in given.We consider also designs to be optimal in the sense of minimax approach.     

Optimal designs for non-competitive enzyme inhibition kinetic models

In this paper, we present a new method for determining optimal designs for enzyme inhibition kinetic models, which are used to model the influence of the concentration of a substrate and an inhibition on the velocity of a reaction. The approach uses a nonlinear transformation of the vector of predictors such that the model in the new coordinates is given by an incomplete response surface model. Although there exist no explicit solutions of the optimal design problem for incomplete response surface models so far, the corresponding design problem in the new coordinates is substantially more transparent, such that explicit or numerical solutions can be determined more easily. The designs for the original problem can finally be found by an inverse transformation of the optimal designs determined for the response surface model. We illustrate the method determining explicit solutions for the D-optimal design and for the optimal design problem for estimating the individual coefficients in a non-competitive enzyme inhibition kinetic model.     

Optimal designs for multivariate logistic mixed models with longitudinal data

This paper considers the optimal design problem for multivariate mixed-effects logistic models with longitudinal data. A decomposition method of the binary outcome and the penalized quasi-likelihood are used to obtain the information matrix. The D-optimality criterion based on the approximate information matrix is minimized under different cost constraints. The results show that the autocorrelation coefficient plays a significant role in the design. To overcome the dependence of the D-optimal designs on the unknown fixed-effects parameters, the Bayesian D-optimality criterion is proposed. The relative efficiencies of designs reveal that both the cost ratio and autocorrelation coefficient play an important role in the optimal designs.     

Constructing optimal designs with constraints

We construct constrained approximate optimal designs by maximizing a criterion subject to constraints. We approach this problem by transforming the constrained optimization problem to one of maximizing three functions of the design weights simultaneously. We used a class of multiplicative algorithms, indexed by a function f(·). These algorithms are shown to satisfy the basic constraints on the design weights of nonnegativity and summation to unity. We also investigate techniques for improving convergence rates by means of some suitable choices of the function f(·).     

First-order optimal designs for non-linear models

This paper presents D-optimal experimental designs for a variety of non-linear models which depend on an arbitrary number of covariates but assume a positive prior mean and a Fisher information matrix satisfying particular properties. It is argued that these optimal designs can be regarded as a first-order approximation of the asymptotic increase of Shannon information. The efficiency of this approximation is compared in some examples, which show how the results can be further used to compute the Bayesian optimal design, when the approximate solution is not accurate enough.     

THE SIMPLE LINEAR CALIBRATION PROBLEM AS AN OPTIMAL EXPERIMENTAL DESIGN

ABSTRACT

The aim of this paper is to consider the linear calibration problem through an optimal design approach, to evaluate the approximate variance of the calibrating value and provide approximate confidence intervals. The sequential approach through Stochastic Approximation is also applied to obtain a D-optimal design is considered.     

A semi-infinite programming based algorithm for finding minimax optimal designs for nonlinear models

Minimax optimal experimental designs are notoriously difficult to study largely because the optimality criterion is not differentiable and there is no effective algorithm for generating them. We apply semi-infinite programming (SIP) to solve minimax design problems for nonlinear models in a systematic way using a discretization based strategy and solvers from the General Algebraic Modeling System (GAMS). Using popular models from the biological sciences, we show our approach produces minimax optimal designs that coincide with the few theoretical and numerical optimal designs in the literature. We also show our method can be readily modified to find standardized maximin optimal designs and minimax optimal designs for more complicated problems, such as when the ranges of plausible values for the model parameters are dependent and we want to find a design to minimize the maximal inefficiency of estimates for the model parameters.     

Algorithmic and analytical construction of efficient designs in small blocks for comparing consecutive pairs of treatments

Optimal block designs in small blocks are explored under the A-, E- and D-criteria when the treatments have a natural ordering and interest lies in comparing consecutive pairs of treatments. We first formulate the problem via approximate theory which leads to a convenient multiplicative algorithm for obtaining A-optimal design measures. This, in turn, yields highly efficient exact designs, under the A-criterion, even when the number of blocks is rather small. Moreover, our approach is seen to allow nesting of such efficient exact designs which is an advantage when the resources for the experiment are available in possibly several stages. Illustrative examples are given and tables of A-optimal design measures are provided. Approximate theory is also seen to yield analytical results on E- and D-optimal design measures.     

Bayesian optimal blocking of factorial designs

The presence of block effects makes the optimal selection of fractional factorial designs a difficult task. The existing frequentist methods try to combine treatment and block wordlength patterns and apply minimum aberration criterion to find the optimal design. However, ambiguities exist in combining the two wordlength patterns and therefore, the optimality of such designs can be challenged. Here we propose a Bayesian approach to overcome this problem. The main technique is to postulate a model and a prior distribution to satisfy the common assumptions in blocking and then, to develop an optimal design criterion for the efficient estimation of treatment effects. We apply our method to develop regular, nonregular, and mixed-level blocked designs. Several examples are presented to illustrate the advantages of the proposed method.     

Rational Regression Models with Continuous Chebyshev Design

In rational regression models, the G-optimal designs are very difficult to derive in general. Even when an G-optimal design can be found, it has, from the point of view of modern nonparametric regression, certain drawbacks because the optimal design crucially depends on the model. Hence, it can be used only when the model is given in advance. This leads to the problem of finding designs which would be nearly optimal for a broad class of rational regression models. In this article, we will show that the so-called continuous Chebyshev Design is a practical solution to this problem.     

On optimality properties of simple block designs in the approximate design theory

Optimality properties of approximate block designs are studied under variations of (1) the class of competing designs, (2) the optimality criterion, (3) the parametric function of interest, and (4) the statistical model. The designs which are optimal turn out to be the product of their treatment and block marginals, and uniform designs when the support is specified in advance. Optimality here means uniform, universal, and simultaneous j_p-optimality. The classical balanced incomplete block designs are embedded into this approach, and shown to be simultaneously j_p-optimal for a maximal system of identifiable parameters. A geometric account of universal optimality is given which applies beyond the context of block designs.     

Optimal few-stage designs

Optimal designs are presented for experiments in which sampling is carried out in stages. There are two Bernoulli populations and it is assumed that the outcomes of the previous stage are available before the sampling design for the next stage is determined. At each stage, the design specifies the number of observations to be taken and the relative proportion to be sampled from each population. Of particular interest are 2- and 3-stage designs.To illustrate that the designs can be used for experiments of useful sample sizes, they are applied to estimation and optimization problems. Results indicate that, for problems of moderate size, published asymptotic analyses do not always represent the true behavior of the optimal stage sizes, and efficiency may be lost if the analytical results are used instead of the true optimal allocation.The exactly optimal few stage designs discussed here are generated computationally, and the examples presented indicate the ease with which this approach can be used to solve problems that present analytical difficulties. The algorithms described are flexible and provide for the accurate representation of important characteristics of the problem.     

Optimal block designs comparing treatments with a control when the errors are correlated

The efficient design of experiments for comparing a control with v new treatments when the data are dependent is investigated. We concentrate on generalized least-squares estimation for a known covariance structure. We consider block sizes k equal to 3 or 4 and approximate designs. This method may lead to exact optimal designs for some v, b, k, but usually will only indicate the structure of an efficient design for any particular v, b, k, and yield an efficiency bound, usually unattainable. The bound and the structure can then be used to investigate efficient finite designs.     

Simulation-based designs for accelerated life tests

In this paper we present a Bayesian decision theoretic approach to the design of accelerated life tests (ALT). We discuss computational issues regarding the evaluation of expectation and optimization steps in the solution of the decision problem. We illustrate how Monte Carlo methods can be used in preposterior analysis to find optimal designs and how the required computational effort can be avoided by using curve-fitting techniques. In so doing, we adopt the recent Monte-Carlo-based approaches of Muller and Parmigiani (1995. J. Amer. Statist. Assoc. 90, 503–510) and Muller (2000. Bayesian Statistics 6, forthcoming) to develop optimal Bayesian designs. These approaches facilitate the preposterior analysis by replacing it with a sequence of scatter plot smoothing/regression techniques and optimization of the corresponding fitted surfaces. We present our development by considering single and multiple-point fixed, as well as, sequential design problems when the underlying life model is exponential, and illustrate the implementation of our approach with some examples.     

Efficient circular neighbour designs for spatial interference model

We consider circular block designs for field-trials when there are two-sided spatial interference between neighbouring plots of the same blocks. The parameter of interest is total effects that is the sum of direct effect of treatment and neighbour effects, which correspond to the use of a single treatment in the whole field. We determine universally optimal approximate designs. When the number of blocks may be large, we propose efficient exact designs generated by a single sequence of treatment. We also give efficiency factors of the usual binary block neighbour balanced designs which can be used when the number of blocks is small.     

Block designs robust against the presence of positional effects

The problem considered is to find optimum designs for treatment effects in a block design (BD) setup, when positional effects are also present besides treatment and block effects, but they are ignored while formulating the model. In the class of symmetric balanced incomplete block designs, the Youden square design is shown to be optimal in the sense of minimizing the bias term in the mean squared error (MSE) of the best linear unbiased estimators of the full set of orthonormal treatment contrasts, irrespective of the value of the positional effects.