Locally and maximin optimal designs for multi-factor nonlinear models

This paper considers the search for locally and maximin optimal designs for multi-factor nonlinear models from optimal designs for sub-models of a lower dimension. In particular, sufficient conditions are given so that maximin D-optimal designs for additive multi-factor nonlinear models can be built from maximin D-optimal designs for their sub-models with a single factor. Some examples of application are models involving exponential decay in several variables.     

Adaptive grid semidefinite programming for finding optimal designs

We find optimal designs for linear models using a novel algorithm that iteratively combines a semidefinite programming (SDP) approach with adaptive grid techniques. The proposed algorithm is also adapted to find locally optimal designs for nonlinear models. The search space is first discretized, and SDP is applied to find the optimal design based on the initial grid. The points in the next grid set are points that maximize the dispersion function of the SDP-generated optimal design using nonlinear programming. The procedure is repeated until a user-specified stopping rule is reached. The proposed algorithm is broadly applicable, and we demonstrate its flexibility using (i) models with one or more variables and (ii) differentiable design criteria, such as A-, D-optimality, and non-differentiable criterion like E-optimality, including the mathematically more challenging case when the minimum eigenvalue of the information matrix of the optimal design has geometric multiplicity larger than 1. Our algorithm is computationally efficient because it is based on mathematical programming tools and so optimality is assured at each stage; it also exploits the convexity of the problems whenever possible. Using several linear and nonlinear models with one or more factors, we show the proposed algorithm can efficiently find optimal designs.     

A-optimal designs for heteroscedastic multifactor regression models

Abstract

This paper searches for A-optimal designs for Kronecker product and additive regression models when the errors are heteroscedastic. Sufficient conditions are given so that A-optimal designs for the multifactor models can be built from A-optimal designs for their sub-models with a single factor. The results of an efficiency study carried out to check the adequacy of the products of optimal designs for uni-factor marginal models when these are used to estimate different multi-factor models are also reported.     

On the determination and construction of optimal designs for comparing a set of test treatments with a set of controls in the presence of a linear trend

In this paper we consider the problem of constructing optimal designs for experimental situations where c controls are to be compared to t test treatments and the treatments are to be applied to experimental units occurring in a linear array and where there may be an unknown linear trend. Methods are given for determining and constructing optimal designs for such situations.     

On Exact K-optimal Designs Minimizing the Condition Number

A new design criterion based on the condition number of an information matrix is proposed to construct optimal designs for linear models, and the resulting designs are called K-optimal designs. The relationship between exact and asymptotic K-optimal designs is derived. Since it is usually hard to find exact optimal designs analytically, we apply a simulated annealing algorithm to compute K-optimal design points on continuous design spaces. Specific issues are addressed to make the algorithm effective. Through exact designs, we can examine some properties of the K-optimal designs such as symmetry and the number of support points. Examples and results are given for polynomial regression models and linear models for fractional factorial experiments. In addition, K-optimal designs are compared with A-optimal and D-optimal designs for polynomial regression models, showing that K-optimal designs are quite similar to A-optimal designs.     

Optimal designs in growth curve models: Part I Correlated model for linear growth: Optimal designs for slope parameter estimation and growth prediction

In the present paper we discuss the situation for a linear growth with correlated structure of the errors and indicate the nature of optimal designs for estimation and prediction problems. We study the intraclass structure of the error distribution. As regards estimation of the slope parameter, we look for robust optimal designs. Here robustness means that optimality should hold for a large variety of correlation parameters. The robust optimal designs for the prediction problem center around a performance measure of the predictors for all design points simultaneously. We have also studied the autocorrelated error structure and found similar results which are reported very briefly.     

Optimal designs for discriminating between some extensions of the Michaelis–Menten model

In this paper some results on the computation of optimal designs for discriminating between nonlinear models are provided. In particular, some typical deviations of the Michaelis–Menten model are considered. A common deviation of this pharmacokinetic model consists on adding a linear term. If two linear models differ in one parameter the T-optimal design for discriminating between them is c-optimal for estimating the added linear term. This is not the case for nonlinear models.     

Search for optimal designs in a three stagenested random model

In this paper we define a class of unbalanced designs, denoted by C_k,s,t, for estimating the components of variance in a k-stage nested random effects linear model. This class contains many of the designs proposed in the literature for nested components of variance models. We focus on the three-state model and discuss the determination of locally optimal designs within this class using a systematic computer search. For large sample sizes we show that approximate optimal designs may be obtained using a limit argument combined with numerical optimization. A comparison of our designs with previously published designs suggests that, in many cases, our designs result in substantial gains in efficiency.     

Robust designs for nearly linear regression

In this paper we seek designs and estimators which are optimal in some sense for multivariate linear regression on cubes and simplexes when the true regression function is unknown. More precisely, we assume that the unknown true regression function is the sum of a linear part plus some contamination orthogonal to the set of all linear functions in the L₂ norm with respect to Lebesgue measure. The contamination is assumed bounded in absolute value and it is shown that the usual designs for multivariate linear regression on cubes and simplices and the usual least squares estimators minimize the supremum over all possible contaminations of the expected mean square error. Additional results for extrapolation and interpolation, among other things, are discussed. For suitable loss functions optimal designs are found to have support on the extreme points of our design space.     

A-optimal design measures for one-way layouts with additive regression

For linear models with one discrete factor and additive general regression term the problem of characterizing A-optimal design measures for inference on (i) treatment effects, (ii) the regression parameters and (iii) all parameters will be considered. In any of these problems product designs can be found which are optimal among all designs, and equal weigth 1/J may be given to each of the J levels of the discrete factor. For problem (i) and (ii) the allocation of the continuous factors for the regression term should follow a suitable optimal design for the corresponding pure regression model, whereas for problem (iii) this would not give an A-optimal product design. For this problem an equivalence theorem for A-optimal product designs will be given. An example will illustrate these results. Finally, by analyzing a model with two discrete factors it will be shown that for enlarged models the best product designs may not be A-optimal.     

Minimax A-, c-, and I-optimal regression designs for models with heteroscedastic errors

It is well known that it is difficult to construct minimax optimal designs. Furthermore, since in practice we never know the true error variance, it is important to allow small deviations and construct robust optimal designs. We investigate a class of minimax optimal regression designs for models with heteroscedastic errors that are robust against possible misspecification of the error variance. Commonly used A-, c-, and I-optimality criteria are included in this class of minimax optimal designs. Several theoretical results are obtained, including a necessary condition and a reflection symmetry for these minimax optimal designs. In this article, we focus mainly on linear models and assume that an approximate error variance function is available. However, we also briefly discuss how the methodology works for nonlinear models. We then propose an effective algorithm to solve challenging nonconvex optimization problems to find minimax designs on discrete design spaces. Examples are given to illustrate minimax optimal designs and their properties.     

D-optimum designs in multi-factor models with heteroscedastic errors

This paper considers the construction of D-optimum designs for Kronecker product and additive regression models when the errors are heteroscedastic. Sufficient conditions are given so that D-optimum designs for the multi-factor models can be built from D-optimum designs for their sub-models with a single factor. A robustness study is included to investigate how design efficiencies change when the efficiency functions are miss-specified.     

Constructing Efficient Experimental Designs for Generalized Linear Models

Exchange algorithms are popular for finding optimal or efficient designs for linear models, but there are few discussions of this type of algorithm for generalized linear models (GLMs) in literature. A new algorithm, generalized Coordinate Exchange Algorithm (gCEA), is developed in this article to construct efficient designs for GLMs. We compare the performance of the proposed algorithm with other optimization algorithms, including point exchange algorithm, columnwise-pairwise algorithm, simulated annealing and generic algorithm, and demonstrate the superior performance of this new algorithm.     

A new characterization of Elfving's method for high dimensional computation

We give a new characterization of Elfving's (1952) method for computing c-optimal designs in k dimensions which gives explicit formulae for the k unknown optimal weights and k unknown signs in Elfving's characterization. This eliminates the need to search over these parameters to compute c-optimal designs, and thus reduces the computational burden from solving a family of optimization problems to solving a single optimization problem for the optimal finite support set. We give two illustrative examples: a high dimensional polynomial regression model and a logistic regression model, the latter showing that the method can be used for locally optimal designs in nonlinear models as well.     

The construction of multi-factor crossover designs in animal husbandry studies

For ethical reasons it is important to try to obtain as much useful information as possible from an animal experiment whilst minimizing the number of animals used. Crossover designs, where applicable, provide an ideal framework for achieving this. If two or more treatment factors are included in the crossover design then the reduction in total animal usage can be considerable. In this paper we consider such designs, defined as multi-factor crossover designs. The designs are applicable when there are several different treatment factors, each at t levels, to be applied to the experimental units. The motivation for investigating these designs was a study conducted at GlaxoSmithKline to determine the preference of male and female dogs for t=5 different types of bed and t=5 different bedding conditions. A construction method is given for forming universally optimal designs for t not too large. Also given is an example for the special case where the number of treatment levels t=6.     

Optimal designs for estimating the slope of a regression

In the common linear model with quantitative predictors we consider the problem of designing experiments for estimating the slope of the expected response in a regression. We discuss locally optimal designs, where the experimenter is only interested in the slope at a particular point, and standardized minimax optimal designs, which could be used if precise estimation of the slope over a given region is required. General results on the number of support points of locally optimal designs are derived if the regression functions form a Chebyshev system. For polynomial regression and Fourier regression models of arbitrary degree the optimal designs for estimating the slope of the regression are determined explicitly for many cases of practical interest.     

Optimum designs for estimating EDp based on raw optical density data

For raw optical density (ROD) data, such as those generated in biological assays employing an ELISA plate reader, ED_p-optimal designs are identified for a family of homogeneous non-linear models with two parameters. In every case, the theoretical ED_p-optimal design is a design with one or two support points. These theoretical optimal designs might not be suitable for many practical applications. To overcome this shortcoming, we have specified ED_p-optimal designs within the class of k-point equally spaced and uniform designs. The efficiency robustness of these designs with respect to initial nominal values of the parameters have been investigated.     

Optimal cross-over designs for nonlinear mixed models using a first-order expansion

We consider the construction of optimal cross-over designs for nonlinear mixed effect models based on the first-order expansion. We show that for AB/BA designs a balanced subject allocation is optimal when the parameters depend on treatments only. For multiple period, multiple sequence designs, uniform designs are optimal among dual balanced designs under the same conditions. As a by-product, the same results hold for multivariate linear mixed models with variances depending on treatments.     

Some sufficient conditions for the type 1 optimality of block designs

In this paper, we investigate the problem of determining block designs which are optimal under type 1 optimality criteria within various classes of designs having υ treatments arranged in b blocks of size k. The solutions to two optimization problems are given which are related to a general result obtained by Cheng (1978) and which are useful in this investigation. As one application of the solutions obtained, the definition of a regular graph design given in Mitchell and John (1977) is extended to that of a semi-regular graph design and some sufficient conditions are derived for the existence of a semi-regular graph design which is optimal under a given type 1 criterion. A result is also given which shows how the sufficient conditions derived can be used to establish the optimality under a specific type 1 criterion of some particular types of semi- regular graph designs having both equal and unequal numbers of replicates. Finally,some sufficient conditions are obtained for the dual of an A- or D-optimal design to be A- or D-optimal within an appropriate class of dual designs.     

Asymptotics in multivariate linear models with optimal experimental designs

The conditions guarantying consistency and asymptotic normality of Least-Square estimators as well as the consistency of the usual tests for linear hypotheses in multivariate linear models are shown to be valid whenever almost optimal experimental designs are used.