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.     

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.     

Optimal regression designs in the presence of random block effects

A- and D-optimal regression designs under random block-effects models are considered. We first identify certain situations where D- and A-optimal designs do not depend on the intra-block correlation and can be obtained easily from the optimal designs under uncorrelated models. For example, for quadratic regression on [−1,1], this covers D-optimal designs when the block size is a multiple of 3 and A-optimal designs when the block size is a multiple of 4. In general, the optimal designs depend on the intra-block correlation. For quadratic regression, we provide expressions for D-optimal designs for any block size. A-optimal designs with blocks of size 2 for quadratic regression are also obtained. In all the cases considered, robust designs which do not depend on the intrablock correlation can be constructed.     

D-optimal designs for Poisson regression models

Most of the current research on optimal experimental designs for generalized linear models focuses on logistic regression models. In this paper, D-optimal designs for Poisson regression models are discussed. For the one-variable first-order Poisson regression model, it has been found that the D-optimal design, in terms of effective dose levels, is independent of the model parameters. However, it is not the case for more complicated models. We investigate how the D-optimal designs depend on the model parameters for the one-variable second-order model and two-variable interaction model. The performance of some “standard” designs that appeal to practitioners is also studied.     

An algorithm for calculating D-optimal designs for polynomial regression through a fixed point

Optimal designs are required to make efficient statistical experiments. By using canonical moments, in 1980, Studden found D_s-optimal designs for polynomial regression models. On the other hand, integrable systems are dynamical systems whose solutions can be written down concretely. In this paper, polynomial regression models through a fixed point are discussed. In order to calculate D-optimal designs for these models, a useful relationship between canonical moments and discrete integrable systems is introduced. By using canonical moments and discrete integrable systems, a new algorithm for calculating D-optimal designs for these models is proposed.     

On representing maximin efficient designs by Taylor series

This paper considers exponential and rational regression models that are nonlinear in some parameters. Recently, locally D-optimal designs for such models were investigated in [Melas, V. B., 2005. On the functional approach to optimal designs for nonlinear models. J. Statist. Plann. Inference 132, 93–116] based upon a functional approach. In this article a similar method is applied to construct maximin efficient D-optimal designs. This approach allows one to represent the support points of the designs by Taylor series, which gives us the opportunity to construct the designs by hand using tables of the coefficients of the series. Such tables are provided here for models with two nonlinear parameters. Furthermore, the recurrent formulas for constructing the tables for arbitrary numbers of parameters are introduced.     

Optimum Experimental Designs for Choosing Between Competitive and Non Competitive Models of Enzyme Inhibition

In the study of the inhibition of enzyme reactions the Michaelis–Menten model is extended to include two experimental variables and three or more parameters. We combine the three-parameter models for competitive and non competitive inhibition in a four-parameter model and use optimum design theory to find D- and Ds-optimum designs for discriminating between the models. These designs are compared with compound T-optimum designs which provide the most powerful tests for discrimination between models. A single design is found with high discrimination efficiency whichever model is true.     

Design optimality in multi-factor generalized linear models in the presence of an unrestricted quantitative factor

In this paper we show that product type designs are optimal in partially heteroscedastic multi-factor linear models. This result is applied to obtain locally D-optimal designs in multi-factor generalized linear models by means of a canonical transformation. As a consequence we can construct optimal designs for direct logistic response as well as for Bradley–Terry type paired comparison experiments.     

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.     

Circular Binary Block Second- and Higher-Order Neighbor Designs

Some new neighbor designs are presented here. Second-order neighbor designs for different configurations are generated in circular binary blocks. Third-order and fourth-order neighbor designs for some cases are also constructed. In all cases, circular blocks are well separated and these designs are obtained through initial block/s. At the end of the study, some models for analysis of these designs are also presented.     

Maximin efficient design of experiment for exponential regression models

In this paper robust and efficient designs are derived for several exponential decay models. These models are widely used in chemistry, pharmacokinetics or microbiology. We propose a maximin approach, which determines the optimal design such that a minimum of the D-efficiencies (taken over a certain range) becomes maximal. Analytic solutions are derived if optimization is performed in the class of minimal supported designs. In general the optimal designs with respect to the maximin criterion have to be determined numerically and some properties of these designs are also studied. We also illustrate the benefits of our approach by reanalysing a data example from the literature.     

Robust designs for linear mixed effects models

Summary.  In health sciences, medicine and social sciences linear mixed effects models are often used to analyse time-structured data. The search for optimal designs for these models is often hampered by two problems. The first problem is that these designs are only locally optimal. The second problem is that an optimal design for one model may not be optimal for other models. In this paper the maximin principle is adopted to handle both problems, simultaneously. The maximin criterion is formulated by means of a relative efficiency measure, which gives an indication of how much efficiency is lost when the uncertainty about the models over a prior domain of parameters is taken into account. The procedure is illustrated by means of three growth studies. Results are presented for a vocabulary growth study from education, a bone gain study from medical research and an epidemiological decline in height study. It is shown that, for the mixed effects polynomial models that are applied to these studies, the maximin designs remain highly efficient for different sets of models and combinations of parameter values.     

Bayesian and maximin optimal designs for heteroscedastic regression models

The authors consider the problem of constructing standardized maximin D‐optimal designs for weighted polynomial regression models. In particular they show that by following the approach to the construction of maximin designs introduced recently by Dette, Haines & Imhof (2003), such designs can be obtained as weak limits of the corresponding Bayesian _q‐optimal designs. They further demonstrate that the results are more broadly applicable to certain families of nonlinear models. The authors examine two specific weighted polynomial models in some detail and illustrate their results by means of a weighted quadratic regression model and the Bleasdale–Nelder model. They also present a capstone example involving a generalized exponential growth model.     

Optimal designs for contingent response models with application to toxicity–efficacy studies

We describe a general family of contingent response models. These models have ternary outcomes constructed from two Bernoulli outcomes, where one outcome is only observed if the other outcome is positive. This family is represented in a canonical form which yields general results for its Fisher information. A bivariate extreme value distribution illustrates the model and optimal design results. To provide a motivating context, we call the two binary events that compose the contingent responses toxicity and efficacy. Efficacy or lack thereof is assumed only to be observable in the absence of toxicity, resulting in the ternary response (toxicity, efficacy without toxicity, neither efficacy nor toxicity). The rate of toxicity, and the rate of efficacy conditional on no toxicity, are assumed to increase with dose. While optimal designs for contingent response models are numerically found, limiting optimal designs can be expressed in closed forms. In particular, in the family of four parameter bivariate location-scale models we study, as the marginal probability functions of toxicity and no efficacy diverge, limiting D optimal designs are shown to consist of a mixture of the D optimal designs for each failure (toxicity and no efficacy) univariately. Limiting designs are also obtained for the case of equal scale parameters.     

Optimal designs for tumor regrowth models

Most growth curves can only be used to model the tumor growth under no intervention. To model the growth curves for treated tumor, both the growth delay due to the treatment and the regrowth of the tumor after the treatment need to be taken into account. In this paper, we consider two tumor regrowth models and determine the locally D- and c-optimal designs for these models. We then show that the locally D- and c-optimal designs are minimally supported. We also consider two equally spaced designs as alternative designs and evaluate their efficiencies.     

Fraction of design space plots for generalized linear models

The use of graphical methods for comparing the quality of prediction throughout the design space of an experiment has been explored extensively for responses modeled with standard linear models. In this paper, fraction of design space (FDS) plots are adapted to evaluate designs for generalized linear models (GLMs). Since the quality of designs for GLMs depends on the model parameters, initial parameter estimates need to be provided by the experimenter. Consequently, an important question to consider is the design's robustness to user misspecification of the initial parameter estimates. FDS plots provide a graphical way of assessing the relative merits of different designs under a variety of types of parameter misspecification. Examples using logistic and Poisson regression models with their canonical links are used to demonstrate the benefits of the FDS plots.     

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.     

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.     

Locally optimal designs for binary dose‐response models

In this article, we consider the problem of seeking locally optimal designs for nonlinear dose‐response models with binary outcomes. Applying the theory of Tchebycheff Systems and other algebraic tools, we show that the locally D‐, A‐, and c‐optimal designs for three binary dose‐response models are minimally supported in finite, closed design intervals. The methods to obtain such designs are presented along with examples. The efficiencies of these designs are also discussed. The Canadian Journal of Statistics 46: 336–354; 2018 © 2018 Statistical Society of Canada     

Model-Robust Design of Conjoint Choice Experiments

Within the context of choice experimental designs, most authors have proposed designs for the multinomial logit model under the assumption that only the main effects matter. Very little attention has been paid to designs for attribute interaction models. In this article, three types of Bayesian D-optimal designs for the multinomial logit model are studied: main-effects designs, interaction-effects designs, and composite designs. Simulation studies are used to show that in situations where a researcher is not sure whether or not attribute interaction effects are present, it is best to take into account interactions in the design stage. In particular, it is shown that a composite design constructed by including an interaction-effects model and a main-effects model in the design criterion is most robust against misspecification of the underlying model when it comes to making precise predictions.