Approximate and exact optimal designs for paired comparisons of partial profiles when there are two groups of factors

For paired comparison experiments involving pairs of multifactor options differing in a specified number of factors the problem of finding optimal designs is considered, when only main effects are to be estimated. It is presumed that the set of factors can be partitioned into two groups such that the number of levels is constant within each group. The optimal designs for this frequently encountered case are also optimal for the corresponding choice experiments under the hypothesis that the parameters in the multinomial logit model are equal to zero.     

Robust sequential designs for approximately linear models

We consider the problem of the sequential choice of design points in an approximately linear model. It is assumed that the fitted linear model is only approximately correct, in that the true response function contains a nonrandom, unknown term orthogonal to the fitted response. We also assume that the parameters are estimated by M-estimation. The goal is to choose the next design point in such a way as to minimize the resulting integrated squared bias of the estimated response, to order n^-1. Explicit applications to analysis of variance and regression are given. In a simulation study the sequential designs compare favourably with some fixed-sample-size designs which are optimal for the true response to which the sequential designs must adapt.     

The effect of small sample on optimal designs for logistic regression models

Asymptotic methods are commonly used in statistical inference for unknown parameters in binary data models. These methods are based on large sample theory, a condition which may be in conflict with small sample size and hence leads to poor results in the optimal designs theory. In this paper, we apply the second order expansions of the maximum likelihood estimator and derive a matrix formula for the mean square error (MSE) to obtain more precise optimal designs based on the MSE. Numerical results indicate the new optimal designs are more efficient than the optimal designs based on the information matrix.     

AN ALGORITHM FOR THE DESIGN OF 2? FACTORIAL EXPERIMENTS ON CONTINUOUS PROCESSES

Saunders & Eccleston (1992) presented an approach to the design of 2-level factorial experiments for continuous processes. It determined sets of contrasts between the observations that could be well estimated, and then selected a design so that those contrasts estimated the parameters of interest. This paper shows that a well-estimated contrast must have a large number of changes of sign or level, and also be ‘paired’ in a particular sense. It develops an algorithm which constructs designs that must have a large number of changes of sign, evenly spread among the contrasts and optimal or near optimal. When such designs exist they are often preferable to those produced by the reverse foldover algorithm of Cheng & Steinberg (1991).     

Efficient design of experiments in the Monod model

Summary. Estimation and experimental design in a non-linear regression model that is used in microbiology are studied. The Monod model is defined implicitly by a differential equation and has numerous applications in microbial growth kinetics, water research, pharmacokinetics and plant physiology. It is proved that least squares estimates are asymptotically unbiased and normally distributed. The asymptotic covariance matrix of the estimator is the basis for the construction of efficient designs of experiments. In particular locally D -, E - and c -optimal designs are determined and their properties are studied theoretically and by simulation. If certain intervals for the non-linear parameters can be specified, locally optimal designs can be constructed which are robust with respect to a misspecification of the initial parameters and which allow efficient parameter estimation. Parameter variances can be decreased by a factor of 2 by simply sampling at optimal times during the experiment.     

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 design for the Bradley–Terry paired comparison model

Paired comparisons are a popular tool for questionnaires in psychological marketing research. The quality of the statistical analysis of the responses heavily depends on the design, i.e. the choice of the alternatives in the comparisons. In this paper we show that the structure of locally optimal designs changes substantially with the parameters in the underlying utility. This fact is illustrated by elementary examples, where the optimal designs can be completely characterized. As an alternative maximin efficient designs are proposed which perform well for all parameter settings. Research supported by grant Ho 1286 of the German Research Council (Deutsche Forschungsgemeinschaft).     

Optimal designs for the power logistic model

We investigate non-sequential designs for estimating model parameters in a power logistic model when the power is assumed to be approximately known and only the ranges for the other two parameters are available. The sensitivity of these designs to nominal values of all the three parameters are studied and our proposed optimal designs are shown to be reasonably robust under moderate deviation from the assumed model. An application to a toxicity experiment involving adult beetles is discussed, including the benefits of using an optimal design.     

The Bayesian D-optimal design for simple beta regression model in two cases (both known and unknown nuisance parameter)

According to investigated topic in the context of optimal designs, various methods can be used to obtain optimal design, of which Bayesian method is one. In this paper, considering the model and the features of the information matrix, this method (Bayesian optimality criterion) has been used for obtaining optimal designs which due to the variation range of the model parameters, prior distributions such as Uniform, Normal and Exponential have been used and the results analysed.     

Minimax designs for approximately linear models with AR(1) errors

We obtain designs for linear regression models under two main departures from the classical assumptions: (1) the response is taken to be only approximately linear, and (2) the errors are not assumed to be independent, but to instead follow a first-order autoregressive process. These designs have the property that they minimize (a modification of) the maximum integrated mean squared error of the estimated response, with the maximum taken over a class of departures from strict linearity and over all autoregression parameters ρ,|ρ,| < 1, of fixed sign. Specific methods of implementation are discussed. We find that an asymptotically optimal procedure for AR(1) models consists of choosing points from that design measure which is optimal for uncorrelated errors, and then implementing them in an appropriate order.     

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.     

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.     

Optimal designs for generalized linear models

Summary This paper solves some D-optimal design problems for certain Generalized Linear Models where the mean depends on two parameters and two explanatory variables. In all of the cases considered the support point of the optimal designs are found to be independent of the unknown parameters. While in some cases the optimal design measures are given by two points with equal weights, in others the support is given by three point with weights depending on the unknown parameters, hence the designs are locally optimal in general. Empirical results on the efficiency of the locally optimal designs are also given. Some of the designs found can also be used for planning D-optimal experiments for the normal linear model, where the mean must be positive. This research was carried out in part at University College, London as an M.Sc. project. Thanks are due to Prof. I. Ford (University of Glasgow) and Prof. A. Giovagnoli (University of Perugia) for their valuable suggestions and critical observations.     

Nearly optimal orthogonally blocked desings for a quadratic mixture model with q components

In experiments with mixtures involving process variables, orthogonal block designs may be used to allow estimation of the parameters of the mixture components independently of estimation of the parameters of the process variables. In the class of orthogonally blocked designs based on pairs of suitably chosen Latin squares, the optimal designs consist primarily of binary blends of the mixture components, regardless of how many ingredients are available for the mixture. This paper considers ways of modifying these optimal designs so that some or all of the runs used in the experiment include a minimum proportion of each mixture ingredient. The designs considered are nearly optimal in the sense that the experimental points are chosen to follow ridges of maxima in the optimality criteria. Specific designs are discussed for mixtures involving three and four components and distinctions are identified for different designs with the same optimality properties. The ideas presented for these specific designs are readily extended to mixtures with q>4 components.     

Optimal design for quasi-likelihood estimation in Poisson regression with random coefficients

Count data may be described by a Poisson regression model. If random coefficients are involved, maximum likelihood is not feasible and alternative estimation methods have to be employed. For the approach based on quasi-likelihood estimation a characterization of design optimality is derived and optimal designs are determined numerically for an example with random slope parameters.     

Robustness properties of minimally‐supported Bayesian D‐optimal designs for heteroscedastic models

Bayesian D‐optimal designs supported on a fixed number of points were found by Dette & Wong (1998) for estimating parameters in a polynomial model when the error variance depends exponentially on the explanatory variable. The present authors provide optimal designs under a broader class of error variance structures and investigate the robustness properties of these designs to model and prior distribution assumptions. A comparison of the performance of the optimal designs relative to the popular uniform designs is also given. The authors' results suggest that Bayesian D‐optimal designs suported on a fixed number of points are more likely to be globaly optimal among all designs if the prior distribution is symmetric and is concentrated around its mean.     

Optimal parametric design with applications to pharmacokinetic and pharmacodynamic trials

This paper considers optimal parametric designs, i.e. designs represented by probability measures determined by a set of parameters, for nonlinear models and illustrates their use in designs for pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) trials. For some practical problems, such as designs for modelling PK/PD relationship, this is often the only feasible type of design, as the design points follow a PK model and cannot be directly controlled. Even for ordinary design problems the parametric designs have some advantages over the traditional designs, which often have too few design points for model checking and may not be robust to model and parameter misspecifications. We first describe methods and algorithms to construct the parametric design for ordinary nonlinear design problems and show that the parametric designs are robust to parameter misspecification and have good power for model discrimination. Then we extend this design method to construct optimal repeated measurement designs for nonlinear mixed models. We also use this parametric design for modelling a PK/PD relationship and propose a simulation based algorithm. The application of parametric designs is illustrated with a three-parameter open one-compartment PK model for the ordinary design and repeated measurement design, and an Emax model for the phamacokinetic/pharmacodynamic trial design.     

Variance of the difference between two estimated responses

Minimization of the maximum and average variance of the difference between estimated responses are taken as design criteria for univariate polynomial regression models. An optimal design under the first criterion is derived for the second-order model and a class of designs nearly optimal under the second criterion is obtained for the general polynomial models.     

Slope-rotatable designs with equal maximum directional variance for second order response surface models

The concept of sloperotaiability with equal maximum directional vari ance for second order response surface models is introduced as a new design property. This requires that the maximum variance of the estimated slope over all possible directions be only a function of p, which is the distance from the design originif is shown that a rotatable design satisfies this property Also, minimization of tiie maximum variance of the estimated slope over all possible directions is proposed as a new design optirnality criterion, and op¬timal designs are called slope-directional minirnax designs. For the class of cquiradial designs, the slope-directional minirnax designs are compared with D— optimal designs.