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.     

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.     

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.     

Designs for weighted least squares regression, with estimated weights

We study designs, optimal up to and including terms that are O(n ^?1), for weighted least squares regression, when the weights are intended to be inversely proportional to the variances but are estimated with random error. We take a finite, but arbitrarily large, design space from which the support points are to be chosen, and obtain the optimal proportions of observations to be assigned to each point. Specific examples of D- and I-optimal design for polynomial responses are studied. In some cases the same designs that are optimal under homoscedasticity remain so for a range of variance functions; in others there tend to be more support points than are required in the homoscedastic case. We also exhibit minimax designs, that minimize the maximum, over finite classes of variance functions, value of the loss. These also tend to have more support points, often resulting from the breaking down of replicates into clusters.     

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 Designs for the Carryover Model with Random Interactions Between Subjects and Treatments

The paper considers a model for crossover designs with carryover effects and a random interaction between treatments and subjects. Under this model, two observations of the same treatment on the same subject are positively correlated and therefore provide less information than two observations of the same treatment on different subjects. The introduction of the interaction makes the determination of optimal designs much harder than is the case for the traditional model. Generalising the results of Bludowsky's thesis, the present paper uses Kushner's method to determine optimal approximate designs. We restrict attention to the case where the number of periods is less than or equal to the number of treatments. We determine the optimal designs in the important special cases that the number of periods is 3, 4 or 5. It turns out that the optimal designs depend on the variance of the random interactions and in most cases are not binary. However, we can show that neighbour balanced binary designs are highly efficient, regardless of the number of periods and of the size of the variance of the interaction effects.     

Robust designs for one-point extrapolation

We consider the construction of designs for the extrapolation of a regression response to one point outside of the design space. The response function is an only approximately known function of a specified linear function. As well, we allow for variance heterogeneity. We find minimax designs and corresponding optimal regression weights in the context of the following problems: (P1) for nonlinear least squares estimation with homoscedasticity, determine a design to minimize the maximum value of the mean squared extrapolation error (MSEE), with the maximum being evaluated over the possible departures from the response function; (P2) for nonlinear least squares estimation with heteroscedasticity, determine a design to minimize the maximum value of MSEE, with the maximum being evaluated over both types of departures; (P3) for nonlinear weighted least squares estimation, determine both weights and a design to minimize the maximum MSEE; (P4) choose weights and design points to minimize the maximum MSEE, subject to a side condition of unbiasedness. Solutions to (P1)–(P4) are given in complete generality. Numerical comparisons indicate that our designs and weights perform well in combining robustness and efficiency. Applications to accelerated life testing are highlighted.     

Optimal two-point designs for the michaelis-menten model with heteroscedastic errors

We construct D-optimal designs for the Michaelis-Menten model when the variance of the response depends on the independent variable. However, this dependence is only partially known. A Bayesian approacn is used to find an optimal design by incorporating the prior lnformation about the variance structure. We demonstrate the method for a class of error variance structures and present efficiencies of these optimal designs under prior mis-specifications. In particular, we show that an erroneous assumption on the variance structure for the Michaelis-Menten model can have serious consequences.     

Modified Robust Second-Order Slope-Rotatable Designs

Generally it is very difficult to construct robust slope-rotatable designs along axial directions. Present paper focuses on modified second-order slope-rotatable designs (SOSRDs) with correlated errors. Modified robust second-order slope-rotatability conditions are derived for a general variance–covariance structure of errors. These conditions get simplified for intraclass correlation structure. A few robust second-order slope-rotatable designs (over all directions, or with equal maximum directional variance slope, or D-optimal slope) are examined with respect to modified robust slope-rotatability. It is observed that robust second-order slope-rotatable designs over all directions, or with equal maximum directional variance slope, or D-optimal slope are not generally modified robust second-order slope-rotatable designs.     

Evaluation of Response Surface Designs in Presence of Errors in Factor Levels

Experimenters are often confronted with the problem that errors in setting factor levels cannot be measured. In the robust design scenario, the goal is to determine the design that minimizes the variability transmitted to the response from the variables’ errors. The prediction variance performance of response surface designs with errors is investigated using design efficiency and the maximum and minimum scaled prediction variance. The evaluation and comparison of response surface designs with and without errors in variables are developed for second order designs on spherical regions. The prediction variance and design efficiency results and recommendations for their use are provided.     

Optimal designs for main effects in linear paired comparison models

In psychology, marketing research and sensory analysis paired comparisons which demand judges to evaluate the trade-off between two alternatives constitute a popular method of data collection. For this situation we present optimal designs in a discrete setting when the alternatives are specified by an analysis of variance model with main effects only. We employ combinatorial tools to achieve optimal designs which have sufficiently small sample sizes. Moreover, optimal designs are constructed when the number of factors presented is restricted for each pair of alternatives.     

Nonproper variance balanced designs and optimality

This communication deals with the construction and optimality of non-proper (unequal block sized) variance balanced (VB) designs obtainable under linear homoscedastic normal model. Several methods of construction of non-proper VB designs have been given. Some constructed designs are universally optimal non-proper variance balanced designs.     

ITERATIVE ANALYSIS OF GENERALIZED LATTICE DESIGNS

Generalized lattice designs are defined. They include as special cases the square and rectangular lattice designs, and the α-designs defined by Patterson and Williams (1976). An iterative procedure is given for the combined estimation of variety effects in generalized lattice designs with optimal or near optimal efficiency factors. This procedure, together with an approximate variance matrix, enables the analysis of efficient generalized lattice designs to be carried out on mini computers.     

A method of selecting the levels of regressor variables in lognormal regression model

Kupper and Meydrech and Myers and Lahoda introduced the mean squared error (MSE) approach to study response surface designs, Duncan and DeGroot derived a criterion for optimality of linear experimental designs based on minimum mean squared error. However, minimization of the MSE of an estimator maxr renuire some knowledge about the unknown parameters. Without such knowledge construction of designs optimal in the sense of MSE may not be possible. In this article a simple method of selecting the levels of regressor variables suitable for estimating some functions of the parameters of a lognormal regression model is developed using a criterion for optimality based on the variance of an estimator. For some special parametric functions, the criterion used here is equivalent to the criterion of minimizing the mean squared error. It is found that the maximum likelihood estimators of a class of parametric functions can be improved substantially (in the sense of MSE) by proper choice of the values of regressor variables. Moreover, our approach is applicable to analysis of variance as well as regression designs.     

Some adjusted orthogonal,variance balanced,multidimensional block designs

A multidimensional block design (MBD) is an experimental design with d > 1 blocking criteria geometrically represented as a d-dimensional lattice with treatment varieties assigned to some or all nodes of the lattice. Intrablock analysis of variance tables for some special classes of two- and three-dimensional block designs with some empty nodes are given. Design plans and efficiencies for 31 two-dimensional designs, each universally optimal in defined classes of designs, and 7 three-dimensional designs, each nearly optimal in defined classes of designs, are listed in the appendices. A need for such designs is apparent when the blocking criteria are implemented successively and empty nodes do not represent wasted experimental units.     

Bayesian optimization design for dose-finding based on toxicity and efficacy outcomes in phase I/II clinical trials

In phase I trials, the main goal is to identify a maximum tolerated dose under an assumption of monotonicity in dose–response relationships. On the other hand, such monotonicity is no longer applied to biologic agents because a different mode of action from that of cytotoxic agents potentially draws unimodal or flat dose–efficacy curves. Therefore, biologic agents require an optimal dose that provides a sufficient efficacy rate under an acceptable toxicity rate instead of a maximum tolerated dose. Many trials incorporate both toxicity and efficacy data, and drugs with a variety of modes of actions are increasingly being developed; thus, optimal dose estimation designs have been receiving increased attention. Although numerous authors have introduced parametric model-based designs, it is not always appropriate to apply strong assumptions in dose–response relationships. We propose a new design based on a Bayesian optimization framework for identifying optimal doses for biologic agents in phase I/II trials. Our proposed design models dose–response relationships via nonparametric models utilizing a Gaussian process prior, and the uncertainty of estimates is considered in the dose selection process. We compared the operating characteristics of our proposed design against those of three other designs through simulation studies. These include an expansion of Bayesian optimal interval design, the parametric model-based EffTox design, and the isotonic design. In simulations, our proposed design performed well and provided results that were more stable than those from the other designs, in terms of the accuracy of optimal dose estimations and the percentage of correct recommendations.     

Comparison of designs for the three-fold nested random model

The quality of estimation of variance components depends on the design used as well as on the unknown values of the variance components. In this article, three designs are compared, namely, the balanced, staggered, and inverted nested designs for the three-fold nested random model. The comparison is based on the so-called quantile dispersion graphs using analysis of variance (ANOVA) and maximum likelihood (ML) estimates of the variance components. It is demonstrated that the staggered nested design gives more stable estimates of the variance component for the highest nesting factor than the balanced design. The reverse, however, is true in case of lower nested factors. A comparison between ANOVA and ML estimation of the variance components is also made using each of the aforementioned designs.     

ON OPTIMIZING MULTI-LEVEL DESIGNS: POWER UNDER BUDGET CONSTRAINTS

This paper derives a procedure for efficiently allocating the number of units in multi‐level designs given prespecified power levels. The derivation of the procedure is based on a constrained optimization problem that maximizes a general form of a ratio of expected mean squares subject to a budget constraint. The procedure makes use of variance component estimates to optimize designs during the budget formulating stages. The method provides more general closed form solutions than other currently available formulae. As such, the proposed procedure allows for the determination of the optimal numbers of units for studies that involve more complex designs. A method is also described for optimizing designs when variance component estimates are not available. Case studies are provided to demonstrate the method.     

D-optimal designs for combined polynomial and trigonometric regression on a partial circle

Consider the D-optimal designs for a combined polynomial and trigonometric regression on a partial circle. It is shown that the optimal design is equally supported and the structure of the optimal design depends only on the length of the design interval and the support points are analytic functions of this parameter. Moreover, the Taylor expansion of the optimal support points can be determined efficiently by a recursive procedure. Examples are presented to illustrate the procedures for computing the optimal designs.     

Minimum,maximum, and average spherical prediction variances for central composite and box-behnken designs

Single value design optimality criteria are often considered when selecting a response surface design. An alternative to a single value criterion is to evaluate prediction variance properties throughout the experimental region and to graphically display the results in a variance dispersion graph (VDG) (Giovannitti-Jensen and Myers (1989)). Three properties of interest are the spherical average, maximum, and minimum prediction variances. Currently, a computer-intensive optimization algorithm is utilized to evaluate these prediction variance properties. It will be shown that the average, maximum, and minimum spherical prediction variances for central composite designs and Box-Behnken designs can be derived analytically. These three prediction variances can be expressed as functions of the radius and the design parameters. These functions provide exact spherical prediction variance values eliminating the implementation of extensive computing involving algorithms which do not guarantee convergence. This research is concerned with the theoretical development of these analytical forms. Results are presented for hyperspherical and hypercuboidal regions.