Robust Linear Calibration

We regard the simple linear calibration problem where only the response y of the regression line y = β₀ + β₁ t is observed with errors. The experimental conditions t are observed without error. For the errors of the observations y we assume that there may be some gross errors providing outlying observations. This situation can be modeled by a conditionally contaminated regression model. In this model the classical calibration estimator based on the least squares estimator has an unbounded asymptotic bias. Therefore we introduce calibration estimators based on robust one-step-M-estimators which have a bounded asymptotic bias. For this class of estimators we discuss two problems: The optimal estimators and their corresponding optimal designs. We derive the locally optimal solutions and show that the maximin efficient designs for non-robust estimation and robust estimation coincide.     

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.     

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.     

Optimal design for the proportional odds model

The authors construct locally optimal designs for the proportional odds model for ordinal data. While they investigate the standard D‐optimal design, they also investigate optimality criteria for the simultaneous estimation of multiple quantiles, namely D_A ‐optimality and the omnibus criterion. The design of experiments for the simultaneous estimation of multiple quantiles is important in both toxic and effective dose studies in medicine. As with c‐optimality in the binary response problem, the authors find that there are distinct phase changes when exploring extreme quantiles that require additional design points. The authors also investigate relative efficiencies of the criteria.     

Optimal discrimination designs for exponential regression models

We investigate optimal designs for discriminating between exponential regression models of different complexity, which are widely used in the biological sciences; see, e.g., Landaw [1995. Robust sampling designs for compartmental models under large prior eigenvalue uncertainties. Math. Comput. Biomed. Appl. 181–187] or Gibaldi and Perrier [1982. Pharmacokinetics. Marcel Dekker, New York]. We discuss different approaches for the construction of appropriate optimality criteria, and find sharper upper bounds on the number of support points of locally optimal discrimination designs than those given by Caratheodory's Theorem. These results greatly facilitate the numerical construction of optimal designs. Various examples of optimal designs are then presented and compared to different other designs. Moreover, to protect the experiment against misspecifications of the nonlinear model parameters, we adapt the design criteria such that the resulting designs are robust with respect to such misspecifications and, again, provide several examples, which demonstrate the advantages of our approach.     

CVX‐based algorithms for constructing various optimal regression designs

CVX‐based numerical algorithms are widely and freely available for solving convex optimization problems but their applications to solve optimal design problems are limited. Using the CVX programs in MATLAB, we demonstrate their utility and flexibility over traditional algorithms in statistics for finding different types of optimal approximate designs under a convex criterion for nonlinear models. They are generally fast and easy to implement for any model and any convex optimality criterion. We derive theoretical properties of the algorithms and use them to generate new A‐, c‐, D‐ and E‐optimal designs for various nonlinear models, including multi‐stage and multi‐objective optimal designs. We report properties of the optimal designs and provide sample CVX program codes for some of our examples that users can amend to find tailored optimal designs for their problems. The Canadian Journal of Statistics 47: 374–391; 2019 © 2019 Statistical Society of Canada     

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.     

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.     

Scaled density models for binary response data and their D- and Ds-optimal designs

We introduce scaled density models for binary response data which can be much more reasonable than the traditional binary response models for particular types of binary response data. We show the maximum-likelihood estimates for the new models and it seems that the model works well with some sets of data. We also considered optimum designs for parameter estimation for the models and found that the D- and D_s-optimum designs are independent of parameters corresponding to the linear function of dose level, but the optimum designs are simple functions of a scale parameter only.     

Optimal designs for the Michaelis–Menten model with correlated observations

In this paper we investigate the problem of designing experiments for generalized least-squares analysis in the Michaelis–Menten model. We study the structure of exact D-optimal designs in a model with an autoregressive error structure. Explicit results for locally D-optimal designs are derived for the case where two observations can be taken per subject. Additionally standardized maximin D-optimal designs are obtained in this case. The results illustrate the enormous difficulties to find exact optimal designs explicitly for nonlinear regression models with correlated observations.     

D‐optimal minimax fractional factorial designs

The D‐optimal minimax criterion is proposed to construct fractional factorial designs. The resulting designs are very efficient, and robust against misspecification of the effects in the linear model. The criterion was first proposed by Wilmut & Zhou (2011); their work is limited to two‐level factorial designs, however. In this paper we extend this criterion to designs with factors having any levels (including mixed levels) and explore several important properties of this criterion. Theoretical results are obtained for construction of fractional factorial designs in general. This minimax criterion is not only scale invariant, but also invariant under level permutations. Moreover, it can be applied to any run size. This is an advantage over some other existing criteria. The Canadian Journal of Statistics 41: 325–340; 2013 © 2013 Statistical Society of Canada     

Optimal designs for statistical analysis with Zernike polynomials

The Zernike polynomials arise in several applications such as optical metrology or image analysis on a circular domain. In the present paper, we determine optimal designs for regression models which are represented by expansions in terms of Zernike polynomials. We consider two estimation methods for the coefficients in these models and determine the corresponding optimal designs. The first one is the classical least squares method and Φ _p -optimal designs in the sense of Kiefer [Kiefer, J., 1974, General equivalence theory for optimum designs (approximate theory). Annals of Statistics, 2 849–879.] are derived, which minimize an appropriate functional of the covariance matrix of the least squares estimator. It is demonstrated that optimal designs with respect to Kiefer's Φ _p -criteria (p>?∞) are essentially unique and concentrate observations on certain circles in the experimental domain. E-optimal designs have the same structure but it is shown in several examples that these optimal designs are not necessarily uniquely determined. The second method is based on the direct estimation of the Fourier coefficients in the expansion of the expected response in terms of Zernike polynomials and optimal designs minimizing the trace of the covariance matrix of the corresponding estimator are determined. The designs are also compared with the uniform designs on a grid, which is commonly used in this context.     

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.     

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.     

Some sufficient conditions for establishing (M,S)-optimality

Two sufficient conditions are given for an incomplete block design to be (M,S- optimal. For binary designs the conditions are (i) that the elements in each row, excluding the diagonal element, of the association matrix differ by at most one, and (ii) that the off-diagonal elements of the block characteristic matrix differ by at most one. It is also shown how the conditions can be utilized for nonbinary designs and that for blocks of size two the sufficient condition in terms of the association matrix can be attained.     

Optimal designs for the logit and probit models for binary data

We consider optimal designs for a class of symmetric models for binary data which includes the common probit and logit models. We show that for a large group of optimality criteria which includes the main ones in the literature (e.g. A-, D-, E-, F- and G-optimality) the optimal design for our class of models is a two-point design with support points symmetrically placed about the ED50 but with possibly unequal weighting. We demonstrate how one can further reduce the problem to a one-variable optimization by characterizing various of the common criteria. We also use the results to demonstrate major qualitative differences between the F - and c-optimal designs, two design criteria which have similar motivation.     

Optimal allocation of time points for the random effects model

In this article the problem of the optimal selection and allocation of time points in repeated measures experiments is considered. D‐ optimal designs for linear regression models with a random intercept and first order auto‐regressive serial correlations are computed numerically and compared with designs having equally spaced time points. When the order of the polynomial is known and the serial correlations are not too small, the comparison shows that for any fixed number of repeated measures, a design with equally spaced time points is almost as efficient as the D‐ optimal design. When, however, there is no prior knowledge about the order of the underlying polynomial, the best choice in terms of efficiency is a D‐ optimal design for the highest possible relevant order of the polynomial. A design with equally‐spaced time points is the second best choice     

Optimal Designs for Approximating a Stochastic Process with Respect to a Minimax Criterion

We study the problem of approximating a stochastic process Y = {Y(t: t ∈ T} with known and continuous covariance function R on the basis of finitely many observations Y(t ₁,), …, Y(t _n ). Dependent on the knowledge about the mean function, we use different approximations ? and measure their performance by the corresponding maximum mean squared error sub _t∈T E(Y(t) ? ?(t))². For a compact T ? ? ^p we prove sufficient conditions for the existence of optimal designs. For the class of covariance functions on T ² = [0, 1]² which satisfy generalized Sacks/Ylvisaker regularity conditions of order zero or are of product type, we construct sequences of designs for which the proposed approximations perform asymptotically optimal.     

Optimal designs for calibration of orientations

This paper concerns designed experiments involving observations of orientations following the models of Prentice (1989) and Rivest &Chang (2006). The authors state minimal conditions on the designs for consistent least squares estimation of the matrix parameters in these models. The conditions are expressed in terms of the axes and rotation angles of the design orientations. The authors show that designs satisfying U₁ + … + U_n = 0 are optimal in the sense of minimizing the estimation error average angular distance. The authors give constructions of optimal n‐point designs when n ≥ 4 and they compare the performance of several designs through approximations and simulation.     

The analytic construction of D-optimal designs for the two-variable binary logistic regression model without interaction

Candidate locally D-optimal designs for the binary two-variable logistic model with no interaction, which comprise 3 and 4 support points lying in the first quadrant of the two-dimensional Euclidean space, were introduced by Haines et al. (D-optimal designs for logistic regression in two variables. In: Lopez-Fidalgo J, Rodrigez-Diaz JM, Torsney B, editors. MODA8 – advances in model-oriented designs and analysis. Heidelberg: Physica-Verlag; 2007. p. 91–98). The authors proved algebraically the global D-optimality of the 3-point design for the special case in which the intercept parameter is equal to?1.5434. However for other selected values of the intercept parameter, the global D-optimality of the proposed 3- and 4-point designs was only demonstrated numerically. In this paper, we provide analytical proofs of the D-optimality of these 3- and 4-point designs for all negative and zero intercept parameters of the binary two-variable logistic model with no interaction. The results are extended to the construction of D-optimal designs on a rectangular design space and illustrated by means of two examples of which one is a real example taken from the literature.