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.     

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 foldover designs

An obvious strategy for obtaining a Doptimal foldover design for p factors at two levels each in 2N runs is to fold a Doptimal main effects plan. We show that this strategy works except when N = 4t + 2 and s is even In that case there are two different classes of D-optimal main effects plans with N runs that have the same determinant. However folding them gives two different values foi the D-optimality criteiion One set of designs is D-optimal The other is not.     

Optimal designs for non-competitive enzyme inhibition kinetic models

In this paper, we present a new method for determining optimal designs for enzyme inhibition kinetic models, which are used to model the influence of the concentration of a substrate and an inhibition on the velocity of a reaction. The approach uses a nonlinear transformation of the vector of predictors such that the model in the new coordinates is given by an incomplete response surface model. Although there exist no explicit solutions of the optimal design problem for incomplete response surface models so far, the corresponding design problem in the new coordinates is substantially more transparent, such that explicit or numerical solutions can be determined more easily. The designs for the original problem can finally be found by an inverse transformation of the optimal designs determined for the response surface model. We illustrate the method determining explicit solutions for the D-optimal design and for the optimal design problem for estimating the individual coefficients in a non-competitive enzyme inhibition kinetic model.     

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.     

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.     

Highly Efficient Designs for Logistic Models with Categorical Variables

Optimal designs for logistic models generally require prior information about the values of the regression parameters. However, experimenters usually do not have full knowledge of these parameters. We propose a design that is D-optimal on a restricted design region. This design assigns an equal weight to design points that contain more information and ignores those design points that contain less information about the regression parameters. The design can be constructed in practice by means of the rank order of the outcome variances. A numerical study compares the proposed design with the D-optimal and completely balanced designs in terms of efficiency.     

Optimal designs for additive mixture model with heteroscedastic errors

This paper presents a study of D- and A-optimality of direct sum designs for additive mixture models when the errors are heteroscedastic. Sufficient conditions are given so that D- and A-optimal designs for additive mixture models can be constructed from the D- and A-optimal designs for homogeneous models in sub-mixture systems.     

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.     

Optimal design for nonlinear regression models

Two results for D _θ-optimal designs for nonlinear regression models are shown to follow directly from approximate design theory. The first result considered is one concerning the replication of exact designs with minimum support, first established by Atkinson and Hunter and by M.J. Box in 1968, while the second pertains to a heteroscedastic model introduced by Velilla and Llosa in 1992. An illustrative example is provided.     

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.     

The Mean Squared Error Optimum Design Criterion for Parameter Estimation in Nonlinear Regression Models

In the context of nonlinear regression models, we propose an optimal experimental design criterion for estimating the parameters that account for the intrinsic and parameter-effects nonlinearity. The optimal design criterion proposed in this article minimizes the determinant of the mean squared error matrix of the parameter estimator that is quadratically approximated using the curvature array. The design criterion reduces to the D-optimal design criterion if there are no intrinsic and parameter-effects nonlinearity in the model, and depends on the scale parameter estimator and on the reparameterization used. Some examples, using a well known nonlinear kinetics model, demonstrate the application of the proposed criterion to nonsequential design of experiments as compared with the D-optimal criterion.     

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.     

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.     

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.     

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.     

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.     

D-minimax Second-order Designs Over Hypercubes for Extrapolation and Restricted Interpolation Regions

The D-minimax criterion for estimating slopes of a response surface involving k factors is considered for situations where the experimental region χ and the region of interest ? are co-centered cubes but not necessarily identical. Taking χ = [ ? 1, 1]^k and ? = [ ? R, R]^k, optimal designs under the criterion for the full second-order model are derived for various values of R and their relative performances investigated. The asymptotically optimal design as R → ∞ is also derived and investigated. In addition, the optimal designs within the class of product designs are obtained. In the asymptotic case it is found that the optimal product design is given by a solution of a cubic equation that reduces to a quadratic equation for k = 3?and?6. Relative performances of various designs obtained are examined. In particular, the optimal asymptotic product design and the traditional D-optimal design are compared and it is found that the former performs very well.     

Robust first-order rotatable lifetime improvement experimental designs

Experimental designs are widely used in predicting the optimal operating conditions of the process parameters in lifetime improvement experiments. The most commonly observed lifetime distributions are log-normal, exponential, gamma and Weibull. In the present article, invariant robust first-order rotatable designs are derived for autocorrelated lifetime responses having log-normal, exponential, gamma and Weibull distributions. In the process, robust first-order D-optimal and rotatable conditions have been derived under these situations. For these lifetime distributions with correlated errors, it is shown that robust first-order D-optimal designs are always robust rotatable but the converse is not true. Moreover, it is observed that robust first-order D-optimal and rotatable designs depend on the respective error variance–covariance structure but are independent from these considered lifetime response distributions.     

D- and V-optimal population designs for the quadratic regression model with a random intercept term

In this paper D- and V-optimal population designs for the quadratic regression model with a random intercept term and with values of the explanatory variable taken from a set of equally spaced, non-repeated time points are considered. D-optimal population designs based on single-point individual designs were readily found but the derivation of explicit expressions for designs based on two-point individual designs was not straightforward and was complicated by the fact that the designs now depend on ratio of the variance components. Further algebraic results pertaining to d-point D-optimal population designs where d≥3 and to V-optimal population designs proved elusive. The requisite designs can be calculated by careful programming and this is illustrated by means of a simple example.