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.     

A candidate-set-free algorithm for generating D-optimal split-plot designs

Summary.  We introduce a new method for generating optimal split-plot designs. These designs are optimal in the sense that they are efficient for estimating the fixed effects of the statistical model that is appropriate given the split-plot design structure. One advantage of the method is that it does not require the prior specification of a candidate set. This makes the production of split-plot designs computationally feasible in situations where the candidate set is too large to be tractable. The method allows for flexible choice of the sample size and supports inclusion of both continuous and categorical factors. The model can be any linear regression model and may include arbitrary polynomial terms in the continuous factors and interaction terms of any order. We demonstrate the usefulness of this flexibility with a 100-run polypropylene experiment involving 11 factors where we found a design that is substantially more efficient than designs that are produced by using other approaches.     

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.     

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.     

Bayesian D-Optimal Designs for Poisson Regression Models

By incorporating informative and/or historical knowledge of the unknown parameters, Bayesian experimental design under the decision-theory framework can combine all the information available to the experimenter so that a better design may be achieved. Bayesian optimal designs for generalized linear regression models, especially for the Poisson regression model, is of interest in this article. In addition, lack of an efficient computational method in dealing with the Bayesian design leads to development of a hybrid computational method that consists of the combination of a rough global optima search and a more precise local optima search. This approach can efficiently search for the optimal design for multi-variable generalized linear models. Furthermore, the equivalence theorem is used to verify whether the design is optimal or not.     

Optimal experimental designs when an independent variable is potentially censored

This paper considers the problem of constructing optimal approximate designs when an independent variable might be censored. The problem is which design should be applied in practice to obtain the best approximate design when a censoring distribution is assumed known in advance. The approach for finite or continuous design spaces deserves different attention. In both cases, equivalent theorems and algorithms are provided in order to calculate optimal designs. Some examples illustrate this approach for D-optimality.     

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.     

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.     

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.     

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.     

An algorithmic approach to construct D-optimal saturated designs for logistic model

In this paper, locally D-optimal saturated designs for a logistic model with one and two continuous input variables have been constructed by modifying the famous Fedorov exchange algorithm. A saturated design not only ensures the minimum number of runs in the design but also simplifies the row exchange computation. The basic idea is to exchange a design point with a point from the design space. The algorithm performs the best row exchange between design points and points form a candidate set representing the design space. Naturally, the resultant designs depend on the candidate set. For gain in precision, intuitively a candidate set with a larger number of points and the low discrepancy is desirable, but it increases the computational cost. Apart from the modification in row exchange computation, we propose implementing the algorithm in two stages. Initially, construct a design with a candidate set of affordable size and then later generate a new candidate set around the points of design searched in the former stage. In order to validate the optimality of constructed designs, we have used the general equivalence theorem. Algorithms for the construction of optimal designs have been implemented by developing suitable codes in R.     

PARAMETER ESTIMATION FOR THE FIXED BLOCK EFFECTS MODEL USING A USUAL DESIGN

ABSTRACT

This paper is devoted to the fixed block effects model analysed with most of the classical designs. First, we find regularities conditions for such designs. Then, we obtain explicitly all the least squares estimators of the model. A particular attention is given to orthogonal blocked designs and their optimal properties.     

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.     

Constructing optimal designs for fitting pharmacokinetic models

We consider some computational issues that arise when searching for optimal designs for pharmacokinetic (PK) studies. Special factors that distinguish these are (i) repeated observations are taken from each subject and the observations are usually described by a nonlinear mixed model (NLMM), (ii) design criteria depend on the model fitting procedure, (iii) in addition to providing efficient parameter estimates, the design must also permit model checking, (iv) in practice there are several design constraints, (v) the design criteria are computationally expensive to evaluate and often numerical integration is needed and finally (vi) local optimisation procedures may fail to converge or get trapped at local optima.We review current optimal design algorithms and explore the possibility of using global optimisation procedures. We use these latter procedures to find some optimal designs.For multi-purpose designs we suggest two surrogate design criteria for model checking and illustrate their use.     

Bayesian optimal blocking of factorial designs

The presence of block effects makes the optimal selection of fractional factorial designs a difficult task. The existing frequentist methods try to combine treatment and block wordlength patterns and apply minimum aberration criterion to find the optimal design. However, ambiguities exist in combining the two wordlength patterns and therefore, the optimality of such designs can be challenged. Here we propose a Bayesian approach to overcome this problem. The main technique is to postulate a model and a prior distribution to satisfy the common assumptions in blocking and then, to develop an optimal design criterion for the efficient estimation of treatment effects. We apply our method to develop regular, nonregular, and mixed-level blocked designs. Several examples are presented to illustrate the advantages of the proposed method.     

Bayesian A- and D-optimal designs for gamma regression model with inverse link function

Bayesian optimal designs have received increasing attention in recent years, especially in biomedical and clinical trials. Bayesian design procedures can utilize the available prior information of the unknown parameters so that a better design can be achieved. With this in mind, this article considers the Bayesian A- and D-optimal designs of the two- and three-parameter Gamma regression model. In this regard, we first obtain the Fisher information matrix of the proposed model and then calculate the Bayesian A- and D-optimal designs assuming various prior distributions such as normal, half-normal, gamma, and uniform distribution for the unknown parameters. All of the numerical calculations are handled in R software. The results of this article are useful in medical and industrial researches.     

Improving early phase oncology clinical trial design: The case for finding the optimal biological dose

Historically early phase oncology drug development programmes have been based on the belief that “more is better”. Furthermore, rule-based study designs such as the “3 + 3” design are still often used to identify the MTD. Phillips and Clark argue that newer Bayesian model-assisted designs such as the BOIN design should become the go to designs for statisticians for MTD finding. This short communication goes one stage further and argues that Bayesian model-assisted designs such as the BOIN12 which balances risk-benefit should be included as one of the go to designs for early phase oncology trials, depending on the study objectives. Identifying the optimal biological dose for future research for many modern targeted drugs, immunotherapies, cell therapies and vaccine therapies can save significant time and resources.     

Optimal U-type design for Bayesian nonparametric multiresponse prediction

This paper presents an extension of the work of Yue and Chatterjee (2010) about U-type designs for Bayesian nonparametric response prediction. We consider nonparametric Bayesian regression model with p responses. We use U-type designs with n runs, m factors and q levels for the nonparametric multiresponse prediction based on the asymptotic Bayesian criterion. A lower bound for the proposed criterion is established, and some optimal and nearly optimal designs for the illustrative models are given.     

Interruptible supersaturated two-level designs

Interruptible designs possess a robustness against possible premature termination of an experiment. We consider such two-level designs for a first-order model and present interruptible sequences which lead to the D-optimal saturated design for four to nine factors if not interrupted. Premature termination of the experiment at any stage results in a supersaturated design with minimum loss of information about the factors. The loss for these designs, which is measured by the pairwise orthogonality between columns, is compared with that of the worst case f o r randomly ordered sequences.     

A Bayesian criterion for selecting super saturated screening designs

Super-saturated designs in which the number of factors under investigation exceeds the number of experimental runs have been suggested for screening experiments initiated to identify important factors for future study. Most of the designs suggested in the literature are based on natural but ad hoc criteria. The “average s²” criteria introduced by Booth and Cox (Technometrics 4 (1962) 489) is a popular choice. Here, a decision theoretic approach is pursued leading to an optimality criterion based on misclassification probabilities in a Bayesian model. In certain cases, designs optimal under the average s² criterion are also optimal for the new criterion. Necessary conditions for this to occur are presented. In addition, the new criterion often provides a strict preference between designs tied under the average s² criterion, which is advantageous in numerical search as it reduces the number of local minima.