Optimal allocation of subjects in a matched pair cluster-randomized trial with fixed number of heterogeneous clusters

In cluster-randomized trials, investigators randomize clusters of individuals such as households, medical practices, schools or classrooms despite the unit of interest are the individuals. It results in the loss of efficiency in terms of the estimation of the unknown parameters as well as the power of the test for testing the treatment effects. To recoup this efficiency loss, some studies pair similar clusters and randomize treatment within pairs. However, the clusters within a treatment arm might be heterogeneous in nature. In this article, we propose a locally optimal design that accounts the clusters heterogeneity and optimally allocates the subjects within each cluster. To address the dependency of design on the unknown parameters, we also discuss Bayesian optimal designs. Performances of proposed designs are investigated numerically through some data examples.     

DUAL‐OBJECTIVE OPTIMAL MIXTURE DESIGNS

Mixture experiments are widely used in many industries and particularly in the manufacture of consumer products. Almost all work to date assumes a single study objective, which is unrealistic. Researchers may want to estimate model parameters and make predictions or extrapolations at the same time. We discuss design issues for determining the optimal proportions of the mixture components when there are two or more objectives in the study and there is a large sample size. We present a general methodology for constructing two types of dual‐objective optimal design for mixture experiments and discuss the general applicability of the design strategy to more complicated types of mixture design problems, including mixture experiments.     

On Exact K-optimal Designs Minimizing the Condition Number

A new design criterion based on the condition number of an information matrix is proposed to construct optimal designs for linear models, and the resulting designs are called K-optimal designs. The relationship between exact and asymptotic K-optimal designs is derived. Since it is usually hard to find exact optimal designs analytically, we apply a simulated annealing algorithm to compute K-optimal design points on continuous design spaces. Specific issues are addressed to make the algorithm effective. Through exact designs, we can examine some properties of the K-optimal designs such as symmetry and the number of support points. Examples and results are given for polynomial regression models and linear models for fractional factorial experiments. In addition, K-optimal designs are compared with A-optimal and D-optimal designs for polynomial regression models, showing that K-optimal designs are quite similar to A-optimal designs.     

Optimal designs for experiments with mixtures: a survey

This is a survey article on known results about analytic solutions and numerical solutions of optimal designs for various regression models for experiments with mixtures. The regression models include polynomial models, models containing homogeneous functions, models containing inverse terms and ratios, log contrast models, models with quantitative variables, and mod els containing the amount of mixture, Optimality criteria considered include D-, A-, E-,φ_p- and I_λ-Optimalities. Uniform design and uniform optimal design for mixture components, and efficiencies of the {q,2} simplex-controid design are briefly discussed.     

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 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.     

Designs for two-colour microarray experiments

Summary.  Designs for two-colour microarray experiments can be viewed as block designs with two treatments per block. Explicit formulae for the A- and D-criteria are given for the case that the number of blocks is equal to the number of treatments. These show that the A- and D-optimality criteria conflict badly if there are 10 or more treatments. A similar analysis shows that designs with one or two extra blocks perform very much better, but again there is a conflict between the two optimality criteria for moderately large numbers of treatments. It is shown that this problem can be avoided by slightly increasing the number of blocks. The two colours that are used in each block effectively turn the block design into a row–column design. There is no need to use a design in which every treatment has each colour equally often: rather, an efficient row–column design should be used. For odd replication, it is recommended that the row–column design should be based on a bipartite graph, and it is proved that the optimal such design corresponds to an optimal block design for half the number of treatments. Efficient row–column designs are given for replications 3–6. It is shown how to adapt them for experiments in which some treatments have replication only 2.     

Bayesian two-stage optimal design for mixture models

In this paper, a Bayesian two-stage D–D optimal design for mixture experimental models under model uncertainty is developed. A Bayesian D-optimality criterion is used in the first stage to minimize the determinant of the posterior variances of the parameters. The second stage design is then generated according to an optimalityprocedure that collaborates with the improved model from the first stage data. The results show that a Bayesian two-stage D–D-optimal design for mixture experiments under model uncertainty is more efficient than both the Bayesian one-stage D-optimal design and the non-Bayesian one-stage D-optimal design in most situations. Furthermore, simulations are used to obtain a reasonable ratio of the sample sizes between the two stages.     

Experimental designs and their efficiencies for spatially correlated observations in two dimensions

Optimality of experimental designs for spatially correlated observations is investigated.come two dimensional correlation structures are discussed and an attempt has been made to find optimal or nearly optimal design for each sitution.The solution lend to designs similar to that used for repeated measurements.The relative efficiency of the proposed designs in comparison to randomized latin square designs is tabulated for some cases.     

Optimal design in average for inference in generalized linear models

This paper considers the problem of optimal design for inference in Generalized Linear Models, when prior information about the parameters is available. The general theory of optimum design usually requires knowledge of the parameter values. These are usually unknown and optimal design can, therefore, not be used in practice. However, one way to circumvent this problem is through so-called “optimal design in average”, or shortly, “ave optimal”. The ave optimal design is chosen to minimize the expected value of some criterion function over a prior distribution. We focus our interest on the aveD _A-optimality, including aveD- and avec-optimality and show the appropriate equivalence theorems for these optimality criterions, which give necessary conditions for an optimal design. Ave optimal designs are of interest when e.g. a factorial experiment with a binary or a Poisson response in to be conducted. The results are applied to factorial experiments, including a control group experiment and a 2×2 experiment.     

Optimal experimental design criterion for discriminating semiparametric models

This paper studies the optimal experimental design problem to discriminate two regression models. Recently, López-Fidalgo et al. [2007. An optimal experimental design criterion for discriminating between non-normal models. J. Roy. Statist. Soc. B 69, 231–242] extended the conventional T-optimality criterion by Atkinson and Fedorov [1975a. The designs of experiments for discriminating between two rival models. Biometrika 62, 57–70; 1975b. Optimal design: experiments for discriminating between several models. Biometrika 62, 289–303] to deal with non-normal parametric regression models, and proposed a new optimal experimental design criterion based on the Kullback–Leibler information divergence. In this paper, we extend their parametric optimality criterion to a semiparametric setup, where we only need to specify some moment conditions for the null or alternative regression model. Our criteria, called the semiparametric Kullback–Leibler optimality criteria, can be implemented by applying a convex duality result of partially finite convex programming. The proposed method is illustrated by a simple numerical example.     

Optimal block designs comparing treatments with a control when the errors are correlated

The efficient design of experiments for comparing a control with v new treatments when the data are dependent is investigated. We concentrate on generalized least-squares estimation for a known covariance structure. We consider block sizes k equal to 3 or 4 and approximate designs. This method may lead to exact optimal designs for some v, b, k, but usually will only indicate the structure of an efficient design for any particular v, b, k, and yield an efficiency bound, usually unattainable. The bound and the structure can then be used to investigate efficient finite designs.     

Nested Latin Hypercube Designs with Sliced Structures

In computer experiments, space-filling designs with a sliced structure or nested structure have received much recent interest and been studied separately. However, it is likely that designs with both structures are needed in some situations, but there are no suitable designs so far. In this paper, we construct a special class of nested Latin hypercube designs with sliced structures, in such a design, a small sliced Latin hypercube design is nested within a large one. The construction method is easy to implement and the number of factors is flexible. Numerical simulations show the usefulness of the newly proposed designs.     

The existence of the strong combined-optimal design

The technique of fold-over is useful for conducting follow-up experiments. Based on the minimum aberration criterion, Li and Lin (2003) developed an algorithm and used computer to search the corresponding optimal foldover designs for 16 and 32 runs in the 2 ^k-p design. In their study, they found that the 2¹⁰⁻⁶ design is the only one that is not a strong combined-optimal design among all the designs. However, they did not interpret the reason causing the phenomenon. This article will explore under what kind of conditions, that the strong combined-optimal design will exist, and the solutions of the related problems.     

Design issues for population growth models

We briefly review and discuss design issues for population growth and decline models. We then use a flexible growth and decline model as an illustrative example and apply optimal design theory to find optimal sampling times for estimating model parameters, specific parameters and interesting functions of the model parameters for the model with two real applications. Robustness properties of the optimal designs are investigated when nominal values or the model is mis-specified, and also under a different optimality criterion. To facilitate use of optimal design ideas in practice, we also introduce a website for generating a variety of optimal designs for popular models from different disciplines.     

Convergence properties of sequential Bayesian D-optimal designs

We establish convergence properties of sequential Bayesian optimal designs. In particular, for sequential D-optimality under a general nonlinear location-scale model for binary experiments, we establish posterior consistency, consistency of the design measure, and the asymptotic normality of posterior following the design. We illustrate our results in the context of a particular application in the design of phase I clinical trials, namely a sequential design of Haines et al. [2003. Bayesian optimal designs for phase I clinical trials. Biometrics 59, 591–600] that incorporates an ethical constraint on overdosing.     

Optimum Mixture Design for the Detection of Synergistic Effects

In mixture experiments, optimal designs for the estimation of parameters, both linear and non-linear, have been discussed by several authors. Optimal designs for the estimation of a subset of parameters have also been investigated. However, designs for testing the effects of certain factors and interactions have been studied only in the context of response surface models. In this article, we attempt to find the optimum design for testing the presence of synergistic effects in a mixture model. The classical F-test has been considered and the optimum design has been obtained so as to maximize the power of the test. It is observed that the barycenters are necessarily the support points of the trace-optimal design.     

Efficient designs for constrained mixture experiments

Many practical experiments on mixtures (where the components sum to one) include additional lower or upper bounds on components, or on linear combinations of them. Usually theory cannot be used to obtain a good design, and algorithmic methods are necessary. Some of the available methods are discussed. Their performance is evaluated on some examples, and the form of the optimal design is investigated.     

Robust designs for experiments with blocks

ABSTRACT

For experiments running in field plots or over time, the observations are often correlated due to spatial or serial correlation, which leads to correlated errors in a linear model analyzing the treatment means. Without knowing the exact correlation matrix of the errors, it is not possible to compute the generalized least-squares estimator for the treatment means and use it to construct optimal designs for the experiments. In this paper, we propose to use neighborhoods to model the covariance matrix of the errors, and apply a modified generalized least-squares estimator to construct robust designs for experiments with blocks. A minimax design criterion is investigated, and a simulated annealing algorithm is developed to find robust designs. We have derived several theoretical results, and representative examples are presented.     

Asymptotically Optimal Design Points for Rejection Algorithms

ABSTRACT

Very fast automatic rejection algorithms were developed recently which allow us to generate random variates from large classes of unimodal distributions. They require the choice of several design points which decompose the domain of the distribution into small sub-intervals. The optimal choice of these points is an important but unsolved problem. Therefore, we present an approach that allows us to characterize optimal design points in the asymptotic case (when their number tends to infinity) under mild regularity conditions. We describe a short algorithm to calculate these asymptotically optimal points in practice. Numerical experiments indicate that they are very close to optimal even when only six or seven design points are calculated.