An introduction to designh optimality with an overview of the literature

A brief introduction to oprimal design theorv is given for those who are not familiar with the subject. A list of 312 selected articles on the theory of optimal design is provided. The bibliography should be sufficiently thorough to be of use to researchers in the field.     

Statistical methodology for binary data from a set of partially structured two-way random cross-classifications

A complete two-way cross-classification design is not practical in many settings. For example, in a toxicological study where 30 male rats are mated with 30 female rats and each mating outcome (successful or unsuccessful)is observed, time and resource considerations can make the use of the complete design prohibitively costly. Partially structured variations of this design are, therefore, of interest (e.g., the balanced disjoint rectangle design, the fully diagonal design, and the "S"-design). Methodology for analyzing binary data from such incomplete designs is illustrated with an example. This methodology, which is based on infinite population sampling arguments, allows the estimation of the mean response, among-row correlation coefficient, among-column correlation coefficient, and the within-cell correlation coefficient as well as their standard errors.     

Regular E-Optimal Spring Balance Weighing Designs with Correlated Errors

The problems linked with an E-optimal spring balance weighing design with correlated errors are discussed. The topic is focus on the determining the maximal eigenvalue of the inverse of the information matrix of estimators. The constructing method of the E-optimal design, based on the incidence matrices of balanced incomplete block designs, is presented.     

The plan of enrichment designs for dealing with high placebo response

To deal with high placebo response in clinical trials for psychiatric and other diseases, different enrichment designs, such as the sequential parallel design, two‐way enriched design, and sequential enriched design, have been proposed and implemented recently. Depending on the historical trial information and the trial sponsors' resources, detailed design elements are needed for determining which design to adopt. To assist in making more suitable decisions, we perform evaluations for selecting required design elements in terms of power optimization and sample size planning. We also discuss the implementation of the interim analysis related to its applicability.     

Lower bounds of various criteria in experimental designs

Criterion is essential for measuring the goodness of an experimental design. In this paper, lower bounds of various criteria in experimental designs will be reviewed according to methodology of their construction. The criteria include most well-known ones which are frequently used as benchmarks for orthogonal array, uniform design, supersaturated design and other types of designs. To derive the lower bounds of these criteria, five different approaches are explored. Some new results are given. Throughout the paper, some relationships among different types of lower bounds are also discussed.     

Bayesian design for estimating the turning point of a quadratic regression

The problem of designing an experiment to estimate the point at which a quadratic regression is a maximum, or minimum. is studied. The efficiency of a design depends on the value of the unknown parameters and sequential design is, therefore, more efficient than non-sequential design. We use a Bayesian criterion which is a weighted trace of the inverse of the information matrix with the weights depending on a prior distribution. If design occurs sequentially the weights can be updated. Both sequential and non-sequential Bayesian designs are compared to non-Bayesian sequential designs. The comparison is both theoretical and by simulation.     

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.     

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.     

Finite sample performance of sequential designs for model identification

Classical regression analysis is usually performed in two steps. In the first step, an appropriate model is identified to describe the data generating process and in the second step, statistical inference is performed in the identified model. An intuitively appealing approach to the design of experiment for these different purposes are sequential strategies, which use parts of the sample for model identification and adapt the design according to the outcome of the identification steps. In this article, we investigate the finite sample properties of two sequential design strategies, which were recently proposed in the literature. A detailed comparison of sequential designs for model discrimination in several regression models is given by means of a simulation study. Some non-sequential designs are also included in the study.     

Improving The Efficiency of The Case-Crossover Design

The case-crossover design has been used by many researchers to study the transient effect of an exposure on the risk of a rare outcome. In a case-crossover design, only cases are sampled and each case will act as his/her own control. The time of failure acts as the case and non failure times act as the controls. Case-crossover designs have frequently been used to study the effect of environmental exposures on rare diseases or mortality. Time trends and seasonal confounding may be present in environmental studies and thus need to be controlled for by the sampling design. Several sampling methods are available for this purpose. In time-stratified sampling, disjoint strata of equal size are formed and the control times within the case stratum are used for comparison. The random semi-symmetric sampling design randomly selects a control time for comparison from two possible control times. The fixed semi-symmetric sampling design is a modified version of the random semi-symmetric sampling design that removes the random selection. Simulations show that the fixed semi-symmetric sampling design improves the variance of the random semi-symmetric sampling estimator by at least 35% for the exposures we studied. We derive expressions for the asymptotic variance of risk estimators for these designs, and show, that while the designs are not theoretically equivalent, in many realistic situations, the random semi-symmetric sampling design has similar efficiency to a time-stratified sampling design of size two and the fixed semi-symmetric sampling design has similar efficiency to a time-stratified sampling design of size three.     

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.     

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.     

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.     

A Bayesian adaptive design for biosimilar trials with time-to-event endpoint

A biosimilar drug is a biological product that is highly similar to and at the same time has no clinically meaningful difference from licensed product in terms of safety, purity, and potency. Biosimilar study design is essential to demonstrate the equivalence between biosimilar drug and reference product. However, existing designs and assessment methods are primarily based on binary and continuous endpoints. We propose a Bayesian adaptive design for biosimilarity trials with time-to-event endpoint. The features of the proposed design are twofold. First, we employ the calibrated power prior to precisely borrow relevant information from historical data for the reference drug. Second, we propose a two-stage procedure using the Bayesian biosimilarity index (BBI) to allow early stop and improve the efficiency. Extensive simulations are conducted to demonstrate the operating characteristics of the proposed method in contrast with some naive method. Sensitivity analysis and extension with respect to the assumptions are presented.     

Characterizing projected designs: repeat and mirror-image runs

Two-level designs are useful to examine a large number of factors in an efficient manner. It is typically anticipated that only a few factors will be identified as important ones. The results can then be reanalyzed using a projection of the original design, projected into the space of the factors that matter. An interesting question is how many intrinsically different type of projections are possible from an initial given design. We examine this question here for the Plackett and Burman screening series with N= 12, 20 and 24 runs and projected dimensions k≤5. As a characterization criterion, we look at the number of repeat and mirror-image runs in the projections. The idea can be applied toany two-level design projected into fewer dimensions.     

Parallel, AA/BB, AB/BA and Balaam's design: efficient and maximin choices when testing the treatment effect in a mixed effects linear regression

When examining the effect of treatment A versus B, there may be a choice between a parallel group design, an AA/BB design, an AB/BA cross‐over and Balaam's design. In case of a linear mixed effects regression, it is examined, starting from a flexible function of the costs involved and allowing for subject dropout, which design is most efficient in estimating this effect. For no carry‐over, the AB/BA cross‐over design is most efficient as long as the dropout rate at the second measurement does not exceed 2ρ/(1 + ρ), ρ being the intraclass correlation. For steady‐state carry‐over, depending on the costs involved, the dropout rate and ρ, either a parallel design or an AA/BB design is most efficient. For types of carry‐over that allow for self carry‐over, interest is in the direct treatment effect plus the self carry‐over effect, with either an AA/BB or Balaam's design being most efficient. In case of insufficient knowledge on the dropout rate or ρ, a maximin strategy is devised: choose the design that minimizes the maximum variance of the treatment estimator. Such maximin designs are derived for each type of carry‐over. Copyright © 2012 John Wiley & Sons, Ltd.     

Simplex based space filling designs

Space filling designs are important for deterministic computer experiments. Even a single experiment can be very time consuming and can have many input parameters. Furthermore the underlying function generating the output is often nonlinear. Thus, the computer experiment has to be designed carefully. There exist many design criteria, which can be numerically optimized. Here, a method is developed, which does not need algorithmic optimization. A mesh of nearly regular simplices is constructed and the vertices of the simplices are used as potential design points. The extraction of a design from these meshes is very fast and easy to implement once the underlying mesh has been constructed. The extracted designs are highly competitive regarding the maximin design criterion and it is easy to extract designs for nonstandard design spaces.     

The robustness of response surface designs with errors in factor levels

ABSRTACT

Since errors in factor levels affect the traditional statistical properties of response surface designs, an important question to consider is robustness of design to errors. However, when the actual design could be observed in the experimental settings, its optimality and prediction are of interest. Various numerical and graphical methods are useful tools for understanding the behavior of the designs. The D- and G-efficiencies and the fraction of design space plot are adapted to assess second-order response surface designs where the predictor variables are disturbed by a random error. Our study shows that the D-efficiencies of the competing designs are considerably low for big variance of the error, while the G-efficiencies are quite good. Fraction of design space plots display the distribution of the scaled prediction variance through the design space with and without errors in factor levels. The robustness of experimental designs against factor errors is explored through comparative study. The construction and use of the D- and G-efficiencies and the fraction of design space plots are demonstrated with several examples of different designs with errors.     

Optimal parametric design with applications to pharmacokinetic and pharmacodynamic trials

This paper considers optimal parametric designs, i.e. designs represented by probability measures determined by a set of parameters, for nonlinear models and illustrates their use in designs for pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) trials. For some practical problems, such as designs for modelling PK/PD relationship, this is often the only feasible type of design, as the design points follow a PK model and cannot be directly controlled. Even for ordinary design problems the parametric designs have some advantages over the traditional designs, which often have too few design points for model checking and may not be robust to model and parameter misspecifications. We first describe methods and algorithms to construct the parametric design for ordinary nonlinear design problems and show that the parametric designs are robust to parameter misspecification and have good power for model discrimination. Then we extend this design method to construct optimal repeated measurement designs for nonlinear mixed models. We also use this parametric design for modelling a PK/PD relationship and propose a simulation based algorithm. The application of parametric designs is illustrated with a three-parameter open one-compartment PK model for the ordinary design and repeated measurement design, and an Emax model for the phamacokinetic/pharmacodynamic trial design.