Generalized confounded row–column designs

Generalized Confounded Row–Column (GCRC) designs for factorial experiments have been introduced and methods of constructing GCRC designs have been discussed. Fractionally replicated GCRC designs have also been constructed. The designs obtained ensure balancing with respect to estimable effects.     

A class of saturated row–column designs

A new class of row–column designs is proposed. These designs are saturated in terms of eliminating two-way heterogeneity with an additive model. The (m,s)-criterion is used to select optimal designs. It turns out that all (m,s)-optimal designs are binary. Square (m,s)-optimal designs are constructed and they are treatment-connected. Thus, all treatment contrasts are estimable regardless of the row and column effects.     

Orthogonal main-effect plans in row–column designs for two-level factorial experiments

Row–column designs for two-level factorial experiments are constructed to estimate all the main effects. We give the interactions for row and column blockings. Based on these blockings, independent treatment combinations are proposed to establish the whole design so that practitioners can easily apply it to their experiments. Some examples are given for illustrations. The estimation of two-factor interactions in these designs is discussed.     

Algorithm for determining whether various two-level fractional factorial split-plot row–column designs are non-isomorphic

The confounding and aliasing scheme for fractional factorial split-plot designs with the units within each wholeplot arranged in rows and columns is described and illustrated. Isomorphism for this design type is described, together with a procedure which considers extensions of the concepts of wordlength patterns and letter patterns that can be used to test isomorphism between designs. Using in part this isomorphism testing procedure, a construction algorithm that may be used to obtain a complete set of such non-isomorphic two-level designs is described. Software based on this construction algorithm was used to obtain a complete set of non-isomorphic designs for up to five wholeplot factors, five subplot factors and up to 64 runs, which is presented as a table of designs. To aid the experimenter in distinguishing between competing designs, the estimation capacity sequence for each design is presented.     

Optimal row–column design for three treatments

The A-optimality problem is solved for three treatments in a row–column layout. Depending on the numbers of rows and columns, the requirements for optimality can be decidedly counterintuitive: replication numbers need not be as equal as possible, and trace of the information matrix need not be maximal. General rules for comparing 3×3$3\times 3$ information matrices for their A-behavior are also developed, and the A-optimality problem is also solved for three treatments in simple block designs.     

Variance-balanced row–column designs involving diallel crosses incorporating specific combining abilities for comparing test lines with a control line

In this paper, the problem of comparing t test lines with a control line under a row–column setup in complete diallel cross experiment is investigated when specific combining ability (sca) effect is included in the model. Three classes of Mating-Environmental Row–Column (MERC) designs have been obtained which are variance balanced for estimating the contrasts pertaining to general combining ability (gca) effects free from sca effects.     

Some new augmented fractional Box–Behnken designs

The augmented Box–Behnken designs are used in the situations in which Box–Behnken designs (BBDs) could not estimate the response surface model due to the presence of third-order terms in the response surface models. These designs are too large for experimental use. Usually experimenters prefer small response surface designs in order to save time, cost, and resources; therefore, using combinations of fractional BBD points, factorial design points, axial design points, and complementary design points, we augment these designs and develop new third-order response surface designs known as augmented fractional BBDs (AFBBDs). These AFBBDs have less design points and are more efficient than augmented BBDs.     

Max–min optimal discriminating designs for several statistical models

In the literature, different optimality criteria have been considered for model identification. Most of the proposals assume the normal distribution for the response variable and thus they provide optimality criteria for discriminating between regression models. In this paper, a max–min approach is followed to discriminate among competing statistical models (i.e., probability distribution families). More specifically, k different statistical models (plausible for the data) are embedded in a more general model, which includes them as particular cases. The proposed optimal design maximizes the minimum KL-efficiency to discriminate between each rival model and the extended one. An equivalence theorem is proved and an algorithm is derived from it, which is useful to compute max–min KL-efficiency designs. Finally, the algorithm is run on two illustrative examples.     

Estimating improvement in prediction with matched case–control designs

When an existing risk prediction model is not sufficiently predictive, additional variables are sought for inclusion in the model. This paper addresses study designs to evaluate the improvement in prediction performance that is gained by adding a new predictor to a risk prediction model. We consider studies that measure the new predictor in a case–control subset of the study cohort, a practice that is common in biomarker research. We ask if matching controls to cases in regards to baseline predictors improves efficiency. A variety of measures of prediction performance are studied. We find through simulation studies that matching improves the efficiency with which most measures are estimated, but can reduce efficiency for some. Efficiency gains are less when more controls per case are included in the study. A method that models the distribution of the new predictor in controls appears to improve estimation efficiency considerably.     

Generation of d–optimal designs in a finite design space

This paper presents some considerations about the numerical procedures for generating D–optimal design in a finite design space. The influence of starting procedures and the finite set of points on the design efficiency is considered. Some modifications of the existing procedures for D–optimal designs generation are described. It is shown that for large number of factors the sequential procedures are more appropriate than the nonsequential ones     

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.     

Orthogonally blocked mixture component–amount designs via projections of F-squares

Orthogonal block designs for Scheffé’s quadratic model have been considered previously by Draper et al. (1993), John (1984), Lewis et al. (1994) and Prescott, Draper, Dean, and Lewis (1993). Prescott and Draper (2004) obtained mixture component–amount designs via projections of standard mixture designs, viz., the simplex-lattice, the simplex-centroid and the orthogonally blocked mixture designs based on latin squares. Aggarwal, Singh, Sarin, and Husain (2009) considered the case of components assuming equal volume fractions and obtained mixture designs in orthogonal blocks using F-squares. In this paper, we construct orthogonal blocks of two and three mixture component–amount blends by projecting the class of four component mixture designs presented by Aggarwal et al. (2009).     

Optimal Latin hypercube designs for the Kullback–Leibler criterion

Space-filling designs are commonly used for selecting the input values of time-consuming computer codes. Computer experiment context implies two constraints on the design. First, the design points should be evenly spread throughout the experimental region. A space-filling criterion (for instance, the maximin distance) is used to build optimal designs. Second, the design should avoid replication when projecting the points onto a subset of input variables (non-collapsing). The Latin hypercube structure is often enforced to ensure good projective properties. In this paper, a space-filling criterion based on the Kullback–Leibler information is used to build a new class of Latin hypercube designs. The new designs are compared with several traditional optimal Latin hypercube designs and appear to perform well.     

Adaptive designs for selecting drug combinations based on efficacy–toxicity response

We propose a new adaptive procedure for dose-finding in clinical trials with combination of two drugs when both efficacy and toxicity responses are available. We model the distribution of this bivariate binary endpoint using the bivariate probit model. The analytic formulae for the Fisher information matrix are obtained, that form the basis for derivation of the locally optimal, minimax, Bayesian, and adaptive designs in the framework of optimal design theory.     

A Mann–Whitney type effect measure of interaction for factorial designs

We propose a measure for interaction for factorial designs that is formulated in terms of a probability similar to the effect size of the Mann–Whitney test. It is shown how asymptotic confidence intervals can be obtained for the effect size and how a statistical test can be constructed. We further show how the test is related to the test proposed by Bhapkar and Gore [Sankhya A, 36:261–272 (1974)]. The results of a simulation study indicate that the test has good power properties and illustrate when the asymptotic approximations are adequate. The effect size is demonstrated on an example dataset.     

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.     

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.     

Conditional logistic regression in cluster-specific 1: m matched treatment–control designs

Conditional logistic regression is a popular method for estimating a treatment effect while eliminating cluster-specific nuisance parameters when they are not of interest. Under a cluster-specific 1: m matched treatment–control study design, we present a new closed-form relationship between the conditional logistic regression estimator and the ordinary logistic regression estimator. In addition, we prove an equivalence between the ordinary logistic regression and the conditional logistic regression estimators, when the clusters are replicated infinitely often, which indicates that potential bias concerns when applying conditional logistic regression to complex survey samples.     

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.