A new variable selection method for uniform designs

As an important class of space-filling designs, uniform designs (UDs) choose a set of points over a certain domain such that these points are uniformly scattered, under a specific discrepancy measure. They have been applied successfully in many industrial and scientific experiments since they appeared in 1980. A noteworthy and practical advantage is their ability to investigate a large number of high-level factors simultaneously with a fairly economical set of experimental runs. As a result, UDs can be properly used as experimental plans that are intended to derive the significant factors from a list of many potential ones. To this end, a new screening procedure is introduced via penalized least squares. A simulation study is conducted to support the proposed method, which reveals that it can be considered quite promising and expedient, as judged in terms of Type I and Type II error rates.     

Efficient three-level screening designs using weighing matrices

Screening is the first stage of many industrial experiments and is used to determine efficiently and effectively a small number of potential factors among a large number of factors which may affect a particular response. In a recent paper, Jones and Nachtsheim [A class of three-level designs for definitive screening in the presence of second-order effects. J. Qual. Technol. 2011;43:1–15] have given a class of three-level designs for screening in the presence of second-order effects using a variant of the coordinate exchange algorithm as it was given by Meyer and Nachtsheim [The coordinate-exchange algorithm for constructing exact optimal experimental designs. Technometrics 1995;37:60–69]. Xiao et al. [Constructing definitive screening designs using conference matrices. J. Qual. Technol. 2012;44:2–8] have used conference matrices to construct definitive screening designs with good properties. In this paper, we propose a method for the construction of efficient three-level screening designs based on weighing matrices and their complete foldover. This method can be considered as a generalization of the method proposed by Xiao et al. [Constructing definitive screening designs using conference matrices. J. Qual. Technol. 2012;44:2–8]. Many new orthogonal three-level screening designs are constructed and their properties are explored. These designs are highly D-efficient and provide uncorrelated estimates of main effects that are unbiased by any second-order effect. Our approach is relatively straightforward and no computer search is needed since our designs are constructed using known weighing matrices.     

Group screening method for the statistical analysis of -optimal mixed-level supersaturated designs

In this paper, we propose the application of group screening methods for analyzing data using E(f_NOD)-optimal mixed-level supersaturated designs possessing the equal occurrence property. Supersaturated designs are a large class of factorial designs which can be used for screening out the important factors from a large set of potentially active variables. The huge advantage of these designs is that they reduce the experimental cost drastically, but their critical disadvantage is the high degree of confounding among factorial effects. Based on the idea of the group screening methods, the f factors are sub-divided into g “group-factors”. The “group-factors” are then studied using the penalized likelihood statistical analysis methods at a factorial design with orthogonal or near-orthogonal columns. All factors in groups found to have a large effect are then studied in a second stage of experiments. A comparison of the Type I and Type II error rates of various estimation methods via simulation experiments is performed. The results are presented in tables and discussion follows.     

Equivalence of factorial designs with qualitative and quantitative factors

Two symmetric fractional factorial designs with qualitative and quantitative factors are equivalent if the design matrix of one can be obtained from the design matrix of the other by row and column permutations, relabeling of the levels of the qualitative factors and reversal of the levels of the quantitative factors. In this paper, necessary and sufficient methods of determining equivalence of any two symmetric designs with both types of factors are given. An algorithm used to check equivalence or non-equivalence is evaluated. If two designs are equivalent the algorithm gives a set of permutations which map one design to the other. Fast screening methods for non-equivalence are considered. Extensions of results to asymmetric fractional factorial designs with qualitative and quantitative factors are discussed.     

Experimental designs for detecting synergy and antagonism between two drugs in a pre‐clinical study

The identification of synergistic interactions between combinations of drugs is an important area within drug discovery and development. Pre‐clinically, large numbers of screening studies to identify synergistic pairs of compounds can often be ran, necessitating efficient and robust experimental designs. We consider experimental designs for detecting interaction between two drugs in a pre‐clinical in vitro assay in the presence of uncertainty of the monotherapy response. The monotherapies are assumed to follow the Hill equation with common lower and upper asymptotes, and a common variance. The optimality criterion used is the variance of the interaction parameter. We focus on ray designs and investigate two algorithms for selecting the optimum set of dose combinations. The first is a forward algorithm in which design points are added sequentially. This is found to give useful solutions in simple cases but can lack robustness when knowledge about the monotherapy parameters is insufficient. The second algorithm is a more pragmatic approach where the design points are constrained to be distributed log‐normally along the rays and monotherapy doses. We find that the pragmatic algorithm is more stable than the forward algorithm, and even when the forward algorithm has converged, the pragmatic algorithm can still out‐perform it. Practically, we find that good designs for detecting an interaction have equal numbers of points on monotherapies and combination therapies, with those points typically placed in positions where a 50% response is expected. More uncertainty in monotherapy parameters leads to an optimal design with design points that are more spread out. Copyright © 2015 John Wiley & Sons, Ltd.     

Orthogonal three-level parallel flats designs for user-specified resolution

Orthogonal factorial and fractional factorial designs are very popular in many experimental studies, particularly the two-level and three-level designs used in screening experiments. When an experimenter is able to specify the set of possibly nonnegligible factorial effects, it is sometimes possible to obtain an orthogonal design belonging to the class of parallel flats designs, that has a smaller run-size than a suitable design from the class of classical fractional factorial designs belonging to the class of single flat designs. Sri-vastava and Li (1996) proved a fundamental theorem of orthogonal s-level, s being a prime, designs of parallel flats type for the user-specified resolution. They also tabulated a series of orthogonal designs for the two-level case. No orthogonal designs for three-level case are available in their paper. In this paper, we present a simple proof for the theorem given in Srivastava and Li (1996) for the three-level case. We also give a dual form of the theorem, which is more useful for developing an algorithm for construction of orthogonal designs. Some classes of three-level orthogonal designs with practical run-size are given in the paper.     

An investigation of a quadratic design criterion for estimation of the hemodynamic response function

Optimal experimental design for estimation of the hemodynamic response function (HRF) is investigated using a nonlinear model with a quadratic mean squared error design criterion. This criterion is used, along with a genetic algorithm, to select locally optimal designs that are shown to be, in most cases, more efficient than designs selected with the more commonly used linear expansion criterion. These designs are also shown to result in lower overall asymptotic estimator variance and bias. The investigation focuses on a single stimulus type, but the criterion can also be used with multiple stimulus types.     

A hybrid elitist pareto-based coordinate exchange algorithm for constructing multi-criteria optimal experimental designs

This paper presents a new Pareto-based coordinate exchange algorithm for populating or approximating the true Pareto front for multi-criteria optimal experimental design problems that arise naturally in a range of industrial applications. This heuristic combines an elitist-like operator inspired by evolutionary multi-objective optimization algorithms with a coordinate exchange operator that is commonly used to construct optimal designs. Benchmarking results from both a two-dimensional and three-dimensional example demonstrate that the proposed hybrid algorithm can generate highly reliable Pareto fronts with less computational effort than existing procedures in the statistics literature. The proposed algorithm also utilizes a multi-start operator, which makes it readily parallelizable for high performance computing infrastructures.     

Variance-balanced designs under interference for dependent observations

It is shown that variance-balanced designs can be obtained from Type I orthogonal arrays for many general models with two kinds of treatment effects, including ones for interference, with general dependence structures. These designs can be used to obtain optimal and efficient designs. Some examples and design comparisons are given.     

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.     

Power of the adjusted Q statistic to evaluate heterogeneity in meta-analyses of cluster randomized trials

Because of its simplicity, the Q statistic is frequently used to test the heterogeneity of the estimated intervention effect in meta-analyses of individually randomized trials. However, it is inappropriate to apply it directly to the meta-analyses of cluster randomized trials without taking clustering effects into account. We consider the properties of the adjusted Q statistic for testing heterogeneity in the meta-analyses of cluster randomized trials with binary outcomes. We also derive an analytic expression for the power of this statistic to detect heterogeneity in meta-analyses, which can be useful when planning a meta-analysis. A simulation study is used to assess the performance of the adjusted Q statistic, in terms of its Type I error rate and power. The simulation results are compared to that obtained from the proposed formula. It is found that the adjusted Q statistic has a Type I error rate close to the nominal level of 5%, as compared to the unadjusted Q statistic commonly used to test for heterogeneity in the meta-analyses of individually randomized trials with an inflated Type I error rate. Data from a meta-analysis of four cluster randomized trials are used to illustrate the procedures.     

D-optimal minimax design criterion for two-level fractional factorial designs

A D-optimal minimax design criterion is proposed to construct two-level fractional factorial designs, which can be used to estimate a linear model with main effects and some specified interactions. D-optimal minimax designs are robust against model misspecification and have small biases if the linear model contains more interaction terms. When the D-optimal minimax criterion is compared with the D-optimal design criterion, we find that the D-optimal design criterion is quite robust against model misspecification. Lower and upper bounds derived for the loss functions of optimal designs can be used to estimate the efficiencies of any design and evaluate the effectiveness of a search algorithm. Four algorithms to search for optimal designs for any run size are discussed and compared through several examples. An annealing algorithm and a sequential algorithm are particularly effective to search for optimal designs.     

A Variable Selection Method for Analyzing Supersaturated Designs

Supersaturated designs are a large class of factorial designs which can be used for screening out the important factors from a large set of potentially active variables. The huge advantage of these designs is that they reduce the experimental cost drastically, but their critical disadvantage is the confounding involved in the statistical analysis. In this article, we propose a method for analyzing data using several types of supersaturated designs. Modifications of widely used information criteria are given and applied to the variable selection procedure for the identification of the active factors. The effectiveness of the proposed method is depicted via simulated experiments and comparisons.     

Influence analysis on crossover design experiment in bioequivalence studies

Crossover designs are commonly used in bioequivalence studies. However, the results can be affected by some outlying observations, which may lead to the wrong decision on bioequivalence. Therefore, it is essential to investigate the influence of aberrant observations. Chow and Tse in 1990 discussed this issue by considering the methods based on the likelihood distance and estimates distance. Perturbation theory provides a useful tool for the sensitivity analysis on statistical models. Hence, in this paper, we develop the influence functions via the perturbation scheme proposed by Hampel as an alternative approach on the influence analysis for a crossover design experiment. Moreover, the comparisons between the proposed approach and the method proposed by Chow and Tse are investigated. Two real data examples are provided to illustrate the results of these approaches. Our proposed influence functions show excellent performance on the identification of outlier/influential observations and are suitable for use with small sample size crossover designs commonly used in bioequivalence studies. Copyright © 2013 John Wiley & Sons, Ltd.     

Efficient designs for Bayesian networks with sub-tree bounds

We present upper and lower bounds for information measures, and use these to find the optimal design of experiments for Bayesian networks. The bounds are inspired by properties of the junction tree algorithm, which is commonly used for calculating conditional probabilities in graphical models like Bayesian networks. We demonstrate methods for iteratively improving the upper and lower bounds until they are sufficiently tight. We illustrate properties of the algorithm by tutorial examples in the case where we want to ensure optimality and for the case where the goal is an approximate solution with a guarantee. We further use the bounds to accelerate established algorithms for constructing useful designs. An example with petroleum fields in the North Sea is studied, where the design problem is related to exploration drilling campaigns. All of our examples consider binary random variables, but the theory can also be applied to other discrete or continuous distributions.     

Entropy of unequal probability sampling designs

There exist many designs for unequal probability sampling. In this paper entropy, which is a measure of randomness, is used to compare eight designs. Both old and commonly used designs and more recent designs are included. Several different and general estimates of entropy are presented. In the quest of finding entropy, expressions for the probability function are derived for different designs. One of them is a recent general design called correlated Poisson sampling. Several designs are close to having maximum entropy, which means that the designs are robust. A few designs yield low entropy and should therefore in general be avoided.     

Two‐stage phase II survival trial design

Recently, molecularly targeted agents and immunotherapy have been advanced for the treatment of relapse or refractory cancer patients, where disease progression‐free survival or event‐free survival is often a primary endpoint for the trial design. However, methods to evaluate two‐stage single‐arm phase II trials with a time‐to‐event endpoint are currently processed under an exponential distribution, which limits application of real trial designs. In this paper, we developed an optimal two‐stage design, which is applied to the four commonly used parametric survival distributions. The proposed method has advantages compared with existing methods in that the choice of underlying survival model is more flexible and the power of the study is more adequately addressed. Therefore, the proposed two‐stage design can be routinely used for single‐arm phase II trial designs with a time‐to‐event endpoint as a complement to the commonly used Simon's two‐stage design for the binary outcome.     

A powerful and efficient algorithm for breaking the links between aliased effects in asymmetric designs

Fractional factorial (FF) designs are no doubt the most widely used designs in experimental investigations due to their efficient use of experimental runs. One price we pay for using FF designs is, clearly, our inability to obtain estimates of some important effects (main effects or second order interactions) that are separate from estimates of other effects (usually higher order interactions). When the estimate of an effect also includes the influence of one or more other effects the effects are said to be aliased. Folding over an FF design is a method for breaking the links between aliased effects in a design. The question is, how do we define the foldover structure for asymmetric FF designs, whether regular or nonregular? How do we choose the optimal foldover plan? How do we use optimal foldover plans to construct combined designs which have better capability of estimating lower order effects? The main objective of the present paper is to provide answers to these questions. Using the new results in this paper as benchmarks, we can implement a powerful and efficient algorithm for finding optimal foldover plans which can be used to break links between aliased effects.     

On the analysis of unbalanced two-level supersaturated designs via generalized linear models

Supersaturated designs (SSDs) are factorial designs in which the number of experimental runs is smaller than the number of parameters to be estimated in the model. While most of the literature on SSDs has focused on balanced designs, the construction and analysis of unbalanced designs has not been developed to a great extent. Recent studies discuss the possible advantages of relaxing the balance requirement in construction or data analysis of SSDs, and that unbalanced designs compare favorably to balanced designs for several optimality criteria and for the way in which the data are analyzed. Moreover, the effect analysis framework of unbalanced SSDs until now is restricted to the central assumption that experimental data come from a linear model. In this article, we consider unbalanced SSDs for data analysis under the assumption of generalized linear models (GLMs), revealing that unbalanced SSDs perform well despite the unbalance property. The examination of Type I and Type II error rates through an extensive simulation study indicates that the proposed method works satisfactorily.     

A multi-objective coordinate-exchange two-phase local search algorithm for multi-stratum experiments

A multi-stratum design is a useful tool for industrial experimentation, where factors that have levels which are harder to set than others, due to time or cost constraints, are frequently included. The number of different levels of hardness to set defines the number of strata that should be used. The simplest case is the split-plot design, which includes two strata and two sets of factors defined by their level of hardness-to-set. In this paper, we propose a novel computational algorithm which can be used to construct optimal multi-stratum designs for any number of strata and up to six optimality criteria simultaneously. Our algorithm allows the study of the entire Pareto front of the optimization problem and the selection of the designs representing the desired trade-off between the competing objectives. We apply our algorithm to several real case scenarios and we show that the efficiencies of the designs obtained present experimenters with several good options according to their objectives.