Implementation of maximin efficient designs in dose‐finding studies

This paper considers the maximin approach for designing clinical studies. A maximin efficient design maximizes the smallest efficiency when compared with a standard design, as the parameters vary in a specified subset of the parameter space. To specify this subset of parameters in a real situation, a four‐step procedure using elicitation based on expert opinions is proposed. Further, we describe why and how we extend the initially chosen subset of parameters to a much larger set in our procedure. By this procedure, the maximin approach becomes feasible for dose‐finding studies. Maximin efficient designs have shown to be numerically difficult to construct. However, a new algorithm, the H‐algorithm, considerably simplifies the construction of these designs. We exemplify the maximin efficient approach by considering a sigmoid Emax model describing a dose–response relationship and compare inferential precision with that obtained when using a uniform design. The design obtained is shown to be at least 15% more efficient than the uniform design. © 2014 The Authors. Pharmaceutical Statistics Published by John Wiley & Sons Ltd.     

Creating catalogues of two-level nonregular fractional factorial designs based on the criteria of generalized aberration

We consider the problem of constructing good two-level nonregular fractional factorial designs. The criteria of minimum G and G₂ aberration are used to rank designs. A general design structure is utilized to provide a solution to this practical, yet challenging, problem. With the help of this design structure, we develop an efficient algorithm for obtaining a collection of good designs based on the aforementioned two criteria. Finally, we present some results for designs of 32 and 40 runs obtained from applying this algorithmic approach.     

Graph based isomorph-free generation of two-level regular fractional factorial designs

We provide a new necessary and sufficient check for testing the isomorphism of two 2-level regular fractional factorial designs. The approach is based on modeling fractional factorial designs as bipartite graphs. We employ an efficient canonical graph labeling approach to compare two designs for isomorphism. We then improve upon the existing non-isomorphic fractional factorial design generation algorithm by reducing the number of candidate designs from which isomorphs need to be removed. Not only does our method generate non-isomorphic designs much faster, it is also able to generate designs with run sizes of 2048 and 4096 runs, which were not generated by the existing methods.     

Algorithmic and analytical construction of efficient designs in small blocks for comparing consecutive pairs of treatments

Optimal block designs in small blocks are explored under the A-, E- and D-criteria when the treatments have a natural ordering and interest lies in comparing consecutive pairs of treatments. We first formulate the problem via approximate theory which leads to a convenient multiplicative algorithm for obtaining A-optimal design measures. This, in turn, yields highly efficient exact designs, under the A-criterion, even when the number of blocks is rather small. Moreover, our approach is seen to allow nesting of such efficient exact designs which is an advantage when the resources for the experiment are available in possibly several stages. Illustrative examples are given and tables of A-optimal design measures are provided. Approximate theory is also seen to yield analytical results on E- and D-optimal design measures.     

An Adaptive Exploration-Exploitation Algorithm for Constructing Metamodels in Random Simulation Using a Novel Sequential Experimental Design

In this article, we propose a novel algorithm for sequential design of metamodels in random simulation, which combines the exploration capability of most one-shot space-filling designs with the exploitation feature of common sequential designs. The algorithm continuously maintains a balance between the exploration and the exploitation search throughout the search process in a sequential and adaptive manner. The numerical results indicate that the proposed approach is superior to one of the existing well-known sequential designs in terms of both the computational efficiency and speed in generating efficient experimental designs.     

Constructing Efficient Experimental Designs for Generalized Linear Models

Exchange algorithms are popular for finding optimal or efficient designs for linear models, but there are few discussions of this type of algorithm for generalized linear models (GLMs) in literature. A new algorithm, generalized Coordinate Exchange Algorithm (gCEA), is developed in this article to construct efficient designs for GLMs. We compare the performance of the proposed algorithm with other optimization algorithms, including point exchange algorithm, columnwise-pairwise algorithm, simulated annealing and generic algorithm, and demonstrate the superior performance of this new algorithm.     

Adaptive grid semidefinite programming for finding optimal designs

We find optimal designs for linear models using a novel algorithm that iteratively combines a semidefinite programming (SDP) approach with adaptive grid techniques. The proposed algorithm is also adapted to find locally optimal designs for nonlinear models. The search space is first discretized, and SDP is applied to find the optimal design based on the initial grid. The points in the next grid set are points that maximize the dispersion function of the SDP-generated optimal design using nonlinear programming. The procedure is repeated until a user-specified stopping rule is reached. The proposed algorithm is broadly applicable, and we demonstrate its flexibility using (i) models with one or more variables and (ii) differentiable design criteria, such as A-, D-optimality, and non-differentiable criterion like E-optimality, including the mathematically more challenging case when the minimum eigenvalue of the information matrix of the optimal design has geometric multiplicity larger than 1. Our algorithm is computationally efficient because it is based on mathematical programming tools and so optimality is assured at each stage; it also exploits the convexity of the problems whenever possible. Using several linear and nonlinear models with one or more factors, we show the proposed algorithm can efficiently find optimal designs.     

Balanced treatment incomplete block designs through integer programming

An algorithm is presented to construct balanced treatment incomplete block (BTIB) designs using a linear integer programming approach. Construction of BTIB designs using the proposed approach is illustrated with an example. A list of efficient BTIB designs for 2 ? v ? 12, v + 1 ? b ? 50, 2 ? k ? min(10, v), r ? 10, r₀ ? 20 is provided. The proposed algorithm is implemented as part of an R package.     

Optimal minimax designs for prediction in heteroscedastic models

We construct optimal designs for heteroscedastic models when the goal is to make efficient prediction over a compact interval. It is assumed that the point or points which are interesting to predict are not known before the experiment is run. Two minimax strategies for minimizing the maximum fitted variance and maximum predictive variance across the interval of interest are proposed and, optimal designs are found and compared. An algorithm for generating these designs is included.     

Optimal and efficient crossover designs for comparing test treatments to a control treatment under various models

We study the optimality, efficiency, and robustness of crossover designs for comparing several test treatments to a control treatment. Since A-optimality is a natural criterion in this context, we establish lower bounds for the trace of the inverse of the information matrix for the test treatments versus control comparisons under various models. These bounds are then used to obtain lower bounds for efficiencies of a design under these models. Two algorithms, both guided by these efficiencies and results from optimal design theory, are proposed for obtaining efficient designs under the various models.     

Maximin efficient design of experiment for exponential regression models

In this paper robust and efficient designs are derived for several exponential decay models. These models are widely used in chemistry, pharmacokinetics or microbiology. We propose a maximin approach, which determines the optimal design such that a minimum of the D-efficiencies (taken over a certain range) becomes maximal. Analytic solutions are derived if optimization is performed in the class of minimal supported designs. In general the optimal designs with respect to the maximin criterion have to be determined numerically and some properties of these designs are also studied. We also illustrate the benefits of our approach by reanalysing a data example from the literature.     

An algorithm for constructing optimal resolvable incomplete block designs

This paper describes an efficient algorithm for the construction of optimal or near-optimal resolvable incomplete block designs (IBDs) for any number of treatments v < 100. The performance of this algorithm is evaluated against known lattice designs and the 414 or-designs of Patterson & Williams [36]. For the designs under study, it appears that our algorithm is about equally effective as the simulated annealing algorithm of Venables & Eccleston [42]. An example of the use of our algorithm to construct the row (or column) components of resolvable row-column designs is given.     

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.     

RANDOMIZED SEARCH STRATEGIES FOR FINDING OPTIMAL OR NEAR OPTIMAL BLOCK AND ROW-COLUMN DESIGNS

We consider a family of effective and efficient strategies for generating experimental designs of several types with high efficiency. These strategies employ randomized search directions and at some stages allow the possibility of taking steps in a direction of decreasing efficiency in an effort to avoid local optima. Hence our strategies have some affinity with the simulated annealing algorithm of combinatorial optimization. The methods work well and compare favourably with other search strategies. We have implemented them for incomplete block designs, optionally resolvable, and for row-column designs.     

On minimax designs when there are two candidate models

This work is motivated by the need to find experimental designs which are robust under different model assumptions. We measure robustness by calculating a measure of design efficiency with respect to a design optimality criterion and say that a design is robust if it is reasonably efficient under different model scenarios. We discuss two design criteria and an algorithm which can be used to obtain robust designs. The first criterion employs a Bayesian-type approach by putting a prior or weight on each candidate model and possibly priors on the corresponding model parameters. We define the first criterion as the expected value of the design efficiency over the priors. The second design criterion we study is the minimax design which minimizes the worst value of a design criterion over all candidate models. We establish conditions when these two criteria are equivalent when there are two candidate models. We apply our findings to the area of accelerated life testing and perform sensitivity analysis of designs with respect to priors and misspecification of planning values.     

An efficient algorithm for constructing optimal design of computer experiments

The long computational time required in constructing optimal designs for computer experiments has limited their uses in practice. In this paper, a new algorithm for constructing optimal experimental designs is developed. There are two major developments involved in this work. One is on developing an efficient global optimal search algorithm, named as enhanced stochastic evolutionary (ESE) algorithm. The other is on developing efficient methods for evaluating optimality criteria. The proposed algorithm is compared to existing techniques and found to be much more efficient in terms of the computation time, the number of exchanges needed for generating new designs, and the achieved optimality criteria. The algorithm is also very flexible to construct various classes of optimal designs to retain certain desired structural properties.     

A semi-infinite programming based algorithm for finding minimax optimal designs for nonlinear models

Minimax optimal experimental designs are notoriously difficult to study largely because the optimality criterion is not differentiable and there is no effective algorithm for generating them. We apply semi-infinite programming (SIP) to solve minimax design problems for nonlinear models in a systematic way using a discretization based strategy and solvers from the General Algebraic Modeling System (GAMS). Using popular models from the biological sciences, we show our approach produces minimax optimal designs that coincide with the few theoretical and numerical optimal designs in the literature. We also show our method can be readily modified to find standardized maximin optimal designs and minimax optimal designs for more complicated problems, such as when the ranges of plausible values for the model parameters are dependent and we want to find a design to minimize the maximal inefficiency of estimates for the model parameters.     

Functional Autoregression for Sparsely Sampled Data

We develop a hierarchical Gaussian process model for forecasting and inference of functional time series data. Unlike existing methods, our approach is especially suited for sparsely or irregularly sampled curves and for curves sampled with nonnegligible measurement error. The latent process is dynamically modeled as a functional autoregression (FAR) with Gaussian process innovations. We propose a fully nonparametric dynamic functional factor model for the dynamic innovation process, with broader applicability and improved computational efficiency over standard Gaussian process models. We prove finite-sample forecasting and interpolation optimality properties of the proposed model, which remain valid with the Gaussian assumption relaxed. An efficient Gibbs sampling algorithm is developed for estimation, inference, and forecasting, with extensions for FAR(p) models with model averaging over the lag p. Extensive simulations demonstrate substantial improvements in forecasting performance and recovery of the autoregressive surface over competing methods, especially under sparse designs. We apply the proposed methods to forecast nominal and real yield curves using daily U.S. data. Real yields are observed more sparsely than nominal yields, yet the proposed methods are highly competitive in both settings. Supplementary materials, including R code and the yield curve data, are available online.     

Construction of Efficient Multi-Level k-Circulant Supersaturated Designs

This article proposes an algorithm to construct efficient balanced multi-level k-circulant supersaturated designs with m factors and n runs. The algorithm generates efficient balanced multi-level k-circulant supersaturated designs very fast. Using the proposed algorithm many balanced multi-level supersaturated designs are constructed and cataloged. A list of many optimal and near optimal, multi-level supersaturated designs is also provided for m ≤ 60 and number of levels (q) ≤10. The algorithm can be used to generate two-level k-circulant supersaturated designs also and some large optimal two-level supersaturated designs are presented. An upper bound to the number of factors in a balanced multi-level supersaturated design such that no two columns are fully aliased is also provided.     

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.