A candidate-set-free algorithm for generating D-optimal split-plot designs

Summary.  We introduce a new method for generating optimal split-plot designs. These designs are optimal in the sense that they are efficient for estimating the fixed effects of the statistical model that is appropriate given the split-plot design structure. One advantage of the method is that it does not require the prior specification of a candidate set. This makes the production of split-plot designs computationally feasible in situations where the candidate set is too large to be tractable. The method allows for flexible choice of the sample size and supports inclusion of both continuous and categorical factors. The model can be any linear regression model and may include arbitrary polynomial terms in the continuous factors and interaction terms of any order. We demonstrate the usefulness of this flexibility with a 100-run polypropylene experiment involving 11 factors where we found a design that is substantially more efficient than designs that are produced by using other approaches.     

On the Choice of a Prior for Bayesian D-Optimal Designs for the Logistic Regression Model with a Single Predictor

The Bayesian design approach accounts for uncertainty of the parameter values on which optimal design depends, but Bayesian designs themselves depend on the choice of a prior distribution for the parameter values. This article investigates Bayesian D-optimal designs for two-parameter logistic models, using numerical search. We show three things: (1) a prior with large variance leads to a design that remains highly efficient under other priors, (2) uniform and normal priors lead to equally efficient designs, and (3) designs with four or five equidistant equally weighted design points are highly efficient relative to the Bayesian D-optimal designs.     

ADJUSTED ORTHOGONAL NESTED ROW-COLUMN DESIGNS

Adjusted orthogonality in nested row-column designs is defined and a sufficient condition established for its existence. It is shown that the properties of an adjusted orthogonal nested row-column design are directly related to those of its separate row and column component designs. A method for constructing efficient adjusted orthogonal designs involving a single replicate of every treatment in each of two blocks is given.     

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.     

On Robust and Efficient Designs for Risk Estimation in Epidemiological Studies

Abstract.  We consider the design problem for the estimation of several scalar measures suggested in the epidemiological literature for comparing the success rate in two samples. The designs considered so far in the literature are local in the sense that they depend on the unknown probabilities of success in the two groups and are not necessarily robust with respect to their misspecification. A maximin approach is proposed to obtain efficient and robust designs for the estimation of the relative risk, attributable risk and odds ratio, whenever a range for the success rates can be specified by the experimenter. It is demonstrated that the designs obtained by this method are usually more efficient than the commonly used uniform design, which allocates equal sample sizes to the two groups.     

Saturated main-effect designs for factorial experiments

The results of a computer search for saturated designs for 2ⁿ factorial experiments with n runs is reported, (where n = 2 mod 4). A complete search of the design space is avoided by focussing on designs constructed from cyclic generators. A method of searching quickly for the best generators is given. The resulting designs are as good as, and sometimes better than, designs obtained via search algorithms reported in the literature. The addition of a further factor having three levels is also considered. Here, too, a complete search is avoided by restricting attention to the most efficient part of the design space under p-efficiency.     

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.     

EFFICIENT BLOCK DESIGNS FOR CORRELATED OBSERVATIONS

Current methods for the design of efficient incomplete block experiments when the observations within a block are dependent usually involve computer searches of binary designs. These searches give little insight into the features that lead to efficiency, and can miss more efficient designs. This paper aims to develop some approximations which give some insight into the features of a design that lead to high efficiency under a generalized least-squares analysis for a known dependence structure, and to show that non-binary designs can be more efficient for some dependence structures. In particular, we show how neighbour balance and end plot balance are related to the design efficiency for low-order autoregressions, and that under moderate positive dependence, replication at lag two can sometimes increase efficiency.     

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.     

An efficient sequential design of clinical trials

We propose an efficient group sequential monitoring rule for clinical trials. At each interim analysis both efficacy and futility are evaluated through a specified loss structure together with the predicted power. The proposed design is robust to a wide range of priors, and achieves the specified power with a saving of sample size compared to existing adaptive designs. A method is also proposed to obtain a reduced-bias estimator of treatment difference for the proposed design. The new approaches hold great potential for efficiently selecting a more effective treatment in comparative trials. Operating characteristics are evaluated and compared with other group sequential designs in empirical studies. An example is provided to illustrate the application of the method.     

Optimal two-stage designs for phase ii clinical trials with differentiation of complete and partial responses

In the usual design and analysis of a phase II trial, there is no differentiation between complete response and partial response. Since complete response is considered more desirable this paper proposes a weighted score method which extends Simon's (1989) two-stage design to the situation where the complete and partial responses are differentiated. The weight assigned to the complete response is suggested by examining the likelihood ratio (LR) statistic for testing a simple hypothesis of a trinomial distribution. Both optimal and minimax designs are tabulated for a wide range of design parameters. The weighted score approach is shown to give more efficient designs, especially when the response probability is moderate to large.     

PROBABILITY-BASED OPTIMAL DESIGN

Optimal design of experiments has generally concentrated on parameter estimation and, to a much lesser degree, on model discrimination. Often an experimenter is interested in a particular outcome and wishes to maximize in some way the probability of this outcome. We propose a new class of compound criteria and designs that address this issue for generalized linear models. The criteria offer a method of achieving designs that possess the properties of efficient parameter estimation and a high probability of a desired outcome.     

Time-to-event calibration-free odds design: A robust efficient design for phase I trials with late-onset outcomes

Compared with most of the existing phase I designs, the recently proposed calibration-free odds (CFO) design has been demonstrated to be robust, model-free, and easy to use in practice. However, the original CFO design cannot handle late-onset toxicities, which have been commonly encountered in phase I oncology dose-finding trials with targeted agents or immunotherapies. To account for late-onset outcomes, we extend the CFO design to its time-to-event (TITE) version, which inherits the calibration-free and model-free properties. One salient feature of CFO-type designs is to adopt game theory by competing three doses at a time, including the current dose and the two neighboring doses, while interval-based designs only use the data at the current dose and is thus less efficient. We conduct comprehensive numerical studies for the TITE-CFO design under both fixed and randomly generated scenarios. TITE-CFO shows robust and efficient performances compared with interval-based and model-based counterparts. As a conclusion, the TITE-CFO design provides robust, efficient, and easy-to-use alternatives for phase I trials when the toxicity outcome is late-onset.     

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.     

A relaxation procedure for calculating (G–)minimax optimal designs

Summary: In nonlinear statistical models, standard optimality functions for experimental designs depend on the unknown parameters of the model. An appealing and robust concept for choosing a design is the minimax criterion. However, so far, minimax optimal designs have been calculated efficiently under various restrictive conditions only. We extend an iterative relaxation scheme originally proposed by Shimizu and Aiyoshi (1980) and prove its convergence under very general assumptions which cover a variety of situations considered in experimental design. Application to different specific design criteria is discussed and issues of practical implementation are addressed. First numerical results suggest that the method may be very efficient with respect to the number of iterations required.*Supported by a grant from the Deutsche Forschungsgemeinschaft. We are grateful to a referee for his constructive suggestions.     

Generalized staggered nested designs for variance components estimation

Staggered nested experimental designs are the most popular class of unbalanced nested designs in practical fields. The most important features of the staggered nested design are that it has a very simple open-ended structure and each sum of squares in the analysis of variance has almost the same degrees of freedom. Based on the features, a class of unbalanced nested designs that is a generalization of the staggered nested design is proposed in this paper. Formulae for the estimation of variance components and their sums are provided. Comparing the variances of the estimators to the staggered nested designs, it is found that some of the generalized staggered nested designs are more efficient than the traditional staggered nested design in estimating some of the variance components and their sums. An example is provided for illustration.     

Bayesian D-Optimal Designs for Poisson Regression Models

By incorporating informative and/or historical knowledge of the unknown parameters, Bayesian experimental design under the decision-theory framework can combine all the information available to the experimenter so that a better design may be achieved. Bayesian optimal designs for generalized linear regression models, especially for the Poisson regression model, is of interest in this article. In addition, lack of an efficient computational method in dealing with the Bayesian design leads to development of a hybrid computational method that consists of the combination of a rough global optima search and a more precise local optima search. This approach can efficiently search for the optimal design for multi-variable generalized linear models. Furthermore, the equivalence theorem is used to verify whether the design is optimal or not.     

On Sampling Designs with Ordered Conditional Inclusion Probabilities

In this paper we consider a family of sampling designs for which increasing first‐order inclusion probabilities imply, in a specific sense, increasing conditional inclusion probabilities. It is proved that the complementary Midzuno, the conditional Poisson, and the Sampford designs belong to this family. It is shown that designs of the family are more efficient than a comparable with‐replacement design. Furthermore, the efficiency gain is explicitly given for these designs.     

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.     

On bounds for the efficiency of block designs for comparing test treatments with a control

In this paper we study the class of augmented balanced incomplete block designs, which are used for comparing a control treatment with a set of test treatments. Under the A- criterion we establish a condition that enables us to determine the most efficient augmented design and we suggest some methods to compute a lower bound for the efficiency of these designs. For 3≤k≤10, v≥k, we list the parameters of the most efficient designs with a lower bound for their efficiency or, if known, mention their optimality.