Three-level main-effects designs exploiting prior information about model uncertainty

To explore the projection efficiency of a design, Tsai, et al [2000. Projective three-level main effects designs robust to model uncertainty. Biometrika 87, 467–475] introduced the Q criterion to compare three-level main-effects designs for quantitative factors that allow the consideration of interactions in addition to main effects. In this paper, we extend their method and focus on the case in which experimenters have some prior knowledge, in advance of running the experiment, about the probabilities of effects being non-negligible. A criterion which incorporates experimenters’ prior beliefs about the importance of each effect is introduced to compare orthogonal, or nearly orthogonal, main effects designs with robustness to interactions as a secondary consideration. We show that this criterion, exploiting prior information about model uncertainty, can lead to more appropriate designs reflecting experimenters’ prior beliefs.     

New adaptive designs for delayed response models

Adaptive designs are effective mechanisms for flexibly allocating experimental resources. In clinical trials particularly, such designs allow researchers to balance short- and long-term goals. Unfortunately, fully sequential strategies require outcomes from all previous allocations prior to the next allocation. This can prolong an experiment unduly. As a result, we seek designs for models that specifically incorporate delays.We utilize a delay model in which patients arrive according to a Poisson process and their response times are exponential. We examine three designs with an eye towards minimizing patient losses: a delayed two-armed bandit rule which is optimal for the model and objective of interest; a newly proposed hyperopic rule; and a randomized play-the-winner rule. The results show that, except when the delay rate is several orders of magnitude different than the patient arrival rate, the delayed response bandit is nearly as efficient as the immediate response bandit. The delayed hyperopic design also performs extremely well throughout the range of delays, despite the fact that the rate of delay is not one of its design parameters. The delayed randomized play-the-winner rule is far less efficient than either of the other methods.     

Robustness of subset response surface designs to missing observations

Experiments designed to investigate the effect of several factors on a process have wide application in modern industrial and scientific research. Response surface designs allow the researcher to model the effects of the input variables on the response of the process. Missing observations can make the results of a response surface experiment quite misleading, especially in the case of one-off experiments or high cost experiments. Designs robust to missing observations can attract the user since they are comparatively more reliable. Subset designs are studied for their robustness to missing observations in different experimental regions. The robustness of subset designs is also improved for multiple levels by using the minimax loss criterion.     

Optimum Critical Value for Pre-Test Estimator

In this paper, methods are proposed in finding the robust design in both Taguchi and Standard setups when a signal factor is present. The robust design is a set of level combinations of control factors so that the effect of controllable noise factors on response is minimum. Both univariate and multivariate methods are used in finding the influential noise factors for the determination of robust designs.     

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.     

Linear least squares estimates and nonlinear means

The consistency and asymptotic normality of a linear least squares estimate of the form (X'X)^-X'Y when the mean is not Xβ is investigated in this paper. The least squares estimate is a consistent estimate of the best linear approximation of the true mean function for the design chosen. The asymptotic normality of the least squares estimate depends on the design and the asymptotic mean may not be the best linear approximation of the true mean function. Choices of designs which allow large sample inferences to be made about the best linear approximation of the true mean function are discussed.     

Sample Size Calculation and Power Analysis of Changes in Mean Response Over Time

Despite tremendous effort on different designs with cross-sectional data, little research has been conducted for sample size calculation and power analyses under repeated measures design. In addition to time-averaged difference, changes in mean response over time (CIMROT) is the primary interest in repeated measures analysis. We generalized sample size calculation and power analysis equations for CIMROT to allow unequal sample size between groups for both continuous and binary measures, through simulation, evaluated the performance of proposed methods, and compared our approach to that of a two-stage model formulization. We also created a software procedure to implement the proposed methods.     

Response surface design evaluation and comparison

Designing an experiment to fit a response surface model typically involves selecting among several candidate designs. There are often many competing criteria that could be considered in selecting the design, and practitioners are typically forced to make trade-offs between these objectives when choosing the final design. Traditional alphabetic optimality criteria are often used in evaluating and comparing competing designs. These optimality criteria are single-number summaries for quality properties of the design such as the precision with which the model parameters are estimated or the uncertainty associated with prediction. Other important considerations include the robustness of the design to model misspecification and potential problems arising from spurious or missing data. Several qualitative and quantitative properties of good response surface designs are discussed, and some of their important trade-offs are considered. Graphical methods for evaluating design performance for several important response surface problems are discussed and we show how these techniques can be used to compare competing designs. These graphical methods are generally superior to the simplistic summaries of alphabetic optimality criteria. Several special cases are considered, including robust parameter designs, split-plot designs, mixture experiment designs, and designs for generalized linear models.     

Fractional Factorial Designs for the Detection of Interactions between Design and Noise Factors

In industrial experiments on both design (control) factors and noise factors aimed at improving the quality of manufactured products, designs are needed which afford independent estimation of all design×noise interactions in as few runs as possible, while allowing aliasing between those factorial effects of less interest. An algorithm for generating orthogonal fractional factorial designs of this type is described for factors at two levels. The generated designs are appropriate for experimenting on individual factors or for experimentation involving group screening of factors.     

A confidence function-based posterior probability design for phase II cancer trials

Single-arm one- or multi-stage study designs are commonly used in phase II oncology development when the primary outcome of interest is tumor response, a binary variable. Both two- and three-outcome designs are available. Simon two-stage design is a well-known example of two-outcome designs. The objective of a two-outcome trial is to reject either the null hypothesis that the objective response rate (ORR) is less than or equal to a pre-specified low uninteresting rate or to reject the alternative hypothesis that the ORR is greater than or equal to some target rate. Three-outcome designs proposed by Sargent et al. allow a middle gray decision zone which rejects neither hypothesis in order to reduce the required study size. We propose new two- and three-outcome designs with continual monitoring based on Bayesian posterior probability that meet frequentist specifications such as type I and II error rates. Futility and/or efficacy boundaries are based on confidence functions, which can require higher levels of evidence for early versus late stopping and have clear and intuitive interpretations. We search in a class of such procedures for optimal designs that minimize a given loss function such as average sample size under the null hypothesis. We present several examples and compare our design with other procedures in the literature and show that our design has good operating characteristics.     

Augmented Box-Behnken Designs for Fitting Third-Order Response Surfaces

Box-Behnken designs are popular with experimenters who wish to estimate a second-order model, due to their having three levels, their simplicity and their high efficiency for the second-order model. However, there are situations in which the model is inadequate due to lack of fit caused by higher-order terms. These designs have little ability to estimate third-order terms. Using combinations of factorial points, axial points, and complementary design points, we augment these designs and develop catalogues of third-order designs for 3–12 factors. These augmented designs can be used to estimate the parameters of a third-order response surface model. Since the aim is to make the most of a situation in which the experiment was designed for an inadequate model, the designs are clearly suboptimal and not rotatable for the third-order model, but can still provide useful information.     

Constructing non-regular robust parameter designs

In recent years there has been considerable attention paid to robust parameter design as a strategy for variance reduction. Of particular concern is the selection of a good experimental plan in light of the two different types of factors in the experiment (control and noise) and the asymmetric manner in which effects of the same order are treated. Recent work has focussed on the selection of regular fractional factorial designs in this setting. In this article, we consider the construction and selection of optimal non-regular experiment plans for robust parameter design. Our approach defines the word-length pattern for non-regular fractional factorial designs with two different types of factors which allows for the choice of optimal design to emphasize the estimation of the effects of interest. We use this new word-length pattern to rank non-regular robust parameter designs. We show that one can easily find minimum aberration robust parameter designs from existing orthogonal arrays. The methodology is demonstrated by finding optimal assignments for control and noise factors for 12, 16 and 20-run orthogonal arrays.     

Asymptotic normality of a weighted integrated squared error of kernel regression estimates with data-dependent bandwidth

Let (X, Y) be a bivariate random vector and let be the regression function of Y on X that has to be estimated from a sample of i.i.d. random vectors (X₁, Y₁),…,(X_n, Y_n) having the same distribution as (X, Y). In the present paper it is shown that the normalized integrated squared error of a kernel estimator with data-driven bandwidth is asymptotically normally distributed.     

The performance of subset response surface designs for estimating third order terms

Response surface designs are widely used in industries like chemicals, foods, pharmaceuticals, bioprocessing, agrochemicals, biology, biomedicine, agriculture and medicine. One of the major objectives of these designs is to study the functional relationship between one or more responses and a number of quantitative input factors. However, biological materials have more run to run variation than in many other experiments, leading to the conclusion that smaller response surface designs are inappropriate. Thus designs to be used in these research areas should have greater replication. Gilmour (2006) introduced a wide class of designs called “subset designs” which are useful in situations in which run to run variation is high. These designs allow the experimenter to fit the second order response surface model. However, there are situations in which the second order model representation proves to be inadequate and unrealistic due to the presence of lack of fit caused by third or higher order terms in the true response surface model. In such situations it becomes necessary for the experimenter to estimate these higher order terms. In this study, the properties of subset designs, in the context of the third order response surface model, are explored.     

Optimal partially balanced nested row-column designs

A partially balanced nested row-column design, referred to as PBNRC, is defined as an arrangement of v treatments in b p × q blocks for which, with the convention that p q, the information matrix for the estimation of treatment parameters is equal to that of the column component design which is itself a partially balanced incomplete block design. In this paper, previously known optimal incomplete block designs, and row-column and nested row-column designs are utilized to develop some methods of constructing optimal PBNRC designs. In particular, it is shown that an optimal group divisible PBNRC design for v = mn kn treatments in p × q blocks can be constructed whenever a balanced incomplete block design for m treatments in blocks of size k each and a group divisible PBNRC design for kn treatments in p × q blocks exist. A simple sufficient condition is given under which a group divisible PBNRC is Ψ_f-better for all f> 0 than the corresponding balanced nested row-column designs having binary blocks. It is also shown that the construction techniques developed particularly for group divisible designs can be generalized to obtain PBNRC designs based on rectangular association schemes.     

New classes of D-optimal edge designs

Edge designs are screening experimental designs that allow a model-independent estimate of the set of relevant variables, thus providing more robustness than traditional designs. In this paper we construct new classes of D-optimal edge designs. This construction uses weighing matrices of order n and weight k together with permutation matrices of order n to obtain D-optimal edge designs. One linear and one quadratic simulated screening scenarios are studied and compared using linear regression and edge designs analysis.     

Bioassay case study applying the maximin D‐optimal design algorithm to the four‐parameter logistic model

Cell‐based potency assays play an important role in the characterization of biopharmaceuticals but they can be challenging to develop in part because of greater inherent variability than other analytical methods. Our objective is to select concentrations on a dose–response curve that will enhance assay robustness. We apply the maximin D‐optimal design concept to the four‐parameter logistic (4PL) model and then derive and compute the maximin D‐optimal design for a challenging bioassay using curves representative of assay variation. The selected concentration points from this ‘best worst case’ design adequately fit a variety of 4PL shapes and demonstrate improved robustness. Copyright © 2015 John Wiley & Sons, Ltd.     

Estimation of a Parameter of Bivariate Pareto Distribution by Ranked Set Sampling

Ranked set sampling is applicable whenever ranking of a set of sampling units can be done easily by a judgement method or based on the measurement of an auxiliary variable on the units selected. In this work, we derive different estimators of a parameter associated with the distribution of the study variate Y, based on a ranked-set sample obtained by using an auxiliary variable X correlated with Y for ranking the sample units, when (X, Y) follows a bivariate Pareto distribution. Efficiency comparisons among these estimators are also made. Real-life data have been used to illustrate the application of the results obtained.     

Interruptible supersaturated two-level designs

Interruptible designs possess a robustness against possible premature termination of an experiment. We consider such two-level designs for a first-order model and present interruptible sequences which lead to the D-optimal saturated design for four to nine factors if not interrupted. Premature termination of the experiment at any stage results in a supersaturated design with minimum loss of information about the factors. The loss for these designs, which is measured by the pairwise orthogonality between columns, is compared with that of the worst case f o r randomly ordered sequences.     

Two-level Orthogonal and Saturated Designs for Estimating Main Effects and Certain Important Interactions

In a two-level factorial experiment, we consider orthogonal designs that allow joint estimation of the grand mean, all main effects, and certain classes of two-level interactions, assuming that the remaining effects are all negligible. Based on a judicious allocation of the factorial effects of interest to the columns of a Hadamard matrix, we propose some general classes of orthogonal and saturated designs which include some existing orthogonal main-effect plans of asymmetric factorials as special cases.