A note on robustness of D-optimal block designs for two-colour microarray experiments

Two-colour microarray experiments form an important tool in gene expression analysis. Due to the high risk of missing observations in microarray experiments, it is fundamental to concentrate not only on optimal designs but also on designs which are robust against missing observations. As an extension of Latif et al. (2009), we define the optimal breakdown number for a collection of designs to describe the robustness, and we calculate the breakdown number for various D-optimal block designs. We show that, for certain values of the numbers of treatments and arrays, the designs which are D-optimal have the highest breakdown number. Our calculations use methods from graph theory.     

Robustness of designed experiments against missing data

This paper investigates the robustness of designed experiments for estimating linear functions of a subset of parameters in a general linear model against the loss of any t( ≥1) observations. Necessary and sufficient conditions for robustness of a design under a homoscedastic model are derived. It is shown that a design robust under a homoscedastic model is also robust under a general heteroscedastic model with correlated observations. As a particular case, necessary and sufficient conditions are obtained for the robustness of block designs against the loss of data. Simple sufficient conditions are also provided for the binary block designs to be robust against the loss of data. Some classes of designs, robust up to three missing observations, are identified. A-efficiency of the residual design is evaluated for certain block designs for several patterns of two missing observations. The efficiency of the residual design has also been worked out when all the observations in any two blocks, not necessarily disjoint, are lost. The lower bound to A-efficiency has also been obtained for the loss of t observations. Finally, a general expression is obtained for the efficiency of the residual design when all the observations of m ( ≥1) disjoint blocks are lost.     

Some new third order designs robust to one missing observation

Abstract

In real experimentation, we often face situations where observations are lost, ignored or unavailable due to some accident or high cost experiments. Missing observations can make the results of a response surface experiment quite misleading. Therefore minimaxloss designs for Augmented Box-Behnken Designs (ABBDs) and Augmented Fractional Box-Behnken Designs (AFBBDs) are formulated under a minimaxloss criterion. These minimaxloss designs are considered to be robust to one missing observation and the investigation has been made in this article. Then G-efficiencies and Relative D-efficiencies of minimaxloss ABBDs and AFBBDs have been discussed.     

Minimum breakdown designs in blocks of size two

In scientific investigations, there are many situations where each two experimental units have to be grouped into a block of size two. For planning such experiments, the variance-based optimality criteria like A-, D- and E-criterion are typically employed to choose efficient designs, if the estimation efficiency of treatment contrasts is primarily concerned. Alternatively, if there are observations which tend to become lost during the experimental period, the robustness criteria against the unavailability of data should be strongly recommended for selecting the planning scheme. In this study, a new criterion, called minimum breakdown criterion, is proposed to quantify the robustness of designs in blocks of size two. Based on the proposed criterion, a new class of robust designs, called minimum breakdown designs, is defined. When various numbers of blocks are missing, the minimum breakdown designs provide the highest probabilities that all the treatment contrasts are estimable. An exhaustive search procedure is proposed to generate such designs. In addition, two classes of uniformly minimum breakdown designs are theoretically verified.     

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.     

Effect of missing plots in some response surface designs

The effect of one or more missing observations for response surface designs arranged in blocks are examined in this paper. The resu lts as applied to a central composite design with orthogonal blocking, and an equirdial design with orthogonal blocking, are reported.     

Robustness of some designs against missing data

This article studies the robustness of several types of designs against missing data. The robustness of orthogonal resolution III fractional factorial designs and second-order rotatable designs is studied when a single observation is missing. We also study the robustness of balanced incomplete block designs when a block is missing and of Youden square designs when a column is missing.     

Missing values in replicated Latin squares

Designs based on any number of replicated Latin squares are examined for their robustness against the loss of up to three observations randomly scattered throughout the design. The information matrix for the treatment effects is used to evaluate the average variances of the treatment differences for each design in terms of the number of missing values and the size of the design. The resulting average variances are used to assess the overall robustness of the designs. In general, there are 16 different situations for the case of three missing values when there are at least three Latin square replicates in the design. Algebraic expressions may be determined for all possible configurations, but here the best and worst cases are given in detail. Numerical illustrations are provided for the average variances, relative efficiencies, minimum and maximum variances and the frequency counts, showing the effects of the missing values for a range of design sizes and levels of replication.     

Robustness of a Class of Partial Diallel Cross Designs to the Unavailability of a Complete Block of Observations

Complete and partial diallel cross designs are examined as to their construction and robustness against the loss of a block of observations. A simple generalized inverse is found for the information matrix of the line effects, which allows evaluation of expressions for the variances of the line-effect differences with and without the missing block. A-efficiencies, based on average variances of the elementary contrasts of the line-effects, suggest that these designs are fairly robust. The loss of efficiency is generally less than 10%, but it is shown that specific comparisons might suffer a loss of efficiency of as much as 40%.     

Symmetry in mixture experiments

Two types of symmetry can arise when the proportions of mixture components are constrained by upper and lower bounds. These two types of symmetry are shown to be useful for blocking first-order designs, as well as for finding the centroid of the experimental region. Orthogonal blocking of first-order mixture designs provides a method of including process variables in the mixture experiment, with the mixture terms orthogonal to the process factors. Symmetric regions are used to develop spherical and rotatable response surface designs for mixtures. The central composite design and designs based on the icosahedron and the dodecahedron are given for four-component mixtures. The uniform shell designs are three-level designs when applied to mixture experiments.     

Multilevel Augmented Pairs Second-Order Response Surface Designs and Their Robustness to Missing Data

Missing observations can occur even in a well-planned experiment. The effect of missing observations can be much more serious when the design is saturated or near saturated. The levels of factor settings that make a design more robust to missing observations are of great importance in the sense that the loss for missing observations becomes minimum. In this study, new augmented pairs minimax loss designs are constructed, which are more robust to one missing design point than the augmented pairs designs presented by Morris (2000 Morris , M. D. ( 2000 ). A class of three-level experimental designs for response surface modeling . Technometrics 42 : 111 – 121 .[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). New designs are compared with augmented pairs designs, central composite designs, and small composite designs under generalized scaled standard deviations. The model used is also studied for the regression coefficient estimates.     

The robustness of chain block designs and coat-of-mail designs

Chain block designs are relatively vulnerable to loss of information when missing values or outliers may occur. An alternative class of designs, coat-of-mail designs, are proposed and the relative robustness of the two types of design are compared.     

A Comparison of Three-Level Orthogonal Arrays in the Presence of Different Correlation Structures in Observations

When the experimenter suspects that there might be a quadratic relation between the response variable and the explanatory parameters, a design with at least three points must be employed to establish and explore this relation (second-order design). Orthogonal arrays (OAs) with three levels are often used as second-order response surface designs. Generally, we assume that the data are independent observations; however, there are many situations where this assumption may not be sustainable. In this paper, we want to compare three-level OAs with 18, 27, and 36 runs under the presence of three specific forms of correlation in observations. The aim is to derive the best designs that can be efficiently used for response surface modeling.     

Identifying Dispersion Effects in Robust Design Experiments—Issues and Improvements

The two experimental methods most commonly used for reducing the effect of noise factors on a response of interest Y aim either to estimate a model of the variability (V(Y), or an associated function), that is transmitted by the noise factors, or to estimate a model of the ratio between the response (Y) and all the control and noise factors involved therein. Both methods aim to determine which control factor conditions minimise the noise factors' effect on the response of interest, and a series of analytical guidelines are established to reach this end. Product array designs allow robustness problems to be solved in both ways, but require a large number of experiments. Thus, practitioners tend to choose more economical designs that only allow them to model the surface response for Y. The general assumption is that both methods would lead to similar conclusions. In this article we present a case that utilises a design based on a product design and for which the conclusions yielded by the two analytical methods are quite different. This example casts doubt on the guidelines that experimental practice follows when using either of the two methods. Based on this example, we show the causes behind these discrepancies and we propose a number of guidelines to help researchers in the design and interpretation of robustness problems when using either of the two methods.     

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.     

Equi-information robust designs: Which designs are possible?

The effects of missing observations in a designed experiment are reviewed. Conditions are determined for a design to retain equal information, i.e. the same generalized variance of unknown parameters, when either any single or any pair of observations is lost. Some examples of designs with this property are given. Although there are many designs which retain equal information for the loss of exactly t observations, where t = 1,2,3,…, it is shown that it is not possible to obtain any design which retains equal information when any one and any two and also any three observations are missing.     

Cost-cautious designs for confirmatory bioassay

Confirmatory bioassay experiments take place in late stages of the drug discovery process when a small number of compounds have to be compared with respect to their properties. As the cost of the observations may differ considerably, the design problem is well specified by the cost of compound used rather than by the number of observations. We show that cost-efficient designs can be constructed using useful properties of the minimum support designs. These designs are particularly suited for studies where the parameters of the model to be estimated are known with high accuracy prior to the experiment, although they prove to be robust against typical inaccuracies of these values. When the parameters of the model can only be specified with ranges of values or by a probability distribution, we use a Bayesian criterion of optimality to construct the required designs. Typically, the number of their support points depends on the prior knowledge for the model parameters. In all cases we recommend identifying a set of designs with good statistical properties but different potential costs to choose from.     

Missing Data Mechanisms for Analysing Longitudinal Data with Incomplete Observations in Both Responses and Covariates

Missing observations in both responses and covariates arise frequently in longitudinal studies. When missing data are missing not at random, inferences under the likelihood framework often require joint modelling of response and covariate processes, as well as missing data processes associated with incompleteness of responses and covariates. Specification of these four joint distributions is a nontrivial issue from the perspectives of both modelling and computation. To get around this problem, we employ pairwise likelihood formulations, which avoid the specification of third or higher order association structures. In this paper, we consider three specific missing data mechanisms which lead to further simplified pairwise likelihood (SPL) formulations. Under these missing data mechanisms, inference methods based on SPL formulations are developed. The resultant estimators are consistent, and enjoy better robustness and computation convenience. The performance is evaluated empirically though simulation studies. Longitudinal data from the National Population Health Survey and Waterloo Smoking Prevention Project are analysed to illustrate the usage of our methods.     

A non-iterative least squares estimation of missing values in experimental designs

In this paper an attempt has been made to obtain a systematic method of estimating the missing values in experimental designs. When the observations are missing in a particular pattern (in RBD and LSD) explicit expressions are given for the estimators of the missing values. This procedure is compared with Yate's iterative procedure by numerical examples.     

Design and analysis of mixture experiments with process variable

A mixture experiment is an experiment in which the response is assumed to depend on the relative proportions of the ingredients present in the mixture and not on the total amount of the mixture. In such experiment process, variables do not form any portion of the mixture but the levels changed could affect the blending properties of the ingredients. Sometimes, the mixture experiments are costly and the experiments are to be conducted in less number of runs. Here, a general method for construction of efficient mixture experiments in a minimum number of runs by the method for projection of efficient response surface design onto the constrained region is obtained. The efficient designs with a less number of runs have been constructed for 3rd, 4th, and 5th component of mixture experiments with one process variable.