Efficient crossover designs in the presence of interactions between direct and carry-over treatment effects

Crossover designs, or repeated measurements designs, are used for experiments in which t treatments are applied to each of n experimental units successively over p time periods. Such experiments are widely used in areas such as clinical trials, experimental psychology and agricultural field trials. In addition to the direct effect on the response of the treatment in the period of application, there is also the possible presence of a residual, or carry-over, effect of a treatment from one or more previous periods. We use a model in which the residual effect from a treatment depends upon the treatment applied in the succeeding period; that is, a model which includes interactions between the treatment direct and residual effects. We assume that residual effects do not persist further than one succeeding period.A particular class of strongly balanced repeated measurements designs with n=t² units and which are uniform on the periods is examined. A lower bound for the A-efficiency of the designs for estimating the direct effects is derived and it is shown that such designs are highly efficient for any number of periods p=2,…,2t.     

Block designs robust against the presence of positional effects

The problem considered is to find optimum designs for treatment effects in a block design (BD) setup, when positional effects are also present besides treatment and block effects, but they are ignored while formulating the model. In the class of symmetric balanced incomplete block designs, the Youden square design is shown to be optimal in the sense of minimizing the bias term in the mean squared error (MSE) of the best linear unbiased estimators of the full set of orthonormal treatment contrasts, irrespective of the value of the positional effects.     

Block designs with block size two

Algorithms are given for the construction of binary block designs with replications and concurrences differing by at most one. The designs are resolvable and/or connected wherever the parameters permit.     

Experimental designs and their efficiencies for spatially correlated observations in two dimensions

Optimality of experimental designs for spatially correlated observations is investigated.come two dimensional correlation structures are discussed and an attempt has been made to find optimal or nearly optimal design for each sitution.The solution lend to designs similar to that used for repeated measurements.The relative efficiency of the proposed designs in comparison to randomized latin square designs is tabulated for some cases.     

Optimal regression designs in the presence of random block effects

A- and D-optimal regression designs under random block-effects models are considered. We first identify certain situations where D- and A-optimal designs do not depend on the intra-block correlation and can be obtained easily from the optimal designs under uncorrelated models. For example, for quadratic regression on [−1,1], this covers D-optimal designs when the block size is a multiple of 3 and A-optimal designs when the block size is a multiple of 4. In general, the optimal designs depend on the intra-block correlation. For quadratic regression, we provide expressions for D-optimal designs for any block size. A-optimal designs with blocks of size 2 for quadratic regression are also obtained. In all the cases considered, robust designs which do not depend on the intrablock correlation can be constructed.     

An easy method of constructing latin square designs balanced for the immediate residual and other order effects

Bradley (1958) proposed a very simple procedure for constructing latin square designs to counterbalance the immediate sequential effect for an even number of treatments. When the number of treatments is odd, balance in a single latin square is not possible. In the present note we have developed an analogous method for the construction of such designs which may be used for an even or odd number of treatments. A proof has also been offered to assure the general validity of the procedure.     

Quantile plots for mean effects in the presence of variance effects for 2k-p designs

In robust parameter design, variance effects and mean effects in a factorial experiment are modelled simultaneously. If variance effects are present in a model, correlations are induced among the naive estimators of the mean effects. A simple normal quantile plot of the mean effects may be misleading because the mean effects are no longer iid under the null hypothesis that they are zero. Adjusted quantiles are computed for the case when one variance effect is significant and examples of 8-run and 16-run fractional factorial designs are examined in detail. We find that the usual normal quantiles are similar to adjusted quantiles for all but the largest and smallest ordered effects for which they are conservative. Graphically, the qualitative difference between the two sets of quantiles is negligible (even in the presence of large variance effects) and we conclude that normal probability plots are robust in the presence of variance effects.     

Optimality in the presence of two factor interactions among the nuisance factors

Here we consider an m way heterogeneity settingin the presence of two factor interactions among the heterogeneity directions . The set of experimental units considered do not exhaust all possible level combinations of the heterogeneity directions ; but the set is such that all heterogeneity effects assumed i n the model are orthogonally estmable.In such a setting , calleda doubly balanced m-way setting , the C-matrix of the reduced normal equations for the treatment effects is derived . Universally optimal designs are obtained in the cases where the settingis (i) Completely regular or (ii) partly regular of a special type . An interesting observation is that there are situations where the universally optimal designsin the present setting are totally different from the designs known t o be universally optimal when there is no interaction effect among the heterogeneity directions. This indicates that the usual optimality criteria are sensitive to validity or otherwise of the usual assumptions of lack of interactions among heterogeneity directions.     

Comparison of normal probability plots and dot plots in judging the significance of effects in two level factorial designs

In this article, we present a study carried out to compare the effectiveness of the normal probability plot (NPP) and a simple dot plot in assessing the significance of the effects in experimental designs with factors at two levels (2 ^k?p designs). Several groups of students who had just completed a course that covered factorial designs were asked to identify the significant effects in a total of 32 situations, 16 of which were represented using NPPs and the other 16 using dot plots. Although the 32 scenarios were said to be different, there were really only 16 different situations, each of which was represented using the two methods to be compared. A simple graphical analysis shows no evidence that there is a difference between the two procedures. However, in designs with 16 runs there are some cases where NPP seems to give slightly better results.     

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.     

Compound designs for dose‐finding in the presence of nondesignable covariates

Compound optimal designs are considered where one component of the design criterion is a traditional optimality criterion such as the D‐optimality criterion, and the other component accounts for higher efficacy with low toxicity. With reference to the dose‐finding problem, we suggest the technique to choose weights for the two components that makes the optimization problem simpler than the traditional penalized design. We allow general bivariate responses for efficacy and toxicity. We then extend the procedure in the presence of nondesignable covariates such as age, sex, or other health conditions. A new breast cancer treatment is considered to illustrate the procedures. Copyright © 2013 John Wiley & Sons, Ltd.     

The construction of multi-factor crossover designs in animal husbandry studies

For ethical reasons it is important to try to obtain as much useful information as possible from an animal experiment whilst minimizing the number of animals used. Crossover designs, where applicable, provide an ideal framework for achieving this. If two or more treatment factors are included in the crossover design then the reduction in total animal usage can be considerable. In this paper we consider such designs, defined as multi-factor crossover designs. The designs are applicable when there are several different treatment factors, each at t levels, to be applied to the experimental units. The motivation for investigating these designs was a study conducted at GlaxoSmithKline to determine the preference of male and female dogs for t=5 different types of bed and t=5 different bedding conditions. A construction method is given for forming universally optimal designs for t not too large. Also given is an example for the special case where the number of treatment levels t=6.     

On the determination and construction of E-optimal block designs in the presence of linear trends

In this paper we consider experimental situations in which v treatments are to be applied to experimental units arranged in b blocks of size k = 3 and where there may be unknown or uncontrollable linear trends (possibly different) within blocks. Methods are given here for determining and constructing E-optimal designs for such situations.     

Multiple-start balanced modified systematic sampling in the presence of linear trend

ABSTRACT

In this paper, we propose a sampling design termed as multiple-start balanced modified systematic sampling (MBMSS), which involves the supplementation of two or more balanced modified systematic samples, thus permitting us to obtain an unbiased estimate of the associated sampling variance. There are five cases for this design and in the presence of linear trend only one of these cases is optimal. To further improve results for the other cases, we propose an estimator that removes linear trend by applying weights to the first and last sampling units of the selected balanced modified systematic samples and is thus termed as the MBMSS with end corrections (MBMSSEC) estimator. By assuming a linear trend model averaged over a super-population model, we will compare the expected mean square errors (MSEs) of the proposed sample means, to that of simple random sampling (SRS), linear systematic sampling (LSS), stratified random sampling (STR), multiple-start linear systematic sampling (MLSS), and other modified MLSS estimators. As a result, MBMSS is optimal for one of the five possible cases, while the MBMSSEC estimator is preferred for three of the other four cases.     

Estimation of the mean of an exponential distribution in the presence of an outlier

Kale and Sinha (1971) have found an estimator of the mean of an exponential distribution in the présence of an outlying observation with higher expected value. Here an alternative estimator of the mean is proposed and it is compared with the estimator of Kale and Sinha (1971) and the maximum likelihood estimator given by Kale (1975). The proposed estimator is found to be more efficient than the latter two estimators in some cases.     

Predictability of designs which adjust for imbalances in prognostic factors

Minimisation is a method often used in clinical trials to balance the treatment groups with respect to some prognostic factors. In the case of two treatments, the predictability of this method is calculated for different numbers of factors, different numbers of levels of each factor and for different proportions of the population at each level. It is shown that if we know nothing about the previous patients except the last treatment allocation, the next treatment can be correctly guessed more than 60% of the time if no biased coin is used. If the two previous assignments are known to have been the same, the next treatment can be guessed correctly around 80% of the time. Therefore, it is suggested that a biased coin should always be used with minimisation. Different choices of biased coin are investigated in terms of the reduction in predictability and the increase in imbalance that they produce. An alternative design to minimisation which makes use of optimum design theory is also investigated, by means of simulation, and does not appear to have any clear advantages over minimisation with a biased coin.     

Nuisance Parameters and the Use of Exploratory Graphical Methods in a Bayesian Analysis

Consider the problem of inference about a parameter θ in the presence of a nuisance parameter v. In a Bayesian framework, a number of posterior distributions may be of interest, including the joint posterior of (θ, ν), the marginal posterior of θ, and the posterior of θ conditional on different values of ν. The interpretation of these various posteriors is greatly simplified if a transformation (θ, h(θ, ν)) can be found so that θ and h(θ, v) are approximately independent. In this article, we consider a graphical method for finding this independence transformation, motivated by techniques from exploratory data analysis. Some simple examples of the use of this method are given and some of the implications of this approximate independence in a Bayesian analysis are discussed.     

Error variance bias in neighbour balance and evenness of distribution designs

Neighbour balance and evenness of distribution designs help to address user concerns in the two‐dimensional layout of agricultural field trials. This is done by minimising the occurrence of pairwise treatment plot neighbours and ensuring that the replications of treatments are spread out across rows and columns of a trial. Such considerations result in a restriction on the normal randomisation process for a row‐column design which can lead to error variance bias. In this paper, uniformity trial data is used to assess the degree of this bias for both resolvable and non‐resolvable designs. Comparisons are made with a similar investigation using Linear Variance spatial designs.     

Model-based study of families of exponential-type estimators in presence of non response

Among other types of non sampling errors, non response error (NRE) is an inherent component of any sample survey, which is supposed to be given much attention during the designing and execution stages. With increasing awareness of these estimators, therefore, there is an urge for the development of suitable techniques for controlling them.

This article proposes two families of estimators for population mean in the presence of non response and discuses various properties under model approach, namely polynomial regression model. The families include some existing estimators. Comparison of efficiencies along with the robustness of the estimators under misspecification of models has been empirically discussed.