Repeated measurements designs with unequal period sizes

Summary This paper is concerned with the designs in which each experimental unit is assigned more than once to a treatment, either different or identical. An easy method of constructing balanced minimal repeated measurements designs with unequal period sizes is presented whenever the number of periods is less than the number of treatments. Strongly balanced minimal repeated measurements designs with unequal period sizes are also constructed whenever the number of periods is less than the number of treatments.     

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.     

Embedded experiments in repeated and overlapping surveys

Summary.  Statistical agencies make changes to the data collection methodology of their surveys to improve the quality of the data collected or to improve the efficiency with which they are collected. For reasons of cost it may not be possible to estimate the effect of such a change on survey estimates or response rates reliably, without conducting an experiment that is embedded in the survey which involves enumerating some respondents by using the new method and some under the existing method. Embedded experiments are often designed for repeated and overlapping surveys; however, previous methods use sample data from only one occasion. The paper focuses on estimating the effect of a methodological change on estimates in the case of repeated surveys with overlapping samples from several occasions. Efficient design of an embedded experiment that covers more than one time point is also mentioned. All inference is unbiased over an assumed measurement model, the experimental design and the complex sample design. Other benefits of the approach proposed include the following: it exploits the correlation between the samples on each occasion to improve estimates of treatment effects; treatment effects are allowed to vary over time; it is robust against incorrectly rejecting the null hypothesis of no treatment effect; it allows a wide set of alternative experimental designs. This paper applies the methodology proposed to the Australian Labour Force Survey to measure the effect of replacing pen-and-paper interviewing with computer-assisted interviewing. This application considered alternative experimental designs in terms of their statistical efficiency and their risks to maintaining a consistent series. The approach proposed is significantly more efficient than using only 1 month of sample data in estimation.     

A review of uniform cross-over designs

Uniform cross-over designs form an important family of experimental designs. They have been applied in many scientific disciplines including clinical trials, agricultural studies and psychological experiments. In this paper we consider the four types of uniform cross-over design, as given by Williams [1949. Experimental designs balanced for the estimation of residual effects of treatments. Aust. J. Sci. Res. 2, 149–168], Cheng and Wu [1980. Balanced repeated measurements designs. Ann. Statist. 8, 1272–1283. Corrigendum 11 (1983) 349], Bate and Jones [2006. The construction of nearly balanced and nearly strongly balanced uniform cross-over designs. J. Statist. Plann. Inference 136, 3248–3267] and Kunert [1983. Optimal design and refinement of the linear model with applications to repeated measurements designs. Ann. Statist. 11, 247–257]. The efficiency of these designs, existence criteria and methods of construction are described.     

Minimal balanced repeated measurements designs

Experimental designs in which treatments are applied to the experimental units, one at a time, in sequences over a number of periods, have been used in several scientific investigations and are known as repeated measurements designs. Besides direct effects, these designs allow estimation of residual effects of treatments along with adjustment for them. Assuming the existence of first-order residual effects of treatments, Hedayat & Afsarinejad (1975) gave a method of constructing minimal balanced repeated measurements [RM(v,n,p)] design for v treatments using n=2v experimental units for p [=(v+1)/2] periods when v is a prime or prime power. Here, a general method of construction of these designs for all odd v has been given along with an outline for their analysis. In terms of variances of estimated elementary contrasts between treatment effects (direct and residual), these designs are seen to be partially variance balanced based on the circular association scheme.     

Bayesian design for estimating the turning point of a quadratic regression

The problem of designing an experiment to estimate the point at which a quadratic regression is a maximum, or minimum. is studied. The efficiency of a design depends on the value of the unknown parameters and sequential design is, therefore, more efficient than non-sequential design. We use a Bayesian criterion which is a weighted trace of the inverse of the information matrix with the weights depending on a prior distribution. If design occurs sequentially the weights can be updated. Both sequential and non-sequential Bayesian designs are compared to non-Bayesian sequential designs. The comparison is both theoretical and by simulation.     

Optimal parametric design with applications to pharmacokinetic and pharmacodynamic trials

This paper considers optimal parametric designs, i.e. designs represented by probability measures determined by a set of parameters, for nonlinear models and illustrates their use in designs for pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) trials. For some practical problems, such as designs for modelling PK/PD relationship, this is often the only feasible type of design, as the design points follow a PK model and cannot be directly controlled. Even for ordinary design problems the parametric designs have some advantages over the traditional designs, which often have too few design points for model checking and may not be robust to model and parameter misspecifications. We first describe methods and algorithms to construct the parametric design for ordinary nonlinear design problems and show that the parametric designs are robust to parameter misspecification and have good power for model discrimination. Then we extend this design method to construct optimal repeated measurement designs for nonlinear mixed models. We also use this parametric design for modelling a PK/PD relationship and propose a simulation based algorithm. The application of parametric designs is illustrated with a three-parameter open one-compartment PK model for the ordinary design and repeated measurement design, and an Emax model for the phamacokinetic/pharmacodynamic trial design.     

Simplex based space filling designs

Space filling designs are important for deterministic computer experiments. Even a single experiment can be very time consuming and can have many input parameters. Furthermore the underlying function generating the output is often nonlinear. Thus, the computer experiment has to be designed carefully. There exist many design criteria, which can be numerically optimized. Here, a method is developed, which does not need algorithmic optimization. A mesh of nearly regular simplices is constructed and the vertices of the simplices are used as potential design points. The extraction of a design from these meshes is very fast and easy to implement once the underlying mesh has been constructed. The extracted designs are highly competitive regarding the maximin design criterion and it is easy to extract designs for nonstandard design spaces.     

Multiple-objective response-adaptive repeated measurement designs for clinical trials

In a response-adaptive design, we review and update the trial on the basis of outcomes in order to achieve a specific goal. Response-adaptive designs for clinical trials are usually constructed to achieve a single objective. In this paper, we develop a new adaptive allocation rule to improve current strategies for building response-adaptive designs to construct multiple-objective repeated measurement designs. This new rule is designed to increase estimation precision and treatment benefit by assigning more patients to a better treatment sequence. We demonstrate that designs constructed under the new proposed allocation rule can be nearly as efficient as fixed optimal designs in terms of the mean squared error, while leading to improved patient care.     

Optimal design of complex experiments with qualitative factors of influence

A complex experiment with qualirarive factors influencing the outcome of the experiment can be seen as a general ANOVA setup. A design of such an experiment will be the assignment at which of the possible levels of the factors the actual experiment should be performed. In this paper optimal designs of such experiments will be characterized with respect to three different optimality criteria including the so called uniform optimality of a design. The possible applications of the main optimization result providing these characterizations can be used to more general experiments. The particular results on these generalizations will be indicated at the end of this paper.     

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.     

Finite sample performance of sequential designs for model identification

Classical regression analysis is usually performed in two steps. In the first step, an appropriate model is identified to describe the data generating process and in the second step, statistical inference is performed in the identified model. An intuitively appealing approach to the design of experiment for these different purposes are sequential strategies, which use parts of the sample for model identification and adapt the design according to the outcome of the identification steps. In this article, we investigate the finite sample properties of two sequential design strategies, which were recently proposed in the literature. A detailed comparison of sequential designs for model discrimination in several regression models is given by means of a simulation study. Some non-sequential designs are also included in the study.     

Constructing optimal designs for fitting pharmacokinetic models

We consider some computational issues that arise when searching for optimal designs for pharmacokinetic (PK) studies. Special factors that distinguish these are (i) repeated observations are taken from each subject and the observations are usually described by a nonlinear mixed model (NLMM), (ii) design criteria depend on the model fitting procedure, (iii) in addition to providing efficient parameter estimates, the design must also permit model checking, (iv) in practice there are several design constraints, (v) the design criteria are computationally expensive to evaluate and often numerical integration is needed and finally (vi) local optimisation procedures may fail to converge or get trapped at local optima.We review current optimal design algorithms and explore the possibility of using global optimisation procedures. We use these latter procedures to find some optimal designs.For multi-purpose designs we suggest two surrogate design criteria for model checking and illustrate their use.     

Applications and Implementations of Continuous Robust Designs

In the literature concerning the construction of robust optimal designs, many resulting designs turn out to have densities. In practice, an exact design should tell the experimenter what the support points are and how many subjects should be allocated to each of these points. In particular, we consider a practical situation in which the number of support points allowed is constrained. We discuss an intuitive approach, which motivates a new implementation scheme that minimizes the loss function based on the Kolmogorov and Smirnov distance between an exact design and the optimal design having a density. We present three examples to illustrate the application and implementation of a robust design constructed: one for a nonlinear dose-response experiment and the other two for general linear regression. Additionally, we perform some simulation studies to compare the efficiencies of the exact designs obtained by our optimal implementation with those by other commonly used implementation 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.     

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.     

Spacing of information in polynomial regression:a simple solution

Consider a k polynomial regression on a single real variable. If n uncorrelated observations are to be taken in a design with support on more than k+1 points, there is an approximate experiment, ν, with support on k+1 points and n observations such that both designs have the same information matrix for the model. A proof of this result is provided. A method to obtain the approximate design ν is given and illustrated by an example. The source of disagreement between Kiefer (1959) and De La Garza (1954) in the solution of this problem is clarified.     

Random Effect Threshold Models for Dose–Response Relationships with Repeated Measurements

A random threshold model for dose--response designs with repeated measurements is introduced. Inference procedures for this model are discussed. The framework of generalized linear models is used to propose a quasi-likelihood inference procedure. The feasibility of this approach is illustrated with the analysis of food science data concerning a forced choice sensory experiment.     

Difference variance dispersion graphs for comparing response surface designs with applications in food technology

Variance dispersion graphs have become a popular tool in aiding the choice of a response surface design. Often differences in response from some particular point, such as the expected position of the optimum or standard operating conditions, are more important than the response itself. We describe two examples from food technology. In the first, an experiment was conducted to find the levels of three factors which optimized the yield of valuable products enzymatically synthesized from sugars and to discover how the yield changed as the levels of the factors were changed from the optimum. In the second example, an experiment was conducted on a mixing process for pastry dough to discover how three factors affected a number of properties of the pastry, with a view to using these factors to control the process. We introduce the difference variance dispersion graph (DVDG) to help in the choice of a design in these circumstances. The DVDG for blocked designs is developed and the examples are used to show how the DVDG can be used in practice. In both examples a design was chosen by using the DVDG, as well as other properties, and the experiments were conducted and produced results that were useful to the experimenters. In both cases the conclusions were drawn partly by comparing responses at different points on the response surface.     

Lee discrepancy on mixed two- and three-level uniform augmented designs

Follow-up experiment is widely applied to various fields such as science and engineering, since it is an indispensable strategy, especially when some additional resources or information become available after the initial design of experiment is carried out. Moreover, some extra factors may be added in the follow-up experiment. One may augment the number of runs and/or factors for the purpose of application. In this paper, the issue of the uniform row augmented designs and column augmented designs with mixed two- and three-level is investigated. The uniformity of augmented designs is discussed under the Lee discrepancy, some lower bounds of Lee discrepancy for the augmented designs are obtained. The construction algorithm of the uniform augmented designs is given. Some numerical examples indicate that uniform augmented designs can be constructed with high efficiency.