Some New Residual Treatment Effects Designs for Comparing Test Treatments with a Control

Pigeon & Raghavarao (1987) introduced control balanced residual treatment effects designs for the situation where one treatment is a control or standard and is to be compared with the v test treatments, and they have also given methods of construction of control balanced residual treatment effects designs and have investigated their efficiencies. In this paper we have developed some new families of control balanced residual treatment effects designs, which are Schur-optimal.     

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.     

A class of saturated row–column designs

A new class of row–column designs is proposed. These designs are saturated in terms of eliminating two-way heterogeneity with an additive model. The (m,s)-criterion is used to select optimal designs. It turns out that all (m,s)-optimal designs are binary. Square (m,s)-optimal designs are constructed and they are treatment-connected. Thus, all treatment contrasts are estimable regardless of the row and column effects.     

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.     

Practical approaches for design and analysis of clinical trials of infertility treatments: crossover designs and the Mantel–Haenszel method are recommended

Crossover designs have some advantages over standard clinical trial designs and they are often used in trials evaluating the efficacy of treatments for infertility. However, clinical trials of infertility treatments violate a fundamental condition of crossover designs, because women who become pregnant in the first treatment period are not treated in the second period. In previous research, to deal with this problem, some new designs, such as re‐randomization designs, and analysis methods including the logistic mixture model and the beta‐binomial mixture model were proposed. Although the performance of these designs and methods has previously been evaluated in large‐scale clinical trials with sample sizes of more than 1000 per group, the actual sample sizes of infertility treatment trials are usually around 100 per group. The most appropriate design and analysis for these moderate‐scale clinical trials are currently unclear. In this study, we conducted simulation studies to determine the appropriate design and analysis method of moderate‐scale clinical trials for irreversible endpoints by evaluating the statistical power and bias in the treatment effect estimates. The Mantel–Haenszel method had similar power and bias to the logistic mixture model. The crossover designs had the highest power and the smallest bias. We recommend using a combination of the crossover design and the Mantel–Haenszel method for two‐period, two‐treatment clinical trials with irreversible endpoints. Copyright © 2015 John Wiley & Sons, Ltd.     

Optimum properties of latin square designs and a matrix inequality

The paper deals with uniform and D-optimality of designs in the two-way elimination of heterogeneities. It is shown that designs which are optimum for the hypothesis that all treatment effects are equal are optimum for some other hypotheses, too. The Proof is based on a new matrix- and determinantal inequality.     

Balanced incomplete Latin square designs

Latin squares have been widely used to design an experiment where the blocking factors and treatment factors have the same number of levels. For some experiments, the size of blocks may be less than the number of treatments. Since not all the treatments can be compared within each block, a new class of designs called balanced incomplete Latin squares (BILS) is proposed. A general method for constructing BILS is proposed by an intelligent selection of certain cells from a complete Latin square via orthogonal Latin squares. The optimality of the proposed BILS designs is investigated. It is shown that the proposed transversal BILS designs are asymptotically optimal for all the row, column and treatment effects. The relative efficiencies of a delete-one-transversal BILS design with respect to the optimal designs for both cases are also derived; it is shown to be close to 100%, as the order becomes large.     

A-Optimal Block Designs with Additional Singly Replicated Treatments

Block designs to which have been added a number of singly-replicated treatments, known as secondary treatments, are particularly useful for experiments where only small amounts of material are available for some treatments, for example new plant varieties. The designs are of particular use in the microarray situation. Such designs are known as 'augmented designs'. This paper obtains the properties of these designs and shows that, with an equal number of secondary treatments in each block, the A-optimal design is obtained by using the A-optimal design for the original block design. It develops formulae for the variance of treatment comparisons, for both the primary and the secondary treatments. A number of examples are used to illustrate the results.     

MULTI-FACTOR BALANCED BLOCK DESIGNS WITH COMPLETE ADJUSTED ORTHOGONALITY FOR ALL PAIRS OF TREATMENT FACTORS

A new series of multi-factor balanced block designs is introduced. Each of these designs has the following properties: (i) each of its k– 1 treatment factors is disposed in a cyclic or multi-cyclic balanced incomplete block design with parameters (v,b,r,k,Λ) = (a(k-l) + 1,a²(k-1) +a, ak, k, k) (a > 1); (ii) the incidence of any one of the treatment factors on any other is balanced; and (iii) after adjustment for blocks only, the relationship between any two of the treatment factors is that of adjusted orthogonality. The treatment factors are thus orthogonal to one another in the within-blocks stratum of the analysis of variance. The designs provide a benchmark with which other designs may be compared.     

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.     

Using explicit clinician preferences in nonrandomized study designs

Nonrandomized study designs are proposed that utilize statements by individual clinicians specifying how they would prefer to treat each patient based on the patient's pre-treatment records. Using these stated preferences allows us to eliminate selection biases in an analysis to estimate treatment effects. The analysis of a pilot study using one of the new designs to examine two orthodontic treatments is presented.     

Cumulative cohort design for dose-finding

We introduce a new design for dose-finding in the context of toxicity studies for which it is assumed that toxicity increases with dose. The goal is to identify the maximum tolerated dose, which is taken to be the dose associated with a prespecified “target” toxicity rate. The decision to decrease, increase or repeat a dose for the next subject depends on how far an estimated toxicity rate at the current dose is from the target. The size of the window within which the current dose will be repeated is obtained based on the theory of Markov chains as applied to group up-and-down designs. But whereas the treatment allocation rule in Markovian group up-and-down designs is only based on information from the current cohort of subjects, the treatment allocation rule for the proposed design is based on the cumulative information at the current dose. We then consider an extension of this new design for clinical trials in which the subject's outcome is not known immediately. The new design is compared to the continual reassessment method.     

Non binary partially neighbor balanced designs for circular blocks

ABSTRACT

Neighbor designs are recommended for the cases where the performance of treatment is affected by the neighboring treatments as in biometrics and agriculture. In this paper we have constructed two new series of non binary partially neighbor balanced designs for v = 2n and v = 2n+1 number of treatments, respectively. The blocks in the design are non binary and circular but no treatment is ever a neighbor to itself. The designs proposed here are partially balanced in terms of nearest neighbors. No such series are known in the literature.     

Construction and analysis of edge designs from skew-symmetric supplementary difference sets

The purpose of screening experiments is to identify the dominant variables from a set of many potentially active variables which may affect some characteristic y. Edge designs were recently introduced in the literature and are constructed by using conferences matrices and were proved to be robust. We introduce a new class of edge designs which are constructed from skew-symmetric supplementary difference sets. These designs are particularly useful since they can be applied for experiments with an even number of factors and they may exist for orders where conference matrices do not exist. Using this methodology, examples of new edge designs for 6, 14, 22, 26, 38, 42, 46, 58, and 62 factors are constructed. Of special interest are the new edge designs for studying 22 and 58 factors because edge designs with these parameters have not been constructed in the literature since conference matrices of the corresponding order do not exist. The suggested new edge designs achieve the same model-robustness as the traditional edge designs. We also suggest the use of a mirror edge method as a test for the linearity of the true underlying model. We give the details of the methodology and provide some illustrating examples for this new approach. We also show that the new designs have good D-efficiencies when applied to first order models.     

Balanced Treatment incomplete block (BTIB) designs for comparing treatments with a control: minimal complete sets of generator designs for k = 3, p = 3(1)10

Bechhofer and Tamhane (1981) proposed a new class of incomplete block designs called BTIB designs for comparing p ≥ 2 test treatments with a control treatment in blocks of equal size k < p + 1. All BTIB designs for given (p,k) can be constructed by forming unions of replications of a set of elementary BTIB designs called generator designs for that (p,k). In general, there are many generator designs for given (p,k) but only a small subset (called the minimal complete set) of these suffices to obtain all admissible BTIB designs (except possibly any equivalent ones). Determination of the minimal complete set of generator designs for given (p,k) was stated as an open problem in Bechhofer and Tamhane (1981). In this paper we solve this problem for k = 3. More specifically, we give the minimal complete sets of generator designs for k = 3, p = 3(1)10; the relevant proofs are given only for the cases p = 3(1)6. Some additional combinatorial results concerning BTIB designs are also given.     

A new special class of peb designs

A new class of partially efficiency-balanced designs is introduced from a practical point of view. This new design includes all equireplicated incomplete block designs available in literature as special cases. The fundamental properties of the design are clarified with relation to other block designs.     

Block-circulant matrices for constructing optimal Latin hypercube designs

Computer simulations are usually needed to study a complex physical process. In this paper, we propose new procedures for constructing orthogonal or low-correlation block-circulant Latin hypercube designs. The basic concept of these methods is to use vectors with a constant periodic autocorrelation function to obtain suitable block-circulant Latin hypercube designs. A general procedure for constructing orthogonal Latin hypercube designs with favorable properties and allowing run sizes being different from a power of 2 (or a power of 2 plus 1), is presented here for the first time. In addition, an expansion of the method is given for constructing Latin hypercube designs with low correlation. This expansion is useful when orthogonal Latin hypercube designs do not exist. The properties of the generated designs are further investigated. Some examples of the new designs, as generated by the proposed procedures, are tabulated. In addition, a brief comparison with the designs that appear in the literature is given.     

Properties of Designs in Experiments on Spatial Lattices

ABSTRACT

When spatial variation is present in experiments, it is clearly sensible to use designs with favorable properties under both generalized and ordinary least squares. This will make the statistical analysis more robust to misspecification of the spatial model than would be the case if designs were based solely on generalized least squares. In this article, treatment information is introduced as a way of studying the ordinary least squares properties of designs. The treatment information is separated into orthogonal frequency or polynomial components which are assumed to be independent under the spatial model. The well-known trend-resistant designs are those with no treatment information at the very low order frequency or polynomial components which tend to have the higher variances under the spatial model. Ideally, designs would be chosen with all the treatment information distributed at the higher-order components. However, the results in this article show that there are limits on how much trend resistance can be achieved as there are many constraints on the treatment information. In addition, appropriately chosen Williams squares designs are shown to have favorable properties under both ordinary and generalized least squares. At all times, the ordinary least squares properties of the designs are balanced against the generalized least squares objectives of optimizing neighbor balance.     

Some families of group divisible designs

Generalizing methods of constructions of Hadamard group divisible designs due to Bush (1979), some new families of semi-regular or regular group divisible designs are produced. Furthermore, new nonisomorphic solutions for some known group divisible designs are given, together with useful group divisible designs not listed in Clatworthy (1973).