Multi-arm response-adaptive designs for circular responses

A multi-arm response-adaptive allocation design is developed for circular treatment outcomes. Several exact and asymptotic properties of the design are studied. Stage-wise treatment selection procedures based on the proposed response-adaptive design are also suggested to exclude the worse performing treatment(s) at earlier stages. Detailed simulation study is carried out to evaluate the proposed selection procedures. The applicability of the proposed methodologies is illustrated through a real clinical trial data on cataract surgery.     

Uniform Design for Experiments with Mixtures

The goal of uniform mixture design is to scatter the design points in the experimental region uniformly. The commonly used criteria, such as mean square distance, are based on the Euclidean distance. Based on the Lee distance, a new criterion is proposed in this article. And an algorithm, called NTLBG, is also proposed to refine the randomly generated design for the experimental design with mixtures. Some examples show that the design generated by the NTLBG algorithm has a lower criteria value.     

Optimal design for classification of functional data

We study the design problem for the optimal classification of functional data. The goal is to select sampling time points so that functional data observed at these time points can be classified accurately. We propose optimal designs that are applicable to either dense or sparse functional data. Using linear discriminant analysis, we formulate our design objectives as explicit functions of the sampling points. We study the theoretical properties of the proposed design objectives and provide a practical implementation. The performance of the proposed design is evaluated through simulations and real data applications. The Canadian Journal of Statistics 48: 285–307; 2020 © 2019 Statistical Society of Canada     

An economic statistical design of the Poisson EWMA control charts for monitoring nonconformities

An economic statistical model of the exponentially weighted moving average (EWMA) control chart for the average number of nonconformities in the sample is proposed. The statistical and economic performance of proposed design are evaluated using the average run length (ARL) and the hourly expected cost, respectively. A Markov chain approach is applied to derive expressions for ARL. The cost model is established based on the general cost function given in Lorenzen and Vance [The economic design of control charts: a unified approach. Technometrics. 1986;28:3–11]. An example is provided to illustrate the application of the proposed model. A sensitivity analysis is also carried out to investigate the effects of model parameters on the solution of the economic statistical design by using the design of experiments (DOE) technique.     

Double-sampling control charts for attributes

In this article, we propose a double-sampling (DS) np control chart. We assume that the time interval between samples is fixed. The choice of the design parameters of the proposed chart and also comparisons between charts are based on statistical properties, such as the average number of samples until a signal. The optimal design parameters of the proposed control chart are obtained. During the optimization procedure, constraints are imposed on the in-control average sample size and on the in-control average run length. In this way, required statistical properties can be assured. Varying some input parameters, the proposed DS np chart is compared with the single-sampling np chart, variable sample size np chart, CUSUM np and EWMA np charts. The comparisons are carried out considering the optimal design for each chart. For the ranges of parameters considered, the DS scheme is the fastest one for the detection of increases of 100% or more in the fraction non-conforming and, moreover, the DS np chart is easy to operate.     

A Bayesian sequential design with adaptive randomization for 2‐sided hypothesis test

Bayesian sequential and adaptive randomization designs are gaining popularity in clinical trials thanks to their potentials to reduce the number of required participants and save resources. We propose a Bayesian sequential design with adaptive randomization rates so as to more efficiently attribute newly recruited patients to different treatment arms. In this paper, we consider 2‐arm clinical trials. Patients are allocated to the 2 arms with a randomization rate to achieve minimum variance for the test statistic. Algorithms are presented to calculate the optimal randomization rate, critical values, and power for the proposed design. Sensitivity analysis is implemented to check the influence on design by changing the prior distributions. Simulation studies are applied to compare the proposed method and traditional methods in terms of power and actual sample sizes. Simulations show that, when total sample size is fixed, the proposed design can obtain greater power and/or cost smaller actual sample size than the traditional Bayesian sequential design. Finally, we apply the proposed method to a real data set and compare the results with the Bayesian sequential design without adaptive randomization in terms of sample sizes. The proposed method can further reduce required sample size.     

A stochastically curtailed two-arm randomised phase II trial design for binary outcomes

Randomised controlled trials are considered the gold standard in trial design. However, phase II oncology trials with a binary outcome are often single-arm. Although a number of reasons exist for choosing a single-arm trial, the primary reason is that single-arm designs require fewer participants than their randomised equivalents. Therefore, the development of novel methodology that makes randomised designs more efficient is of value to the trials community. This article introduces a randomised two-arm binary outcome trial design that includes stochastic curtailment (SC), allowing for the possibility of stopping a trial before the final conclusions are known with certainty. In addition to SC, the proposed design involves the use of a randomised block design, which allows investigators to control the number of interim analyses. This approach is compared with existing designs that also use early stopping, through the use of a loss function comprised of a weighted sum of design characteristics. Comparisons are also made using an example from a real trial. The comparisons show that for many possible loss functions, the proposed design is superior to existing designs. Further, the proposed design may be more practical, by allowing a flexible number of interim analyses. One existing design produces superior design realisations when the anticipated response rate is low. However, when using this design, the probability of rejecting the null hypothesis is sensitive to misspecification of the null response rate. Therefore, when considering randomised designs in phase II, we recommend the proposed approach be preferred over other sequential designs.     

A clustering-based coordinate exchange algorithm for generating G-optimal experimental designs

In the optimal experimental design literature, the G-optimality is defined as minimizing the maximum prediction variance over the entire experimental design space. Although the G-optimality is a highly desirable property in many applications, there are few computer algorithms developed for constructing G-optimal designs. Some existing methods employ an exhaustive search over all candidate designs, which is time-consuming and inefficient. In this paper, a new algorithm for constructing G-optimal experimental designs is developed for both linear and generalized linear models. The new algorithm is made based on the clustering of candidate or evaluation points over the design space and it is a combination of point exchange algorithm and coordinate exchange algorithm. In addition, a robust design algorithm is proposed for generalized linear models with modification of an existing method. The proposed algorithm are compared with the methods proposed by Rodriguez et al. [Generating and assessing exact G-optimal designs. J. Qual. Technol. 2010;42(1):3–20] and Borkowski [Using a genetic algorithm to generate small exact response surface designs. J. Prob. Stat. Sci. 2003;1(1):65–88] for linear models and with the simulated annealing method and the genetic algorithm for generalized linear models through several examples in terms of the G-efficiency and computation time. The result shows that the proposed algorithm can obtain a design with higher G-efficiency in a much shorter time. Moreover, the computation time of the proposed algorithm only increases polynomially when the size of model increases.     

Empirical Likelihood Inference for the Rao‐Hartley‐Cochran Sampling Design

The Hartley‐Rao‐Cochran sampling design is an unequal probability sampling design which can be used to select samples from finite populations. We propose to adjust the empirical likelihood approach for the Hartley‐Rao‐Cochran sampling design. The approach proposed intrinsically incorporates sampling weights, auxiliary information and allows for large sampling fractions. It can be used to construct confidence intervals. In a simulation study, we show that the coverage may be better for the empirical likelihood confidence interval than for standard confidence intervals based on variance estimates. The approach proposed is simple to implement and less computer intensive than bootstrap. The confidence interval proposed does not rely on re‐sampling, linearization, variance estimation, design‐effects or joint inclusion probabilities.     

Orthogonal series density estimation for complex surveys

We propose an orthogonal series density estimator for complex surveys, where samples are neither independent nor identically distributed. The proposed estimator is proved to be design-unbiased and asymptotically design-consistent. The asymptotic normality is proved under both design and combined spaces. Two data driven estimators are proposed based on the proposed oracle estimator. We show the efficiency of the proposed estimators in simulation studies. A real survey data example is provided for an illustration.     

A Bayesian adaptive design for two-stage clinical trials with survival data

A randomized two-stage adaptive Bayesian design is proposed and studied for allocation and comparison in a phase III clinical trial with survival time as treatment response. Several exact and limiting properties of the design and the follow-up inference are studied, both numerically and theoretically, and are compared with a single-stage randomized procedure. The applicability of the proposed methodology is illustrated by using some real data.     

A powerful test for Balaam's design

The crossover trial design (AB/BA design) is often used to compare the effects of two treatments in medical science because it performs within‐subject comparisons, which increase the precision of a treatment effect (i.e., a between‐treatment difference). However, the AB/BA design cannot be applied in the presence of carryover effects and/or treatments‐by‐period interaction. In such cases, Balaam's design is a more suitable choice. Unlike the AB/BA design, Balaam's design inflates the variance of an estimate of the treatment effect, thereby reducing the statistical power of tests. This is a serious drawback of the design. Although the variance of parameter estimators in Balaam's design has been extensively studied, the estimators of the treatment effect to improve the inference have received little attention. If the estimate of the treatment effect is obtained by solving the mixed model equations, the AA and BB sequences are excluded from the estimation process. In this study, we develop a new estimator of the treatment effect and a new test statistic using the estimator. The aim is to improve the statistical inference in Balaam's design. Simulation studies indicate that the type I error of the proposed test is well controlled, and that the test is more powerful and has more suitable characteristics than other existing tests when interactions are substantial. The proposed test is also applied to analyze a real dataset. Copyright © 2015 John Wiley & Sons, Ltd.     

A general adaptive allocation design for continuous responses in the presence of covariates

Several adaptive allocation designs are available in the clinical trial literature for allocating the entering patients among two competing treatments, having binary responses and skewing the allocation in favor of the better treatment. No adaptive design is available for continuous responses in the presence of prognostic factors, which is not model based. In the present paper, a general allocation design is introduced which assumes no specific regression model or distribution of responses. Some performance characteristics of the design are studied. Some related inference, following the allocation, is also studied. The proposed procedure is compared with some possible competitors. A real data set is used to illustrate the applicability of the proposed design.     

Sequential estimation for covariate-adjusted response-adaptive designs

In clinical trials, a covariate-adjusted response-adaptive (CARA) design allows a subject newly entering a trial a better chance of being allocated to a superior treatment regimen based on cumulative information from previous subjects, and adjusts the allocation according to individual covariate information. Since this design allocates subjects sequentially, it is natural to apply a sequential method for estimating the treatment effect in order to make the data analysis more efficient. In this paper, we study the sequential estimation of treatment effect for a general CARA design. A stopping criterion is proposed such that the estimates satisfy a prescribed precision when the sampling is stopped. The properties of estimates and stopping time are obtained under the proposed stopping rule. In addition, we show that the asymptotic properties of the allocation function, under the proposed stopping rule, are the same as those obtained in the non-sequential/fixed sample size counterpart. We then illustrate the performance of the proposed procedure with some simulation results using logistic models. The properties, such as the coverage probability of treatment effect, correct allocation proportion and average sample size, for diverse combinations of initial sample sizes and tuning parameters in the utility function are discussed.     

Adaptive Crossover Design for Normal Responses

In a response-adaptive design, we review and update the trial on the basis of outcomes in order to achive a specific goal. In clinical trials our goal is to allocate a larger number of patients to the better treatment. In the present paper, we use a response adaptive design in a two-treatment two-period crossover trial where the treatment responses are continuous. We provide probability measures to choose between the possible treatment combinations AA, AB, BA, or BB. The goal is to use the better treatment combination a larger number of times. We calculate the allocation proportions to the possible treatment combinations and their standard errors. We also derive some asymptotic results and provide solutions on related inferential problems. The proposed procedure is compared with a possible competitor. Finally, we use a data set to illustrate the applicability of our proposed design.     

Adaptive grid semidefinite programming for finding optimal designs

We find optimal designs for linear models using a novel algorithm that iteratively combines a semidefinite programming (SDP) approach with adaptive grid techniques. The proposed algorithm is also adapted to find locally optimal designs for nonlinear models. The search space is first discretized, and SDP is applied to find the optimal design based on the initial grid. The points in the next grid set are points that maximize the dispersion function of the SDP-generated optimal design using nonlinear programming. The procedure is repeated until a user-specified stopping rule is reached. The proposed algorithm is broadly applicable, and we demonstrate its flexibility using (i) models with one or more variables and (ii) differentiable design criteria, such as A-, D-optimality, and non-differentiable criterion like E-optimality, including the mathematically more challenging case when the minimum eigenvalue of the information matrix of the optimal design has geometric multiplicity larger than 1. Our algorithm is computationally efficient because it is based on mathematical programming tools and so optimality is assured at each stage; it also exploits the convexity of the problems whenever possible. Using several linear and nonlinear models with one or more factors, we show the proposed algorithm can efficiently find optimal designs.     

A three-stage variable selection method for supersaturated designs

A supersaturated design (SSD) is a design whose run size is not enough for estimating all main effects. Such a design is commonly used in screening experiments to screen active effects based on the effect sparsity principle. Traditional approaches, such as the ordinary stepwise regression and the best subset variable selection, may not be appropriate in this situation. In this article, a new variable selection method is proposed based on the idea of staged dimensionality reduction. Simulations and several real data studies indicate that the newly proposed method is more effective than the existing data analysis methods.     

Sequential design for nonparametric inference

The performance of nonparametric function estimates often depends on the choice of design points. Based on the mean integrated squared error criterion, we propose a sequential design procedure that updates the model knowledge and optimal design density sequentially. The methodology is developed under a general framework covering a wide range of nonparametric inference problems, such as conditional mean and variance functions, the conditional distribution function, the conditional quantile function in quantile regression, functional coefficients in varying coefficient models and semiparametric inferences. Based on our empirical studies, nonparametric inference based on the proposed sequential design is more efficient than the uniform design and its performance is close to the true but unknown optimal design. The Canadian Journal of Statistics 40: 362–377; 2012 © 2012 Statistical Society of Canada     

The Mean Squared Error Optimum Design Criterion for Parameter Estimation in Nonlinear Regression Models

In the context of nonlinear regression models, we propose an optimal experimental design criterion for estimating the parameters that account for the intrinsic and parameter-effects nonlinearity. The optimal design criterion proposed in this article minimizes the determinant of the mean squared error matrix of the parameter estimator that is quadratically approximated using the curvature array. The design criterion reduces to the D-optimal design criterion if there are no intrinsic and parameter-effects nonlinearity in the model, and depends on the scale parameter estimator and on the reparameterization used. Some examples, using a well known nonlinear kinetics model, demonstrate the application of the proposed criterion to nonsequential design of experiments as compared with the D-optimal criterion.     

Optimal predictive design augmentation for spatial generalised linear mixed models

A typical model for geostatistical data when the observations are counts is the spatial generalised linear mixed model. We present a criterion for optimal sampling design under this framework which aims to minimise the error in the prediction of the underlying spatial random effects. The proposed criterion is derived by performing an asymptotic expansion to the conditional prediction variance. We argue that the mean of the spatial process needs to be taken into account in the construction of the predictive design, which we demonstrate through a simulation study where we compare the proposed criterion against the widely used space-filling design. Furthermore, our results are applied to the Norway precipitation data and the rhizoctonia disease data.