Variance-penalized response-adaptive randomization with mismeasurement

We consider response-adaptive design of clinical trials under a variance-penalized criterion in the presence of mismeasurement. An explicit expression for the variance-penalized criterion with misclassified dichotomous responses is derived for response-adaptive designs and some properties are discussed. A new target proportion of treatment allocation is proposed under the criterion and related simulation results are presented.     

Some Classes of Binary Block Neighbor Designs

Neighbor designs are useful to neutralize the neighbor effects. In this paper two classes of these designs are constructed in circular binary blocks of size 4, 8, …, 24. First class consists of six infinite series of nearest neighbor designs in which each pair of distinct treatments appears once as neighbors. Second class also deals with six infinite series of these designs in which each pair of distinct treatments appears twice as neighbors. A catalog of nearest neighbor designs is also compiled in circular binary blocks for odd number of treatments from 23 to 99.     

A Bayesian adaptive blinded sample size adjustment method for risk differences

Adaptive sample size adjustment (SSA) for clinical trials consists of examining early subsets of on trial data to adjust estimates of sample size requirements. Blinded SSA is often preferred over unblinded SSA because it obviates many logistical complications of the latter and generally introduces less bias. On the other hand, current blinded SSA methods for binary data offer little to no new information about the treatment effect, ignore uncertainties associated with the population treatment proportions, and/or depend on enhanced randomization schemes that risk partial unblinding. I propose an innovative blinded SSA method for use when the primary analysis is a non‐inferiority or superiority test regarding a risk difference. The method incorporates evidence about the treatment effect via the likelihood function of a mixture distribution. I compare the new method with an established one and with the fixed sample size study design, in terms of maximization of an expected utility function. The new method maximizes the expected utility better than do the comparators, under a range of assumptions. I illustrate the use of the proposed method with an example that incorporates a Bayesian hierarchical model. Lastly, I suggest topics for future study regarding the proposed methods. Copyright © 2015 John Wiley & Sons, Ltd.     

A cusum control chart approach for screening active effects in orthogonal-saturated experiments

The analysis of designs based on saturated orthogonal arrays poses a very difficult challenge since there are no degrees of freedom left to estimate the error variance. In this paper we propose a heuristic approach for the use of cumulative sum control chart for screening active effects in orthogonal-saturated experiments. A comparative simulation study establishes the powerfulness of the proposed method.     

Universally Optimal Designs Balanced for Neighbor Effects

The performance of a treatment is affected by the treatments applied to its adjacent plots, especially in the experiments of agriculture, horticulture, forestry, serology and industry. Neighbor designs ensure that treatment comparisons are least affected by neighbor effects, therefore, this is a rich field of investigation. In this paper, criterion for construction of universally optimal neighbor balanced designs is discussed.     

Optimal Designs for the Carryover Model with Random Interactions Between Subjects and Treatments

The paper considers a model for crossover designs with carryover effects and a random interaction between treatments and subjects. Under this model, two observations of the same treatment on the same subject are positively correlated and therefore provide less information than two observations of the same treatment on different subjects. The introduction of the interaction makes the determination of optimal designs much harder than is the case for the traditional model. Generalising the results of Bludowsky's thesis, the present paper uses Kushner's method to determine optimal approximate designs. We restrict attention to the case where the number of periods is less than or equal to the number of treatments. We determine the optimal designs in the important special cases that the number of periods is 3, 4 or 5. It turns out that the optimal designs depend on the variance of the random interactions and in most cases are not binary. However, we can show that neighbour balanced binary designs are highly efficient, regardless of the number of periods and of the size of the variance of the interaction effects.     

The performance of subset response surface designs for estimating third order terms

Response surface designs are widely used in industries like chemicals, foods, pharmaceuticals, bioprocessing, agrochemicals, biology, biomedicine, agriculture and medicine. One of the major objectives of these designs is to study the functional relationship between one or more responses and a number of quantitative input factors. However, biological materials have more run to run variation than in many other experiments, leading to the conclusion that smaller response surface designs are inappropriate. Thus designs to be used in these research areas should have greater replication. Gilmour (2006) introduced a wide class of designs called “subset designs” which are useful in situations in which run to run variation is high. These designs allow the experimenter to fit the second order response surface model. However, there are situations in which the second order model representation proves to be inadequate and unrealistic due to the presence of lack of fit caused by third or higher order terms in the true response surface model. In such situations it becomes necessary for the experimenter to estimate these higher order terms. In this study, the properties of subset designs, in the context of the third order response surface model, are explored.     

Two-stage k-sample designs for the ordered alternative problem

In preclinical studies and clinical dose-ranging trials, the Jonckheere-Terpstra test is widely used in the assessment of dose-response relationships. Hewett and Spurrier (1979) presented a two-stage analog of the test in the context of large sample sizes. In this paper, we propose an exact test based on Simon's minimax and optimal design criteria originally used in one-arm phase II designs based on binary endpoints. The convergence rate of the joint distribution of the first and second stage test statistics to the limiting distribution is studied, and design parameters are provided for a variety of assumed alternatives. The behavior of the test is also examined in the presence of ties, and the proposed designs are illustrated through application in the planning of a hypercholesterolemia clinical trial. The minimax and optimal two-stage procedures are shown to be preferable as compared with the one-stage procedure because of the associated reduction in expected sample size for given error constraints.     

Constructing optimal projection designs

ABSTRACT

The early stages of many real-life experiments involve a large number of factors among which only a few factors are active. Unfortunately, the optimal full-dimensional designs of those early stages may have bad low-dimensional projections and the experimenters do not know which factors turn out to be important before conducting the experiment. Therefore, designs with good projections are desirable for factor screening. In this regard, significant questions are arising such as whether the optimal full-dimensional designs have good projections onto low dimensions? How experimenters can measure the goodness of a full-dimensional design by focusing on all of its projections?, and are there linkages between the optimality of a full-dimensional design and the optimality of its projections? Through theoretical justifications, this paper tries to provide answers to these interesting questions by investigating the construction of optimal (average) projection designs for screening either nominal or quantitative factors. The main results show that: based on the aberration and orthogonality criteria the full-dimensional design is optimal if and only if it is optimal projection design; the full-dimensional design is optimal via the aberration and orthogonality if and only if it is uniform projection design; there is no guarantee that a uniform full-dimensional design is optimal projection design via any criterion; the projection design is optimal via the aberration, orthogonality and uniformity criteria if it is optimal via any criterion of them; and the saturated orthogonal designs have the same average projection performance.     

论小康社会的法治模式

小康社会法治模式是依据法治的分类学说和全面建设小康社会的现实社会基础而提出的一种社会转型时期的法治形态。小康社会法治模式是法治的初级形态,它既具有法治的普适性特点,又有与法治常态相区别的特殊性。小康社会全面落实依法治国方略,就是要分步骤地落实党领导人民治理国家的各项具体法治。