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.     

A comparative study of adaptive trial designs for dose optimization

Recently, the US Food and Drug Administration Oncology Center of Excellence initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development. The agency pointed out that the current paradigm for dose selection—based on the maximum tolerated dose (MTD)—is not sufficient for molecularly targeted therapies and immunotherapies, for which efficacy may not increase after the dose reaches a certain level. In these cases, it is more appropriate to identify the optimal biological dose (OBD) that optimizes the risk–benefit tradeoff of the drug. Project Optimus has spurred tremendous interest and urgent need for guidance on designing dose optimization trials. In this article, we review several representative dose optimization designs, including model-based and model-assisted designs, and compare their operating characteristics based on 10,000 randomly generated scenarios with various dose-toxicity and dose-efficacy curves and some fixed representative scenarios. The results show that, compared with model-based designs, model-assisted methods have advantages of easy-to-implement, robustness, and high accuracy to identify OBD. Some guidance is provided to help biostatisticians and clinicians to choose appropriate dose optimization methods in practice.     

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.     

Orthogonal arrays of strength three from regular 3-wise balanced designs

The construction given in Kreher, J Combin Des 4 (1996) 67 is extended to obtain new infinite families of orthogonal arrays of strength 3. Regular 3-wise balanced designs play a central role in this construction.     

Optimal experimental designs when an independent variable is potentially censored

This paper considers the problem of constructing optimal approximate designs when an independent variable might be censored. The problem is which design should be applied in practice to obtain the best approximate design when a censoring distribution is assumed known in advance. The approach for finite or continuous design spaces deserves different attention. In both cases, equivalent theorems and algorithms are provided in order to calculate optimal designs. Some examples illustrate this approach for D-optimality.     

Block Designs Robust Against the Presence of an Aberration in a Treatment-Control Setup

The author considers the problem of finding designs insensitive to the presence of an outlier in a treatment-control block design setup for estimating the set of elementary contrasts between the effects of each test treatment and a control treatment. The criterion of robustness suggested by Mandal (1989 Mandal , N. K. ( 1989 ). On robust designs . Cal. Stat. Assoc. Bull. 38 : 115 – 119 . [Google Scholar]) in block design setup for estimating a full set of orthonormal treatment contrasts is adapted. A new class viz. partially balanced treatment incomplete block designs (PBTIBD) is introduced and it is shown that balanced treatment incomplete block designs (BTIBD) and PBTIB designs, under certain conditions, are robust in the previous sense. Such designs are important in the sense that the inference on the treatment contrasts under consideration remain unaffected by the presence of an outlier.     

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.     

A note on the nonexistence of the constant block-sum balanced incomplete block designs

Abstract

Due to important practical applications and considerations in biomedical clinical trials, fixed block-sum designs are of interest. We show that in general, the constant block-sum balanced incomplete block designs do not exist.     

Randomized response multivariate designs for categorical data

Three approaches to multivariate estimation for categorical data using randomized response (RR) are described. In the first approach, practical only for 2×2 contingency tables, a multi-proportions design is used. In the second approach, a separate RR trial is used for each variate and it is noted that the multi­variate design matrix of conditional probabilities is given by the Kroneeker product of the univariate design matrices of each trial, provided that the trials are independent of each other in a certain sense. The third approach requires only a single randomization and thus may be viewed as the use of vector response. Finally, a special-purpose bivariate design is presented.