Unifying CRM and EWOC designs for phase I cancer clinical trials

The main goal of phase I cancer clinical trials is to determine the highest dose of a new therapy associated with an acceptable level of toxicity for the use in a subsequent phase II trial. The continual reassessment method (CRM) [O’Quigley, J., Pepe, M., Fisher, L., 1990. Continual reassessment method: a practical design for phase I clinical trials in cancer. Biometrics 46, 33–48] and escalation with overdose control (EWOC) [Babb, J., Rogatko, A., Zacks, S., 1998. Cancer phase I clinical trials: efficient dose escalation with overdose control. Statist. Med. 17 (10), 1103–1120] are two model-based designs used for phase I cancer clinical trials. A few modifications of the (original) CRM and EWOC have been made by many authors. In this paper, we show how CRM and EWOC can be unified and present a hybrid design. We study the characteristics of the approach of the hybrid design. The comparisons of the three designs (CRM, EWOC, and the hybrid design) are presented by convergence rates and overdose proportions. The simulation results show that the hybrid design generally has faster convergence rates than EWOC and smaller overdose proportions than CRM, especially when the true maximum tolerated dose (MTD) is above the mid-level of the dose range considered. The performance of these three designs is also evaluated in terms of sensitivity to outliers.     

Nonparametric control charts based on runs and Wilcoxon-type rank-sum statistics

In this article, we introduce three new distribution-free Shewhart-type control charts that exploit run and Wilcoxon-type rank-sum statistics to detect possible shifts of a monitored process. Exact formulae for the alarm rate, the run length distribution, and the average run length (ARL) are all derived. A key advantage of these charts is that, due to their nonparametric nature, the false alarm rate (FAR) and in-control run length distribution is the same for all continuous process distributions. Tables are provided for the implementation of the charts for some typical FAR values. Furthermore, a numerical study carried out reveals that the new charts are quite flexible and efficient in detecting shifts to Lehmann-type out-of-control situations.     

The extended GWMA control chart

This study extends the generally weighted moving average (GWMA) control chart by imitating the double exponentially weighted moving average (DEWMA) technique. The proposed chart is called the double generally weighted moving average (DGWMA) control chart. Simulation is employed to evaluate the average run length characteristics of the GWMA, DEWMA and DGWMA control charts. An extensive comparison of these control charts reveals that the DGWMA control chart with time-varying control limits is more sensitive than the GWMA and the DEWMA control charts for detecting medium shifts in the mean of a process when the shifts are between 0.5 and 1.5 standard deviations. Additionally, the GWMA control chart performs better when the mean shifts are below the 0.5 standard deviation, and the DEWMA control performs better when the mean shifts are above the 1.5 standard deviation. The design of the DGWMA control chart is also discussed.     

Generally weighted moving average control charts with fast initial response features

The generally weighted moving average (GWMA) control chart is an extension model of exponentially weighted moving average (EWMA) control chart. Recently, some approaches have been proposed to modify EWMA charts with fast initial response (FIR) features. We introduce these approaches in GWMA-type charts. Via simulation, various control schemes are designed and then their average run lengths are computed and compared. Based on the overall performance, it is showed that the DGWMA chart is the best choice especially when the shift is moderate, and the GWMA charts provided with additional FIR feature have a good performance only in detecting large shifts during the initial stage.     

A likelihood ratio test for goodness‐of‐fit of recessive and dominant models for case–control studies

Testing goodness‐of‐fit of commonly used genetic models is of critical importance in many applications including association studies and testing for departure from Hardy–Weinberg equilibrium. Case–control design has become widely used in population genetics and genetic epidemiology, thus it is of interest to develop powerful goodness‐of‐fit tests for genetic models using case–control data. This paper develops a likelihood ratio test (LRT) for testing recessive and dominant models for case–control studies. The LRT statistic has a closed‐form formula with a simple $\chi^{2}(1)$ null asymptotic distribution, thus its implementation is easy even for genome‐wide association studies. Moreover, it has the same power and optimality as when the disease prevalence is known in the population. The Canadian Journal of Statistics 41: 341–352; 2013 © 2013 Statistical Society of Canada     

Alternative Factors for Control Chart Construction

Conflicting decision signals resulting from Shewhart Mean and Variability Control Charts produce undesirable consequences. Therefore, we construct “six-sigma” control charts by alternative methods to avoid problems associated with Control Charts yielding different signals. By adjusting methods for control chart construction for dispersion charts, we produce new reference tables. The new tables provide consistent signals and appear similar and familiar to users of historical tables.     

A Multivariate Synthetic Control Chart for Monitoring the Process Mean Vector of Skewed Populations Using Weighted Standard Deviations

This article proposes a multivariate synthetic control chart for skewed populations based on the weighted standard deviation method. The proposed chart incorporates the weighted standard deviation method into the standard multivariate synthetic control chart. The standard multivariate synthetic chart consists of the Hotelling's T ² chart and the conforming run length chart. The weighted standard deviation method adjusts the variance–covariance matrix of the quality characteristics and approximates the probability density function using several multivariate normal distributions. The proposed chart reduces to the standard multivariate synthetic chart when the underlying distribution is symmetric. In general, the simulation results show that the proposed chart performs better than the existing multivariate charts for skewed populations and the standard T ² chart, in terms of false alarm rates as well as moderate and large mean shift detection rates based on the various degrees of skewnesses.     

The computational aspects of multiple attribute sampling procedures

One method of controlling the quality of incoming lots is through attribute sampling. To simultaneously control several (possibly dependent) attributes, properly chosen single attribute sampling plans can be merged into a multiple attribute sampling plan. The general form of such a plan is given and various alternatives are discussed. The multinomial distribution is used to develop formulae necessary for an analysis of a multiple attribute plan. Due to the lengthy nature of the calculations involved, a computer algorithm is outlined.     

Determining Optimal Number of Samples for Constructing Multivariate Control Charts

Normally, an average run length (ARL) is used as a measure for evaluating the detecting performance of a multivariate control chart. This has a direct impact on the false alarm cost in Phase II. In this article, we first conduct a simulation study to calculate both in-control and out-of-control ARLs under various combinations of process shifts and number of samples. Then, a trade-off analysis between sampling inspection and false alarm costs is performed. Both the simulation results and trade-off analysis suggest that the optimal number of samples for constructing a multivariate control chart in Phase I can be determined.     

On a statistic useful in dimensionality reduction in multivariable linear stochastic system

In this paper we study the sampling properties of a test statistic which has important applications in the area of linear stochastic control systems with multi-inputs and multi-outputs. The statistic is the ratio of a partial sum of the eigenvalues of a sample covariance matrix and its trace. It turns out that using a method due to Sugiura we may derive a useful approximation for its distribution up to and including terms of order l/n, where n denotes the appropriate size. Numerical illustrations using real data are given.