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.     

Improved randomized response in additive scrambling models

Randomized response models deal with stigmatizing variables appearing in health surveys. Additive and subtractive scrambling in split sample and double response yield unbiased mean and sensitivity estimators of high precision. The split sample method is protective of privacy. The double response method is as protective only conditionally. To achieve the maximum efficiency, the scrambling variables must be similar to each other and the probability of obtaining a true response must be as large as possible. The randomized response procedures yield more efficient estimates of the average total number of classes missed by university students.     

Improved estimation methods for unrelated question randomized response techniques

The randomized response technique (RRT) is an important tool, commonly used to avoid biased answers in survey on sensitive issues by preserving the respondents’ privacy. In this paper, we introduce a data collection method for survey on sensitive issues combining both the unrelated-question RRT and the direct question design. The direct questioning method is utilized to obtain responses to a non sensitive question that is related to the innocuous question from the unrelated-question RRT. These responses serve as additional information that can be used to improve the estimation of the prevalence of the sensitive behavior. Furthermore, we propose two new methods for the estimation of the proportion of respondents possessing the sensitive attribute under a missing data setup. More specifically, we develop the weighted estimator and the weighted conditional likelihood estimator. The performances of our estimators are studied numerically and compared with that of an existing one. Both proposed estimators are more efficient than the Greenberg's estimator. We illustrate our methods using real data from a survey study on illegal use of cable TV service in Taiwan.     

Enabling robust assessment of QTc prolongation in early phase clinical trials

Since the implementation of the International Conference on Harmonization (ICH) E14 guideline in 2005, regulators have required a “thorough QTc” (TQT) study for evaluating the effects of investigational drugs on delayed cardiac repolarization as manifested by a prolonged QTc interval. However, TQT studies have increasingly been viewed unfavorably because of their low cost effectiveness. Several researchers have noted that a robust drug concentration‐QTc (conc‐QTc) modeling assessment in early phase development should, in most cases, obviate the need for a subsequent TQT study. In December 2015, ICH released an “E14 Q&As (R3)” document supporting the use of conc‐QTc modeling for regulatory decisions. In this article, we propose a simple improvement of two popular conc‐QTc assessment methods for typical first‐in‐human crossover‐like single ascending dose clinical pharmacology trials. The improvement is achieved, in part, by leveraging routinely encountered (and expected) intrasubject correlation patterns encountered in such trials. A real example involving a single ascending dose and corresponding TQT trial, along with results from a simulation study, illustrate the strong performance of the proposed method. The improved conc‐QTc assessment will further enable highly reliable go/no‐go decisions in early phase clinical development and deliver results that support subsequent TQT study waivers by regulators.     

Pairwise comparisons of treatments with ordinal responses in a two-way setting

In clinical studies, pairwise comparisons are frequently performed to examine differences in efficacy between treatments. The statistical methods of pairwise comparisons are available when treatment responses are measured on an ordinal scale. The Wilcoxon–Mann–Whitney test and the latent normal model are popular examples. However, these procedures cannot be used to compare treatments in parallel groups (a two-way design) when overall type I error must be controlled. In this paper, we explore statistical approaches to the pairwise testing of treatments that satisfy the requirements of a two-way layout. The results of our simulation indicate that the latent normal approach is superior to the Wilcoxon–Mann–Whitney test. Clinical examples are used to illustrate our suggested testing methods.     

Adaptive phase I/II clinical trials for drug combination assessment in oncology using the outcomes of each cycle

Many new anticancer agents can be combined with existing drugs, as combining a number of drugs may be expected to have a better therapeutic effect than monotherapy owing to synergistic effects. Furthermore, to drive drug development and to reduce the associated cost, there has been a growing tendency to combine these as phase I/II trials. With respect to phase I/II oncology trials for the assessment of dose combinations, in the existing methodologies in which efficacy based on tumor response and safety based on toxicity are modeled as binary outcomes, it is not possible to enroll and treat the next cohort of patients unless the best overall response has been determined in the current cohort. Thus, the trial duration might be potentially extended to an unacceptable degree. In this study, we proposed a method that randomizes the next cohort of patients in the phase II part to the dose combination based on the estimated response rate using all the available observed data upon determination of the overall response in the current cohort. We compared the proposed method to the existing method using simulation studies. These demonstrated that the percentage of optimal dose combinations selected in the proposed method is not less than that in the existing method and that the trial duration in the proposed method is shortened compared to that in the existing method. The proposed method meets both ethical and financial requirements, and we believe it has the potential to contribute to expedite drug development.     

Smoothing the difference-based estimates of variance using variational mode decomposition

We propose a variational mode decomposition approach to estimate the variance function in a nonparametric heteroscedastic fixed design regression model. A data-driven estimator is constructed by applying variational mode decomposition technique to the difference-based initial estimates. The numerical results show that the proposed estimator performs better than the existing variance estimation procedures in the mean square sense.     

A stratified unrelated question randomized response model using Neyman allocation

This paper applies stratified random sampling using Neyman allocation to Mangat et al. (1992 Mangat, N.S., Singh, R., Singh, S. (1992). An improved unrelated question randomized response strategy. Cal. Stat. Assoc. Bull. 42:277–281.[Crossref] , [Google Scholar]) unrelated question randomized response (RR) strategy for both completely truthful reporting and less than completely truthful reporting. It is shown that, for the prior information given, our new model is more efficient in terms of variance (in the case of completely truthful reporting) and mean square error (in terms of less than completely truthful reporting) than Kim and Elam's (2007 Kim, J.M., Elam, M.E. (2007). A stratified unrelated question randomized response model. Stat. Papers 48:215–233.[Crossref], [Web of Science ®] , [Google Scholar]) model. Numerical illustrations and graphs are also given in support of the present study.