• The Korean Journal of Applied Statistics
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• v.26 no.4
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• pp.675-686
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• 2013

The Korea Food and Drug Administration(KFDA) recommends the use of a $2{\times}2$ crossover design to assess the bioequivalence of generic drugs. However, a standard $2{\times}2$ crossover design for bioequivalence trials is often considered problematic due to ethical and economic issues as highly variable drugs are usually required by large numbers of subjects when designing the trial. To overcome this problem a $2{\times}4$ crossover design has been a recommended option as per US regulations; in addition, a $2{\times}3$ crossover design has also recently drawn special attention as an efficient alternative. The current KFDA regulation requires an ANOVA table for every bioequivalence study; however, ANOVA tables of $2{\times}4$ and $2{\times}3$ crossover designs have never been published in the literature. This study shows the derivation of tables of analysis of variance for a $2{\times}4$ cross-over design and a $2{\times}3$ cross-over design. We also suggest a sample size formulas for $2{\times}2$, $2{\times}4$ and $2{\times}3$ crossover designs to provide information on the selection of efficient designs for highly variable drugs.

• The Korean Journal of Applied Statistics
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• v.14 no.2
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• pp.345-355
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• 2001

동일한 유효성분을 가지면서 용량 혹은 형식 만이 다른 제제의 개발이 증가되고 이에 따른 두 제제 이상의 생물학적 동등성시험의 필요성이 제기되었다. 이에 이용주 등(1998)은 온단세트론 제제에 대한 생물학적 동등시험에서 3$\times$3 교차설계법을 적용하였다. 그러나 3$\times$3 교차설계법에서 각 순서에 피험자의 수가 다르거나 실험중에 결락(dropout)되는 피험자가 발생하는 경우에는 일반적인 통계적 방법은 적용할 수 없었다. 본 연구에서는 이러한 경우에 제제효과의 추론에 대한 통계적 방법과 생물학적 동등성 시험 방법을 제안하고 모의실험을 통하여 생물학적 동등성평가의 정도를 측정하였다.

• The Korean Journal of Applied Statistics
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• v.28 no.3
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• pp.529-540
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• 2015

A cross-over design is frequently used in clinical trials (especially in bioequivalence tests with a parametric method) for the comparison of two treatments. Missing values frequently take place in cross-over designs in the second period. Usually, subjects that have missing values are removed and analyzed. However, it can be unsuitable in clinical trials with a small sample size. In this paper, we compare single imputation methods in a $2{\times}2$ cross-over design when missing values exist in the second period. Additionally, parametric and nonparametric methods are compared after applying single imputation methods. A Monte-Carlo simulation study compares type I error and the power of methods.

• The Journal of The Korea Institute of Intelligent Transport Systems
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• v.11 no.4
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• pp.70-79
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• 2012

A design guide to type-3 PLLs for FMCW radars is provided. To do that, the cross-over frequencies of the open-loop transfer functions were normalized to 1 Hz and closed-loop properties were compared through simulations using Pspice. As a result, several guides to design type-3 PLLs were provided: 1) secure 45 degrees of phase margin, 2) locate two zeroes at an identical frequency, and 3) poles may be added to raise order of the PLL at higher frequencies than the cross-over frequency of the open-loop transfer function about ten times.

• Journal of the Korean Society for Library and Information Science
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• v.31 no.3
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• pp.165-208
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• 1997

The purpose of this study is to evaluate the characteristics of user interface that affect the searching behavior of OPAC users. and then to propose how to design user-friendly interfaces of OPACS. An experiment was conducted on two systems with different interfaces to grasp the effect of user interface to search process and search outcome. A $2\times2$ cross-over design was used for the experiment. Sixty five searchers participated in the experiment. Several statistical techniques such as carry-over effect and system effect of a $2\times2$ cross-over design, $\chi^2$ test, t- test, McNemar test, test of marginal homogeneity through maximum likelihood method, factor analysis, regression analysis, and analysis of variance were applied according to the hypotheses tested and the data analyzed.

• The Korean Journal of Applied Statistics
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• v.23 no.1
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• pp.139-150
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• 2010

In recent years, more generic drug products became available. The current regulation for assessing the bioequivalence of two drug formulations is based on the concept of average bioequivalence. This approach has been indicated to be insufficient for assessing switchability between two drug formulations and US FDA has adopted individual bioequivalence as one of the bioequivalence criterion since 2001. The US FDA recommends that individual bioequivalence be assessed based on $2\;{\times}\;4$ crossover design, while a $2\;{\times}\;3$ crossover design may be used as an alternative design to reduce the length and cost of the study. In this paper, a statistical procedure for assessment of individual bioequivalence under $3\;{\times}\;2$ crossover designs is proposed and some statistical points are discussed with $2\;{\times}\;3$ crossover design and $2\;{\times}\;3$ extra-reference design through simulation studies.

• The Korean Journal of Rehabilitation Nursing
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• v.18 no.1
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• pp.38-45
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• 2015

Purpose: This study was attempted in order to verify the effects of moxibustion on aged back pain and activities of daily living. Methods: A research design is quasi-experiment with pre-post test design in nonequivalent control group. As for data collection and experimental treatment, it accidentally sampled totally 50 people with 24 people for the experimental group and 26 people for the control group who appeal for chronic back pain aged over 60 who visited 4 senior centers where are located in N city from November 7, 2012 to December 3, 2012. Experimental treatment was carried out moxibustion totally 12 times by 3 times for 4 weeks in the experimental group. Data analysis was made by using SPSS program. As an analytical technique, the experimental group and the control group were analyzed the homogeneity verification with t-test, Fisher's exact test and $x^2$ test and the hypothesis verification with t-test. Results: The back pain level was reduced in the experimental group than the control group. The disability of daily living activities was reduced in the experimental group than in the control group. Conclusion: Moxibustion was considered to be likely useful therapeutic method for effects of chronic back pain and disability of daily living activities in aged.

• Biomolecules & Therapeutics
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• v.8 no.3
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• pp.269-275
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• 2000

Silibinin(silybin) is the active component of silymarin from Silybum marianum and has hepato-protective effect. It is water-insoluble and has low bioavailability. To improve its bioavailability, self-micro-emulsifying drug delivery system (SMEDDS) has been developed by Hanmi Pharmaceutical Company (Silyma $n^{R}$ 140 soft capsule). In this study, the pharmacokinetic profiles of Silyma $n^{R}$ were examined and compared it with a reference preparation, L Caps140 of B Pharmaceutical Company. This study was approved by Yonsei University Severance Hospital IRB(approval No. CR0004) and followed the bioequivalence test guideline of Korean FDA. Eighteen healthy adult volunteers were allocated based on 2$\times$2 Latin square cross-over design. They were given 2 capsules (each contains silymarin 140 mg (60 mg as silibinin)) of either drug at each period and crossed over after a week of drug-free washout period. Blood concentration of silibinin was measured by HPLC. The $C_{max}$ and AUC of the Silyma $n^{R}$ were 1542.0 $\pm$ 402.7 ng/ml and 3323.3 $\pm$ 824.7 ng.h/ml, respectively, and were significantly higher than those of reference preparation. The Tmax was 0.8 $\pm$ 0.3 h and significantly shorter than reference preparation. The $K_{e}$ and $T_{1}$2/ of both drugs were comparable. Percent differences in means against reference preparation were +88.3% for AUC, +222.6% for $C_{max}$, and -61.1% for $T_{max}$./.>././.>./.

• International Journal of Advanced Culture Technology
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• v.8 no.3
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• pp.123-132
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• 2020

In contemporary times, there is an increasing demand for a dedicated healthcare environment, all over the world. The main motivation for this demand is the level of awareness manifested by the users and reflected on their expectations. Therefore new research strategies and design actions are investigated in order to answer to the users' needs and to provide objective design tools for the specialist. This study continues a series of previous developments of the Healthcare Environment Color Index that should be used for public facilities in Korea and abroad. The cross-cultural approach is a new opportunity for exchanging know-how and for testing and calibrating the perception of the users on the color index. The gathering of results was made based on the online survey provided in this phase in English version for the Romanian users. The survey was intended as an objective mean of research and an efficient way of disseminating information on the subject thus contributing to increasing the level of awareness of the users. A total of 86 Romanian and 89 Koreans with valid answers took part in the survey. Comparative visualizations of the results showed significant similarities concerning the patterns of color preferences but also cultural and emotional differences. As a result both categories of users proved to be aware of the relation between healthcare environment color and its effects on health. They also showed a common understanding on the potential of the color index. As a result the most appealing colors to be applied to the healthcare environment were the series G and B, and the most effective ones were proved to be the ranges of high lightness and low saturation but also the medium high lightness and medium saturation. Both the similarities and the differences of choice between Romanians and Koreans show that cultural and emotional differences of color recognition are important and that should be taken into consideration in design, in order to generate an inclusive and efficient healthcare environment.

• International Journal of Fluid Machinery and Systems
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• v.10 no.3
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• pp.240-253
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• 2017

Latin hypercube sampling is widely used design-of-experiment technique to select design points for simulation which are then used to construct a surrogate model. The exploration/exploitation properties of surrogate models depend on the size and distribution of design points in the chosen design space. The present study aimed at evaluating the performance characteristics of various surrogate models depending on the Latin hypercube sampling (LHS) procedure (sample size and spatial distribution) for a diverse set of optimization problems. The analysis was carried out for two types of problems: (1) thermal-fluid design problems (optimizations of convergent-divergent micromixer coupled with pulsatile flow and boot-shaped ribs), and (2) analytical test functions (six-hump camel back, Branin-Hoo, Hartman 3, and Hartman 6 functions). The three surrogate models, namely, response surface approximation, Kriging, and radial basis neural networks were tested. The important findings are illustrated using Box-plots. The surrogate models were analyzed in terms of global exploration (accuracy over the domain space) and local exploitation (ease of finding the global optimum point). Radial basis neural networks showed the best overall performance in global exploration characteristics as well as tendency to find the approximate optimal solution for the majority of tested problems. To build a surrogate model, it is recommended to use an initial sample size equal to 15 times the number of design variables. The study will provide useful guidelines on the effect of initial sample size and distribution on surrogate construction and subsequent optimization using LHS sampling plan.