• Communications for Statistical Applications and Methods
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• v.19 no.6
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• pp.781-791
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• 2012

A $2{\times}2$ Cross-over design is widely used in clinical trials for comparison studies of two kinds of drugs or medical treatments. This design has many statistical methods such as Hills-Armitage's (1979) method or Koch's (1972) method. In this paper, we propose a nonparametric test for $2{\times}2$ Cross-over design based on a two-sample test suggested by Baumgartner et al. (1998). In addition, a Monte Carlo simulation study is adapted to compare the power of the proposed methods with those of previous methods.

• 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.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.

• 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.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 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.

• 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.

• Journal of Pharmaceutical Investigation
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• v.24 no.2
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• pp.67-72
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• 1994

Bioequivalence (BE) test of biphenyl dimethyl dicarboxylate (DDB) tablets was performed. Normal healthy male volunteers (n = 20) were randomly divided into 2 groups, and reference $(Nissel{\circledR})$ and test $(Livital{\circledR})$ tablets of DDB $(25mg{\times}8\;Tab.\;= \;200\;mg)$ were given orally by balanced two-period cross-over design. The serum concentration was determined by high performance liquid chromatography. The pharmacokinetic parameters, AUC, $C_{max}$, and $T_{max}$ obtained after drug administration were statistically analyzed. Statistical evaluation of the data involved an analysis of variance (ANOVA) for cross-over design. The results were within 20% differences of mean value in AUC, $C_{max}$, and $T_{max}$ between reference and test tablets. The results of ANOVA showed no significant differences for "between group or subject" and "period". The test tablet was bioequivalent with the reference tablet in the AUC, $C_{max}$, and $T_{max}$.

• The Journal of the Society of Korean Medicine Diagnostics
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• v.19 no.2
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• pp.91-100
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• 2015

Objectives The aim of this study is to develop a structured clinical protocol related with acquisition of radial pulse wave in the randomized, $2{\times}2$ cross-over design, and cold-heat intervention trial for a pilot and preliminary study. Methods The protocol was contrived based on wide ranging literature searches for cold-heat intervention experiments and radial pulse diagnoses. Results Sample size of 60 subjects was calculated based on an effect size derived from the previous study designed to detect the pre-post cold-heat differences in the radial pulse. Each subjects will be randomly assigned to the cold (first) to heat (last) group (n=30) or heat (first) to cold (last) group (n=30). All subjects will fill out a case report form and questionnaires related with pattern identification, dietary patterns, sleep quality, and physical activity will be surveyed and used as a secondary outcomes. Safety assessment will be reported at the final stage. Conclusions This protocol will provide an additional reference to future studies related with observation of radial pulse during any interventions and also expect to be used as a guideline for acquisition of reliable radial pulse wave data.

• ETRI Journal
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• v.33 no.5
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• pp.731-740
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• 2011

Reconfigurable computing using a field-programmable gate-array (FPGA) device has become a promising solution in system design because of its power efficiency and design flexibility. To bring the benefit of FPGA to many application programmers, there has been intensive research about automatic translation from high-level programming languages (HLL) such as C and C++ into hardware. However, the large gap of syntaxes and semantics between hardware and software programming makes the translation challenging. In this paper, we introduce a new approach for the translation by using the widely used GCC compiler. By simply adding a hardware description language (HDL) backend to the existing state-of- the-art compiler, we could minimize an effort to implement the translator while supporting full features of HLL in the HLL-to-HDL translation and providing high performance. Our translator, called GCC2Verilog, was implemented as the GCC's cross compiler targeting at FPGAs instead of microprocessor architectures. Our experiment shows that we could achieve a speedup of up to 34 times and 17 times on average with 4-port memory over PICO microprocessor execution in selected EEMBC benchmarks.