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

• Journal of the Korean Data and Information Science Society
• /
• v.28 no.4
• /
• pp.743-754
• /
• 2017

Assessing bioequivalence between original drug and generic drug is traditionally based on $2{\times}2$ crossover design. As bioequivalence trials for highly variable drugs are getting popular, the required sample size based on $2{\times}2$ crossover design would be very large, which might cause the ethical concerns. Regulatory agencies like EMA and MFDS recommended higher order crossover designs such as $2{\times}4$, $4{\times}2$ and $4{\times}4$ crossover designs. Alternatively, a $2{\times}3$ dual design may be recommended in terms of economical and ethical points of view in comparison with the $2{\times}4$ crossover design for highly variable drug. In this study, we consider some statistical characteristics of $2{\times}3$ dual design and propose statistical procedures for calculating sample size and assessing bioequivalence based on $2{\times}3$ dual design. We also discuss the proposed procedures from the perspective of newly revised bioequivalence guidance issued by MFDS.

• The Korean Journal of Applied Statistics
• /
• v.29 no.2
• /
• pp.279-289
• /
• 2016

Bioequivalence trials based on higher order crossover designs have recently been conducted for highly variable drugs since the Ministry of Korea Food and Drug Safety (MFDS) added new regulations in 2013 to widen bioequivalence limits for highly variable drugs. However, a statistical discussion of higher order crossover designs have not been discussed yet. This research proposes the statistical inference of bioequivalence based on $3{\times}3$ crossover design and discusses it with the MFDS regulations. An illustrated example is also given.

• The Korean Journal of Applied Statistics
• /
• v.14 no.2
• /
• pp.345-355
• /
• 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
• /
• v.23 no.1
• /
• pp.139-150
• /
• 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 the Korean Data and Information Science Society
• /
• v.25 no.6
• /
• pp.1181-1193
• /
• 2014

Currently Ministry of food and drug safety allows add-on trial when the bioequivalence between two drugs fails to show since July 1, 2008. However, bioequivalence of highly variable drugs based on $2{\times}2$ crossover designs would require too many subjects, so the alternative designs like $2{\times}4$ or $2{\times}3$ crossover experiments are preferred. In this paper, we propose and discuss the statistical procedures for add-on trials in $2{\times}4$ and $2{\times}3$ crossover designs.

• The Journal of the Korea institute of electronic communication sciences
• /
• v.14 no.3
• /
• pp.489-496
• /
• 2019

In this paper, we design and fabricate an ultra small dual crossed dipole antenna operating at 2.4 GHz frequency. In order to miniaturize the size of the antenna so that it can be applied to a mobile device, a cross dipole is disposed on the upper two layers and a reflection plane, a horizontal matching circuit and a ground plane are arranged on each layer. The circuit was connected by a vertical through-hole. The size of the fabricated antenna is $21.61mm{\times}16.88mm{\times}1.27mm$, the measured reflection coefficient is -31.5 dB, and the bandwidth below -10 dB is 112 MHz. In addition, since the gain of the antenna is -4 dBi, it has the omnidirectional radiation characteristic, so it can be applied to various fields as an antenna for mobile devices.

• Fire Science and Engineering
• /
• v.24 no.3
• /
• pp.93-98
• /
• 2010

Even though the sprinkler system is a essential fire suppression system, the design engineers do not fully understand the concept of design area which sprinklers operate. They frequently made a mistake to form design area and calculate it. The shape of design area is a square or a rectangle which branch side line is a little longer than the cross main side. NFPA demands to lengthen the branch side to 1.2 times than the cross main side and FM demands 1.4 times. The longer the branch side at the same design area is, the bigger the water quantity and pressure is. At the results of hydraulic calculation of design areas, when the branch side is longer 1.2 times, the water quantity became 4.6% bigger than exact square and the pressure came to 4.67% bigger. When it is longer 1.4 times, the water quantity and the pressure are bigger 7.52%, 14.51%. Therefore, the sprinkler design engineers should follow the general rule of design area, exact square or rectangle which length along the branch line is a little longer than length along the cross main, to design more stable system.

• Journal of Pharmaceutical Investigation
• /
• v.28 no.4
• /
• pp.231-239
• /
• 1998

A $3{\times}2$ crossover design is considered for the bioequivalence of two test formulations with a control. It could be considered as a better choice over $3{\times}3$ crossover design because of the cost and experimental duration. Oh et al.(1998) derived $3{\times}2$ crossover design and discussed its benefits over the typical crossover designs. We consider here the statistical models for $3{\times}2$ crossover design and show its statistical properties. The statistical procedures for the bioequivalence in $3{\times}2$ crossover design are shown through an example and the results are summarized by satisfying the 3 standards that proposed by the Korea Food and Drug Administration Guidelines for Bioequivalence.

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