• 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.

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

• Journal of the Korean Data and Information Science Society
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• v.25 no.6
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• pp.1181-1193
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• 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 Korean Journal of Applied Statistics
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• v.24 no.1
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• pp.161-167
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• 2011

The primary variables are often systematically related to other influences apart from drug effect. For instance, there may be relationships to covariates such as health conditions or prognostic factors. When a $2{\times}2$ crossover experiment for bioequivalence is designed, the statistical adjustment for the influence of covariates should be considered if some covariates influence the drug effect. Statistical inference for assessing average bioequivalence for a $2{\times}2$ crossover design with covariates is given and an illustrated example is presented with discussion.

• 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 Applied Statistics
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• v.29 no.2
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• pp.279-289
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• 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
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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.

• Journal of Pharmaceutical Investigation
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• v.34 no.5
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• pp.379-383
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• 2004

Statistical interpretations in a bioequivalence trial are considered and studied when the missing observations occurred in $2\;{\times}\;2$ crossover experiment. Patel (1985) suggested the approximate test procedures for carryover effect and drug effect in $2\;{\times}\;2$ crossover design when some of data are missing in the second period. A modified Patel method is newly proposed to the bioequivalence trial and it is compared with the current method through the simulation study.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.5 no.5
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• pp.1011-1016
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• 2001

In this paper, a narrow-band bandpass filter using microstrip open-loop resonators with coupled and crossing lines is designed and fabricated. This filter has many advantages such as compact in size, low weight and the characteristic of the elliptic-function narrow-band bandpass filtering. The configuration consists of two identical microstrip open loop resonators, coupled line and crossing line. By using open loop resonators, the size of the filter can be reduced about 50% compared with the ring resonators. A crossing line gives two notchs in the stopband, which have sharp selectivity in the passband. Centered at 2.455GHz, the calculated microstrip bandpass filter shows a bandwidth of 1.22%, which makes it very attractive for application in the wireless LAN. The filter is fabricated by photo-etching process. The fabricated bandpass filter shows that the bandwidth is 0.85% for 2.458GHz and the size is only $2.6cm\times1cm$.

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