• 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.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 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.18 no.1
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• pp.159-171
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• 2005

The US Food and Drug Administration(FDA) recommends that population bioequivalence and individual bioequivalence would be assessed to address the prescribability and switchability between a brand-name drug and its new formulation or generic copy in its 2001 guidance document. The test for population bioequivalence in the latest FDA guidance is recommended in 2 x 4 crossover design, but it turns out to be very conservative. Recently Lee, Shao & Chow(2002), Chow, Shao & Wang(2003) and McNally, Iyer & Mathew(2002) proposed new statistical methods for assessing population bioequivalence between drugs to correct the biasness of current FDA method. Since 2 x 2 crossover experiment is most welcomed design in bioequivalence testing, we adopt their methods to 2 x 2 crossover designs and compare their methodologies with FDA one through the simulation study.

• Journal of the Society of Naval Architects of Korea
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• v.30 no.4
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• pp.17-22
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• 1993

The intersection problem of three-dimensional free form surfaces can be solved by geometrical and numerical methods. Up to now, the subdivision technique, which is classified under the former, has been largely employed to find the cross section of ship hull form. In this paper, an algorithm is presented for intersecting ship hull form in high speed. The high speed calculation algorithm is based on simple numerical methods, such as the secant method, false position method and bisection method. The algorithm is directly applicable to depicting arbitrary ship cross sections, drawing ship lines and constructing the offset table.

• 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 $2.6cm\times1cm$.

• Journal of KIISE:Software and Applications
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• v.27 no.12
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• pp.1219-1226
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• 2000

본 논문에서는 유전자 알고리즘과 피라미드(다단계 또는 다 해상도)를 결합한 새로운 영상분할 방법을 제안하다. 먼저, 영상을 피라미드의 해상도가 낮은 상위 단계로 분할하고 좋은 적합도를 가진 염색체의 개체군을 얻는다. 둘째, 해상도를 높인 다음 단계의 입력으로 앞 단계에서 얻은 염색체들을 사용하며, 더욱 세분화된 분할이 이루어지도록 염색체를 진화시키다. 유전자 알고리즘의 적합함수는 각 영역의 규질성과 peakiness를 이용하여 정의하였다. 교차는 교차점을 중심으로 영상을 2분하여 서로 교환하는 1점 교환법을 사용하였으며, 돌연변이는 병합과 분할이 이루어지도록 설계하였다. 본 논문은 저 해상도에서 가능성(적합성)이 큰 유전자를 신속히 구한 훙 단계적으로고 해상도에서 적합한 유전자로 진화시켜 나가는 방법으로 처음부터 최고 해상도에 유전자 알고리즘을 적용하는 종전의 방법보다 훨씬 더 효율적이며 유전자 알고리즘과 다단계 기법의 이상적인 결합이라 할 수 있다. 분할 결과에서도 타 알고리즘에 비하여 우수하거나 비슷한 결과를 얻었다.