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A Comparative Study of Statistical Methods for Population Bioequivalence in 2 X 2 Crossover Design

2 X 2 교차설계법에서 모집단 생물학적 동등성 검정 방법 비교

  • Park Sang-Gue (Division of Mathematics and Statistics, Chung-Ang University) ;
  • Lim Nam-Kyoo (Department of Information and Statistics, Daejeon University) ;
  • Lee Jae-Young (Division of Management Engineering, KAIST Graduate School of Management Seoul) ;
  • Kim Byung-Chun (KAIST Graduate School of Management Seoul)
  • 박상규 (중앙대학교 수학통계학부) ;
  • 임남규 (대전대학교 정보통계학과) ;
  • 이재영 (KAIST 테크노경영대학원 경영공학과) ;
  • 김병천 (KAIST 테크노경영대학원)
  • Published : 2005.03.01

Abstract

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.

최근 미국을 위시한 선진국에서 제제간의 생물학적 동등성을 판단하는 기준이 생체 이용률의 평균치를 비교하는 시험에서 분산까지 같이 고려하는 기준으로 바뀌고 있다. 처방성과 교차사용성을 의미하는 모집단과 개인 생물학적 동등성이 바로 그것이다. US FDA에서는 2 × 4 교차설계법을 활용해서 제제간의 생동성을 입증하는 것을 추천하고 있다. 현재 US FDA에서 제안하고 있는 모집단 생물학적 동등성 평가 방법은 통계적으로 문제점을 가지고 있어 최근 Lee, Shao & Chow(2002), Chow, Shao & Wang(2003), 그리고 McNally, Iyer & Mathew(2002)에 의해서 수정된 평가 방법들이 제안되고 있다. 본 연구 논문에서는 그동안 제제간의 생물학적 동등성 평가 설계법이였던 2×2 교차설계법을 이용해서 모집단 생물학적 동등성을 평가하는 방법을 논의하고 최근 제안된 방법들을 모의실험을 통해 비교하여 가장 적절한 방법론을 제안한다.

Keywords

References

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Cited by

  1. On Evaluation of Bioequivalence for Highly Variable Drugs vol.24, pp.6, 2011, https://doi.org/10.5351/KJAS.2011.24.6.1055