The Korean Journal of Applied Statistics (응용통계연구)

The Korean Statistical Society (한국통계학회)
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A comparison of multiple hypothesis testing methods and combination methods in seamless Phase II/III clinical trials

심리스 제2상/제3상 임상시험에서 다중가설검정방법과 결합검정방법의 비교연구

  • Han, Song (LG Chem, Ltd) ;
  • Yoo, Hanna (Department of Computer Software, Busan University of Foreign Studies) ;
  • Lee, Jae Won (Department of Statistics, Korea University)
  • 한송 (LG화학(주)) ;
  • 유한나 (부산외국어대학교 컴퓨터소프트웨어학부) ;
  • 이재원 (고려대학교 통계학과)
  • Received : 2018.05.11
  • Accepted : 2018.12.05
  • Published : 2019.02.28
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Abstract

An adaptive seamless Phase II/III clinical trial design enables a reduction in the sample size (in comparison to a conventional design) that also shortens the clinical development time. It is also very effective in clinical trials since it can have higher statistical power than Phase III alone. In this study, we use extensive simulation studies to compare several multiple hypothesis testing methods that can help select the best doses in a Phase II study along with several methods to combine p-values of the Phase II and Phase III study.

최근에 제안된 심리스(seamless) 제 2상/제 3상 임상시험 디자인은 기존의 임상시험 디자인들과 비교하여 피험자수를 줄일 수 있을 뿐만 아니라 임상 개발 시간을 단축시킬 수 있다는 장점을 가지고 있어 임상시험연구자들의 많은 관심을 끌고 있다. 또한 제 3상 시험을 단독으로 진행 하였을 때보다 더 높은 검정력을 가질 수 있으므로 임상시험에서 매우 효율적이라 말할 수 있다. 본 논문에서는 제 2상에서 최고효과 용량군을 선정하기 위한 여러 가지 다중가설 검정방법들을 제시하고 제 2상에서 최고효과 용량군을 선정한 후에 제 2상과 제 3상을 결합하는 여러 가지 유의확률 결합검정방법들을 제시하였다. 또한 모의실험을 통해서 심리스 제 2상/제 3상 임상설계가 적용되었을 때 여러 가지 방법들을 비교함으로써, 제 2상/제 3상 표본의 크기 조합이나 분산의 크기가 다른 여러 가지 상황에서 가장 적절한 방법을 선택하는 가이드라인을 제시하고자 한다.

Keywords

Table 3.1. Contigency table of hypothesis test

GCGHDE_2019_v32n1_1_t0001.png 이미지

Table 5.1. Sample size of effect size and standard deviation

GCGHDE_2019_v32n1_1_t0002.png 이미지

Table 5.2. Comparison of power (α = 0.025, σ = 3) under effect size (0, 0, 0, 1)

GCGHDE_2019_v32n1_1_t0003.png 이미지

Table 5.3. Comparison of power (α = 0.025, σ = 3) under effect size (0.5, 0.5, 0.5, 1)

GCGHDE_2019_v32n1_1_t0004.png 이미지

Table 5.4. Comparison of power (α = 0.025, σ = 5) under effect size (0, 0, 0, 1)

GCGHDE_2019_v32n1_1_t0005.png 이미지

Table 5.5. Comparison of power (α = 0.025, σ = 5) under effect size (0.5, 0.5, 0.5, 1)

GCGHDE_2019_v32n1_1_t0006.png 이미지

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