The Korean Journal of Applied Statistics (응용통계연구)

The Korean Statistical Society (한국통계학회)
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Maximum Tolerated Dose Estimation with Dose De-Escalation Design in a Phase I Clinical Trials

제 1상 임상시험에서 용량 감량을 허용하는 MTD 추정법

  • Jang, Eunah (Department of Biomedicine.Health Science, The Catholic University of Korea) ;
  • Kim, Dongjae (Department of Biomedicine.Health Science, The Catholic University of Korea)
  • 장은아 (가톨릭대학교 의생명.건강과학과) ;
  • 김동재 (가톨릭대학교 의생명.건강과학과)
  • Received : 2014.09.29
  • Accepted : 2014.11.10
  • Published : 2014.12.31
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Abstract

The main purpose of phase I clinical trials is to estimate the Maximum Tolerated Dose (MTD), which minimizes side effect and assures safety of a new drug by evaluating the toxicity at each dose-level. The conventional MTD estimation methods is Standard method (Storer, 1989; Korn et al., 1994), Accelerated Titration Designs (Simon et al., 1997) and DM method (Dixon and Mood, 1948) etc. In this paper, MTD estimation method with de-escalation is suggested phase I clinical trials. The proposed MTD estimation method is compared to Accelerated Titration Designs, SM3 without de-escalation method and SM3 with de-escalation method using a Monte Carlo simulation.

제 1상 임상시험의 주목적은 시험약의 독성을 평가하여 부작용을 최소화하고 안전하게 투여할 수 있는 적정 용량인 최대허용용량(Maximum Tolerated Dose; MTD)의 추정이다. 기존에 최대허용용량 추정 방법에는 SM방법(Storer, 1989; Korn 등, 1994), ATD방법(Simon 등, 1997) 그리고 DM방법(Dixon과 Mood, 1948) 등이 있다. 본 논문에서는 초기 가속 단계를 적용하여 약효가 없는 낮은 용량에 많은 피험자들이 배정되는 점을 보완하고, 이 초기 가속 단계로 빠르게 용량을 증가함으로 인해 떨어진 안전성을 개선하기 위해 용량감량을 허용하는 방법을 적용시켜 MTD 를 추정하는 방법을 제안하였다. 기존의 방법들과 본 논문에서 제안한 방법을 모의실험을 통해 비교하였다.

Keywords

References

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