응용통계연구 (The Korean Journal of Applied Statistics)

  • 제27권7호
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  • Pages.1115-1123
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  • 2014
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  • 1225-066X(pISSN)
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  • 2383-5818(eISSN)
한국통계학회 (The Korean Statistical Society)
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제 1상 임상시험에서 용량 감량을 허용하는 MTD 추정법

Maximum Tolerated Dose Estimation with Dose De-Escalation Design in a Phase I Clinical Trials

  • 장은아 (가톨릭대학교 의생명.건강과학과) ;
  • 김동재 (가톨릭대학교 의생명.건강과학과)
  • Jang, Eunah (Department of Biomedicine.Health Science, The Catholic University of Korea) ;
  • Kim, Dongjae (Department of Biomedicine.Health Science, The Catholic University of Korea)
  • 투고 : 2014.09.29
  • 심사 : 2014.11.10
  • 발행 : 2014.12.31
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⟨ 이전 논문 다음 논문 ⟩

초록

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.

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.

키워드

참고문헌

  1. Chevret, S. (1993). The continual reassessment method in cancer phase I clinical trials, A simulation study, Statistics in Medicine, 12, 1093-1108. https://doi.org/10.1002/sim.4780121201
  2. Dixon, W. J. and Mood, A. M. (1948). A method for obtaining and analyzing sensitivity data, Journal of the American Statistical Association, 43, 109-126. https://doi.org/10.1080/01621459.1948.10483254
  3. Goodman, S. N., Zhurak, M. L. and Piantadosi, S. (1995). Some practical improvements in the continualreassessment method for phase I studies, Statistics in Medicine, 14, 1149-1161. https://doi.org/10.1002/sim.4780141102
  4. Korn, E. L., Midthune, D., Chen, T. T., Rubinstein, L. V., Christian, M. C. and Simon, R. M. (1994). Acomparison of two phase I trial designs, Statistics in Medicine, 13, 1799-1806. https://doi.org/10.1002/sim.4780131802
  5. Lee, N. M. and Kim, D. (2012). Two-stage maximum tolerated dose estimation by stopping rule in phase I clinical trials, Journal of the Korean Statistical Society, 19, 57-64. https://doi.org/10.5351/CKSS.2012.19.1.057
  6. O'Quigley, J. and Chevret, S. (1991). Method for dose finding studies in cancer clinical trials: A review and results of a Monte Carlo study, Statistics in Medicine, 10, 1647-1664. https://doi.org/10.1002/sim.4780101104
  7. Simon, R., Freidlin, B., Rubinstein, L., Arbuck, S.G. and Collins, J. (1997). Accelerated Titration Designs for Phase I Clinical Trials in Oncology, Journal of the National Cancer Institute, 89, 1138-1147. https://doi.org/10.1093/jnci/89.15.1138
  8. Storer, B. E. (1989). Design and analysis of phase I clinical trials, Biometrics, 45, 925-937. https://doi.org/10.2307/2531693