Communications for Statistical Applications and Methods

The Korean Statistical Society (한국통계학회)
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Maximum Tolerated Dose Estimate by Curve Fitting in Phase I Clinical Trial

제1상 임상시험에서 곡선적합을 이용한 MTD 추정법

  • Heo, Eun-Ha (Department of Biostatistics, The Catholic University of Korea) ;
  • Kim, Dong-Jae (Department of Biostatistics, The Catholic University of Korea)
  • 허은하 (가톨릭대학교 의학통계학과) ;
  • 김동재 (가톨릭대학교 의학통계학과)
  • Received : 20100900
  • Accepted : 20111100
  • Published : 2011.03.31
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Abstract

The purpose of a Phase I clinical trial is to estimate the maximum tolerated dose, MTD, of a new drug. In this paper, the MTD estimation method is suggested by curve fitting the dose-toxicity data to an S-shaped curve. The suggested MTD estimation method is compared with established MTD estimation procedures using a Monte Carlo simulation study.

제 1상 입상시험의 주된 목적은 신약의 최대허용용량(Maximum tolerated dose; MTD)의 추정이다. 본 논문에서는 실험으로 얻어진 Dose-toxicity data를 S자 모형에 적합 시켜 MTD를 추정하는 방법을 제안하였다. 멈춤 규칙(stopping rule)에 의해 MTD가 결정되는 방법과 미리 정해진 표본수에서 실험을 종료하고 MTD를 추정하는 기존의 추정방법을 본 논문에서 제안한 방법과 모의실험을 통하여 비교하였다.

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References

  1. 강승호 (2002). 1상 임상실험에서 수정된 CRM에 대한 연구, <응용통계연구>, 15, 323–336. https://doi.org/10.5351/KJAS.2002.15.2.323
  2. 김동욱, 길순경 (2009). 제 1상 임상시험의 SM, CRM, ATD에서 결정된 MTD의 정확성과 안전성비교, <한국통계학회 논문집>, 16, 51–65. https://doi.org/10.5351/CKSS.2009.16.1.051
  3. 박인혜 (1999). <제 1상 축차 임상시험의 최대 허용용량 추정법>, 가톨릭대학교 의학통계학과 의학통계전공 석사논문.
  4. Chevret, S. (1993). The continual reassessment method in cancer phase I clinical trials: A simulation study, Statistics in Medicine, 12, 1093–1108.
  5. Dixon, W. J. and Mode, A. M. (1948). A method for obtaining and analyzing sensitivity data, Journal of the American Statistical Association, 43, 109–126.
  6. Faries, D. (1994). Practical modifications of the continual reassessment method for phase I cancer clinical trials, Journal of Biopharmaceutical Statistics, 4, 147–164. https://doi.org/10.1080/10543409408835079
  7. Goodman, S. N., Zhurak, M. L. and Piantadosi, S. (1995). Some practical improvements in the continual reassessment method for phase I studies, Statistics in Medicine, 14, 1149–1161. https://doi.org/10.1002/sim.4780141102
  8. Johns, H. and Joiner, M. C. (1991). A simple method for fitting curves to dose-effect data for functional damage, International Journal of Radiation Biology, 60, 533–541.
  9. Korn, E. L., Midthune, D., Chen, T. T., Rubinstein, L. V., Christian, M. C. and Simon, R. M. (1994). A comparison of two phase I trial designs, Statistics in Medicine, 13, 1799–1806. https://doi.org/10.1002/sim.4780131802
  10. 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, 1647-16641093-1108. https://doi.org/10.1002/sim.4780101104
  11. Storer, B. E. (1989). Design and analysis of phase I clinical trials, Biometrics, 45, 925–937. https://doi.org/10.2307/2531693