DOI QR코드

DOI QR Code

Two-Stage Maximum Tolerated Dose Estimation by Stopping Rule in a Phase I Clinical Trial

제1상 임상시험에서 Stopping Rule을 이용한 두 단계 MTD 추정법

  • Lee, Na-Mi (Department of Biostatistics, The Catholic University of Korea) ;
  • Kim, Dong-Jae (Department of Biostatistics, The Catholic University of Korea)
  • 이나미 (가톨릭대학교 의학통계학과) ;
  • 김동재 (가톨릭대학교 의학통계학과)
  • Received : 20111000
  • Accepted : 20111100
  • Published : 2012.01.30

Abstract

Phase I clinical trials determine the maximum tolerated dose(MTD) of a new drug. In this paper, we proposed a two-stage MTD estimation method by a Stopping rule in a phase I clinical trial. The suggested MTD estimation method is compared to the standard design(SM3) and the continual reassessment method(CRM) using a Monte Carlo simulation study.

제 1상 임상시험에서 주목표는 부작용이 발생하지 않고 피험자가 견딜 수 있는 한도 내에서 최대 용량인 최대허용용량(Maximum Tolerated Dose; MTD)을 결정하는 것이다. 최대허용용량을 결정하는 방법에는 SM방법, CRM방법 등이 있는데 본 논문에서는 기존의 Stopping rule을 변형한 두 단계 MTD 추정방법을 제안하였다. 기존의 방법들을 본 논문에서 제안한 방법과 모의실험을 통하여 비교하였다.

Keywords

References

  1. 강승호(2002). 1상 임상실험에서 수정된 CRM에 대한 연구, <응용통계연구>, 15, 323-336.
  2. 김동욱, 길순경 (2009). 제 1상임상시험의 SM, CRM, ATD에서 결정된 MTD의 정확성과 안전성비교, <한국통계학회논문집>, 16, 51-65.
  3. 박인혜 (1999). 제 1상 축차 임상시험의 최대 허용용량 추정법, 가톨릭대학교 의학통계학과 의학통계 전공 석사논문.
  4. Ahn, C. (1998). An evaluation of phase I cancer clinical trial designs, Statistics in Medicine, 17, 1537-1549. https://doi.org/10.1002/(SICI)1097-0258(19980730)17:14<1537::AID-SIM872>3.0.CO;2-F
  5. Chevret, S. (1993). The continual reassessment method in cancer phaseⅠclinical trials: A simulation study, Statistics in Medicine, 12, 10930-1108.
  6. 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. https://doi.org/10.2307/2280071
  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. 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
  9. 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
  10. O'Quigley, J., Pepe, M. and Fisher, M. (1990). Continual reassessment method: A practical design for phase I clinical trials in cancer, Biometrics, 46, 33-48. https://doi.org/10.2307/2531628
  11. O'Quigley, J. and Shen, L. Z. (1996). Continual reassessment method: A likelihood approach, Biometrics, 52, 163-174.
  12. Simon, R., Freidlin, B., Rubinstein, L., Arbuck, S. G., Collins, J. and Christian, M. C. (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
  13. Storer, B. E. (1989). Design and analysis of phase I clinical trials, Biometrics, 45, 925-937. https://doi.org/10.2307/2531693

Cited by

  1. Maximum Tolerated Dose Estimation with Dose De-Escalation Design in a Phase I Clinical Trials vol.27, pp.7, 2014, https://doi.org/10.5351/KJAS.2014.27.7.1115
  2. Adjusted maximum tolerated dose estimation by stopping rule in phaseⅠclinical trial vol.23, pp.6, 2012, https://doi.org/10.7465/jkdi.2012.23.6.1085