The Korean Journal of Applied Statistics (응용통계연구)

The Korean Statistical Society (한국통계학회)
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Maximum tolerated dose estimation by Biased coin design and stopping rule in Phase I clinical trial

제 1상 임상시험에서 Biased Coin Design과 멈춤규칙을 이용한 MTD 추정법

  • Jeon, Soyoung (Department of Biomedicine.Health Science, The Catholic University of Korea) ;
  • Kim, Dongjae (Department of Biomedicine.Health Science, The Catholic University of Korea)
  • 전소영 (가톨릭대학교 의생명.건강과학과) ;
  • 김동재 (가톨릭대학교 의생명.건강과학과)
  • Received : 2019.11.25
  • Accepted : 2019.12.17
  • Published : 2020.04.30
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Abstract

Phase I clinical trials (Dose Finding Studies) are the first step in administering new drugs developed through animal experiments or in vitro experiments to humans. An important area of interest in designing Phase I clinical trials is determining the dose that provides the greatest efficacy and acceptable safe dose to the patient. In this paper, we propose a method to determine the maximum tolerated dose considering efficacy and safety using Biased coin design and stopping rule. The proposed method is compared with existing methods through simulation.

'투약용량 발견 시험(Dose Finding Study)'라고도 불리는 제 1상 임상시험은 동물 실험 혹은 시험관 실험을 통하여 개발된 신약물질을 사람에게 실시하는 첫 단계이다. 제1상 임상시험의 가장 주요한 목적은 환자에게 허용할 수 있고 최대의 효능을 가진 복용량을 결정하는 것이다. 본 논문에서는 이를 고려하여 최대허용용량(MTD)를 결정할 수 있는 적절한 추정방법을 제안하였다. 이 방법은 Biased coin design과 멈춤규칙을 이용하여 MTD를 추정한다. 제안하는 방법은 모의실험을 통해 기존의 방법들과 비교하였다.

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References

  1. 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
  2. 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
  3. Dixon, W. J. and Mode, A. M. (1948). A method for obtaining and analyzing sensitivity data, Journal of the American Statistical Association, 43, 109-128. https://doi.org/10.1080/01621459.1948.10483254
  4. Efron, B. (1971). Forcing a sequential experiment to be balanced, Biometrika, 58, 403-417. https://doi.org/10.1093/biomet/58.3.403
  5. Goodman, S. N., Zahurak, 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
  6. Kang, S. (2002). Investigation on the modified continual reassessment method in phase I clinical trial, The Korean Journal of Applied Statistics, 15), 323-336. https://doi.org/10.5351/KJAS.2002.15.2.323
  7. 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
  8. Lee, N. and Kim, D. (2012). Two-stage maximum tolerated dose estimation by stopping rule in Phase I clinical trial, The Korean Statistical Society, 19, 57-64.
  9. Lim, H. (2018). New Drug Development and Clinical Trials, Bullsbook.
  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, 1647-1664. https://doi.org/10.1002/sim.4780101104
  11. 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
  12. O'Quigley, J. Shen, L.Z. (1996). Continual reassessment method: a likelihood approach , Biometrics, 52, 673-684. https://doi.org/10.2307/2532905
  13. Park, I. (1999). The estimation of maximal tolerated dose in sequential phase I clinical trials (Master's Thesis of Science), The Catholic University of Korea.
  14. Storer, B. E. (1989). Design and analysis of phase I clinical trials, Biometrics, 45, 925-937. https://doi.org/10.2307/2531693
  15. Storer, B. E. (2001). An evaluation of phase I clinical trial designs in the continuous dose response setting, Statistics in Medicine, 20, 2399-2408. https://doi.org/10.1002/sim.903