The Korean Journal of Applied Statistics (응용통계연구)

The Korean Statistical Society (한국통계학회)
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Adaptive continual reassessment method: A maximum tolerated dose estimation method in phase I clinical trial

MTD 추정법: 적응형 연속 재평가 방법

  • EunKyung Park (Department of Biomedicine & Health Sciences, The Catholic University Graduate School) ;
  • Eun Jeong Min (Department of Biomedicine & Health Sciences, The Catholic University Graduate School)
  • 박은경 (가톨릭대학교 의생명.건강과학과) ;
  • 민은정 (가톨릭대학교 의생명.건강과학과)
  • Received : 2024.02.06
  • Accepted : 2024.04.02
  • Published : 2024.08.31
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Abstract

The objective of Phase I clinical trials is to ascertain the maximum tolerated dose (MTD) that is safe for human administration. Accurately determining the MTD within an acceptable safety margin is imperative, necessitating evaluations up to sufficiently high doses. To estimate the MTD, a plethora of methods have been developed, encompassing algorithm-based, model-based, and model-assisted techniques. In this paper, a new dose exploration method based on continual reassessment method (CRM) is proposed to address for the shortcomings of existing dose exploration methods. Through a comprehensive simulation study, this method's efficacy was compared against that of existing methodologies across a variety of scenarios. The findings from this study underscore its enhanced precision and safety in estimating the MTD, alongside a reduction in the number of subjects required for testing.

제 1상 임상시험의 목적은 사람이 견딜 수 있는 최대 허용 용량(maximum tolerated dose; MTD)을 결정하여 안전성이 허용되는 범위하에 충분히 높은 용량까지 올바르게 평가하는 것이 중요하다. MTD를 추정하는 방법은 알고리즘 기반, 모델 기반 및 모델 보조방법을 포함한 여러 가지 방법이 고안되었다. 본 논문에서는 기존 용량 탐색 방법의 단점을 보완하기 위해 연속 재평가 방법(continual reassessment method; CRM)에 기반한 새로운 용량 탐색 방법을 제안하여 다양한 문제 상황에서 기존 용량 탐색 방법들과의 성능을 비교하기 위해 시뮬레이션 연구를 수행하였다. 연구의 결과 MTD 추정에서의 정확도와 안전성을 높일 수 있고, 적은 시험대상자를 사용한다는 점에서 가장 우월한 성능을 보임을 확인하였다.

Keywords

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