• Communications for Statistical Applications and Methods
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• 제19권6호
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• pp.877-884
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• 2012

Phase I trials determine the maximum tolerated dose(MTD) and the recommended dose(RD) for subsequent Phase II trials. In this paper, a MTD estimation method applied to a biased coin design is proposed for Phase I Clinical Trials. The suggested MTD estimation method is compared to the SM3 method and the NM method (Lee and Kim, 2012) using a Monte Carlo simulation study.

• 품질경영학회지
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• 제39권2호
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• pp.329-336
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• 2011

The purpose of Phase I clinical trial is to identify the maximum tolerated dose with specific toxicity rate. The standard TER design does not guarantee the pre-specified toxicity rate. It depends on the dose-toxicity curves. Therefore it is necessary to check the expected toxicity rate of various dose-toxicity curves before we conduct clinical trials. We developed TERAplusB library to help this situation, especially in cancer research. This package will help design the cancer clinical trial. We can compare the expected toxicity rates, the expected number of patients, and the expected times calculated with various dose-toxicity curves. This process will help find the best clinical trial design of the proposed drug.

• Communications for Statistical Applications and Methods
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• 제19권1호
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• pp.57-64
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• 2012

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.

• Communications for Statistical Applications and Methods
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• 제18권2호
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• pp.179-187
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• 2011

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.

• 응용통계연구
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• 제27권1호
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• pp.13-20
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• 2014

제 1상 임상시험의 목적은 피험자가 견딜 수 있는 최대의 용량인 최대허용용량(Maimum Tolerated Dose; MTD)을 추정하는 것이다. 최대허용용량을 추정하는 방법으로는 SM방법, ATD방법, CRM방법 등이 있다. 본 연구에서는 제 1상 임상시험에서 멈춤규칙을 이용한 최대허용용량 추정법을 제안하였다. 제안한 최대허용용량 추정법은 연속재평가방법(Continual Reassessment Method; CRM)과 모의실험을 통해 비교하였다.

• 한국운동역학회지
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• 제32권1호
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• pp.24-30
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• 2022

Objective: The purpose of this study was to determine the factors of successful and unsuccessful movements through the analysis of kinematics and muscle activity of the Free Aerial Cartwheel on the balance beam. Method: Subjects (Age: 22.8 ± 2.4 yrs., Height: 158.7 ± 5.0 cm, Body mass: 54.1 ± 6.4 kg, Career: 13 ± 2.4 yrs.) who were currently active as female gymnasts participated in the study. They had no history of surgical treatment within 3 months. Subject criteria included more than 10 years of professional experience in college and professional level of gymnastics and the ability to conduct the Free Aerial Cartwheel on the Balance Beam. Each subject performed 10 times of Free Aerial Cartwheel on the balance beam. One successful trial and one unsuccessful trial (failure) among 10 trials were selected for the comparison. Results: It was found that longer time required in case of unsuccessful trial when performing the Free Aerial Cartwheel on the balance beam compared with successful trial. It is expected to be the result of movement in the last landing section (i.e. phase 5). In addition, it was found that the center of gravity of the body descends at a high speed to perform the jump (i.e. phase 2) in order to obtain a sufficient jumping height when the movement is successful while the knee joint is rapidly extended to perform a jump when movement fails. In the single landing section after the jump (i.e. phase 4), if the ankle joint rapidly dorsiflexed after take-off and the hip joint rapidly flexed, so landing was not successful. Conversely, in a successful landing movement, muscle activity of the biceps femoris was greatly activated resulting no shaking in the last landing section (i.e. phase 5). Conclusion: In order to succeed in this movement, it is necessary to perform a strong jump after rapidly descending the center of gravity of the body using the force of the biceps femoris muscle. Further improvement of the skills on the balance beam requires the analysis of the game-like situation with continuous research on kinematic and kinematic analysis of various techniques, jumps, turns, etc.

• Communications for Statistical Applications and Methods
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• 제6권2호
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• pp.543-564
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• 1999

The principal aim of a sequential phase I clinical trial in which the toxicity reponses of a group of patient(s) determine the dose level of the next patient(s) group is to estimate the maximal tolerated dose(MTD) of a new drug, In this paper we compared with a simulation study the performance of the MTD estimates that are determined by a stopping rule in a design and also those that are determined by analyzing the data after a clinical trial is terminated. To the latter belong the mean median mode and maximum likelihood estimates. For the Standard Methods the stopping rule MTD is quite inefficient but the median MTD has a best efficiency and is robust with respect to the three different toxicity curves. The problem of non-convergence of MLE MTD is severe. A more improved MTD estimate is produced by combining the advantages of the various MTD estimates and its efficiency is better than the single median MTD estimate especially for the toxicity curve of an unlucky choice of dose levels. The simulation results suggest that simple types of phase I designs can be combined with relatively standard analytic techniques to provide a more efficient MTD estimate.

• Journal of the Korean Data and Information Science Society
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• 제23권6호
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• pp.1085-1091
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• 2012

제 1상 임상시험의 주목적은 신약 후보 물질의 독성을 평가하여 부작용 및 안전하게 투여할 수 있는 약물의 적정한 용량인 최대허용용량의 추정이다. 기존에 최대허용용량을 추정하는 방법에는 표준방법 (Storer, 1989; Korn 등, 1994) 그리고 NM방법 (Lee와 Kim, 2012) 등이 있다. 본 연구에서는 많은 피험자들이 낮은 용량에 많이 할당되는 점을 보완하고 기존의 최대허용용량 추정법보다 적은 수의 피험자로 실험하기 위해서 기존 최대허용용량 추정법을 수정한 멈춤 규칙을 적용시킨 추정법을 제안하였다. 기존의 방법들과 새롭게 제시한 방법을 모의실험을 통하여 비교하였다.

• 응용통계연구
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• 제32권5호
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• pp.741-752
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• 2019

제1상 임상시험의 주목적은 최대허용용량(maximum tolerated dose; MTD)을 결정하는 것이다. MTD 결정을 통해 다음 임상시험에 사용될 용량이 제한되므로 투약용량 발견 시험이라고도 불리며 매우 중요한 단계이다. MTD를 결정하는 방법에는 대표적으로 DM 방법, SM 방법, CRM 방법이 있다. 본 논문에서는 기존 수정된 CRM 방법에 초기가속화 단계를 적용하여 낮은 용량에 다수의 피험자가 할당되는 문제점을 보완하는 새로운 MTD 추정 방법을 제안하였고 기존 방법들과의 비교를 위해 모의실험을 실시하였다.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 1995년도 춘계학술대회
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• pp.17-19
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• 1995