• The Korean Journal of Applied Statistics
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• v.27 no.1
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• pp.13-20
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• 2014

Phase I Clinical Trials estimate a Maximum Tolerated Dose(MTD). In this paper, an MTD estimation method applied stopping rule is proposed for Phase I Clinical Trials. The suggested MTD estimation method is compared to the Continual Reassessment Method(CRM) method using a Monte Carlo simulation study.

• Journal of the Korean Data and Information Science Society
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• v.23 no.6
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• pp.1085-1091
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• 2012

Phase I clinical trials are designed to identify an appropriate dose; the maximum tolerated dose, which assures safety of a new drug by evaluating the toxicity at each dose-level. The adjusted maximum tolerated dose estimation is presented by stopping rule in phase I clinical trial on this research. The suggested maximum tolerated dose estimation is compared to the standard method3 and NM method using a Monte Carlo simulation study.

• The Korean Journal of Applied Statistics
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• v.27 no.7
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• pp.1115-1123
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• 2014

The main purpose of phase I clinical trials is to estimate the Maximum Tolerated Dose (MTD), which minimizes side effect and assures safety of a new drug by evaluating the toxicity at each dose-level. The conventional MTD estimation methods is Standard method (Storer, 1989; Korn et al., 1994), Accelerated Titration Designs (Simon et al., 1997) and DM method (Dixon and Mood, 1948) etc. In this paper, MTD estimation method with de-escalation is suggested phase I clinical trials. The proposed MTD estimation method is compared to Accelerated Titration Designs, SM3 without de-escalation method and SM3 with de-escalation method using a Monte Carlo simulation.

• Communications for Statistical Applications and Methods
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• v.19 no.1
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• pp.57-64
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• 2012

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.

• Communications for Statistical Applications and Methods
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• v.16 no.1
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• pp.51-65
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• 2009

The purpose of a phase I clinical trial is to determine the maximum tolerated dose(MTD) of a new drug. This paper investigates the performance of standard method, continual reassessment method and accelerated titration designs in phase I clinical trials. Especially we study the precision and safety at the MTD of these methods. We utilize hyperbolic tangent function and power function to define dose-toxicity model. For each method, expected toxicity rate at MTD is computed and compared with target toxicity probability. We also suggest some modifications of these methods and show some improvements in performance.

• The Korean Journal of Applied Statistics
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• v.15 no.2
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• pp.323-336
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• 2002

In this paper we consider the modified continual reassessment method in which a cohort consists of three patients. Simulation has been a main research tool in the investigation of CRM. In this paper we propose complete enumeration as an alternative of simulation. Using new method we show that the expected toxicity rate at the MTD converges to the target toxicity rate well as the sample size increases.

• Proceedings of the Korea Water Resources Association Conference
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• 2005.05b
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• pp.1413-1416
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• 2005

본 연구에서는 인접하는 유역과 어떠한 동적인 상호작용없이 유출이 독립적으로 결정되는 자연방류형 단일저류지를 대상으로 기존의 연구에서 임계지속기간 결정에 빈번히 이용되었던 최대첨두유량 발생시간, 최대저류용량 발생시간, 최대 저류비 발생시간을 기준으로 한 임계지속기간을 산정하여 분석하므로써 자연방류형 단일저류지의 임계지속기간의 결정에 있어 합리적인 성과를 도출하고자 하였다. 적용결과, 최대 저류용량을 기준으로 한 경우에는 저류지 규모와 같은 제약조건을 가져오게 되고, 최대 저류비를 기준으로 한 경우에는 강우지속기간에 따라 저류비는 지속적으로 감소하므로 두 기준을 통하여 임계지속기간을 결정하는 것은 적합하지 않은 것으로 판단되었다. 따라서 허용방류량 고정개념을 통하여 최대 저류비, 최대 저류용량을 통하여 임계지속기간을 산정하였다. 그 결과 자연방류형 단일 저류지에서는 최대 저류용량을 통하여 적정 임계지속기간을 검토할 수 없는 것으로 판단되었다. 그러므로 최대 저류비를 이용하여 자연방류형 저류지에서의 최대 저류비를 발생시키는 시간분포를 정리한 결과 전체적으로 Huff 2분위가 최대 저류비를 발생시키는 것으로 나타났다. 그리고 첨두저류비 변화율을 검토한 결과 매우 제한적인 조건이기는 하지만 허용방류량 고정개념을 이용한 경우에 한하여 지속기간별 최대 첨두유량의 임계지속기간과 자연방류형 단일저류지의 임계지속 기간을 동일하게 간주하는 것이 큰 무리는 아닌 것으로 판단되었다.

• The Korean Journal of Applied Statistics
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• v.33 no.2
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• pp.137-145
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• 2020

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.

• The Korean Journal of Applied Statistics
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• v.32 no.5
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• pp.741-752
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• 2019

The purpose of a Phase I Clinical Trial is to determine the maximum tolerated dose (MTD). MTD is important because it affects subsequent clinical trials; however, the existing method has a problem due to an inadequate dose allocated to patients. In this paper, an MTD estimation method is proposed to complement the problems of the existing MTD estimation method. The suggested method applies the initial acceleration step to the modified continual reassessment method. Monte Carlo Simulation Study is adapted to compare a suggested MTD estimation method with the standard design and the modified continual reassessment method.

• The Korean Journal of Applied Statistics
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• v.35 no.2
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• pp.251-263
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• 2022

Phase I clinical trial is called 'Dose finding study'. It is first step of experimenting on humans with new drugs developed through animal experiments or vitro experiments. The important area of interest in designing Phase I clinical trial is determining the dose that acceptable level to the patients and provides the greatest efficacy. In this paper, we explain about methods to determine the maximum tolerated dose using various stopping rules. The SM3, NM, Rim, J3, BSM methods are compared through simulation. And we consider how the methods might be reformed. As a result of the simulation, BSM estimated the MTD closest to the target toxicity probability. J3 method required the least number of subjects. These results are due to the feature of the stopping rules of both methods. The BSM adds 2 or 1 subject at the same dose level when there is a toxic reaction. In addition, the J3 method has a smaller number of subjects than the other methods. If the methods are improved by combining these features, MTD can be estimated more efficiently. If the total number of subjects can be reduced while using the stopping rule of the BSM, accurate estimation is possible for a small number of subjects.