• Communications for Statistical Applications and Methods
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• v.18 no.2
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• pp.179-187
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• 2011

The purpose of a Phase I clinical trial is to estimate the maximum tolerated dose, MTD, of a new drug. In this paper, the MTD estimation method is suggested by curve fitting the dose-toxicity data to an S-shaped curve. The suggested MTD estimation method is compared with established MTD estimation procedures using a Monte Carlo simulation study.

• 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.

• 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.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.6
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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.

• Environmental Mutagens and Carcinogens
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• v.19 no.2
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• pp.108-111
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• 1999

Correlation between the tumorigenic dose (TD) and the maximum tolerated dose (MTD) was examined to search for the most relevant TD values related to the MTD. Using benzo(a)pyrene (B(a)P) 2-yr bioassay data, correlation coefficients between values of $TD_{1-}$50/ and the MTD were estimated from linearized or non-linearlized dose-response curves. The highest correlation coefficients (0.9966-1.0000) were obtained from T $D_{1-}$10/ in linearized dose-response curves while the highest (0.9966-1.0000) were estimated from $TD _{5-}$10/ in non-linearized dose-response eurves. These data suggest that TDs-lo were more closely related to the MTD than the ,$TD_{5-}$10/ in B(a)P 2-yr bioassay and that in lieu of the $TD_{50}$ they could be efficiently applicable to risk assessment and management.ent.

• 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.

• Communications for Statistical Applications and Methods
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• v.6 no.2
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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.

• 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.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.