• Journal of Korean Society for Quality Management
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• v.39 no.2
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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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• 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.

• 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.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.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.

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.172-176
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• 2018

Mandatory registration of clinical trials in public registry can ensure the transparency of clinical trials. Public clinical trial registry of can provide current chronological and geographical distribution of clinical trial throughout the country. We used public clinical trial registry provided by Ministry of Food and Drug Safety to analyze current status of clinical trial from 2014 to 2016 in South Korea. The number of clinical trials in antineoplastic and immunomodulating agents area was the greatest, followed by cardiovascular system and antiinfectives for systemic use as a whole. From 2014 to 2016, overall number of clinical trials decreased while the number of phase I clinical trials increased. Seoul accounted for more than half number of clinical trials in Korea. Supports for clinical trials in non-metropolitan area needs to be considered.

• 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.

• 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.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.

• Communications for Statistical Applications and Methods
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• v.18 no.5
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• pp.581-594
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• 2011

The traditional method of 3+3 standard design and model-based Bayesian continual reassessment method (CRM) are commonly used in Phase I clinical trials to identify the maximal tolerated dose(MTD) of a new drug. In this paper we review clinical examples of Phase I trials that were carried out in patients with refractory or relapsed leukemia and myelodysplastic syndrome. The recently proposed 3+1+1 design and rolling-6 design can shorten the trial duration, when a very slow accrual of patients with a simple 3+3 standard design may result in the untimely termination of trials. Too conservative approaches in determining the dose levels in Phase I clinical trials can leave clinical investigators unable to accurately determine the MTD. When determining future patient doses, the designs that use a time-to-event CRM can cooperate late toxicities by accounting for the proportion of the observation period of each enrolled patient. With the CRM design, simulations under different scenarios during the trial are important in detecting the under- or over-estimation of the initial estimate of the dose-limiting toxicity rate for each dose level. We present the advantages and drawbacks of the designs used in Phase I clinical trials for leukemia patients.