• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.11a
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• pp.35-39
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• 1997

Recent development of human genetics and techniques of gene transfer and expression have opened the way for investigating novel approaches based on the genetic modification of cells to treat both inherited and acquired diseases. This approach is referred to as gene therapy. Over the past few years, gene therapy has moved from the laboratory to phase I clinical trials. Although the clinical performance of gene transfer experiments is still in an early phase of development, the NIH of Health Recombinant DNA Advisory Comittee (RAC) has approved more than 150 protocols that involve gene transfer or putative gene therapy procedures in clinical settings. Many sectors of society in United States have participated in the design and formulation of these clinical trials through local Institutional Review Boards, the National Institutes of Health (NIH) RAC, the Chemotherapy Evaluation Program of the National Cancer institute, and the FDA. Currently, clinical trials involving gene modification are under way at many medical centers throughout the United Slates. The goals of these trials are as follows. (1) The design should be directed to short-term achievable goals. (2) Each clinical trial is best considered as an intermediate step in a multistep process. (3) The design should identify evaluable proximate endpoints for toxicity and for efficacy, (4) The potential benefits and possible risks for patients participating in these trial should be defined.

• Journal of the Korean Data and Information Science Society
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• v.15 no.4
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• pp.973-980
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• 2004

Phase I clinical trials are often pharmacologically oriented and usually attempt to find the best dose of drug to employ. However, other purposes like determination of sizes and types of side effects and toxicity and organ system involved are equally important. Estimation of treatment effects or side effects is usually ignored since it is usually based on too small sample, even though Phase II clinical trials would be designed based on the Phase I studies. Statistical methods for constructing the approximate confidence interval for population median in case of small sample are considered and an improved method is proposed. The proposed estimator is compared with current methods through simulation studies.

• 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.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.30-39
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• 2018

Introduction: The aim of this study protocol is to share and disclose the methodology used to develop an evidence-based clinical practice guideline (CPG) of therapeutic interventions used in Korean medicine for patients with stroke. Methods: The CPG development process will consist of two phases. In phase I, a development committee will be established, and they will decide the key questions to be answered. A systematic review and meta-analysis will be performed to answer these key questions by searching relevant randomized controlled trials and systematic reviews. Draft recommendations will be developed according to the evidence level and recommendation grades primarily determined using the GRADE methodology. Panels comprised of external experts will be formed, and surveys and a face-to-face meeting will be conducted to reach a consensus on the recommendations. A preliminary guideline will be created after final review by the development committee. In phase II, we will conduct clinical trials and economic analysis to supplement the lack of evidence found in the phase I. Conclusion: The CPG is expected to help doctors practicing Korean medicine in clinics or hospitals with making decisions based on the most reliable evidence, ultimately leading to the provision of optimal care for patients with stroke.

• 대한임상약리학회:학술대회논문집
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• 1998.12a
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• pp.44-44
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• 1998

• 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 Journal of KAIRB
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• v.5 no.1
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• pp.14-20
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• 2023

Purpose: To obtain fundamental data on selection tools for an internal audit and develop a new guideline. We scored the indicated points from the internal audit, identified the research progress and problems that occurred, and confirmed the validity of the risk factors involved. Methods: Of the 63 internal audits conducted by Keimyung University Dongsan Hospital from 2014 to 2021, we analyzed 55 clinical trials with an inspection checklist. We excluded 8 that failed to transfer data and refused to comply with the internal audit. The statistical summary of the collected data was verified and interpreted by using frequency analysis and a chi-square test. Result: Of total 55 cases included in the internal audit, sponsor-initiated trial (SIT) was 63.6% (vs. investigator-initiated trial [IIT]), clinical trial for investigational drug was 71.0% (vs. nonclinical or clinical trial for investigational device), domestic multicenter trial was 60.0% (vs. single center or multinational multicenter trial), and trial requisition for MFDS approval was 69.1% (vs. exception for MFDS approval). The 10 areas of the clinical trial inspection checklist (reports, protection of subjects, compliance with protocols, records, management of investigational drug and/or device, delegation of duties, qualification of investigators, management of specimen, contract-agreement and approval of protocols, and preservation of recorded documents) were weighted between 2 to 5 points. The average of the total points was 16.09±13.2 and 20 clinical trials were above the average. As a result of comparing the average of the total points weighted by year, the highest score was in 2020. The 4 factors that play significant roles in determining the internal quality were (1) principal subjects that initiated the clinical trials (p=0.049), (2) type (p=0.003), (3) phase of clinical trials (p=0.024), and (4) number of registered subjects reported at the time of continuing deliberation (p=0.019). Of the 10 areas of the clinical trial inspection checklist, 'record' was the most inappropriate and insufficient. We found more indicated points; the quality of performance declined in IIT, nonclinical trials, and other clinical trials that were not in phase I1-IV4, and the study of more than 30 registered subjects at the time of continuing review. Conclusion: If an institution has an internal audit selection tool that reflects the aforementioned risk factors, it will be possible to effectively manage high-risk studies; thereby, contributing to an efficient internal audit and improving the quality of clinical trials.

• Journal of Korean Traditional Oncology
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• v.20 no.1
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• pp.11-21
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• 2015

Objectives : The cancer incidence and cancer burden is increasing. In addition, the use of botanical agents in cancer care is increasing. This article aims to review a research strategy for botanical agents. Methods : The clinical studies of anticancer botanical agents and the papers about clinical research methodology of botanical agents were reviewed. Results : In phase I study, safety confirmation, optimal dose determination and drug interaction study are important. Most botanical agents have low toxicity and some have non-monotone dose response. Therefore, dose-response curve must be evaluated separately from the dose-toxicity curve to determine optimal dose. Although anticancer botanical agents can't shrink tumor size rapidly, they do extend survival. So, in phase II study, response should be evaluated by the survival. Conclusions : Clinical research of botanical agents in cancer is different from traditional methods and strategies. Considering the characteristics of botanical agents and experimental mechanism is necessary in conducting botanical based clinical trials.

• Korean Journal of Transplantation
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• v.31 no.4
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• pp.157-169
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• 2017

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.

• 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.