• 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.37 no.4
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• pp.411-444
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• 2024

The objective of Phase I clinical trials is to ascertain the maximum tolerated dose (MTD) that is safe for human administration. Accurately determining the MTD within an acceptable safety margin is imperative, necessitating evaluations up to sufficiently high doses. To estimate the MTD, a plethora of methods have been developed, encompassing algorithm-based, model-based, and model-assisted techniques. In this paper, a new dose exploration method based on continual reassessment method (CRM) is proposed to address for the shortcomings of existing dose exploration methods. Through a comprehensive simulation study, this method's efficacy was compared against that of existing methodologies across a variety of scenarios. The findings from this study underscore its enhanced precision and safety in estimating the MTD, alongside a reduction in the number of subjects required for testing.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.3
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• pp.384-389
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• 2005

These experiments were conducted to evaluate the feeding value of rice protein concentrate (RPC) in weaning pigs. In expt. I, a 5-week feeding trial was conducted with 126 pigs (L${\times}$Y${\times}$D; 21 d-old; 5.32${\pm}$0.34 kg). Treatments were spray-dried plasma protein (SDPP; control), soy protein concentrate (SPC) and RPC (phase 1), and dried porcine soluble (DPS; control), SPC and RPC (phase 2). An ileal digestibility trial was also conducted to compare digestibility of amino acids in the tested protein sources. In expt. II, 160 weaning pigs (L${\times}$Y${\times}$D; 21 d-old; 5.65${\pm}$0.35 kg) were used in a 5-week feeding trial to determine the optimal inclusion level of RPC in the diet. Treatments were control (9% SPC), and three levels of RPC instead of SPC in the diets (3, 6 and 9%). During phase 1, pigs fed SDPP showed better (p<0.05) ADG and FCR compared with those fed SPC or RPC, while there was no difference in ADFI among treatments. During phase 2, however, pigs fed DPS showed lower (p<0.05) ADG than those fed SPC or RPC. During the total period, there were no significant differences in ADG, ADFI and FCR among treatments. The apparent ileal digestibilities of his, lys, phe, thr and met were not different among the tested protein sources. The apparent ileal digestibilities of arg, ile, leu and val were lower (p<0.05) in RPC than SDPP. The true ileal digestibilities of arg and leu were lower (p<0.05) in RPC than SDPP and SPC. However, that of met was higher (p<0.05) in RPC than SDPP. In expt. II, there were no significant differences in ADG and FCR when SPC was substituted with RPC up to 9% during the total period. In conclusion, based on our experimental results, RPC would replace SPC in the complex prestarter diet, which is somewhat cheaper than SPC.

• Asian-Australasian Journal of Animal Sciences
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• v.12 no.8
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• pp.1285-1291
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• 1999

A feeding trial was carried out over 238 days to determine the effect of compensatory growth in crossbred calves having 166 kg body weight. Fifteen crossbred calves were divided into two groups of five calves (G1 group) and ten calves (G2 group) as per randomized block design. Growth study was conducted on the feeding of wheat straw based diet containing 60 and 30 percent concentrate supplying equal amount of protein in group G1 and G2 respectively for 119 days (phase - I). At the end of phase-I, calves of G2 group were subdivided in to two groups (G3 and G4). One sub group (G4) received 60% concentrate in their diet (during 120 to 238 days of experiment) while other subgroup G3 received 30% concentrate in their diet (phase-II). The calves of G1 group continued to receive the same diet as during phase-I experiment. Mean DM intake was significantly higher in calves fed high level of concentrate (in G1 and G4 groups), which resulted in significantly higher digestibility of all nutrients except NDF. Nitrogen balance was positive in all the groups and showed significant differences in phase-II (higher nitrogen retention in G4 group than G1 group). ME intake was significantly affected by the level of dietary concentrate, being higher in high concentrate fed group (G1 and G4 than G2 and G3 group). Higher daily body weight gain in the calves of G4 group during phase-II than in G1 and G3 groups was due to compensatory growth on shifting animals from low concentrate to high concentrate based ration. Average daily body weight gain was higher in phase-I than in the phase-II. Protein and energy intake per unit body weight gain were significantly lower in calves fed high concentrate diet.

• 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.

• The Journal of the Korea Contents Association
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• v.13 no.4
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• pp.281-289
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• 2013

As the number of clinical trials conducted in Korea increases, the need of the Electronic Data Capture (EDC) system for effective clinical data management is also increased. Recently, the Korea Food and Drug Association published 'Guideline for the Electronic Clinical Trial Data Management and Processing' and it would be the foundation for establishing regulation of electronic clinical data management. In this research, we conducted the survey regarding adoption rate of EDC system in clinical trials in hospitals, Contract Research Organizations (CRO), and pharmaceutical companies. And the perceived importance and the ease of application for the Guideline were investigated. The adoption rates of EDC system was 77.6% but it mostly applied to less than five trials. Also EDC system was mostly used in phase I and phase II trials and the utilization rate of CRO was the highest. The perceived importance for the Guideline was high among all three organizations but, in case of the perceived ease of its application, CRO was the highest. Also, the perceived importance of the clinical data standard was high and the standard for data collection was mostly required. However, the comprehension for the global standard of the electronic data was relatively low, so that education is required. This result would be the foundation to increase the electronic clinical trials and develop proper regulation and principles for clinical data standards in Korea.

• 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.

• Radiation Oncology Journal
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• v.35 no.4
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• pp.325-331
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• 2017

Purpose: There is controversy regarding the cosmetic outcome after accelerated partial breast radiation (APBR). We report the cosmetic outcome from a single-arm prospective clinical trial of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I breast cancer (BC), using a novel fractionation schedule. Materials and Methods: Forty-two patients aged ${\geq}65$, with Stage I BC who underwent breast-conserving surgery were enrolled in a phase I/II study evaluating a 2-week course of APBR. Thirty eligible patients received 40 Gy in 4 Gy daily fractions. Cosmetic outcome was assessed subjectively by physician/patient and objectively by using a computer program (BCCT.core) before APBR, during, and after completion of the treatment. Results: The median age was 72 years, the median tumor size was 0.8 cm, and the median follow-up was 50.5 months. The 5-year locoregional control in this cohort was 97% and overall survival 87%. At the last follow-up, patients and physicians rated cosmesis as 'excellent' or 'good' in 100% and 91 %, respectively. The BCCT.core program scored the cosmesis as 'excellent' or 'good' in 87% of the patients at baseline and 81% at the last follow-up. The median $V_{50}$ (20 Gy) of the whole breast volume (WBV) was 37.2%, with the median WBV $V_{100}$ (40 Gy) of 10.9%. Conclusion: An excellent rate of tumor control was observed in this prospective trial. By using multiple assessment techniques, we are showing acceptable cosmesis, supporting the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

• 대한임상약리학회:학술대회논문집
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• 1995.12a
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• pp.45-45
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• 1995

• Journal of Power Electronics
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• v.8 no.2
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• pp.141-147
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• 2008

This paper deals with a new and improved control technique for shunt active filters (AF) used for compensating unwanted harmonic currents injected in the mains due to nonlinear varying loads. This work is motivated by the need to find a permanent solution to the rigorous hit and trial method for evaluating system parameters in an indirect control of AF. A fuzzy pre-compensated PI (Proportional-Integral) controller is used to fuzzify the reference DC voltage of AF to the controller input so that the overshoots and undershoots in its DC link voltage are minimized and the settling time is improved. A three-phase diode rectifier with R-L (Resistive-Inductive) load is used as a non-linear load to study the effectiveness of the proposed controller of the AF. Robustness to filter parameter variations, insensitivity to controller parameter variations, and transient response has been taken as performance evaluation parameters. The results are shown through simulations in Matlab using power system block sets to demonstrate the capability of the proposed controller of the AF.