• 응용통계연구
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• 제33권2호
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• pp.137-145
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• 2020

'투약용량 발견 시험(Dose Finding Study)'라고도 불리는 제 1상 임상시험은 동물 실험 혹은 시험관 실험을 통하여 개발된 신약물질을 사람에게 실시하는 첫 단계이다. 제1상 임상시험의 가장 주요한 목적은 환자에게 허용할 수 있고 최대의 효능을 가진 복용량을 결정하는 것이다. 본 논문에서는 이를 고려하여 최대허용용량(MTD)를 결정할 수 있는 적절한 추정방법을 제안하였다. 이 방법은 Biased coin design과 멈춤규칙을 이용하여 MTD를 추정한다. 제안하는 방법은 모의실험을 통해 기존의 방법들과 비교하였다.

• Asian-Australasian Journal of Animal Sciences
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• 제18권3호
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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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• 제12권8호
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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.

• 대한기관윤리심의기구협의회지
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• 제5권1호
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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.

• 한국콘텐츠학회논문지
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• 제13권4호
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• pp.281-289
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• 2013

최근 국내 임상시험의 양적 증가와 더불어, 임상시험 자료를 효율적으로 관리할 수 있는 Electronic Data Capture(EDC) 시스템의 도입 요구가 증가하고 있다. 이에 따라 식품의약품안전청에서는 '임상시험 전자 자료 처리 및 관리를 위한 가이드라인'을 발표하였다. 이는 향후 국내 임상시험 전자 자료 관리에 관한 법률 제정을 위한 기초가 될 것으로 기대한다. 이 연구에서는 국내 임상시험 관련 기관인 병원과 임상시험 수탁기관(CRO), 그리고 제약회사에서의 EDC 시스템 이용 현황과 관계자들이 인식하는 가이드라인 및 전자 자료 표준의 중요성 및 적용 용이성과 이해도를 조사하였다. 국내 임상시험 관련 기관에서의 EDC 시스템 이용률은 77.6% 이었지만 EDC 시스템을 이용한 임상시험 건수는 5건 미만이 가장 많았다. EDC 시스템은 주로 약물동력학 시험을 하는 phase I과 임상효과와 안전성을 평가하는 phase II 임상시험에서 주로 이용되었고, 기관별로는 CRO의 이용률이 가장 높았다. 모든 집단에서 가이드라인의 중요성은 높게 인식하였으나, 적용 용이성 측면에서는 CRO에서 가장 높았다. 또한, 임상시험 전자 자료 표준의 중요성을 높게 인식하였고, 전자 자료 수집에 있어 표준의 필요성을 높게 인식하였다. 그러나 임상시험 전자 자료 국제표준인 Clinical Data Interchange Standard Consortium(CDISC)에 대한 이해도는 아직 낮은 수준이었다. 이 연구 결과는 국내 임상시험 전자화를 위한 기초자료로 활용될 수 있으며 임상시험 자료 표준에 관한 정책수립에도 활용될 수 있을 것이다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 추계학술대회
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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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• 제35권4호
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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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• 대한임상약리학회 1995년도 정기총회 및 추계학술대회
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• pp.45-45
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• 1995

• Journal of Power Electronics
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• 제8권2호
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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.

• Communications for Statistical Applications and Methods
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• 제16권1호
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• pp.51-65
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• 2009

제 1상 임상시험은 사람을 대상으로 처음 실시되므로 약물 투여의 안전성과 정확성이 신중히 고려되어야 한다. 따라서 제 1상 임상시험에서는 적은 수의 피험자를 통해 최대허용용량(maximum tolerated dose)을 정확하게 찾아야 한다. 제 1상 임상시험에서 최대허용용량을 결정하는 방법에는 표준방법(standard method), 연속재평가방법(continual reassessment method) 그리고 가속적정계획(accelerated titration designs) 방법이 있다. 본 연구에서는 동일한 모형에서 세 방법을 동시에 고려하여 최대허용용량의 안전성과 정확성을 살펴보았다. 또한 세 방법에 대해 최대허용용량에서 기대독성확률을 구하여 비교하였다. 그리고 ATD와 CRM의 단점을 보완한 수정된 ATD와 수정된 CRM을 포함하여 여러 방법들을 동일한 모형에서 동시에 그 성능을 비교하였다.