• 한국통계학회:학술대회논문집
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• 한국통계학회 2002년도 추계 학술발표회 논문집
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• pp.79-83
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• 2002

A phase III clinical trial of a new drug for neutropenia induced by chemotherapy is presented and consider adding random effects in crossover design which was used in the clinical study. The diagnostics for its heteroscedasticity based on score statistic is derived for detecting homoscedasticity of errors in crossover design. A small simulation study is peformed to investigate the finite sample behaviour of the test statistic which is known to have an asymptotic chi-square distribution under the null hypothesis.

• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.323-328
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two torasemide tablets, Torem tablet (Roche Korea Co., Ltd., Korea, reference drug) and Boryung Torsemide tablet (Boryung Pharmaceutical Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (furosemide) to human serum, serum samples were extracted using 5 mL of ethyl acetate. Compounds were analyzed by reverse-phase HPLC method with UV detection. This method showed linear response over the concentration range of 0.05 ug/mL with correlation coefficient of 0.999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ug/mL which was sensitive enough for pharmacokinetic studies. Twenty-eight healthy male Korean volunteers received each medicine at the torasemide dose of 20 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of torasemide were monitored by an HPLC-UV for over a period of 12 hr after the administration. $AUC_{t}$(the area under the serum concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum serum drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the serum concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_{t}$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_{t}$ ratio and the $C_{max}$ ratio for Boryung Torsemide/Torem were log 0.97-10g 1.03 and log 0.93log 1.12, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Boryung Torsemide tablet and Torem tablet are bioequivalent.

• Korean Journal of Acupuncture
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• 제26권1호
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• pp.41-49
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• 2009

Objective : To make comprehensive picture of clinical trials using moxibustion and their results by today, then help a strategy for moxibustion-derived clinical studies in the future. Methods : Surveyed literatures containing randomized controled clinical trial (RCT) from PubMed and Korean journals. Analysis was performed according to distribution mainly by study subject, target diseases, study design, and its efficacy. Results : Fifty two literatures were selected according to inclusion criteria of randomized controled clinical study. Moxibustion-derived RCT have been rapidly increased from 2003 since the first was published in China in 1992. The main subjects of RCT are associated with immunity, cancer, arthritis, chronic colitis and urogenital disorders, which are connected to cold-elated pathogenesis. The average number of subjects was 94, and direct-moxibustion was mainly applied. The control groups were set up by giving conventional therapy, herbal medicine, acupuncture or only observation. The most of RCTs showed positive results. Conclusions : This study would be helpful for designing or conducting RCTs to develop the scientific development of moxibustion.

• 한방안이비인후피부과학회지
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• 제20권3호
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• pp.138-146
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• 2007

Objective : To observe the trend in clinical study on atopic dermatitis(AD) over the last 3 years in order to develop a study methodology of AD in Oriental Medicine. Methods : Using the Pub med on line site; search terms: atopic dermatitis, field as title/abstract, limitation as published in the last 3 years, only items with links to full text, Humans, Clinical Trial, English. I observed the study contents of all this research and focused on the classification of treatments. I also observed of AD clinical trials registered on a clinical trial site(www.clinicaltrial.gov) on 23rd of June, 2007: study contents, localization and study designs. Results : Through the Pub Med site, I found 169 articles. Classified according to study subject, the studies related to treatment were 114(67.5%); physiology, pathology and prevention 12(7.1%); Diagnosis and Evaluation(7.1%); psychological aspects including quality of life 10(5.9%); diet and management 10(5.9%); epidemiology 7(4.1%); and others 7(4.1%). However, the treatment study of herb-medicine as intervention showed only 1 article. Futhermore, it wasn't based on Oriental Medicine philosophy. In the clinical trial site, there were 31 studies in which patients were recruited or planned for the future. The study on efficacy and safety of the medicine produced 14 trials, 5 comparative trials, 2 phototherapy, 2 diagnosis, 6 physiology and pathology, and 2 epidemiology. The trial institutions were concentrated in U.S.A. Conclusion : I suggest we'd better try to make a good clinical guideline and standardization of diagnosis and herb-medicine in order to develop a clinical study methodology of AD as soon as possible in the future. Even though it 's very hard to find the study methodology, we should aim to achieve positive results and show the evidence of the efficacy and safety of herb-medicine treatment for AD using Oriental Medicine.

• 생물정신의학
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• 제19권4호
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• pp.164-171
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• 2012

The placebo effect, a response observed during the placebo arm of a clinical trial, is produced by the psychobiological action of the placebo as well as by other potential contributors to symptom amelioration such as spontaneous improvement, regression to the mean, biases, concurrent treatments, and study design. From a psychological viewpoint, there are many mechanisms that contribute to placebo effects, including expectations, conditioning, learning, and anxiety reduction. Placebo responses are also mediated by opioid and non-opioid mechanisms including dopamine, serotonin, cholecystokinin, and immune mediators. During recent years, a trend towards increased placebo effects in clinical trials of neuropsychiatric drugs has been noted. Indeed, the placebo effects observed in clinical trials constitute an increasing problem and interfere with signal-detection analyses of potential treatments. Several potential factors including protocol/study design and conduct related factors may account for the placebo effect observed in clinical trials. This paper reviews key issues related to this problem and aims to identify potential solutions.

• Clinical and Experimental Pediatrics
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• 제55권11호
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• pp.403-407
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• 2012

Noninferiority trials test whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use. With continuous improvements in health technologies, standard care, and clinical outcomes, the incremental benefits of newly developed treatments may be only marginal over existing treatments. Sometimes assigning patients to a placebo is unethical. In such circumstances, there has been increasing emphasis on the use of noninferiority trial designs. Noninferiority trials are more complex to design, conduct, and interpret than typical superiority trials. This paper reviews the concept of noninferiority trials and discusses some important issues related to them.

• 한방안이비인후피부과학회지
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• 제32권2호
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• pp.68-93
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• 2019

Objective : This study summarized the characteristics of clinical trials for atopic dermatitis medicines approved by the Ministry of Food and Drug Safety(MFDS). This study may be a reference for the design of clinical trials of atopic dermatitis herbal medicine treatment which may be carried out later. Method : The characteristics of the clinical trial were analyzed for clinical trials registered with ClinicalTrials.gov, CRIS, and the Korea Health Industry Development Institute among the clinical trial approval statuses posted on the website of the MFDS. Result : 1. Clinical trial drugs were developed in various formulations such as oral medicines, injections, dermatologic agents, and similar proportions. Relatively little clinical trials were found for herbal medicine. 2. In the control evaluation test, most of the treatments for the control group were performed with placebo using Vehicle. 3. In most clinical trials, one intervention group was in the form of a parallel assignment with only one treatment. 4. The age of the subjects was 11 out of 28 studies including minors, and clinical trials targeting minors were also found to be significant. 5. In the case of atopic dermatitis, the cases of subacute chronic or atopic dermatitis more than 6 months or more than 1 year were often used. 6. Most clinical trials were divided into mild to moderate atopic dermatitis or moderate to severe atopic dermatitis. The SCORAD index, EASI, IGA, BSA, and NRS were used as the evaluation criteria. 7. Regulations for the drugs used prior to the trial period for the treatment of atopic dermatitis vary somewhat from one clinical trial to another. 8. IGA was used most often as a primary efficacy tool, and SCORAD index, EASI, and NRS were also used.

• 한방재활의학과학회지
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• 제20권2호
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• pp.63-77
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• 2010

Objectives : It is known that abdominal obesity increases the possibility of cardiovascular diseases, early death, and metabolic syndrome including dyslipidemia and insulin resistance. Clinical trials have been under way to verify the effectiveness of treatment for abdominal obesity. The objective of this study is to set criteria about how effective oriental medicine and acupuncture are in abdominal obesity. Methods : I manually search "www.clinicaltrial.gov", 4 Korean medical databases and 4 Korean medical journals of abdominal obesity. Search terms used were "abdominal obesity" or "visceral obesity". In order to see detail review, searching was performed from 01, 01, 2005 to 11, 31, 2009. And I classified all the searched studies into design, intervention, purpose, end point, diseases, condition and etc. Results : 1. I could search total 67 trials in "www.clinicaltrial.gov". I found 9, 10, 13, 8, 6 clinical trial from 2005 to 2009 every year. 2. Test on both gender and adult or adult and senior have been most frequent. 3. Randomization clinical trial is 51 cases that occupied 96.2%. 38 cases use control group. 4. Body mass index(BMI) and waist circunference(WC) are major criteria of abdominal obesity clincal trial. WC, BMI, abdominal fat mass, body weight are measured at end point of abdominal obesity clincal trial. 5. I could search total 86 cases in domestic study. I found 15, 23, 23, 20, 5 cases from 2005 to 2009 every year. 6. Test on female and adult have been most frequent in domestic study. 7. Randomization clincal trial is only 2 cases that occupied 2.3%. 62 cases use control group in domestic study. 8. BMI, body fat percent, WC, visceral-subcutaneous fat ratio(VSR), waist-hip ratio(WHR) are criteria of abdominal obesity clincal trial in domestic study. WC, BMI, abdominal fat mass, body weight are measured at end point of abdominal obesity clincal trial in domestic study. Conclusions : To improve abdominal obesity study in traditional korean medicine, it is need to activate clinical trial, meta analysis, develope of clinical practice guidelines, co-works with conventional medicine and etc.

• Communications for Statistical Applications and Methods
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• 제18권5호
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• pp.581-594
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• 2011

제 1상 임상시험 계획에서 신약제의 최대허용용량을 추정하기 위해 전통적 방법인 표준 3+3계획과 모형중심의 베이지안 방법을 적용시킨 연속재평가방법이 주로 사용되고 있다. 본 논문에서는 치료불응 또는 재발된 백혈병이나 골수형성 이상증후군 환자를 대상으로 시행한 제 1상 임상시험의 연구계획을 개관하였다. 단순한 표준 3+3계획으로 환자확보 기간이 길어져 연구를 완성하지 못하고 때 이르게 중단할 수밖에 없는 실정에 반하여, 최근에 제시된 표준 3+1+1계획과 Rolling-6 계획은 연구기간을 크게 단축시킬 수 있다. 제1상 임상시험의 용량수준 선택과정에서 너무 보수적인 연구자의 태도는 최대허용용량의 정확한 추정을 불가능하게 한다. 새로운 환자에게 투여할 용량수준을 결정할 시점에서 용량제한 독성반응이 아직 나타나지 않은 환자의 관측시간 및 늦게 나타나는 환자의 독성반응 시간을 모두 감안한 연속재평가방법인 TITE-CRM계획이 유용하며, 이러한 CRM계획으로 진행되는 임상시험 시행 중 모의실험으로 각 용량수준에서 용량제한 독성반응율이 과대 또는 과소 추정되는지를 파악할 수 있음이 장점이다. 백혈병환자 대상의 임상연구에서 채택되는 제 1상 임상시험의 여러 연구계획의 장, 단점을 제시한다.

• 응용통계연구
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• 제32권5호
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• pp.741-752
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• 2019

제1상 임상시험의 주목적은 최대허용용량(maximum tolerated dose; MTD)을 결정하는 것이다. MTD 결정을 통해 다음 임상시험에 사용될 용량이 제한되므로 투약용량 발견 시험이라고도 불리며 매우 중요한 단계이다. MTD를 결정하는 방법에는 대표적으로 DM 방법, SM 방법, CRM 방법이 있다. 본 논문에서는 기존 수정된 CRM 방법에 초기가속화 단계를 적용하여 낮은 용량에 다수의 피험자가 할당되는 문제점을 보완하는 새로운 MTD 추정 방법을 제안하였고 기존 방법들과의 비교를 위해 모의실험을 실시하였다.