• Journal of Pharmaceutical Investigation
• /
• v.35 no.5
• /
• pp.323-328
• /
• 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
• /
• v.26 no.1
• /
• pp.41-49
• /
• 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.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.20 no.3
• /
• pp.138-146
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.19 no.4
• /
• pp.164-171
• /
• 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
• /
• v.55 no.11
• /
• pp.403-407
• /
• 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.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.32 no.2
• /
• pp.68-93
• /
• 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.

• Journal of Korean Medicine Rehabilitation
• /
• v.20 no.2
• /
• pp.63-77
• /
• 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.

• The Korean Journal of Applied Statistics
• /
• v.32 no.5
• /
• pp.741-752
• /
• 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.

• The Korean Journal of Applied Statistics
• /
• v.27 no.1
• /
• pp.13-20
• /
• 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
• /
• v.18 no.5
• /
• pp.581-594
• /
• 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.