• Genomics & Informatics
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• v.16 no.3
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• pp.52-58
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• 2018

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials.

• Korean Journal of Clinical Pharmacy
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• v.32 no.3
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• pp.166-177
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• 2022

Background: Recently clinical trials have expanded extensively in Korea; thus, ensuring the rights of subjects participating in clinical trials is imperative. Accordingly, national regulations on subject recruitment advertisement were enforced from October 25, 2018. In this study, the effect of this regulation was evaluated by analyzing the difference in the provision of information before and after enforcement of the regulation. Methods: Recruitment advertisements for clinical trial subjects 3 years before and after enforcement of the regulation were collated by the significance sampling approach. Print-based (newspapers, buses, and subways) and web-based (clinical trial center websites and online platforms) materials for recruitment in clinical trials of phase 1 to 4 for investigational drugs, medical devices, and oriental medicine were considered. Chi-square tests were conducted for inter-group comparisons. SPSS version 26 was employed for statistical analyses. Results: A total of 137 advertisements were collected comprising 60 pre- and 77 post-regulation enforcement. The overall rate of delivery of critical information in advertisements increased significantly from 47.5% before regulation to 93.2% after regulation enforcement. Particularly, details on expected adverse events augmented significantly (p<0.001). Benefits from participation in clinical trial reduced significantly from 88.3% to 70.1% (p<0.05). As the information provision amplified, the inclusion of professional terms increased. Conclusions: Enforcement of regulations has led to a surge in the amount of information and challenging terms contained in advertisements for recruiting subjects. Therefore, additional efforts are required by subjects to completely understand the information provided in the advertisements.

• Biomedical Science Letters
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• v.28 no.2
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• pp.67-82
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• 2022

The prevalence of SARS-CoV-2 led to inconsistent public health policies that resulted in COVID-19 containment failure. These factors resulted in increased hospitalization and death. To prevent viral spread and achieve herd immunity, the only safe and effective measure is to provide to vaccinates. Ever since the release of the SARS-CoV-2 nucleotide sequence in January of 2020, research centers and pharmaceutical companies from many countries have developed different types of vaccines including mRNA, recombinant protein, and viral vector vaccines. Prior to initiating vaccinations, phase 3 clinical trials are necessary. However, no vaccine has yet to complete a phase 3 clinical trial. Many products obtained "emergency use authorization" from governmental agencies such as WHO, FDA etc. The Korean government authorized the use of five different vaccines. The viral vector vaccine of Oxford/AstraZeneca and the Janssen showed effectiveness of 76% and 66.9%, respectively. The mRNA vaccine of Pfizer-BioNTech and Moderna showed effectiveness of 95% and 94.1%, respectively. The protein recombinant vaccine of Novavax showed an effectiveness of 90.4%. In this review, we compared the characteristics, production platform, synthesis principles, authorization, protective effects, immune responses, clinical trials and adverse effects of five different vaccines currently used in Korea. Through this review, we conceptualize the importance of selecting the optimal vaccine to prevent the COVID-19 pandemic.

• Journal of Korean Academy of Nursing Administration
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• v.16 no.3
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• pp.348-359
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• 2010

Purpose: This study aimed to evaluate the performance of Clinical Research Nurses (CRNs) and the importance of their roles at the Regional Clinical Trial Centers (RCTCs). Method: A questionnaire focused on the role of CRNs was crafted by a researcher and the content validity was verified by a panel of experts on clinical research. The subjects of this study were 91 CRNs and Clinical Research Coordinators (CRCs), who were Korean registered nurses working at nine RCTCs. 77 subjects yielded valid data were analyzed using descriptive analysis, the Mann-Whitney U test, Spearman's rank order correlation coefficient, and Kruskal-Wallis test. Results: The performance of CRNs and the recognition in the importance of their roles were statistically significant different in age, education, CRN careers, positions, employment status and the phase of clinical trial. The role of direct caregiver was performed most often by CRNs. The role of coordinator of care and research (pre-study) was considered the most important role but performed the least frequent. Conclusions: The role of CRNs can easily be differentiated from CRCs who are not registered nurses. The domains of CRNs should be clearly identified and established. Moreover, research should be carried out on CRN training programs to cultivate competence in CRNs.

• The Korean Journal of Applied Statistics
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• v.35 no.2
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• pp.251-263
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• 2022

Phase I clinical trial is called 'Dose finding study'. It is first step of experimenting on humans with new drugs developed through animal experiments or vitro experiments. The important area of interest in designing Phase I clinical trial is determining the dose that acceptable level to the patients and provides the greatest efficacy. In this paper, we explain about methods to determine the maximum tolerated dose using various stopping rules. The SM3, NM, Rim, J3, BSM methods are compared through simulation. And we consider how the methods might be reformed. As a result of the simulation, BSM estimated the MTD closest to the target toxicity probability. J3 method required the least number of subjects. These results are due to the feature of the stopping rules of both methods. The BSM adds 2 or 1 subject at the same dose level when there is a toxic reaction. In addition, the J3 method has a smaller number of subjects than the other methods. If the methods are improved by combining these features, MTD can be estimated more efficiently. If the total number of subjects can be reduced while using the stopping rule of the BSM, accurate estimation is possible for a small number of subjects.

• 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.

• The Journal of Pediatrics of Korean Medicine
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• v.37 no.3
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• pp.75-93
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• 2023

Objectives We aimed to analyze the registration status of interventional clinical trials in children and adolescents with chronic cough. Methods All interventional clinical trials registered up to 3 July, 2023 on the international clinical trial registry platform (ICTRP) of the World Health Organization (WHO) were analyzed. Information was extracted including study design, interventions, inclusion and exclusion criteria, and outcome indicators. Results A total of 18 interventional clinical trials were analyzed. For study design, multicentre trials, randomized allocation, parallel group design and phase 4 trials were the most frequently reported. Blinding was used in 44.4% and informed consents were obtained from 61.1%. For intervention, drugs were used in 61.1%, using placebo control group in 27.8%. Quality of life questionnaires were most frequently reported in 50% as the primary outcome, and adverse events were the most as the secondary outcome. In most cases, the assessment timepoints were after two weeks. Conclusions Based on the characteristics of clinical trial design analyzed in this study, it is necessary to design traditional Korean medicine clinical trials with improved quality and accuracy of information.

• The Korean Journal of Applied Statistics
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• v.32 no.1
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• pp.1-13
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• 2019

An adaptive seamless Phase II/III clinical trial design enables a reduction in the sample size (in comparison to a conventional design) that also shortens the clinical development time. It is also very effective in clinical trials since it can have higher statistical power than Phase III alone. In this study, we use extensive simulation studies to compare several multiple hypothesis testing methods that can help select the best doses in a Phase II study along with several methods to combine p-values of the Phase II and Phase III study.

• The Journal of Korean Obstetrics and Gynecology
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• v.20 no.3
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• pp.213-228
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• 2007

Purpose: This master‘s thesis to evaluate the grade of life after medication a Dangguijakyak-san(pasabu) and Gyejibongnyeong-hwan(cheongwal) with in postmenopausal women get lowering quality of life caused by vasomotor symptoms with hot flush. Methods: A subject who signing on the clinical trial written consent by self-will is registered this clinical trial after decided suitable by selection and exception standard, after take a medical experiment and checkup according to clinical trial plan. Registered subject should valuated by settled schedule after take the testing medicine 1,2 during thirty-day. In this period, a subject allocated at relatively better suited experimental group by oriental doctor after consideration of general efficacy and nature of a medicine at second visiting. Results: The result of comparison in the remedial value with sixteen patients who ended the experiment is like next list. 1. There's no regarded difference of comparison in general conditions between two patient groups. 2. There's no regarded difference during observation period before take medicine. 3. By period of measurement, there's something regarded differences most of patients of two parts after taking medicine. 4. There's no regarded difference at alteration phase of each standard according to kind of medicine. 5. There's no abnormal views reflected at allergy, Laboratory and Physical Examination during experiment. Conclusion: This experiment evidence a Dangguijakyak-san and Gyejibongnyeong-hwan can help for improvement generally life quality of postmenopausal women and certify safety of herbs.

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2425-2430
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• 2013

A simple, fast and robust analytical method was developed to determine imatinib in human plasma using liquid chromatography-tandem mass spectrometry with electrospray ionization in the positive ion mode. Imatinib and labeled internal standard were extracted from plasma with a simple protein precipitation. The chromatographic separation was performed using an isocratic elution of mobile phase involving 5.0 mM ammonium formate in water-5.0 mM ammonium formate in methanol (30:70, v/v) over 3.0 min on reversed-stationary phase. The detection was performed using a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. The developed method was validated with lower limit of quantification of 10 ng/mL. The calibration curve was linear over 10-2000 ng/mL ($R^2$ > 0.99). The method validation parameters met the acceptance criteria. The spiked samples and standard solutions were stable under conditions for storage and handling. The reliable method was successfully applied to real sample analyses and thus a pharmacokinetic study in 27 healthy Korean male volunteers.