Trials In Korea Research Articles

Regional disparities in the availability of cancer clinical trials in Korea.

Unequal access to cancer clinical trials is an important issue, given the potential benefits of participation for cancer patients. We evaluated regional disparities in access to cancer clinical trials in Korea. From the Ministry of Food and Drug Safety database, we extracted 2,465 records of all cancer clinical trials approved between January 2012 and April 2023. To measure disparities in cancer clinical trial access, we calculated the ratio of clinical trials open to non-capital areas relative to those open to capital areas. We then analyzed temporal trends in this ratio, which we termed the trial geographical equity index (TGEI). Disparities in access to cancer clinical trials, as indicated by the TGEI, did not significantly improve during the study period (regression coefficient, 0.002; p=0.59). However, for phase II/III trials sponsored by global pharmaceutical companies, the TGEI improved significantly (regression coefficient, 0.021; p<0.01). In contrast, the TGEI deteriorated for trials initiated by investigators or those testing domestically developed therapeutics (regression coefficient, -0.015; p=0.05). Furthermore, the increasing trend of TGEI for phase II/III trials sponsored by global companies began to reverse after 2019, coinciding with the outbreak of coronavirus disease 2019 (COVID-19). Over the past decade, access to cancer clinical trials has improved in Korea, particularly for phase II/III trials evaluating therapeutics from global companies. However, this increase in accessibility has not extended to trials initiated by investigators or those assessing domestically developed therapeutics. Additionally, the impact of COVID-19 on disparities in clinical trial access should be closely monitored.

1714P Geographical disparities in access to cancer clinical trials in Korea

1714P Geographical disparities in access to cancer clinical trials in Korea

Preclinical safety assessment of the suction-assisted intradermal injection of the SARS-CoV-2 DNA vaccine candidate pGO-1002 in white rabbit.

pGO-1002, a non-viral DNA vaccine that expresses both spike and ORF3a antigens of SARS-CoV-2, is undergoing phase 1 and phase 2a clinical trials in Korea and the US. A preclinical repeated-dose toxicity study in New Zealand white rabbits in compliance with Good Laboratory Practice (GLP) was conducted to assess the potential toxicity, local tolerance, and immunogenicity of the vaccine and GeneDerm suction device. The dose rate was 1.2mg/head pGO-1002, and this was administered intradermally to a group of animals (eight animals/sex/group) three times at 2-week intervals, followed by a 4-week recovery period. After each administration, suction was applied to the injection site using the GeneDerm device. Mortality, clinical signs, body weight, food consumption, skin irritation, ophthalmology, body temperature, urinalysis, and clinical pathology were also monitored. Gross observations and histopathological evaluation were performed. Overall, pGO-1002 administration-related changes were confined to minor damage or changes at the injection site, increased spleen weight and minimal increased cellularity in white pulp. All changes of injection site were considered local inflammatory changes or pharmacological actions due to the vaccine with the changes in spleen considered consistent with vaccine-induced immune activation. All findings showed reversibility during the 4-week recovery period. Animals vaccinated with pGO-1002, administered by intradermal injection and followed by application of suction with GeneDerm, developed humoral and cellular responses against the SARS-CoV-2 antigens consistent with prior studies in rats. Collectively, it was concluded that the pGO-1002 vaccine was safe and effective under these experimental conditions and these data supported future human study of the vaccine, now known as GLS-5310, for clinical trial use.

A Prospective Single-Center Study of Incidence of Atorvastatin-Induced Myalgia in Korean Patients: Application of the Statin Myalgia Clinical Index

Background: Statin-induced myalgia is a common cause of discontinuation and a barrier that interferes with long-term treatment. The incidence of myalgia reported by previous atorvastatin trials in Korea ranged from 0.8% to 3.4%. This study assessed the incidence of myalgia after atorvastatin was administered to Korean patients with dyslipidemia. In addition, the Statin Myalgia Clinical Index (SMCI) was used to assess the likelihood that a patient’s myalgia was caused by atorvastatin.Methods: Dyslipidemic patients were eligible to participate if they were statin-naïve or treated with statins other than atorvastatin. Muscle complaints were assessed at the baseline, the 10-weeks visit and the final follow-up visit (16 weeks or later). The SMCI score was calculated if a patient developed myalgia, which was rated as probable, possible or unlikely related to the statin.Results: A total of 89 patients were analyzed. The atorvastatin doses ranged from 10 to 80 mg. Six (7%) patients reported new and unexplained muscle pain. Information on the timing of myalgia relative to stopping was unavailable in two patients. After excluding these two patients, three (3.4%) out of 87 patients were classified by the SMCI as having possible or probable atorvastatin-associated myalgia.Conclusions: In this study, the incidence of myalgia was higher than the incidences reported by the previous trials in Korea. However, the incidence of statin-associated myalgia assessed using SMCI was comparable to those of the trials. The SMCI may help diagnosis of statin-associated myalgia in clinical practice and optimize treatment for patients with myalgia.

A Study on the Characteristics of Healthy Volunteers who Participate in Phase I Clinical Trials in Korea.

The phase I trial is the first step in administering a drug to humans, but it has no therapeutic purpose. Under the absence of therapeutic purpose, healthy volunteers demonstrated different motivations, unlike the actual patients participating in trials. There were many reported motivations, such as financial motivation, contributing to the health science, accessing ancillary health care benefits, scientific interest or interest in the goals of the study, meeting people, and general curiosity. The aim of this study was to identify the motivation and characteristics of healthy volunteers participating in phase I trials in the Republic of Korea. We gave surveys to 121 healthy volunteers to study their demographic characteristics and the reasons of participation. We identified whether the decision to participate in the research was influenced by demographic factors and whether the perception and attitudes toward the research were influenced by the characteristics of the healthy volunteers. After completion of the first survey, 12 healthy volunteers who had participated in a phase I clinical trial were selected to answer the second interview. According to our survey, most healthy volunteers were unmarried men and economically dependent. Most of them participated in the study because of financial reward. The most important factor to measure financial reward was the research period. Also, 43% of the volunteers were university students, 42% answered "university graduation" and 55% were residing in family-owned houses. Many healthy volunteers were found to be living in family homes and to have a student status or lack of economic independence. Results of the survey showed that 64% of respondents indicated having more than one clinical trial participation. In-depth interviews showed that healthy volunteers had diverse motivation to participate in research and that healthy volunteer perceive the clinical trial positively. The main motivation for healthy volunteers' participation in research was "financial reward." Healthy volunteers also considered research schedules, processes, and safety, and had a positive perception of clinical trials, but they thought that the public has a negative perception.

Abstract P20: Continuity of oncology clinical trials during the Coronavirus Disease-2019 pandemic in Korea

Abstract Coronavirus-19 outbreak caused concern of lowering performance of clinical trials, including delays in initiation, lower enrollment, or more frequent deviations related with visit schedule change. Korea, with the sixth largest number of industry-sponsored interventional drug trials in the world, has been controlling COVID-19 outbreak rather successfully and maintaining daily medical practice in most areas of the country. We investigated performance of oncology clinical trials before and after COVID-19 in Korea. We retrospectively identified and reviewed the files, notes, and source documents of ongoing breast cancer clinical trials during January to May 2019 and January to May 2020 in a single cancer center conducting oncology trials in Korea. Number of enrolled patients, drop-outs, protocol deviations including study visit delay or visit omission were measured. We investigated 77 ongoing studies from January to May 2020, and 67 from the same period in 2019. The numbers of newly initiated trials and new enrollment were not decreased during COVID-19 outbreak period. After outbreak of COVID-19, number of onsite monitoring was decreased, however total number of monitoring was maintained as remote monitoring was increased. Remote monitoring comprised 44% of all monitoring visit in 2020, and found 30%(15/50) of protocol deviations detected by all monitoring visit. Of the 26 study visit related protocol deviations during February to May 2020, 10(38%) cases were COVID-19 related. Thirteen percent(3/24) of study drop out cases were COVID-19 related, from subjects’ demand due to fear of visiting hospital. Although monitoring access was limited, vigorous countermeasures successfully maintained performance of oncology clinical trials during COVID-19 outbreak in Korea. Remote monitoring visits successfully complemented restricted onsite monitoring. COVID-19 related protocol deviations and drop-out cases were noted, mostly from subjects’ concerns about travel. Future regulations and guidelines should pursue developing alternatives of face-to-face contact visit as needed. Citation Format: Hee Kyung Ahn, Soohyeon Lee, Seon-A Jang, Ji-Yeon Kim, Jin Seok Ahn, Yeon Hee Park. Continuity of oncology clinical trials during the Coronavirus Disease-2019 pandemic in Korea [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr P20.

Trends of clinical trials from 2017 to 2019 in Korea: an integrated analysis based on the Ministry of Food and Drug Safety (MFDS) and the Clinical Research Information Service (CRIS) registries.

Public disclosure of approved clinical trials in a reliable registry can provide the transparency of the study. Although the registration of clinical trials has increased remarkably, the integrity of the data is not always satisfactory. In this study, we analyzed public clinical trial databases updated by the Ministry of Food and Drug Safety (MFDS) and Clinical Research Information Service (CRIS) registry to provide an overview of the trends of clinical trials approved between 2017 and 2019 in Korea. Information on clinical trials approved between January 1, 2017 and December 31, 2019 was collected from two databases. Trial information was categorized and summarized by study phase, therapeutic area, and location of the participating centers. A total of 655 to 715 clinical trials were newly approved annually by MFDS during the period from 2017 to 2019. Phase 1 clinical trials accounted for the largest proportion (31.0%), followed by phase 3 (29.5%), investigator-initiated trials (24.1%), phase 2 (14.6%), and phase 4 (0.5%). The number of clinical trials classified as an Antineoplastic and immunomodulating agent was the greatest (40.1%) regardless of the study phase. The similar result was obtained from CRIS registry where therapeutic area Neoplasms (15.9%) accounted for the largest number. The number of clinical trials performed in Seoul and Gyeonggi-do was approximately 70% of the total trials. In conclusion, our study provided a comprehensive overview of clinical trials in Korea from 2017 to 2019. The discrepancy between clinical trial registries could be resolved by introducing standardized database and guidelines.

Chocolate consumption and the prevalence of metabolic syndrome in the Korean adult population: an analysis based on the 2014-2016 Korea National Health and Nutrition Examination Survey.

BACKGROUND/OBJECTIVESRecent studies have reported chocolate consumption has beneficial effects on blood pressure, obesity, and dyslipidemia, which are components of metabolic syndrome (MetS). However, evidence regarding these relationships in Asia is limited. The aim of this study was to investigate relations between chocolate consumption and MetS in Korea.SUBJECTS/METHODSStudy subjects were 6,982 adults aged 19-64 years free of major chronic diseases that participated in the 2014–2016 Korea National Health and Nutrition Examination Survey. Information on chocolate consumption was obtained using food frequency questionnaires. For primary analysis, subjects were divided into two groups: non-consumer (n = 3,741, 53.6%); consumer (n = 3,241, 46.4%). In order to investigate dose-response effects on MetS, chocolate consumers were divided into quartiles based on amounts consumed: Q1 (n = 789, 24.3%); Q2 (n = 837, 25.8%); Q3 (n = 863, 26.6%); Q4 (n = 752, 23.2%) in second analysis.RESULTSChocolate consumers; 1) were more physically active(P < 0.0001); 2) less likely to smoke(P < 0.0001); 3) paid more attention to food nutrition labels (P < 0.0001), and 4) had healthier dietary patterns, that is, they consumed vegetables, fruits, and dairy products more frequently(P < 0.0001) than non-consumers. Furthermore, chocolate consumers had a 30% lower risk of MetS (odds ratio, 0.70; 95% confidence interval, 0.58–0.86; P = 0.0005). However, dose-response effects between chocolate intake and MetS was not found by secondary analysis after excluding non-consumers.CONCLUSIONSIn conclusion, chocolate consumers had healthier lifestyles and dietary patterns and a lower prevalence of MetS than non-consumers, as determined by our primary analysis. Although dose-response effects were not found to be significant among chocolate consumers during secondary analysis, the patterns were partially similar. This cross-sectional finding shows chocolate consumption does not increase the risk of MetS. The prospective studies and intervention trials in Korea are needed to confirm this cross-sectional finding.

Regeneration of cartilage defect using an artificial engineered cartilage with an injectable property

Background & Aim Regeneration of cartilage defect remains an unmet medical need despite extensive studies for a long time. We have aimed to fabricate high-quality articular cartilage with an injectable property using fetal cartilage-derived chondrogenic progenitor cells (hFCPCs). Methods, Results & Conclusion hFCPCs were obtained from a GA12-16 fetus after IRB approval and with the written consent of the donor. The artificial engineered cartilage was produced using hFCPCs and a proprietary 3D tissue fabrication technology without involving any types of scaffolds. The engineered cartilage is composed of mature articular chondrocytes and rich in sulfated glycosaminoglycans (sGAG) and type II collagen. Importantly, it has a pliable mechanical property enabling its injection in a surgical syringe for administration. We have proven its pre-clinical safety in a GLP tox and tumorigenicity studies and its efficacy for cartilage regeneration in several animal models of knee cartilage defect. Considering its allogeneic nature, we speculate that our tissue-engineered cartilage could be an off-the-shelf therapy with high therapeutic potential and surgical easiness for clinical use. We are currently working on GMP manufacturing and IND submission for clinical trials in Korea.

5G commercialization and trials in Korea

5G commercialization and trials in Korea

The Impact of COVID-19 on the Conduct of Clinical Trials for Medical Products in Korea.

BackgroundThe number of clinical trials conducted in Korea continues to increase and an increasing proportion focus on severe and rare incurable diseases. After the start of the severe acute respiratory syndrome, coronavirus disease 2019 (COVID-19), Korea Centers for Disease Control and Prevention (KCDC) developed guidelines to prevent the spread of infection. This study evaluated the impact of COVID-19 and the KCDC guideline on the conduct of clinical research in Korea. The purpose was to develop recommendations on how to minimize the risk of infection while enabling subjects to take part in the trials if no better alternative treatment options were available.MethodsThe impact on subject's scheduled visits and major milestones of clinical trials in Korea were measured by conducting a survey among clinical project manager (CPMs) working at global clinical research organization. The policy on monitor's access to hospital and site initiation meetings was investigated through correspondence with clinical trial center of 39 hospitals. The Top 25 pharmaceutical companies' official press and public clinical trial registry database were used to analyze companies' trial strategy during the pandemic and COVID-19 clinical research status, respectively.ResultsOf 85 CPMs, 12% reported that trial subjects' scheduled visits had been affected in their project. Monitors' access to hospital for source data verification was restricted at all sites in February 2020. Accordingly, 43% of 105 CPMs reported that the COVID-19 epidemic had an effect on study major milestones and data cleaning and database lock accounted for > 60% of milestones affected. In addition, 87% sites advised not to have site initiation meetings and 52% pharmaceutical companies suspended recruitment or new study start-up due to the pandemic. On the other hands, the number of COVID-19 related clinical trials increased rapidly in Korea and worldwide, with investigator-initiated trials accounting for 47% and 63% of all trials locally and globally, respectively. Most trials were phase 2 and were in the recruitment stage.ConclusionThe COVID-19 and the KCDC guideline influenced all parties involved in clinical trials in Korea. In order to ensure the safety and well-being of trial subjects during the pandemic, new approaches are required for clinical trials to respond to the impact actively. Method of non-contact is developed to replace and supplement the face-to-face contact and alternatives to reduce the travel is introduced to decrease the risk of infection for all trial participants in whole trial process. The relevant regulations should be developed and the guidelines for foreign countries need to be adopted in accordance with the situation in Korea. COVID-19 trial is rapidly increasing worldwide and continuous support of health authorities, regulation, and facilities is required for developing the treatments with protecting all trial participants.

Perspectives on Adopting the Guideline for Multi-regional Clinical Trials in Korea: A Multi-stakeholder Survey

Perspectives on Adopting the Guideline for Multi-regional Clinical Trials in Korea: A Multi-stakeholder Survey

AOJS-5 - Investigator initiated clinical trials in Korea; current issues and perspectives focusing in breast cancer trial

AOJS-5 - Investigator initiated clinical trials in Korea; current issues and perspectives focusing in breast cancer trial

Trends of clinical trials from 2014 to 2016 in South Korea.

Mandatory registration of clinical trials in public registry can ensure the transparency of clinical trials. Public clinical trial registry of can provide current chronological and geographical distribution of clinical trial throughout the country. We used public clinical trial registry provided by Ministry of Food and Drug Safety to analyze current status of clinical trial from 2014 to 2016 in South Korea. The number of clinical trials in antineoplastic and immunomodulating agents area was the greatest, followed by cardiovascular system and antiinfectives for systemic use as a whole. From 2014 to 2016, overall number of clinical trials decreased while the number of phase I clinical trials increased. Seoul accounted for more than half number of clinical trials in Korea. Supports for clinical trials in non-metropolitan area needs to be considered.

실질적인 임상시험 대상자 보호를 위하여: 한국 내 임상시험 대상자 보호 프로그램도입의 현황과 한계*,**

Korea has witnessed rapid growth in the clinical trial industry in past 10 years. Public concern regarding the rights and safety of human research participants has been a major issue in the field. As the need for a more effective system of protection for human subjects grows, one which surpasses the scope of the Institutional Review Board (IRB), the Korean Ministry of Food and Drug Safety (MFDS) has issued its “Operation Guidelines for Human Research Protection Program (HRPP)” in 2014. It is the first government-initiated adoption of a HRPP in the world. This study shows that there is great deal of variation in clinical trial institutes in terms of their size and systems of operation and that many small- to medium-sized clinical trial institutes are not willing to adopt HRPP. The current MFDS HRPP policy does not reflect the differences in the various clinical trial institutes, which leads to a low adoption rate in HRPP in Korea. Furthermore, the government-initiated HRPP policy may puts more burdens on smaller organizations. Despite the limitations of the current HRPP policy, it is argued in this article that strong leadership to promote HRPP by the Korean government can improve clinical trial participant protection and the quality of clinical trials in Korea. Future policy for establishing and promoting HRPP in Korea should encompass considerations of the variability in the characteristics of clinical trial institutes as well as measures for enhancing the understanding of HRPP in the research community.

Consecutive analysis of mutation spectrum in the dystrophin gene of 507 Korean boys with Duchenne/Becker muscular dystrophy in a single center.

Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked recessive muscle diseases caused by mutations in the large and complex dystrophin gene. We analyzed the dystrophin gene in 507 Korean DMD/BMD patients by multiple ligation-dependent probe amplification and direct sequencing. Overall, 117 different deletions, 48 duplications, and 90 pathogenic sequence variations, including 30 novel variations, were identified. Deletions and duplications accounted for 65.4% and 13.3% of Korean dystrophinopathy, respectively, suggesting that the incidence of large rearrangements in dystrophin is similar among different ethnic groups. We also detected sequence variations in >100 probands. The small variations were dispersed across the whole gene, and 12.3% were nonsense mutations. Precise genetic characterization in patients with DMD/BMD is timely and important for implementing nationwide registration systems and future molecular therapeutic trials in Korea and globally. Muscle Nerve 55: 727-734, 2017.

A Case of Panagglutination on Antibody Identification in a Multiple Myeloma Patient Receiving Daratumumab

Herein, we report a patient showing panagglutination in the unexpected antibody identification test after the administration of daratumumab. The patient was a 66-year-old woman who had undergone multiple cycles of chemotherapy and autologous peripheral blood stem cell transplantation for treating multiple myeloma; however, despite treatment, she had relapsed. Therefore, daratumumab, on clinical trials in Korea, started to be administered. After administration of daratumumab, the result of antibody screening test was positive, on the contrary to the result prior to the administration. Moreover, all positive reactions were shown in the antibody identification to the panel cells. After destroying CD38 antigens on the surface of RBCs using DTT, negative results were obtained. Daratumumab?a novel therapeutic human CD38 monoclonal antibody that can be used as targeted immunotherapy?is an FDA-approved drug for treating multiple myeloma. Because CD38 is expressed not only on myeloma cells, but also on red blood cells (RBCs), the use of daratumumab might lead to RBC agglutinations, and thereby resulting in false-positive results on the pre-transfusion tests. Therefore, caution is needed in case of a patient receiving daratumumab. Furthermore, additional test using DTT is required, especially when panagglutination was shown in the antibody identification test, as in this case.

중국어 통역사의 법정통역 규범 인식 연구 - 정확성 관련 규범을 중심으로

Criminal court trials in Korea guarantee the free assistance of an interpreter to defendants who are unable to understand or speak the language used in court according to Article 14 of the International Covenant on Civil and Political Rights. Interpreters assisting them must be capable of interpreting at a professional level in order to guarantee them a proper defense. However, it is also important to have court interpreting norms in the form of a manual to guide interpreters towards making right ethical choices during their task. Existing education booklets for court interpreting norms in Korea are different from court interpreting manuals of advanced countries in terms of how they are written and explained. In the study, Chinese interpreters were interviewed in an effort to figure out how they perceive court interpreting norms regarding interpretation accuracy. Results of the research showed that all interpreters were aware of the court interpreting norms in Korea, but had been applying it in different adapted forms in order to satisfy institution expectancy norms.

Transplanting Jury Trials in South Korean Legal Soils: Comparative Analysis with Jury Trials in the United States

Jury trials, known as common-law institution centering on the UK and the USA, for the first time in Korean adjudicatory history, have been transplanted into Korean legal soils under cultural and political climate with legal roots of the “Civil Participation in Criminal Trial Act (CPCTA) of 2007” since 2008. This research examines legal and operational issues of jury trials through comparative analysis between the United States and South Korea. Several legal characteristics of 2013 revision bill of CPCTA, proposed by the Committee of Civil Participation in the Judiciary (CCPJ), are to be pointed out: so-called “civil participation” approach, de facto binding power of jury verdict and sentencing, and a stricter standard for a jury verdict or decision (3/4 majority). Statistical results from planting jury trials in both American and Korean legal system proved to be very similar. Meanwhile, a 2013 revision bill has to overcome several practical and legal obstacles, such as low usage of jury trials, the high rate of judicial dismissal of defendants’ petitions, and violation of Article 27 of the Korean Constitution. Under the current legislative scheme, judges in Korean courts need to operate jury trials in such a careful and respectful way that the revision may neglect neither a defendant’s right to jury trial nor jury’s verdict. Legal scholars, experts, and legislators with interests in implementing jury trials in Korea should research on ways to expand the system to other judicial procedures such as juvenile, civil, family, and administrative cases.

Current Status and Challenges of Cancer Clinical Trials in Korea.

PurposeCancer clinical trials in Korea have rapidly progressed in terms of quantity and quality during the last decade. This study evaluates the current status of cancer clinical trials in Korea and their associated problems.Materials and MethodsWe analyzed the clinical trials approved by the Korea Food and Drug Administration (KFDA) between 2007 and 2013. A nationwide on-line survey containing 22 questions was also performed with several cooperative study groups and individual researchers in 56 academic hospitals.ResultsThe number of cancer clinical trials approved by the KFDA increased almost twofold from 2007 to 2013. The number of sponsor-initiated clinical trials (SITs) increased by 50% and investigator-initiated clinical trials (IITs) increased by almost 640%. Three hundred and forty-four clinical trials were approved by the KFDA between 2012 and 2013. At the time of the on-line survey (August 2013), 646 SITs and 519 IITs were ongoing in all hospitals. Six high volume hospitals were each conducting more than 50 clinical trials, including both SITs and IITs. Fifty-six investigators (31%) complained of the difficulties in raising funds to conduct clinical trials.ConclusionThe number of cancer clinical trials in Korea rapidly increased from 2007 to 2013, as has the number of multicenter clinical trials and IITs run by cooperative study groups. Limited funding for IIT is a serious problem, and more financial support is needed both from government agencies and public donations from non-profit organizations.