Analysis of Medication Errors Reported by Community Pharmacists in the Republic of Korea: A Cross-Sectional Study.

Background and objectives: We aimed to describe medication-related incidents or medication errors (MEs) reported by community pharmacists and analyze the prevalent medications involved. Materials and Methods: We extracted ME reports from databases comprising patient safety incidents reported to the Korean Pharmaceutical Association between January 2013 and June 2021. Medications were analyzed according to the second (therapeutic subgroup) and fifth (chemical substance) levels of the Anatomical Therapeutic Chemical classification. Results: A total of 9046 MEs were identified, most of which were near miss reports (88.3%). Among the errors that reached the patients (521 cases), harmful incidents accounted for 76.8%. Most MEs occurred during prescription (89.5%), while harmful MEs occurred mainly during dispensing (73.3%). In the prescription step, wrong drugs (44.8%), dosing errors (27.0%), and wrong durations (14.0%) were common. Anti-inflammatory and anti-rheumatic products (M01), drugs for acid-related disorders (A02), and antihistamines for systemic use (R06) were the most frequently reported medication classes involved. Harmful incidents were most common for dosing errors (31.0%) and wrong drugs (26.8%) and were common with warfarin, levothyroxine, and glimepiride. Conclusions: The MEs reported by community pharmacists were mainly prescribing errors, most of which were rectified before reaching patients. The prevalent medications involved in harmful errors include anti-diabetic, anti-thrombotic, and anti-inflammatory agents.

Me-too validation study for in vitro skin irritation test with a reconstructed human epidermis model, KeraSkin™ for OECD test guideline 439.

We conducted a me-too validation study to confirm the reproducibility, reliability, and predictive capacity of KeraSkin™ skin irritation test (SIT) as a me-too method of OECD TG 439. With 20 reference chemicals, within-laboratory reproducibility (WLR) of KeraSkin™ SIT in the decision of irritant or non-irritant was 100%, 100%, and 95% while between-laboratory reproducibility (BLR) was 100%, which met the criteria of performance standard (PS, WLR≥90%, BLR≥80%). WLR and BLR were further confirmed with intra-class correlation (ICC, coefficients >0.950). WLR and BLR in raw data (viability) were also shown with a scatter plot and Bland-Altman plot. Comparison with existing VRMs with Bland-Altman plot, ICC and kappa statistics confirmed the compatibility of KeraSkin™ SIT with OECD TG 439. The predictive capacity of KeraSkin™ SIT was estimated with 20 reference chemicals (the sensitivity of 98.9%, the specificity of 70%, and the accuracy of 84.4%) and additional 46 chemicals (for 66 chemicals [20 + 46 chemicals, the sensitivity, specificity and accuracy: 95.2%, 82.2% and 86.4%]). The receiver operating characteristic (ROC) analysis suggested a potential improvement of the predictive capacity, especially sensitivity, when changing cut-off (50% → 60-75%). Collectively, the me-too validation study demonstrated that KeraSkin™ SIT can be a new me-too method for OECD TG 439.

ß-Lactoglobulin Peptide Fragments Conjugated with Caffeic Acid Displaying Dual Activities for Tyrosinase Inhibition and Antioxidant Effect.

The regulation of tyrosinase activity and reactive oxygen species is of great importance for the prevention of dermatological disorders in the fields of medicine and cosmetics. Herein, we report a strategy based on solid-phase peptide chemistry for the synthesis of ß-lactoglobulin peptide fragment/caffeic acid (CA) conjugates (CA-Peps) with dual activities of tyrosinase inhibition and antioxidation. The purity of the prepared conjugates, CA-MHIR, CA-HIRL, and CA-HIR, significantly increased to 99%, as acetonide-protected CA was employed in solid-phase coupling reactions on Rink amide resins. The tyrosinase inhibitory activities of all CA-Pep derivatives were higher than the activity of kojic acid, and CA-MHIR exhibited the highest tyrosinase inhibition activity (IC50 = 47.9 µM). Moreover, CA-Pep derivatives displayed significantly enhanced antioxidant activities in the peroxidation of linoleic acid as compared to the pristine peptide fragments. All CA-Pep derivatives showed no cytotoxicity against B16-F1 melanoma cells.

Prescription Trends of Psychotropics in Children and Adolescents with Autism Based on Nationwide Health Insurance Data.

Children with autism are often medicated to manage emotional and behavioral symptoms; yet, data on such pharmacotherapy is insufficient. In this study, we investigated the Korean National Health Insurance Claims Database (NHICD) information related to autism incidence and psychotropic medication use. From the 2010-2012 NHICD, we selected a total of 31,919,732 subjects under 19 years old. To examine the diagnostic incidence, we selected patients who had at least one medical claim containing an 10th revision of International Statistical Classification of Diseases and Related Health Problems (ICD-10) code for pervasive developmental disorder, F84, not diagnosed in the previous 360 days. Psychotropics were categorized into seven classes. Then, we analyzed the data to determine the mean annual diagnostic incidence and psychotropic prescription trends. Diagnostic incidence was 17,606 for the 3 years, with a mean annual incidence per 10,000 population of 5.52. Among them, 5,348 patients were prescribed psychotropics. Atypical antipsychotics were the most commonly used, followed by antidepressants. An older age, male sex, and the availability of medical aid were associated with a higher rate of prescription than observed for a younger age, female sex, and the availability of health insurance. Psychotropic drugs were used for less than one-third of patients newly diagnosed with autism, and prescription differed by sex and age. Increased diagnostic incidence is associated with an increased prescription of psychotropic drugs. Therefore, medication-related safety data and policies for psychotropic drugs in autism should be prepared.

Detection and Molecular Characterization of Cryptosporidium spp. from Wild Rodents and Insectivores in South Korea.

In order to examine the prevalence of Cryptosporidium infection in wild rodents and insectivores of South Korea and to assess their potential role as a source of human cryptosporidiosis, a total of 199 wild rodents and insectivore specimens were collected from 10 regions of South Korea and screened for Cryptosporidium infection over a period of 2 years (2012-2013). A nested-PCR amplification of Cryptosporidium oocyst wall protein (COWP) gene fragment revealed an overall prevalence of 34.2% (68/199). The sequence analysis of 18S rRNA gene locus of Cryptosporidium was performed from the fecal and cecum samples that tested positive by COWP amplification PCR. As a result, we identified 4 species/genotypes; chipmunk genotype I, cervine genotype I, C. muris, and a new genotype which is closely related to the bear genotype. The new genotype isolated from 12 Apodemus agrarius and 2 Apodemus chejuensis was not previously identified as known species or genotype, and therefore, it is supposed to be a novel genotype. In addition, the host spectrum of Cryptosporidium was extended to A. agrarius and Crosidura lasiura, which had not been reported before. In this study, we found that the Korean wild rodents and insectivores were infected with various Cryptosporidium spp. with large intra-genotypic variationa, indicating that they may function as potential reservoirs transmitting zoonotic Cryptosporidium to livestock and humans.

High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice.

BACKGROUND: Prostate cancer is the most frequently diagnosed cancer in Western men, and more men have been diagnosed at younger ages in recent years. A high-fat Western-style diet is a known risk factor for prostate cancer and increases oxidative stress. METHODS: We evaluated the association between dietary animal fat and expression of antioxidant enzymes, particularly glutathione peroxidase 3 (GPx3), in the early stages of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Six-week-old male nontransgenic and TRAMP mice were placed on high animal fat (45% Kcal fat) or control (10% Kcal fat) diets and sacrificed after 5 or 10 weeks. RESULTS: The histopathological score increased with age and high-fat diet consumption. The histopathological scores in dorsal and lateral lobes increased in the 10-week high-fat diet group (6.2±0.2 and 6.2±0.4, respectively) versus the 10-week control diet group (5.3±0.3 and 5.2±0.2, respectively). GPx3 decreased both at the mRNA and protein levels in mouse prostate. GPx3 mRNA expression decreased (∼36.27% and ∼23.91%, respectively) in the anterior and dorsolateral prostate of TRAMP mice fed a high-fat diet compared to TRAMP mice fed a control diet. Cholesterol treatment increased PC-3 human prostate cancer cell proliferation, decreased GPx3 mRNA and protein levels, and increased H2 O2 levels in culture medium. Moreover, increasing GPx3 mRNA expression by troglitazone in PC-3 cells decreased cell proliferation and lowered H2 O2 levels. CONCLUSIONS: Dietary fat enhances prostate cancer progression, possibly by suppressing GPx3 expression and increasing proliferation of prostate intraepithelial neoplasia (PIN) epithelial cells.

The first case of Capillaria hepatica infection in a nutria (Myocastor coypus) in Korea.

This study reports the first case of Capillaria hepatica infection in a nutria in Korea. Ten nutrias, captured near the Nakdong River, were submitted to our laboratory for necropsy. White-yellowish nodules were found in the liver of 1 of the nutrias at necropsy. Histologically, the lesions were granulomatous, and infiltrations of lipid-laden macrophages, eosinophils, and several multinucleated giant cells were observed. The lesions consisted of numerous eggs and necrotic hepatocytes. The eggs were lemon-shaped and had polar plugs at the ends of both long sides. The eggs were morphologically identified as those of C. hepatica. Worldwide, C. hepatica infection in nutrias is very rare. Nutrias are a kind of livestock, as well as wildlife; therefore, an epidemiological study for parasitic infections needs to be conducted.

Characteristics of fall-from-height patients: a retrospective comparison of jumpers and fallers using a multi-institutional registry.

OBJECTIVE: Fall from height (FFH) is a major public health problem that can result in severe injury, disability, and death. This study investigated how the characteristics of jumpers and fallers differ. METHODS: This was a retrospective study of FFH patients enrolled in an Emergency Department-based Injury In-depth Surveillance (EDIIS) registry between 2011 and 2018. Depending on whether the injury was intentional, FFH patients who had fallen from a height of at least 1 m were divided into two groups: jumpers and fallers. Patient characteristics, organ damage, and death were compared between the two groups, and factors that significantly affected death were identified using multivariable logistic analysis. RESULTS: Among 39,419 patients, 1,982 (5.0%) were jumpers. Of the jumpers, 977 (49.3%) were male, while 30,643 (81.9%) of fallers were male. The jumper group had the highest number of individuals in their 20s, with the number decreasing as age increased. In contrast, the number of individuals in the faller group rose until reaching their 50s, after which it declined. More thoracoabdominal, spinal, and brain injuries were found in jumpers. The in-hospital mortality of jumpers and fallers was 832 (42.0%) and 1,268 (3.4%), respectively. Intentionality was a predictor of in-hospital mortality, along with sex, age, and fall height, with an odds ratio of 7.895 (95% confidence interval, 6.746-9.240). CONCLUSION: Jumpers and fallers have different epidemiological characteristics, and jumpers experienced a higher degree of injury and mortality than fallers. Differentiated prevention and treatment strategies are needed for jumpers and fallers to reduce mortality in FFH patients.

Nanog reverses the effects of organismal aging on mesenchymal stem cell proliferation and myogenic differentiation potential.

Although the therapeutic potential of mesenchymal stem cells (MSCs) is widely accepted, loss of cell function due to donor aging or culture senescence are major limiting factors hampering their clinical application. Our laboratory recently showed that MSCs originating from older donors suffer from limited proliferative capacity and significantly reduced myogenic differentiation potential. This is a major concern, as the patients most likely to suffer from cardiovascular disease are elderly. Here we tested the hypothesis that a single pluripotency-associated transcription factor, namely Nanog, may reverse the proliferation and differentiation potential of bone marrow-derived MSC (BM-MSC) from adult donors. Microarray analysis showed that adult (a)BM-MSC expressing Nanog clustered close to Nanog-expressing neonatal cells. Nanog markedly upregulated genes involved in cell cycle, DNA replication, and DNA damage repair and enhanced the proliferation rate and clonogenic capacity of aBM-MSC. Notably, Nanog reversed the myogenic differentiation potential and restored the contractile function of aBM-MSC to a similar level as that of neonatal (n)BM-MSC. The effect of Nanog on contractility was mediated--at least in part--through activation of the TGF-ß pathway by diffusible factors secreted in the conditioned medium of Nanog-expressing BM-MSC. Overall, our results suggest that Nanog may be used to overcome the effects of organismal aging on aBM-MSC, thereby increasing the potential of MSC from aged donors for cellular therapy and tissue regeneration.

Implementation of Systematic Bioanalysis of Antibody-Drug Conjugates for Preclinical Pharmacokinetic Study of Ado-Trastuzumab Emtansine (T-DM1) in Rats.

Antibody-drug conjugates (ADCs) are composed of monoclonal antibodies covalently bound to cytotoxic drugs by a linker. They are designed to selectively bind target antigens and present a promising cancer treatment without the debilitating side effects of conventional chemotherapies. Ado-trastuzumab emtansine (T-DM1) is an ADC that received US FDA approval for the treatment of HER2-positive breast cancer. The purpose of this study was to optimize methods for the quantification of T-DM1 in rats. We optimized four analytical methods: (1) an enzyme-linked immunosorbent assay (ELISA) to quantify the total trastuzumab levels in all drug-to-antibody ratios (DARs), including DAR 0; (2) an ELISA to quantify the conjugated trastuzumab levels in all DARs except DAR 0; (3) an LC-MS/MS analysis to quantify the levels of released DM1; and (4) a bridging ELISA to quantify the level of anti-drug antibodies (ADAs) of T-DM1. We analyzed serum and plasma samples from rats injected intravenously with T-DM1 (20 mg/kg, single dose) using these optimized methods. Based on these applied analytical methods, we evaluated the quantification, pharmacokinetics, and immunogenicity of T-DM1. This study establishes the systematic bioanalysis of ADCs with validated assays, including drug stability in matrix and ADA assay, for future investigation on the efficacy and safety of ADC development.

Activation of Nod1 and Nod2 induces innate immune responses of prostate epithelial cells.

BACKGROUND: Nod1 and Nod2 are cytosolic receptors which are responsible for sensing bacterial peptidoglycan derivatives. In this study, we determined whether Nod1 and Nod2 are involved in the innate immune responses of prostate epithelial cells. METHODS: The expression of Nod1 and Nod2 was examined by RT-PCR and immunohistochemistry. ELISA was performed to determine the production of cytokines/chemokines. Activation of NF-κB and MAPK was examined using western blot analysis. RESULTS: The Nod1 gene was distinctly expressed in all tested cells including DU145, PC3, and TRAMP-C2 cells, whereas Nod2 expression was weak. Both Nod1 and Nod2 proteins were expressed in normal mouse prostate epithelia with difference of expression levels. Tri-DAP (Nod1 agonist), but not MDP (Nod2), increased the production of IL-8 (or KC) and IL-6 in prostate epithelial cells. Tri-DAP and MDP could upregulate the gene expression of COX-2 and activate NF-κB and MAPK. In addition, Tri-DAP and MDP synergized with TLR agonists to induce the production of IL-8/KC or IL-6 in PC3 and TRAMP-C2 cells. We finally showed that Nod1 and Nod2 were also expressed in a wide range of prostate lesions including prostate intraepithelial neoplasm (PIN), phyllodes-like tumor, and adenocarcinoma in TRAMP (transgenic adenocarcinoma of the mouse prostate) mice, even though the expression level of Nod1 and Nod2 was different. CONCLUSION: These results indicate that Nod1 and Nod2 may play important roles in the innate immune response of prostate epithelial cells and the development and progression of prostate cancer.

Terahertz dynamic imaging of skin drug absorption.

Terahertz (THz) imaging is a nondestructive, label-free, rapid imaging technique which gives the possibility of a real-time tracing of drugs within the skin. We evaluated the feasibility of THz dynamic imaging for visualizing serial changes in the distribution and penetration of a topical agent, dimethyl sulfoxide (DMSO) containing ketoprofen, using excised mouse skins. THz imaging was performed for 6 h after drug application to the skin and was compared with the results obtained using the Franz cell diffusion test, a standard in vitro skin absorption test. THz dynamic reflection imaging showed that the reflection signals decreased rapidly during the early time period, and remained constant through the late time period. The area of drug permeation within the skin layer on THz imaging increased with time. The dynamic pattern of THz reflection signal decrease was similar to that of DMSO absorption analyzed by the Franz cell diffusion test, which indicates that THz imaging mainly reflects the DMSO component. This study demonstrates that THz imaging technique can be used for imaging the spatial distribution and penetration of drug-applied sites.

Effect of fluorescent whitening agent on the transcription of cell damage-related genes in zebrafish embryos.

7-Diethylamino-4-methylcoumarin (DEMC) is a fluorescent whitening agent (FWAs). There have been some studies on DEMC's protective effects against biological activity but there are few papers about the in vivo toxicity of DEMC. In this study, we used wild-type zebrafish embryos 3 days post fertilization (dpf). Test solutions with DEMC concentrations were negative control (without vehicle), 0 (with vehicle, 0.01% v/v ethanol), 0.25, 0.5, 0.75, 1.0, 1.25, 1.5 and 2 ppm. Embryos and larvae were counted for survival rate and hatching rate. Heart rates were also counted at 2.5 and 3.0 dpf. At 3.0 dpf, quantitative RT-PCR was performed with some samples (0, 0.25, 0.75 and 1.25 ppm) to determine the toxic effect to DEMC by detecting the expression levels of toxic-responsive genes. We used 11 genes, which included oxidative stress-related genes [sod(Mn), sod(Cu,Zn) and hsp70], mitochondrial metabolism-related genes (coxI, pyc, cyt and cyclinG1) and apoptosis-related genes (c-jun, bcl2, bax and p53). High-concentration DEMC-treated groups showed significant different survival rate, hatching rate and heart rate compared with low-concentration DEMC-treated groups. The LC50 of this chemical, 0.959 ppm, was calculated. We also confirmed that some genes in the DEMC exposure groups showed significantly up-regulations in expression levels compared with control groups. We concluded that the fluorescence agent, DEMC, has possible developmental toxicities and alteration effect of gene expression, which are related to oxidative stress, mitochondrial metabolism and apoptosis in zebrafish embryos.

Analysis on the Effectiveness and Characteristics of Treatment Modalities for Bowen's Disease: An Observational Study.

Treatment options for Bowen's disease (BD) include surgical excision, cryotherapy, curettage with cautery, topical 5-fluorouracil or imiquimod, and photodynamic therapy. However, it is not clear which treatment is the most effective due to lack of studies. We reviewed the electronic medical records of 158 patients who were diagnosed with BD and treated at Seoul St. Mary's Hospital from January 2011 to December 2020. Treatment modalities were surgical excision, cryotherapy, photodynamic therapy, and imiquimod. A total of 121 patients was enrolled in this study. The average treatment period was longest for cryotherapy, followed by imiquimod, PDT, and excision (119.53, 87.75, 68.50, and 1 day, respectively). The therapeutic efficacy was highest in the surgical excision group (100%) and lowest in the PDT group (62.5%). The recurrence rate was highest in the imiquimod group (33.33%). Surprisingly, only in patients treated with cryotherapy, satellite lesions developed in 9.09% of them during follow-up. Surgical excision exhibited the highest clearance rate and the lowest recurrence rate, and its treatment period was the shortest, confirming that it remains the gold standard. In contrast, since cryotherapy demonstrated a relatively high recurrence rate including development of satellite lesions, careful monitoring is required when performing cryotherapy for treatment of BD.

Treatment of Actinic Keratosis: The Best Choice through an Observational Study.

Actinic keratosis (AK) is a precancerous lesion that can progress to invasive squamous cell carcinoma if untreated. However, no gold standard treatment has been established. We aimed to investigate the management of AK by comparing the effectiveness and treatment duration of treatment modalities, including cryotherapy, imiquimod (IMQ), and photodynamic therapy (PDT). We reviewed the medical records of 316 patients diagnosed with AK at Seoul St. Mary's Hospital from February 2015 to May 2020, and a total of 195 patients were included. The clearance rate was the highest in PDT, followed by cryotherapy and IMQ (82.4%, 71.2%, and 68.0%, respectively). The recurrence rate was the lowest in cryotherapy, followed by PDT and IMQ (3.5%, 6.7%, and 10.5%, respectively, p < 0.05). The average treatment duration was shortest with PDT, followed by IMQ and cryotherapy (5.5 weeks, 6.8 weeks, and 9.1 weeks, respectively, p < 0.05). The number of hospital visits was lowest for PDT, followed by cryotherapy and IMQ (1.8, 2.8, and 3.6, respectively, p < 0.05). PDT showed the highest clearance rate, a moderate recurrence rate, the shortest treatment duration, and the least number of visits, suggesting that PDT could be the first choice for treatment of AK. Considering the advantages as a topical agent, IMQ could also be a treatment option.

Evaluation of Atopic Dermatitis and Cutaneous Infectious Disorders Using Sequential Pattern Mining: A Nationwide Population-Based Cohort Study.

According to previous studies, the increased risk of cutaneous infectious disorders in patients with atopic dermatitis (AD) is related to impaired epidermal function, abnormal systemic immune function, and lower antimicrobial peptides. In this study, we analyzed the association between AD and cutaneous infectious disorders in the real world using sequential pattern mining (SPM). We analyzed National Health Insurance data from 2010-2013 using SPM to identify comorbid cutaneous infectious diseases and the onset durations of comorbidities. Patients with AD were at greater risk for molluscum contagiosum (adjusted odds ratio (aOR), 5.273), impetigo (aOR, 2.852), chickenpox (aOR, 2.251), otitis media (aOR, 1.748), eczema herpeticum (aOR, 1.292), and viral warts (aOR, 1.105). In SPM analysis, comorbidity of 1.06% shown in molluscum contagiosum was the highest value, and the duration of 77.42 days documented for molluscum contagiosum was the shortest onset duration among all the association rules. This study suggests that AD is associated with an increased risk of cutaneous infectious disorders. In particular, care should be taken regarding its high relevance with impetigo, molluscum contagiosum, and otitis media, which may help in preventing AD from worsening through appropriately preventing and managing the condition.

Prevalence of murine norovirus infection in Korean laboratory animal facilities.

Currently, murine noroviruses (MNV) are the most prevalent viral pathogens identified in laboratory animal facilities. While several reports exist concerning the prevalence of MNV in North American research facilities, very few reports are available for other parts of the world, including Korea. This study evaluated the prevalence of MNV infection in 745 murine sera collected from 15 animal facilities in Korea by enzyme linked immunosorbent assay (ELISA). Positive cases were subcategorized by murine strain/genetics, housing environments and animal sources. In summary, 6.6% of inbred/outbred mice purchased from commercial vendors were seropositive, 9.6% of in-house colonies were seropositive and 27.0% of genetically modified mice (GMM) were seropositive. Partial gene amplification of fecal isolates from infected animals showed that they were homologous (100%) with MNV-4.

ChemSkin Reference Chemical Database for the Development of an In Vitro Skin Irritation Test.

Since the animal test ban on cosmetics in the EU in 2013, alternative in vitro safety tests have been actively researched to replace in vivo animal tests. For the development and evaluation of a new test method, reference chemicals with quality in vivo data are essential to assess the predictive capacity and applicability domain. Here, we compiled a reference chemical database (ChemSkin DB) for the development and evaluation of new in vitro skin irritation tests. The first candidates were selected from 317 chemicals (source data n = 1567) searched from the literature from the last 20 years, including previous validation study reports, ECETOC, and published papers. Chemicals showing inconsistent classification or those that were commercially unavailable, difficult or dangerous to handle, prohibitively expensive, or without quality in vivo or in vitro data were removed, leaving a total of 100 chemicals. Supporting references, in vivo Draize scores, UN GHS/EU CLP classifications and commercial sources were compiled. Test results produced by the approved methods of OECD Test No. 439 were included and compared using the classification table, scatter plot, and Pearson correlation analysis to identify the false predictions and differences between in vitro skin irritation tests. These results may provide an insight into the future development of new in vitro skin irritation tests.

Value Frameworks: Adaptation of Korean Versions of Value Frameworks for Oncology.

This study sought to adapt the existing value framework (VF) to produce a reliable and valid Korean oncology VF. Two VFs developed by The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) were selected for examination in the present study. Forward and backward translations were conducted for six high-priced drugs indicated for non-small-cell lung cancer and multiple myeloma. Inter-rater reliability was measured based on the intraclass correlation coefficient (ICC) and variation was described using the coefficient of variation. The relative weights of factors critically considered by Korean oncologists were derived following the analytic hierarchy process (AHP), and focus group interviews (FGIs) were used to obtain qualitative data regarding the applications of these two VFs in the Korean setting. The ICCs of the Korean VFs were 0.895 (0.654-0.983) for ASCO and 0.726 (0-0.982) for ESMO translations, suggesting excellent reliability for ASCO and good reliability for ESMO. AHP demonstrated that clinical benefit has the highest priority, which is consistent with the ASCO VF. The FGIs suggested that the result for AHP is acceptable and that both ESMO and ASCO VFs should be used complementarily. Although further evaluation with a larger sample size is needed, the Korean versions of ESMO/ASCO VFs are valid and reliable tools and are acceptable to Korean stakeholders, yet they should be applied with caution.