Sorafenib for 9,923 Patients with Hepatocellular Carcinoma: An Analysis from National Health Insurance Claim Data in South Korea.

Background/Aims: Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea. Methods: This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study. Results: Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib; 2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400-600 mg (9.6 months). Conclusions: Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.

Antibiotic Use during Pregnancy in South Korea Using 2011-2020 National Health Insurance Claims Data.

BACKGROUND: Since antimicrobial overuse and misuse can have substantial impacts on both public health and fetal well-being, it is essential to gain comprehensive insights into antimicrobial consumption patterns in pregnant women. This study aims to demonstrate antimicrobial utilization in pregnant women. METHODS: We conducted a population-based cohort study using National Health Insurance claims data from January 2009 to December 2020 in South Korea. The target population was pregnancies in women aged 15-45 years who gave birth between 2011 and 2019. The outcome measure was the percentage of antibiotic prescriptions by trimester, subgroup, diagnostic category, and therapeutic category. Antibiotics were defined as J01 in the WHO ATC/DDD classification. To analyze the factors that influenced antibiotic prescriptions, we conducted multivariate logistic regression analysis. RESULTS: Antibiotics were prescribed at least once in 1,808,588 (50%) of the 3,614,478 pregnancies. The proportion of deliveries with exposure to antibiotic therapy during pregnancy increased from 48% in 2011 to 54.8% in 2020. The prescription rate of antibiotics was highest in mothers younger than 25 years old, and it was lowest in participants aged 30-34 years. Also, antibiotic use was highest in the first trimester (30%) and lowest in the second trimester (18.2%). The most commonly used class was J01D (other beta-lactam antibacterials), which includes cephalosporins, and it accounted for 57% of the prescribed antibiotics. An increased probability of being prescribed antibiotics was associated with those younger than 25 years old, insurance (Medical Aid), hospitalization experience, an increase in physician visits, and comorbidities. For comorbidities, the OR was higher for respiratory tract infection (RTI), sexually transmitted infection, and urinary tract infection compared to those without disease, whereas it was decreased for diabetes and epilepsy. CONCLUSION: The prescribing rate of antibiotics to pregnant women in South Korea has remained stably high. Also, an increase in the use of broad-spectrum beta-lactam penicillin was noted. It is necessary to monitor antibiotics in pregnant women generally in accordance with recommendations.

Trends in National Pharmaceutical Expenditure in Korea during 2011 - 2020.

BACKGROUND: This study aimed to identify the trends in pharmaceutical expenditure (PE), share of PE in health expenditure (HE), and trends in expenditure by pharmacological groups (ATC level 1 classification) in Korea for a 10-year period (2011 - 2020) and compare the data with those of other Organisation for Economic Co-operation and Development (OECD) countries. Using the findings, we determined the current status of pharmaceutical expenditure (PE) management in Korea and derived the implications for establishing future macroscopic policies on PE. MATERIALS AND METHODS: We analyzed the OECD Health Statistics and the Korean national health insurance claims database from January 2011 through December 2020. The outcome measures were HE, PE, and pharmaceutical sales data for ATC level 1 medicines from OECD Health Statistics data during 2011 - 2020. As OECD collects limited ATC level 1 data, we used the HIRA health insurance claims data for PEs of ATC level-1 classification, including D, L, P, and S. RESULTS: PE in Korea increased by 38.5% from 19.9 billion USD in 2011 to 27.6 billion USD in 2020, whereas the share of PE in HE decreased by 6.3%p from 26.4% in 2011 to 20.1% in 2020. In 2020, Korea ranked third in PE per capita (760.9 USD PPP) and had the highest share of PE (20.1%) among the 19 OECD countries studied. By ATC level 1 class, the highest PE was A (alimentary tract and metabolism) at 4.3 billion USD, and L (antineoplastic and immunomodulating agents) had the highest increase at 13.4%; in contrast, J (anti-infectives for systemic use) had the lowest increase in annual average PE at -0.2% in 2020 relative to 2011. Among the 17 OECD countries, Korea had the highest and the third-highest expenditures for ATC codes A and J, respectively. CONCLUSION: PE in Korea has continued to increase between 2011 and 2020, indicating the need for macroscopic management of PE. Our results on PE by ATC code may help health authorities in establishing future policies on PE.

Analysis of Changes in Antibiotic Use Patterns in Korean Hospitals during the COVID-19 Pandemic.

With the onset of the coronavirus disease 2019 (COVID-19) pandemic, changes in patient care and antibiotic use have occurred in hospitals. The data of the National Health Insurance System's claims of inpatients from all hospitals in Korea between January 2019 and December 2020 were obtained from the Health Insurance Review & Assessment Service and analyzed. The trend in the use of all antibacterial agents in both hospitals declined for the total number of COVID-19 patients at the bottom 10% and those in the top 10%. Specifically, a decreasing trend in the use of broad-spectrum antibacterial agents predominantly prescribed for community-acquired cases and narrow-spectrum beta-lactam agents were observed in both hospitals. In the aftermath of the COVID-19 pandemic, the total use of antibacterial agents has gradually decreased among patients with pneumonia and those with severe COVID-19. In contrast, its use has increased gradually among those with mild to moderate COVID-19. A decreasing trend in overall antibiotic use was observed during the COVID-19 pandemic, and an increasing trend in antibiotic use was observed in patients with mild to moderate COVID-19 in Korean hospitals.

Factors related to polypharmacy and hyper-polypharmacy for the elderly: A nationwide cohort study using National Health Insurance data in South Korea.

Polypharmacy may cause adverse health outcomes in the elderly. This study examined the prevalence of continuous polypharmacy and hyper-polypharmacy, factors associated with polypharmacy, and the most frequently prescribed medications among older adults in South Korea. This was a retrospective observational study using National Health Insurance claims data. In total, 7,358,953 Korean elderly patients aged 65 years and older were included. Continuous polypharmacy and hyper-polypharmacy were defined as the use of ≥5 and ≥10 medications, respectively, for both ≥90 days and ≥180 days within 1 year. A multivariate logistic regression analysis was conducted with adjustment for general characteristics (sex, age, insurance type), comorbidities (12 diseases, number of comorbidities, and Elixhauser Comorbidity Index [ECI] classification), and healthcare service utilization. Among 7.36 million elderly patients, 47.8% and 36.9% had polypharmacy for ≥90 and ≥180 days, and 11.9% and 7.1% of patients exhibited hyper-polypharmacy for ≥90 and ≥180 days, respectively. Male sex, older age, insurance, comorbidities (cardio-cerebrovascular disease, diabetes mellitus, depressive disorder, dementia, an ECI score of ≥3), and healthcare service utilization were associated with an increased probability of polypharmacy. The therapeutic class with the most prescriptions was drugs for acid-related disorders (ATC A02). The number of outpatient visit days more strongly influenced polypharmacy than hospitalizations and ED visits. This study provides health policymakers with important evidence about the critical need to reduce polypharmacy among older adults.

Institutionalizing Health Technology Assessment and Priority Setting in South Korea's Universal Health Coverage Journey.

This study charts the chronological developments of the three institutions that were established in South Korea for priority setting in health. In 2007, the Evidence-based Medicine Team and the Center for New Health Technology Assessment (CnHTA) were established and nested in the Health Insurance Review and Assessment Service (HIRA). In December 2008, the National Evidence-based Healthcare Collaborating Agency (NECA) was launched, to which the CnHTA was transferred in 2010. Since then, non-drug technologies have been reviewed by NECA and drugs have been reviewed by HIRA. Political debates about how to embrace expensive but important health technologies that were not on the benefits list led to the creation of the Participatory Priority Setting Committee (PPSC) in 2012. The PPSC, led by the general public, has played a key role in advancing the path toward universal health coverage by revitalizing the list of essential, yet previously overlooked, medical technologies. PPSC offers these technologies a second chance at coverage. HIRA and NECA served to strengthen evidence-based and efficiency-based decision-making in the health system via CnHTA, and PPSC served to strengthen social value-based decision making via priority setting in Korea. The reassessment by PPSC may be relevant in countries where the economy is growing and citizens want to rapidly expand the benefits list.

Data collection framework for electronic medical record-based real-world data to evaluate the effectiveness and safety of cancer drugs: a nationwide real-world study of the Korean Cancer Study Group.

Background: Electronic medical records (EMRs) have the highest value among real-world data (RWD). The aim of the present study was to propose a data collection framework of EMR-based RWD to evaluate the effectiveness and safety of cancer drugs by conducting a nationwide real-world study based on the Korean Cancer Study Group. Methods: We considered all patients who received ramucirumab plus paclitaxel (RAM/PTX) for gastric cancer and trastuzumab emtansine (T-DM1) for breast cancer at relevant institutions in South Korea. Standard operating procedures for systematic data collection were prospectively developed. Investigator reliability was evaluated using the concordance rate between the recommended input value for representative fictional cases and the input value of each investigator. Reliability of collected data was evaluated twice during the study period at three institutions randomly selected using the concordance rate between the previously collected data and data collected by an independent investigator. The reliability results of the investigators and collected data were used for revision of the electronic data capture system and site training. Results: Between the starting date of medical insurance coverage and December 2018, a total of 1063 patients at 56 institutions in the RAM/PTX cohort and 824 patients at 60 institutions in the T-DM1 cohort were included. Mean investigator reliability in the RAM/PTX and T-DM1 cohorts was 73.5% and 71.9%, respectively. Mean reliability of collected data in the RAM/PTX and T-DM1 cohort was 90.0% for both cohorts in the first analysis and 89.0% and 84.0% in the second analysis, respectively. Mean missing values of the RAM/PTX and T-DM1 cohorts at the time of simulation of fictional cases and final data analysis decreased from 20.7% to 0.46% and from 18.5% to 0.76%, respectively. Conclusion: This real-world study provides a framework that ensures relevance and reliability of EMR-based RWD for evaluating the effectiveness and safety of cancer drugs.

Cost-benefit analysis of the integrated pharmaceutical supply chain information service after the establishment of the Korean Pharmaceutical Information Service.

Background: The Korean Pharmaceutical Information Service (KPIS) was established in October 2007 to increase the transparency of the pharmaceutical supply chain by integrating relevant information. This study aimed to describe the KPIS program and perform a cost-benefit analysis of the KPIS. Methods: We conducted a cost-benefit analysis based on cost savings in terms of National Health Insurance (NHI). The outcome measures were the net financial benefit and benefit-cost ratio over the 12 years since the establishment of the KPIS. The cost estimate included the costs of labor and business operations, the development of an information entry system, and office maintenance. Financial benefits were defined as savings resulting from the implementation of the program based on KPIS data. Social benefits were defined as the prevention of recalled medicines from entering the supply chain and the decrease in inventory and disposal. Results: The KPIS clearly resulted in a net financial benefit, saving 37.2 million USD, which was 2.6 times higher than the cost of implementation. While the benefit-cost ratio was less than one during the first period, it exceeded 3.4 during the second period. After calculating and integrating social benefits, the net benefit increased to 571.6 million USD, and the benefit-cost ratio was 24.8. A sensitivity analysis of the annual benefit showed that the net benefit varied from a low of -1.5 million USD to a high of 24.7 million USD according to the program implementation year. Conclusion: The establishment of the KPIS and a system for collecting information on the pharmaceutical supply chain showed meaningful financial and social benefits when compared to the input cost. Since no other countries have an integrated pharmaceutical information system that incorporates all information from production to administration, the example of the KPIS can provide a precedent for other countries.

Impact and challenges of enactment for advanced regenerative medicine in South Korea.

The Korean government has enacted the Act on Advanced Regenerative Medicine and Advanced Biological products (ARMAB) in August 2019, and it has been implemented in 2020. We reviewed the changes made by ARMAB compared to the existing Pharmaceutical Affairs Act and discussed future challenges to accelerate regenerative medicine while ensuring safety and efficacy. This act and regulations focused on the key elements of act as follows: the definition of advanced regenerative medicine (RM), the licensing of related facilities, safety management such as long-term follow-up, clinical research review committee, and establishment of a roadmap. Our study shows that Korea has achieved the second highest number of first approvals for regenerative medicine indications worldwide through expedited approvals encouraging innovation, while maintaining patient safety by mandating long-term follow-up. Additionally, the establishment of an interactive system for retrieval of patients' data and reporting of safety information by manufacturers electronically demonstrates Korea's commitment to innovation for Advanced RM and patient safety.

Prevalence and predictors of medication-related emergency department visit in older adults: A multicenter study linking national claim database and hospital medical records.

Objectives: Older adults are more likely to experience drug-related problems (DRP), which could lead to medication-related emergency department visits (MRED). To properly evaluate MRED, the entire history of drug use should be evaluated in a structured manner. However, limited studies have identified MRED with complete prescription records. We aimed to evaluate the prevalence and risk factors of MRED among community-dwelling older patients by linking national claims data and electronic medical records using a standardized medication related admission identification method. Methods: We included older patients who visited the emergency departments of four participating hospitals in 2019. Among the 54,034 emergency department (ED) visitors, we randomly selected 6,000 patients and structurally reviewed their medical records using a standardized MRED identification method after linking national claims data and electronic medical records. We defined and categorized MRED as ED visits associated with adverse drug events and those caused by the underuse of medication, including treatment omission and noncompliance and assessed as having probable or higher causality. We assessed preventability using Schumock and Thornton criteria. Results: MRED was observed in 14.3% of ED visits, of which 76% were preventable. In addition, 32.5% of MRED cases were related to underuse or noncompliance, and the rest were related to adverse drug events. Use of antipsychotics, benzodiazepines, anticoagulants, traditional nonsteroidal anti-inflammatory drugs without the use of proton pump inhibitors, P2Y12 inhibitors, insulin, diuretics, and multiple strong anticholinergic drugs were identified as predictors of MRED. Conclusion: One in seven cases of ED visits by older adults were medication related and over three-quarters of them were preventable. These findings suggest that DRPs need to be systemically screened and intervened in older adults who visit ED.

Trends in orphan drug use and spending among children and adolescents during 2010-2020 in Korea.

Background: Since 2014 in Korea, the Ministry of Food and Drug Safety has designated orphan drugs (ODs) for the treatment of rare diseases. This study investigated the market share and 20 most frequently prescribed therapeutic subgroups of ODs among children and adolescents in Korea. Methods: This study referenced the Korean national health insurance database from January 2010 through December 2020. The outcome measures were the number of prescriptions and expenditures on ODs. Results: Among children aged 0-12 years, the number of patients using ODs increased from 11,264 in 2010 to 14,017 in 2020. Expenditures on ODs and their proportion of total pharmaceutical expenditures also tripled from 13.3 million USD (1.2%) in 2010 to 46.4 million USD (6.2%) in 2020. Among the overall population and adolescents aged 13-17 years, the percentage of total pharmaceutical expenditures for ODs increased from 0.4% in 2010 to 3.2% in 2020 and from 2.1% in 2010 to 11.2% in 2020, respectively. The highest numbers and drug costs of child patients were for H01 (pituitary and hypothalamic hormones and analogues, 44,839) and A16 (other alimentary tract and metabolism products, 160 million USD). The individual ODs with the highest drug costs were A16AB09 (idursulfase, 82.4 million USD) and M09AX07 (nusinersen, 36.2 million USD). Conclusion: Although the market size of ODs remained small in Korea, both the number of approved ODs and the proportion of total pharmaceutical expenditures for ODs have increased. Additional policies related to designation and reimbursement should be put in place to ensure timely access to ODs.

Association Between Statins and the Risk of Kidney Cancer Incidence and Mortality Using the Korean National Health Insurance Claims Database.

BACKGROUND: Conflicting results have been reported regarding the potential preventive effects of statins on the risk of cancer. This study investigated the associations of statin use with the incidence and mortality of kidney cancer in South Korea. METHODS: In this retrospective population-based cohort study using the National Health Insurance claims database, we compared patients aged 45-70 years who had used statins for at least 6 months to non-statin users matched by age and sex from 2005 to June 2013. The main outcomes were kidney cancer incidence and mortality according to statin use. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). RESULTS: In the cohort of 1 008 101 people, the aHRs for the association between statin use and the outcomes were .84 (95% CI: 0.71-.99) for kidney cancer incidence and .65 (95% CI: 0.41-.98) for kidney cancer mortality. In the matched cohort of 337 578, the risk per 1000 people of cancer incidence and mortality was 1.63, 1.07, and .24, .17 in statin users and non-users, respectively. In matched cohort, the risk of kidney cancer incidence and mortality decreased, but it is not statistically significant. Also, there was no linear relationship with increased doses. CONCLUSION: Statin use might be associated with a decreased risk of kidney cancer incidence and mortality, but it showed no statistical significance. This study was a large-scale analysis, however, further studies that are larger and multinational in scope are needed to confirm the beneficial effects of statins on survival.

Health Care Utilization and Anti-Cancer Drug Expenditure for Six Solid Cancers in Korea From 2007 to 2019.

Background: The burden of care continues to rise considerably worldwide and the challenge of diversity in cancer research has become important. We aimed to examine trends of cancer care utilization and anti-cancer medication among patients with six solid cancers (gastric, colorectal, liver, lung, breast, and prostate cancer) in South Korea. Methods: This study analyzed patients diagnosed with six types of solid cancer from 2007 to 2019 using data from the National Health Insurance claims database. We analyzed the total number of cancer cases, each patient's length of stay (LOS) in a hospital, the number of outpatient physician visits, total medical care costs, total out-of-pocket (OOP) costs, and expenditures on anti-cancer drugs. Results: Utilization of healthcare services and spending on cancer care including anti-cancer drugs both increased in the 13-year study period. The average LOS was the highest for colorectal cancer patients at 43.5 days, and breast cancer patients had the highest average number of physician visits at 11.8. Breast cancer patients had the highest total medical costs (USD 923 million), anti-cancer drug spending (USD 156 million), and the largest increase (5 times) over the 13-year period. The anti-cancer drugs with the largest market shares were ramucirumab for gastric cancer; oxaliplatin for colorectal cancer; sorafenib for liver cancer; pembrolizumab, nivolumab, for lung cancer; trastuzumab for breast cancer; and bicalutamide for prostate cancer. Conclusion: This study was a large-scale analysis from a nationally representative database of the total population. The study also shows the pattern of cancer care in an Asian country and can provide implications for future cancer research.

Statins and the risk of gastric, colorectal, and esophageal cancer incidence and mortality: a cohort study based on data from the Korean national health insurance claims database.

BACKGROUND: This study investigated the association between the use of statins, the incidence of gastric, colorectal, and esophageal cancers, and mortality between January 2005 and June 2013 in South Korea. METHODS: We compared patients aged 45-70 years statin users for at least 6 months to non-statin users matched by age and sex, from 2004 to June 2013 using the National Health Insurance database. Main outcomes were gastric, colorectal, and esophageal cancer incidence and mortality. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) among overall cohort and matched cohort after propensity score matching with a 1:1 ratio. RESULTS: Out of 1,008,101 people, 20,473 incident cancers, 3938 cancer deaths occurred and 7669 incident cancer, 1438 cancer death in matched cohort. The aHRs for the association between the risk of cancers and statin use were 0.7 (95% CI 0.65-0.74) for gastric cancer, 0.73 (95% CI 0.69-0.78) for colorectal cancer, and 0.55 (95% CI 0.43-0.71) for esophageal cancer. There were associations between statin use and decreased gastric cancer mortality (HR 0.46, 95% CI 0.52-0.57), colorectal cancer mortality (HR 0.43, 95% CI 0.36-0.51), and esophageal cancer mortality (HR 0.41, 95% CI 0.27-0.50) in the overall cohort and this pattern was similar in the matched cohort. DISCUSSION: Statin use for at least 6 months was significantly associated with a lower risk of stomach, colorectal, and esophageal cancer incidence as well as cancer mortality after a diagnosis.

Development of the Korean Standardized Antimicrobial Administration Ratio as a Tool for Benchmarking Antimicrobial Use in Each Hospital.

BACKGROUND: The Korea National Antimicrobial Use Analysis System (KONAS), a benchmarking system for antimicrobial use in hospitals, provides Korean Standardized Antimicrobial Administration Ratio (K-SAAR) for benchmarking. This article describes K-SAAR predictive models to enhance the understanding of K-SAAR, an important benchmarking strategy for antimicrobial usage in KONAS. METHODS: We obtained medical insurance claims data for all hospitalized patients aged ≥ 28 days in all secondary and tertiary care hospitals in South Korea (n = 347) from January 2019 to December 2019 from the Health Insurance Review & Assessment Service. Modeling was performed to derive a prediction value for antimicrobial use in each institution, which corresponded to the denominator value for calculating K-SAAR. The prediction values of antimicrobial use were modeled separately for each category, for all inpatients and adult patients (aged ≥ 15 years), using stepwise negative binomial regression. RESULTS: The final models for each antimicrobial category were adjusted for different significant risk factors. In the K-SAAR models of all aged patients as well as adult patients, most antimicrobial categories included the number of hospital beds and the number of operations as significant factors, while some antimicrobial categories included mean age for inpatients, hospital type, and the number of patients transferred from other hospitals as significant factors. CONCLUSION: We developed a model to predict antimicrobial use rates in Korean hospitals, and the model was used as the denominator of the K-SAAR.

Changes in antibiotic consumption patterns after the implementation of the National Action Plan according to the Access, Watch, Reserve (AWaRe) classification system.

OBJECTIVE: The Korean government published the first National Action Plan (NAP) on antimicrobial resistance (AMR) in August 2016, followed by a second plan in November 2021. The objective of this study was to analyze changes in antibiotic use patterns after the implementation of the NAP in South Korea. METHODS: We analyzed National Health Insurance claims data for hospitals and clinics from January 2011 to December 2020. Consumption was measured using a defined daily dose per 1000 inhabitants per day (DID). We analyzed data for each year, dimension, and category of the Access, Watch, Reserve classification system by the World Health Organization. Monthly inpatient and outpatient antibiotic use were calculated, and an interrupted time-series (ITS) analysis to assess the trend in antibiotic use was conducted. RESULTS: The consumption of antibiotics increased from 25.78 DID in 2011 to 29.06 DID in 2016, then decreased in 2017 after the implementation of the NAP on AMR. The watch group showed a temporal decrease after the implementation of the NAP; however, these figures increased until 2019, and the reserve group showed a downward trend beginning in 2017. According to the ITS analysis, the level (ß2) and the slope of the trend (ß3) of total antibiotic use decreased by 0.17 and 0.001, respectively. After implementation of the NAP, antibiotic use was reduced from 7.18 DID in 2016 to 4.84 DID in 2017 for amoxicillin and beta-lactamase inhibitors, 0.86 DID to 0.70 DID for ciprofloxacin, and 0.66 DID to0.66 DID for levofloxacin. CONCLUSION: After the implementation of the NAP in South Korea, antibiotic use in terms of total antibiotics and fluoroquinolone in the watch and reserve groups decreased. Further policies to improve the use of antibiotics in the watch and reserve groups are needed.

Aging and the Prevalence of Polypharmacy and Hyper-Polypharmacy Among Older Adults in South Korea: A National Retrospective Study During 2010-2019.

Background: Polypharmacy has become a global health problem and is associated with adverse health outcomes in the elderly. This study evaluated the prevalence of polypharmacy and hyper-polypharmacy in elderly patients in South Korea during 2010-2019. Methods: We analyzed the outpatient care of persons aged ≥65 years covered by National Health Insurance (NHI) using NHI claims data from 2010 to 2019. Polypharmacy was defined as the use of ≥5 medications, and hyper-polypharmacy was defined as the use of ≥10 medications, and we examined them over periods of ≥90 days and ≥180 days. The average annual percent change (AAPC) was calculated using Joinpoint statistical software. Results: The prevalence of polypharmacy among ≥90 days of medication use elderly decreased from 42.5% in 2010 to 41.8% in 2019, and the prevalence of hyper-polypharmacy for ≥90 days increased from 10.4% to 14.4%. The prevalence of polypharmacy for ≥180 days increased from 37.8% in 2010 to 38.1% in 2019, and the prevalence of hyper-polypharmacy for ≥180 days increased from 6.4% to 9.4%. The prevalence of polypharmacy for ≥90 days and ≥180 days steadily increased among elderly patients, with AAPCs of 3.7 and 4.5, respectively. Conclusion: The prevalence of polypharmacy for ≥90 days and ≥180 days remained stably high, with rates of about 42 and 38%, respectively, and hyper-polypharmacy increased over the past 10 years in South Korea. Therefore, strategies to address polypharmacy need to be implemented. Further research is also required to identify the clinical outcomes (including mortality risks) associated with polypharmacy.

First-trimester exposure to benzodiazepines and risk of congenital malformations in offspring: A population-based cohort study in South Korea.

BACKGROUND: Benzodiazepines are frequently prescribed during pregnancy; however, evidence about possible teratogenicity is equivocal. We aimed to evaluate the association between first-trimester benzodiazepine use and the risk of major congenital malformations. METHODS AND FINDINGS: Using Korea's nationwide healthcare database, we conducted a population-based cohort study of women who gave birth during 2011 to 2018 and their live-born infants. The exposure was defined as one or more benzodiazepine prescriptions during the first trimester. We determined the relative risks (RRs) and confidence intervals (CIs) of overall congenital malformations and 12 types of organ-specific malformations. Infants were followed from birth to death or 31 December 2019, whichever came first (up to 8 years of age). Propensity score fine stratification was employed to control for 45 potential confounders. Among a total of 3,094,227 pregnancies, 40,846 (1.3%) were exposed to benzodiazepines during the first trimester (mean [SD] age, 32.4 [4.1] years). The absolute risk of overall malformations was 65.3 per 1,000 pregnancies exposed to benzodiazepines versus 51.4 per 1,000 unexposed pregnancies. The adjusted RR was 1.09 (95% CI 1.05 to 1.13, p < 0.001) for overall malformations and 1.15 (1.10 to 1.21, p < 0.001) for heart defects. Based on mean daily lorazepam-equivalent doses, the adjusted RRs for overall malformations and heart defects were 1.05 (0.99 to 1.12, p = 0.077) and 1.12 (1.04 to 1.21, p = 0.004) for <1 mg/day and 1.26 (1.17 to 1.36, p < 0.001) and 1.31 (1.19 to 1.45, p < 0.001) for >2.5 mg/day doses, respectively, suggesting a dose-response relationship. A small but significant increase in risk for overall and heart defects was detected with several specific agents (range of adjusted RRs: 1.08 to 2.43). The findings were robust across all sensitivity analyses, and negative control analyses revealed a null association. Study limitations include possible exposure misclassification, residual confounding, and restriction to live births. CONCLUSIONS: In this large nationwide cohort study, we found that first-trimester benzodiazepine exposure was associated with a small increased risk of overall malformations and heart defects, particularly at the higher daily dose. The absolute risks and population attributable fractions were modest. The benefits of benzodiazepines for their major indications must be considered despite the potential risks; if their use is necessary, the lowest effective dosage should be prescribed to minimize the risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT04856436.

Ramucirumab plus paclitaxel as a second-line treatment in HER2-positive gastric cancer: subgroup analysis of a nationwide, real-world study in Korea (KCSG-ST19-16).

BACKGROUND: A subgroup analysis of data from a nationwide study (KCSG-ST19-16) was performed to evaluate the efficacy and safety of second-line ramucirumab plus paclitaxel treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma. METHODS: The KCSG-ST19-16 study enrolled a total of 1063 patients from 56 hospitals in South Korea with advanced gastric or GEJ adenocarcinoma, who had received second-line treatment with ramucirumab plus paclitaxel. HER2 status was known for 994 (93.5%) of these patients, who were thus included in the subgroup analysis. RESULTS: In total, 163 of 994 patients (16.4%), had HER2-positive gastric or GEJ adenocarcinoma. The objective response rate to ramucirumab plus paclitaxel treatment was significantly higher in patients with HER2-positive disease compared to those with HER2-negative disease (23.0% [95% confidence interval (CI), 15.9-30.1] vs. 15.1% [95% CI, 12.3-17.9], p = 0.025). The median progression-free survival was longer in patients with HER2-positive versus HER2-negative disease, but the difference was not statistically significant (4.3 months [95% CI, 3.7-5.3] vs 3.7 months [95% CI, 3.4-4.0], p = 0.054). There was no statistically significant difference in median overall survival (OS) between the groups (9.8 months [95% CI, 8.9-12.3] vs 10.1 months [95% CI, 9.2-10.9], p = 0.564). CONCLUSIONS: In patients with HER2-positive gastric or GEJ adenocarcinoma, the objective response rate to second-line treatment with ramucirumab plus paclitaxel was significantly higher compared to patients with HER2-negative disease. However, an increased response to treatment was not associated with an improvement in OS.

Analysis of the Korean generic medicine market: Factors affecting the market share of generic medicines.

This study probed the market share of generic medicines by patients' age and sex, type of medical facilities, route of administration, number of generic brands, market size (drug expenditure), and therapeutic class and investigated factors associated with a high market share of generic medicines in Korea. We analyzed using national health insurance data between 2010 and 2019. The dependent variable was the generic medicine market share, measured as the number of prescriptions and expenditures. Multivariable regression analysis was conducted using the numbers of generic brands, market size by each ingredient and therapeutic class, relative price, the number of prescriptions, and therapeutic class. Total pharmaceutical expenditures have increased due to the high use of single-source drugs. The number of prescriptions and expenditures for generic medicines were 0.3 billion prescriptions and $7.8 billion, respectively, accounting for 46.5% and 46% of the total market. Multivariate analysis showed that the number of prescriptions (>20 thousand) and the market size of main active ingredients (>$1 million) were associated with an increased market share, whereas the number of generic brands (compared to <3) was associated with reduced generic medicine market share. In conclusion, we found that supply policies to promote the market entry of generic medicines by mandating price consistency between generic medicines and off-patent original medicines had limitations in increasing the generic medicine market share. Policy should be put in place both to ensure the timely market entry of generic medicines and to promote the use of cheaper generic medicines.