Cost-of-illness changes before and after the diagnosis of systemic lupus erythematosus: a nationwide, population-based observational study in Korea.

OBJECTIVES: To estimate the direct healthcare cost progression from before to after systemic lupus erythematosus (SLE) diagnosis and to compare healthcare costs by disease severity. METHODS: Patients with incident SLE diagnosed between 2008 and 2018 were identified from the Korean National Health Insurance database. Annual direct healthcare costs for 5 years before and after SLE were estimated and compared with those of age-, sex-, and calendar month-matched (1:4) controls, without SLE. Direct healthcare costs were compared by disease severity of SLE using regression analysis. RESULTS: Among 11 173 patients with SLE and 45 500 subjects without SLE, annual direct healthcare costs per person increased in the year before SLE diagnosis and peaked in the first year after diagnosis. They were 7.7-fold greater in the SLE patients than in the subjects without SLE ($5,871 vs $759). Severe SLE was associated with 3.284-fold (95% CI 3.075-3.507) higher annual costs than mild SLE during the year after diagnosis. Older age (age 60-79 years), lupus nephritis, interstitial lung diseases, and comorbidities such as avascular necrosis and chronic kidney disease were associated with higher annual direct healthcare costs (times [95% CI]) in the first year after diagnosis; aged 60-69, 1.119 [1.034-1.211], aged 70-79, 1.470 [1.342-1.611], 1.794 [1.711-1.881], 1.435 [1.258-1.638], 6.208 [4.541-8.487], and 1.858 [1.673-2.064], respectively. CONCLUSION: Patients with SLE incurred significantly high direct healthcare costs than subjects without SLE during the first year after diagnosis. Disease severity, older age, major organ involvements and comorbidities were associated with increased healthcare costs.

Longitudinal study of the impact of three major regulations on the Korean pharmaceutical industry in the last 30 years.

BACKGROUND: The pharmaceutical industry is heavily regulated. Partly for this reason, new drugs generally take over 10 years from the product development stage to market entry. Although regulations affect the pharmaceutical industry over a long period, previous studies investigating the impact of new regulatory policies have usually focused on the short period before and after implementing that policy. Therefore, the purpose of this study is to examine whether and how significantly regulatory policies affect long-term innovation in the pharmaceutical industry in Korea. METHODS: This study focused on three significant regulatory policies: the introduction of the product patent system, changes in the Good Manufacturing Practice (GMP) system, and the Drug Expenditure Rationalization Plan (DERP). The study used interrupted time series (ITS) analysis to investigate the long-term impacts of the policies before and after implementation. RESULTS: Our results show that introducing the product patent system in 1987 significantly increased the number of Korean patent applications. The effect of the revised GMP policies was also statistically significant, both before and after implementation and between pre-emptive companies and non-pre-emptive ones. However, due to the companies' negotiations with the regulatory authorities or the regulatory system that links drug approval and price evaluation, the DERP did not significantly delay new drug registration in Korea. CONCLUSION: This study showed that the policies of the product patent system, GMP policies, and DERP regulations have significantly encouraged pharmaceutical companies to strive to meet regulatory requirements and promote innovation in Korea. The study suggests that it is necessary for companies to pre-emptively respond to systemic changes in development and production strategies to deal with regulatory changes and achieve sustainable growth. Also, our study results indicate that since government policies motivate the innovative system of the pharmaceutical industry, governmental authorities, when formulating pharmaceutical policies, need to consider the impact on the long-term innovation of the industry.

Comparison of healthcare resource utilization and medical costs between patients with seropositive and seronegative rheumatoid arthritis.

OBJECTIVES: To compare healthcare utilization and medical costs between patients with seronegative (SN) and seropositive (SP) rheumatoid arthritis (RA). METHODS: We conducted a nationwide population study using the Korean health insurance claims database in 2016. We divided patients with RA into SN and SP groups and compared healthcare utilization including medications, medical utilization, and direct medical costs for 1 year between the groups in a cross-sectional analysis. Differences in costs between patients with SPRA and SNRA were assessed using the quantile regression model. We performed longitudinal analysis using data from 2012 and 2016 to examine changes over time. RESULTS: A total of 103,815 SPRA and 75,809 SNRA patients were included in the analyses. The SPRA group used significantly more methotrexate (73.2% versus 30.3%) and biologic agents (7.9% versus 2.9%) than the SNRA group. The number of RA-related outpatient visits [6.0 ± 3.7 versus 4.4 ± 4.0 times/year, standardized difference (SD) = 0.41] and annual medical costs per patient ($1027 versus $450/year, SD = 0.25) were higher in the SPRA group than the SNRA group. Quantile regression results indicated that the incremental cost of seropositivity on total medical costs of RA patients gradually increased as medical costs approached the upper quantile. The annual direct medical costs for each patient between 2012 and 2016 increased in both groups: by 25.1% in the SPRA group and 37.6% in the SNRA group. CONCLUSION: Annual RA-related direct medical costs and RA-related healthcare utilization per patient are higher in patients with SPRA than those with SNRA.

Uptake of Biosimilars and Its Economic Implication for the Treatment of Patients with Rheumatoid Arthritis in Korea.

BACKGROUND: We aimed to examine the uptake of infliximab and etanercept biosimilars in patients with rheumatoid arthritis (RA) and its economic implication for healthcare expenditure. METHODS: Using Korean Health Insurance Review and Assessment Service National Patient Samples, we extracted RA patients who used biologic disease modifying anti-rheumatic drugs (bDMARDs) between 2009 and 2018. Descriptive statistics were used to explain the basic features of the data. We calculated the proportion of users of each bDMARD among total patients with bDMARDs half-yearly. We assessed changes in the utilization proportions of bDMARDs including 4 tumor necrosis factor inhibitors (TNFis) and 2 non-TNFis, which have been approved for RA in Korea: etanercept, infliximab, adalimumab, golimumab, tocilizumab, and abatacept, and analyzed the changes in market share of biosimilars among the bDMARDs after their introduction. Overall trends of medical costs for each bDMARD were presented over the 10-year period. RESULTS: Since the introduction of the biosimilar TNFis in 2012, the proportion of their use among bDMARDs steadily increased to 15.8% in 2018. While there has been a gradual increase in the use of biosimilar TNFis, the use of the corresponding originators has been decreasing. The introduction of biosimilar TNFis has resulted in a decrease in the medical costs of patients using either originator or biosimilar TNFis. CONCLUSION: In Korea, the proportional use of biosimilar TNFis has gradually increased since their introduction. The availability of less expensive biosimilar TNFis seems to have brought about a decrease in the medical costs of users of the originators.

Causality Assessment Guidelines for Adverse Events Following Immunization with a Focus on Guillain-Barré Syndrome.

South Korea operates a National Vaccine Injury Compensation Program (VICP) for people who experience adverse events following immunization (AEFI). To run this program rationally, it is a prerequisite to confirm whether adverse events were caused by immunization. Guillain-Barré syndrome (GBS), a severe neurological disease with limb pain and muscle weakness as cardinal symptoms, is attracting attention as an AEFI. However, algorithm or guidelines for assessing the causality between vaccination and the incidence of GBS are lacking. We aimed to develop guidelines for causality assessment of GBS as an AEFI and suggest using these guidelines in alignment with the VICP. We systematically searched for other previously published algorithms or guidelines and found a WHO-AEFI guideline used worldwide; however, it only provides general instructions and is not tailored to specific adverse events. We translated and locally adapted the structure of this guideline and then added contents related to GBS. The GBS-specific guideline consists of four steps: case ascertainment of GBS, checklist (including (1) order of incidence, (2) temporal proximity, (3) evidence for other causes and (4) published evidence), an algorithm, and final classification. We listed key information on confirming GBS and whether any other causes of GBS were present. For real world application of the guideline along with the VICP, we collaborated with a panel of neurologists, epidemiologic investigators, and committee members from the VICP. To ensure transparency and a scientific approach, regular updates and collaboration with neurologists are essential. We expect that this guideline will contribute to logical causality assessment and compensation decisions for GBS and will provide the basic structure for causality assessment of other AEFIs.

An increased disease burden of autoimmune inflammatory rheumatic diseases in Korea.

OBJECTIVES: To estimate the prevalence, medical utilization, and recent changes in the economic burden of autoimmune rheumatic diseases (AIRDs) in Korea. METHODS: Using a nationwide claims database that includes all medical claims made by approximately 50 million Korean residents, the prevalences of seropositive rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and others between 2012 and 2016 were calculated. Changes in medical utilization and the direct medical costs of each AIRD from 2012 to 2016 were also evaluated. RESULTS: Based on the data for 2016, seropositive RA was the most common AIRD in Korea with 96,330 cases (188.5/100,000 population), followed by AS (30,006, 58.7/100,000 population), SLE (19,441, 38.0/100,000 population), Behçet's disease (BD, 14,943, 29.2/100,000 population), primary Sjögren syndrome (pSS, 12,018, 23.5/100,000 population), and systemic sclerosis (SSc, 3606, 7.1/100,000 population). In terms of medical utilization, patients with eosinophilic granulomatosis with polyangiitis visited outpatient clinics the most frequently (9.8 times/year/patient), while hospitalization was most frequent in microscopic polyangiitis patients (1.0 time/year/patient). Total medical costs for all AIRDs increased from $154,348,011 in 2012 to $262,481,974 in 2016. The annual medical cost per patient in 2016 was the highest in microscopic polyangiitis ($6223/year), followed by psoriatic arthritis ($3,362/year), and granulomatosis with polyangiitis ($2823/year). CONCLUSIONS: In Korea, the most prevalent AIRD is seropositive RA, followed by AS, SLE, BD, pSS, and SSc. The economic burden of AIRDs has risen substantially in the last 5 years due not only to an increase in their prevalence but also to an increase in medical costs per patient.

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study.

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5 years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1 × gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective.

Impact of Osteoarthritis on Household Catastrophic Health Expenditures in Korea.

BACKGROUND: Osteoarthritis (OA) is a disease of old age whose prevalence is increasing. This study explored the impact of OA on household catastrophic health expenditure (CHE) in Korea. METHODS: We used data on 5,200 households from the Korea Health Panel Survey in 2013 and estimated annual living expenses and out-of-pocket (OOP) payments. Household CHE was defined when a household's total OOP health payments exceeded 10%, 20%, 30%, or 40% of the household's capacity to pay. To compare the OOP payments of households with OA individuals and those without OA, OA households were matched 1:1 with households containing a member with other chronic disease such as neoplasm, hypertension, heart disease, cerebrovascular disease, diabetes, or osteoporosis. The impact of OA on CHE was determined by multivariable logistic analysis. RESULTS: A total of 1,289 households were included, and households with and without OA patients paid mean annual OOP payments of $2,789 and $2,607, respectively. The prevalence of household CHE at thresholds of 10%, 20%, 30%, and 40% were higher in households with OA patients than in those without OA patients (P < 0.001). The presence of OA patients in each household contributed significantly to CHE at thresholds of 10% (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.16-1.87), 20% (OR, 1.29; 95% CI, 1.01-1.66), and 30% (OR, 1.37; 95% CI, 1.05-1.78), but not of 40% (OR, 1.17; 95% CI, 0.87-1.57). CONCLUSION: The presence of OA patients in Korean households is significantly related to CHE. Policy makers should try to reduce OOP payments in households with OA patients.

Doppler assessment of fetal aortic isthmus flow in twin.

OBJECTIVE: The purpose of this study was to investigate the aortic isthmus (AoI) flow difference between larger fetus and smaller fetus of twin; and to evaluate the predictive value of early diagnosis of hemodynamic change in twin growth. METHODS: This prospective study on 49 pairs of twin fetuses was performed to obtain AoI blood flow data. Cases with structural or chromosomal abnormalities and co-twin death were excluded. The interval from examination to delivery was within 4 weeks and 3 cases over 4 weeks interval were re-examined. Assessment of fetal AoI Doppler parameters were peak systolic velocity (PSV), end-diastolic velocity, times-averaged maximum velocities, pulsatility index (PI), and resistance index (RI). According to the direction of the diastolic flow in the AoI, antegrade and retrograde flow were made and was used to analyze the perinatal outcomes of each fetus. The predictive value of AoI Doppler parameters in predicting fetal growth was obtained by using ANOVA and logistic regression analysis of quantitative variables in each fetus of twins. RESULTS: There were significant differences in the gestational weeks at delivery, birth weight and the incidence of growth discordance over 20% or more between monochorionic twin and dichorionic twin. The AoI PI and RI were significantly higher in smaller fetus than in larger regardless of chorionicity. Retrograde flow was noted in 8 of 98 cases (8.2%) and the only one case was of the larger fetus and the others were smaller fetuses of twin. Significant correlations were found between the AoI PI and birthweight (P=0.018) and between the PSV and growth discordance (P=0.032). In monochorionic twin, linear correlation was shown between the AoI PI and birthweight (P=0.004) and between AoI PI and growth discordance (P=0.031). Also, the meaningful correlation between the PSV and birthweight (P=0.036) was found by using logistic regression analyses. CONCLUSION: On the basis of our observation, AoI PI has revealed their hemodynamic status and this result may improve the understanding of growth patterns in twins.

New initiatives for pharmacovigilance in South Korea: introducing the Korea Institute of Drug Safety and Risk Management (KIDS).

PURPOSE: Pharmacovigilance plays a vital role in ensuring that patients receive appropriate medical products that are safe and effective. This paper aims to describe the history of pharmacovigilance in Korea and introduce the establishment and goal of the KIDS. METHODS: In Korea, the adverse drug reactions (ADR) reporting system was launched in 1988 by the Korea Ministry of Food and Drug Safety (MFDS) and spontaneous ADR reports have been collected from health care professionals and the general public. Although the ADR reporting system has begun, the reporting rate was very low in the first 10 years, and safety actions were done passively in response to the US Food and Drug Administration (FDA) or European Medicines Agency (EMA)'s safety alert and communications. RESULTS: Therefore, the Korea Institute of Drug Safety and Risk Management (KIDS) was established in April 2012 as a new initiative for pharmacovigilance. CONCLUSIONS: The KIDS will continue to contribute to the improvement of Korean pharmacovigilance by collecting, managing, and analyzing consumer-centered drug safety information.

Utilization of evidence-based treatment in elderly patients with chronic heart failure: using Korean Health Insurance claims database.

BACKGROUND: Chronic heart failure accounts for a great deal of the morbidity and mortality in the aging population. Evidence-based treatments include angiotensin-2 receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, and aldosterone antagonists. Underutilization of these treatments in heart failure patients were frequently reported, which could lead to increase morbidity and mortality. The aim of this study was to evaluate the utilization of evidence-based treatments and their related factors for elderly patients with chronic heart failure. METHODS: This is retrospective observational study using the Korean National Health Insurance claims database. We identified prescription of evidence based treatment to elderly patients who had been hospitalized for chronic heart failure between January 1, 2005, and June 30, 2006. RESULTS: Among the 28,922 elderly patients with chronic heart failure, beta-blockers were prescribed to 31.5%, and ACE-I or ARBs were prescribed to 54.7% of the total population. Multivariable logistic regression analyses revealed that the prescription from outpatient clinic (prevalent ratio, 4.02, 95% CI 3.31-4.72), specialty of the healthcare providers (prevalent ratio, 1.26, 95% CI, 1.12-1.54), residence in urban (prevalent ratio, 1.37, 95% CI, 1.23-1.52) and admission to tertiary hospital (prevalent ratio, 2.07, 95% CI, 1.85-2.31) were important factors associated with treatment underutilization. Patients not given evidence-based treatment were more likely to experience dementia, reside in rural areas, and have less-specialized healthcare providers and were less likely to have coexisting cardiovascular diseases or concomitant medications than patients in the evidence-based treatment group. CONCLUSIONS: Healthcare system factors, such as hospital type, healthcare provider factors, such as specialty, and patient factors, such as comorbid cardiovascular disease, systemic disease with concomitant medications, together influence the underutilization of evidence-based pharmacologic treatment for patients with heart failure.

A population-based case-crossover study of polyethylene glycol use and acute renal failure risk in the elderly.

AIM: To evaluate the possibility of an association between polyethylene glycol (PEG) and acute renal failure (ARF) in elderly patients using a health insurance claims database. METHODS: We conducted a population-based case-crossover study using information obtained from Korean Health Insurance Review and Assessment Service (HIRA) claims from January 1, 2005 to December 31, 2005 (Seoul, Korea). The study population consisted of elderly patients who received PEG prior to experiencing their first ARF-related hospitalization from April 1, 2005 to December 31, 2005. For each patient, one case and two control periods were matched. PEG use in a 2- or 4-wk window period prior to hospitalization for ARF was compared with PEG use in two earlier 2- or 4-wk control window periods. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI, adjusting for concomitant uses of diuretics, angiotensin converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, antibiotics, anti-cancer drugs, and contrast media. RESULTS: Within the HIRA database which contained 1,093,262 elderly patients, 1156 hospitalized ARF cases were identified. Among these cases, PEG was prescribed to 17 (1.5%) patients before hospitalization. The adjusted ORs when applying the 2- and 4-wk window periods were 0.4 (95% CI: 0.03-5.24) and 2.1 (95% CI: 0.16-27.78), respectively. CONCLUSION: No increased risk of ARF was found in elderly PEG users. However, based on the limited number of study subjects, further analysis should be performed to confirm these results.