Horizontal healthcare utilization inequity in patients with rare diseases in Korea.

BACKGROUND: Rare diseases (RDs) are difficult to diagnose and expensive to treat. Thus, the South Korean government has implemented several policies to help RD patients, including the Medical Expense Support Project, supporting low- to middle-income RD patients. However, no study in Korea has yet addressed health inequity in RD patients. This study assessed inequity trends in the medical utilization and expenditures of RD patients. METHODS: This study measured the horizontal inequity index (HI) of RD patients and an age- and sex-matched control group using the National Health Insurance Service data from 2006 to 2018. Sex, age, number of chronic diseases, and disability variables were used to model expected medical needs and adjust the concentration index (CI) for medical utilization and expenditures. RESULTS: The HI index of healthcare utilization in RD patients and the control group ranged from -0.0129 to 0.0145, increasing until 2012 and fluctuating since then. This increasing trend was more apparent for inpatient utilization in the RD patient group than in the outpatient group. The same index in the control group ranged from -0.0112 to -0.0040 without a significant trend. The healthcare expenditure HI in RD patients rose from -0.0640 to -0.0038, showing pro-poor values but moving toward a pro-rich state. In the control group, the HI for healthcare expenditures remained between 0.0029 and 0.0085. CONCLUSIONS: The HI of inpatient utilization and inpatient expenditures increased in a pro-rich state. The study results showed that implementing a policy that supports inpatient service utilization could help achieve health equity for RD patients.

Cost-Effectiveness of Extending the National Influenza Vaccination Program in South Korea: Does Vaccination of Older Adults Provide Health Benefits to the Entire Population?

The South Korean government has successfully improved influenza vaccination coverage for individuals aged 65 years or older as part of its National Immunization Program (NIP). Those aged 50-64 years without funded vaccination care have significantly lower vaccination rates and face a substantial risk of influenza-related complications. We use a dynamic epidemiological and economic model to investigate the cost-effectiveness of expanding the universal vaccine fund to include those aged 50-64. The epidemiological model is estimated using the susceptibility-infection-recovery model and influenza and influenza-like illness incidence rates, which were calculated by the National Health Insurance Service-National Sample Cohort from the 2008/09 to 2012/13 influenza seasons but excluding the 2009/10 season for pandemic influenza A (H1N1). The decision tree economic model is assessed from societal and healthcare sector perspectives. The proposed policy would eliminate 340,000 annual influenza cases and prevent 119 unnecessary deaths. From a societal perspective, the proposed policy would reduce costs by USD 68 million. From a healthcare perspective, the cost is USD 4318 per quality-adjusted life years. Within the study range, sensitivity analyses found consistent cost-effectiveness results. The influenza vaccine for adults aged 50-64 appears to be cost-saving or cost-effective and, thus, should be considered for the NIP.

Cost-Effectiveness of Influenza Vaccination Strategies in Adults: Older Adults Aged ≥65 Years, Adults Aged 50-64 Years, and At-Risk Adults Aged 19-64 Years.

The high disease burden of influenza in elderly and chronically ill adults may be due to the suboptimal effectiveness and mismatch of the conventional trivalent influenza vaccine (TIV). This study evaluated the cost-effectiveness of quadrivalent (QIV), adjuvanted trivalent (ATIV), and high-dose quadrivalent (HD-QIV) vaccines versus TIV used under the current Korean National Immunization Program (NIP) in older adults aged ≥65 years. We also evaluated the cost-effectiveness of programs for at-risk adults aged 19-64 and adults aged 50-64. A one-year static population model was used to compare the costs and outcomes of alternative vaccination programs in each targeted group. Influenza-related parameters were derived from the National Health Insurance System claims database; other inputs were extracted from the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed from a societal perspective. In the base case analysis (older adults aged ≥65 years), HD-QIV was superior, with the lowest cost and highest utility. Compared with TIV, ATIV was cost-effective (ICER $34,314/quality-adjusted life-year [QALY]), and QIV was not cost-effective (ICER $46,486/QALY). The cost-effectiveness of HD-QIV was robust for all parameters except for vaccine cost. The introduction of the influenza NIP was cost-effective or even cost-saving for the remaining targeted gr3oups, regardless of TIV or QIV.

Validity of EQ-5D utility index and minimal clinically important difference estimation among patients with chronic obstructive pulmonary disease.

BACKGROUND: The discriminatory ability of multi-attribute utility (MAU) measures compared to condition-specific measures (CSM) in assessing health-related quality of life (HRQoL) among patients with chronic obstructive pulmonary disease (COPD) is an unsettled issue. This study investigated the quality of life of patients with COPD with three different HRQoL instruments and examined whether they could differentiate between adjacent severity groups in a statistically and clinically meaningful manner. In the process, the minimal clinically important differences (MCID) of the EQ-5D utility index were estimated. METHODS: Cross-sectional survey data were collected from patients with mild to very severe COPD in South Korea. In addition to demographic and clinical information, the following HRQoL questionnaires were used: The three-level five-dimensional Euro-Quality of Life tool (EQ-5D-3L), the EQ-Visual Analog Scale (EQ-VAS), and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). Patients' health-related quality of life was analyzed with reference to severity groups based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. To investigate the discriminatory ability of the HRQoL instruments between COPD severity groups, tests examining variance, covariance, and standardized mean difference were performed. After estimating the MCID of the EQ-5D utility index using the anchor-based method, we investigated whether the differences in the EQ-5D utility scores between groups exceeded the clinically meaningful minimum level. RESULTS: A total of 298 patients completed this study. All the quality of life scores showed statistically significant differences between the GOLD severity groups. The pooled MCID estimate for the EQ-5D utility index was 0.028 (range: 0.017-0.033). Even after adjusting for other factors affecting quality of life, the EQ-5D utility index differentiated the GOLD groups well. CONCLUSIONS: We conclude that the EQ-5D utility index is a valid instrument for measuring the quality of life of patients with COPD, and the pooled MCID estimate for the EQ-5D utility index was 0.028.

Increasing Prevalence and Mortality of Asthma With Age in Korea, 2002-2015: A Nationwide, Population-Based Study.

PURPOSE: The prevalence of asthma is increasing globally as the world population increases; however, and the prevalence and mortality of asthma have not been extensively investigated. Also, the effects of severity and aging on asthma prevalence and mortality are unknown. We aimed to investigate trends of the prevalence and mortality of asthma as well as health care uses and costs over 14 years according to disease severity by using real-world data in Korea. METHODS: Using the National Health Insurance Sharing Service database, we extracted asthmatic patients having diagnosis codes of asthma and prescription records of antiasthmatic medications from 2002 to 2015 and categorized them according to asthma exacerbation and regular treatment. We defined asthma-associated death in terms of patients' prescription records within 3 months before all-cause death, then linked with the Cause of Death Statistics. The annual asthma-related health care uses and costs were analyzed. RESULTS: The prevalence rates of asthma (1.6% to 2.2%) and severe asthma (SA; 3.5% to 6.1% among total asthmatics) have increased steadily over the decade in Korea, where the proportion of elderly asthmatics having increased. The asthma-related health care uses and costs had increased during the study period with the highest uses/costs in SA. The asthma mortality had a steady rising trend from 16.2 to 28.0 deaths per 100,000 with the highest mortality in SA. CONCLUSIONS: The prevalence and mortality of asthma as well as SA increases along with the burden of health care uses/costs. More active interventions, including changes in health care policies, are needed to reduce the prevalence and mortality of asthma, especially SA.

Mapping analysis to estimate EQ-5D utility values using the COPD assessment test in Korea.

BACKGROUND: There is no research on mapping algorithms between EQ-5D and COPD assessment test (CAT) in Korea. The purpose of this study was to develop mapping algorithms that predict EQ-5D-3 L utility from the CAT in patients with COPD. METHODS: Survey data of 300 COPD patients were collected from three tertiary teaching hospitals in Korea. To predict EQ-5D-3 L utility from the CAT, various models were assessed. Models were developed using randomly split training samples. Subsequently, the models were validated based on root mean square error (RMSE) and mean absolute error (MAE) in validation samples. The models were also validated using the bootstrap method, which involves iterative splitting, training, and validating of the sample data at least 10,000 times. Average RMSEs and MAEs were used as criteria for model selection. RESULTS: The recommended mapping algorithms were based on ordinary least squares (OLS) regression models, which revealed five CAT items (chest tightness, breathlessness, activity, leaving home, and energy) as statistically significant on the EQ-5D-3 L. The mapping models estimated the overall mean of EQ-5D-3 L utilities effectively, but EQ-5D-3 L utilities for severe (low utility) patients (< 0.6) were overestimated as the observed EQ-5D-3 L utilities were often distributed over 0.6. CONCLUSION: Mapping algorithms can be used to predict EQ-5D-3 L utilities from the CAT. However, mapping algorithms should be used cautiously when applied to groups with greater disease severity.

Cost-effectiveness of influenza vaccine strategies for the elderly in South Korea.

OBJECTIVES: Despite a high vaccine uptake rate of over 80% in South Korea, the disease burden of influenza is still high among the elderly, which may be due to low effectiveness of vaccines. Therefore, the cost-effectiveness of use among the elderly was analyzed in order to compare the current trivalent influenza vaccine (TIV) with a quadrivalent influenza vaccine (QIV) or MF59-adjuvanted trivalent influenza vaccine (ATIV). METHODS: A static lifetime Markov model was used. It was assumed that the model would be repeated until individuals reached the age of 100. Cost-effectiveness was analyzed across three age groups (65-74 years, 75-84 years, and ≥85 years), and the at-risk group was studied. RESULTS: Compared to the TIV, the QIV was expected to reduce the number of influenza infections by 342,873, complications by 17,011, hospitalizations by 8,568, and deaths by 2,031. The QIV was highly cost-effective when compared to the TIV, with a base case incremental cost-effectiveness ratio (ICER) estimated at USD 17,699/QALY (1USD = 1,151KRW), and the ICER decreased with age and was USD 3,431/QALY in the group aged 85 and above. Sensitivity analysis revealed that the ICER was sensitive to the QIV price, the proportion of influenza B, and vaccine mismatching. On the other hand, the ATIV was expected to reduce the number of influenza cases and complications by 1,812,395 and 89,747, respectively, annually, yielding cost-saving among all ages. ATIV price and vaccine efficacy were the most influential parameters for the ICER of ATIV. CONCLUSIONS: The QIV and ATIV strategies were considered more cost-effective in comparison to the TIV for vaccination strategies implemented for the elderly. However, owing to a lack of data on the effectiveness of ATIV among the elderly, a large-scale effectiveness study is required.

Easy cuts, easy rebound: Drug expenditures with massive price cuts in Korea.

BACKGROUNDS: Since 2012, the Korean government has introduced 46.5% price cut for off-patent medicines in order to reign everescalating drug expenditure. This study sought to appraise the impact of the price cut measure (in the context of Korean National Health Insurance system). METHODS: We employed Korean National Health Insurance database from January 2007 until December 2016 for 120 month period. An interrupted time series analysis with segmented regression analysis was conducted to estimate the impact of price cut on overall drug spending. RESULTS: Drug spending significantly dropped with the price cut by 186.22 billlion Korean Won (KRW) (p < 0.0001) and the trend after the price cut has also significantly decreased by 1.33 billion KRW (p = 0.002). However, it was predicted that total expenditures showed an increasing trend and bounced back to the original level. Quantity prescribed had no significance with the price cut. Unit price had a substantial drop (ß = -41.68, p < 0.0001) with the price-cut, but the trend after the intervention has increased (ß = 0.16, p = 0.656) with no significance. CONCLUSIONS: Although the price cut has successfully countered the everescalating pharmaceutical expenditures in Korea, the impact was temporary. A lack of demand-side measures resulted in an ineffectiveness and unsustainability of policy effect. Thus, more aggressive demand-side measures should be introduced in the Korean context,and both the demand and supply-sides should be balanced.

Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea.

BACKGROUND: As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. METHODS: A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer's perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). RESULTS: In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. CONCLUSION: Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy.

Cost-effectiveness of vortioxetine versus venlafaxine (extended release) in the treatment of major depressive disorder in South Korea.

OBJECTIVE: To assess the cost-effectiveness of vortioxetine versus venlafaxine XR (extended-release) in major depressive disorder (MDD) patients in South Korea. METHODS: A 1-year cost-effectiveness analysis from a limited societal perspective was performed using a combined model consisting of a decision-tree and a Markov model. Patients entered the model when initiating or switching antidepressant treatment following inadequate response to previous treatment. Remission, relapse and recovery were the main health states. RESULTS: Vortioxetine dominated venlafaxine XR, with quality-adjusted life year (QALY) gains of 0.0131 and cost savings of KRW 623,229/year [US$530/year] from a limited societal perspective. Safety contributed more than efficacy to the incremental QALY gains. More patients were in recovery after initial treatment and after 1 year with vortioxetine (31%, 40%) compared to venlafaxine XR (23%, 36%). Vortioxetine remained dominant in 98% of probabilistic simulations. CONCLUSION: Vortioxetine dominated venlafaxine XR in South Korea and is a relevant treatment option for MDD patients initiating or switching therapy.

Cost-utility of ferric carboxymaltose (Ferinject®) for iron-deficiency anemia patients with chronic heart failure in South Korea.

BACKGROUND: Iron-deficiency anemia (IDA) is prevalent in patients with advanced chronic heart failure (CHF). It affects the patients' overall physical condition and is suggested as a strong outcome predictor in CHF. Recent clinical trials suggested that intravenous iron supplementation improves CHF functional status and quality of life. The aim of this study was to assess the cost-effectiveness of ferric carboxymaltose(FCM) in CHF patients with IDA. METHODS: Ferric carboxymaltose, an intravenous iron preparation, was compared with placebo. The target population comprised CHF patients with IDA in hospital and outpatient care settings. We conducted this study from the Korean healthcare payers' perspective with a time horizon of 24 weeks. One clinical trial provided the clinical outcomes of ferric carboxymaltose therapy. The improvement rates of the New York Heart Association (NYHA) functional class in the placebo and ferric carboxymaltose groups were used to estimate effectiveness in the base-case model. We also conducted a scenario 2 analysis using quality of life investigated in the clinical trial. A panel survey was conducted to obtain the ratio of healthcare resource use based on NYHA class in Korea. Cost-effectiveness was expressed as incremental cost (US dollars) per quality-adjusted life-year (QALY) gained. RESULTS: In the base-case analysis, the incremental cost-effectiveness ratio (ICER) of ferric carboxymaltose compared with placebo was $22,192 (₩25,010,451) per QALY gained. The sensitivity analysis showed robust results, with the ICERs of ferric carboxymaltose ranging from $5,156 to $29,796 per QALY gained. In the scenario 2 analysis, ICER decreased to $12,598 (₩14,198,501) per QALY gained. CONCLUSIONS: Iron repletion with ferric carboxymaltose for IDA in CHF patients was cost-effective compared with placebo.

Analysis on relationship between the accident and injury occurrence and the absence appearance of adults in South Korea.

The purpose of this study is to examine relationship between the accident and injury occurrence and the absence appearance in adults. Materials of this study were based on the raw data of "Korea National Health and Nutrition Examination Survey 2011", which was conducted by the Ministry of Health and Welfare (MW) and Korea Centers for Disease Control and Prevention (CDC) in 2011. Totally 5904 people were targeted by selecting data without missing value in addition to age in more than 20 years old. And the appearance of absence through the occurrence of injury had the final subjects of absence targeting 379 people among 5904 people. An analytical method was made by using SPSS WIN program (Version 12.0). As a result of research, the occurrence of injury was higher (p< 0.01) in men than women. The age group was high in the 30s (about 1.5 times, p< 0.05) and the 40 s (about 1.9 times, p< 0.01). The higher in household income (about 1.5 times, p< 0.05) and educational level (about 1.6 times, p< 0.001) led to the higher occurrence of injury. As for the occurrence of absence, fall and slip (abut 1.8 times, p< 0.05) had higher absence than other accidents. As for a place of cure, the absence were higher (p< 0.001) in users of emergency room than entering hospital/clinic. Finally, the more bed-ridden led to the higher absence (p< 0.001).

Diverse influences of androgen-disrupting chemicals on immune responses mounted by macrophages.

Androgen-disrupting chemicals (ADCs) can alter male sexual development. Although the effects of ADCs on hormone disruption have been studied, their influence on the immune response is not fully understood. To investigate the effects of ADCs on innate immunity, we tested eight candidate ADCs for their influence on macrophages by measuring nitric oxide (NO) production and cell viability. Our results showed that treatment with a mixture of lipopolysaccharide and hexachlorobenzene increased NO production in RAW 264.7 cells, a murine macrophage cell line. In contrast, compared to exposure to a negative control, exposure to di-2-ethylhexyl adipate (DEHA), benzylbutyl phthalate (BBP), testosterone (TTT), or permethrin decreased NO production. DEHA, BBP, and TTT inhibited NO production in an inducible nitric oxide synthase-dependent manner. Treatment with bisphenol A (BPA), nonylphenol (NNP), or tributyltin chloride (TBTC) reduced NO production and induced cell death. While BPA induced RAW 264.7 cell death through apoptosis, NNP and TBTC caused cell death through necrosis. These results offer insights into the influences of ADCs on the innate immune system.

Recurrence Rate after Herniotomy only versus Discectomy in Lumbar Disc Herniation.

OBJECTIVE: Lumbar disc herniation (LDH) recurrence necessitating reoperation can pose problems following spinal surgery, with an overall reported incidence of approximately (3-13%). The purpose of this study is to identify the rate of recurrent disc herniation, to discuss the radiologic indications for herniotomy and to analyze clinical outcomes compared with conventional discectomy. METHODS: This study is a retrospective case control study. The authors retrospectively reviewed 114 patients who underwent herniotomy & conventional discectomy by a single surgeon for single-level LDH between June 2009 and May 2012. Herniotomy group was 57 patients and conventional discectomy group was 57 patients that were selected from 631 patients using stratified randomization. Evaluation for LDH recurrence included detailed medical chart and radiologic review and telephone interview. Postoperative VAS and the Korean version of ODI were examined one week after surgery. Clinical outcome was investigated according to Odom's criteria from three months to three years. RESULTS: Of the 114 patients for whom the authors were able to definitively assess symptomatic recurrence status, four patients (7%) experienced LDH recurrence following single-level herniotomy and three patients (5.2%) conventional discectomy. There were no differences in the VAS and Korean version of ODI between herniotomy group and conventional discectomy group. The herniotomy group had better results than the conventional discectomy group in clinical outcome from three months to three years, but the difference was not significant. CONCLUSION: There were no significant differences in clinical outcome between herniotomy and conventional discectomy. Recurrence rates following herniotomy for LDH compare favorably with those in patients who have undergone conventional discectomy, lending further support for its effectiveness in treating herniotomy.

Is the Cross-sectional Area after Unilateral Open Door Laminoplasty Wider than that after Midline Splitting Laminoplasty ? : Mathematical Approach.

OBJECTIVE: The aim of this study was to compare geometrically cross-sectional areas of two different laminoplasty techniques in same opening size. Some investigators have studied the expanded areas of the two different techniques using imaging study. Although it is unclear that postoperative spinal canal is correlated with the surgical outcome we just focused on mathematical and geometrical correlation of the expandable area with surgical opening size in different laminoplasty techniques. METHODS: To predict the expandable area by a midline splitting technique and a unilateral open door technique, we placed an imaginary isosceles triangle in the spinal canal and drew graphs for the equation of the expandable areas in same opening size using the Pythagorean theorem and mathematical program. To substitute the constant figures of mathematical formula we estimated the normal cervical spine CT scans of 50 Korean adults. RESULTS: We subtracted the imaginary triangle from the spinal canal and were left with the remaining area of the spinal canal that was not changed before and after surgery. In same opening size the expandable area by the midline splitting technique was same but slightly wider than the unilateral open door technique, irrespective of the triangular shape. For a normal isosceles triangle the results were the same. CONCLUSION: Using mathematical proof, the expandable area after the midline splitting technique was same but slightly larger than that after the unilateral open door technique, irrespective of the size of the lamina opening.

Eliciting public preference for health-care resource allocation in South Korea.

OBJECTIVES: To identify the principles the public considers important and the trade-offs between different values in health-care resource allocation practices. METHODS: This study approached the issue in both qualitative and quantitative ways. In a qualitative study, two focus groups discussed the issues of resource allocation in health care. To facilitate the discussion, a simple ranking task and a series of pairwise choice practices were implemented. A discrete choice experiment survey questionnaire was also administered to a sample of the general population. Attributes and levels were determined through literature reviews and the results from the focus group interview. We used a random-effect probit model to assess the effects of each attribute. RESULTS: Through the focus group interviews, we found strong public support for the principle of equal opportunity. The participants thought that the severity of disease was the most important criterion when setting priorities. The majority supported the idea that the most disadvantaged should have the highest priority even when their health gains are less than those of others. The discrete choice experiment results showed that the severity of disease, health gains, and patients' socioeconomic status significantly influence their choices, with each parameter having an expected sign. CONCLUSION: The results showed that Koreans support not only health maximization but also equal opportunity, fair resource allocation, and equality.

[Current state and challenges of pharmacoeconomic evaluation in Korea].

Since the positive listing system for prescription drug reimbursement has been introduced in Korea, the number of pharmacoeconomic evaluation studies has increased. However it is not clear if the quality of pharmacoeconomic evaluation study has improved. Due to the lack of randomized clinical studies in Korean health care setting, Korean economic evaluation studies have typically integrated the local cost data and foreign clinical data. Therefore methodological issues can be raised in regard to data coherence and consistency. But the quality of data was not questiened and the potential bias has not been investigated yet. Even though changes in policy have encouraged the undertaking of pharmacoeconomic evaluations, there is few public-side funding for validation study of cost-effectiveness models and data. Several companies perform economic evaluation studies to be submitted on behalf of their own products, but do not want the study results to be disclosed to the academic community or public. To improve the present conduct of pharmacoeconomic evaluations in Korea, various funding sources need to be developed, and, like other multidisciplinary areas, the experts in different fields of study should collaborate to ensure the validity and credibility of pharmacoeconomic evaluations.