Values, challenges, and responses associated with high-priced potential cures: perspectives of diverse stakeholders in South Korea.

BACKGROUND: The emergence of high-priced potential cures has sparked significant health policy discussions in South Korea, where the healthcare system is funded through a single-payer National Health Insurance model. We conducted focus group interviews (FGIs) and accompanying surveys with diverse stakeholders to comprehensively understand related issues and find better solutions to the challenges brought by these technologies. METHODS: From October to November 2022, 11 FGIs were conducted with stakeholders from various sectors, including government payers, policy and clinical experts, civic and patient organisations, and the pharmaceutical industry, involving a total of 25 participants. These qualitative discussions were supplemented by online surveys to effectively capture and synthesise stakeholder perspectives. RESULTS: Affordability was identified as a critical concern by 84% of stakeholders, followed by clinical uncertainty (76%) and limited value for money (72%). Stakeholders expressed a preference for both financial-based controls and outcome-based pricing strategies to mitigate these challenges. Despite the support for outcome-based refunds, payers raised concerns about the feasibility of instalment payment models, whether linked to outcomes or not, due to the specific challenges of the Korean reimbursement system and the potential risk of 'cumulative liabilities' from ongoing payments for previously administered treatments. In addition, the FGIs highlighted the need for clear budgetary limits for drugs with high uncertainties, with mixed opinions on the creation of special silo funds (64.0% agreement). Less than half (48%) endorsed the use of external reference pricing, currently applied to such essential drugs in South Korea. A significant majority (84%), predominantly non-pharma stakeholders, advocated for addressing cost-effectiveness uncertainty through re-assessment once long-term clinical data become available. CONCLUSIONS: This study uncovers a broad agreement among stakeholders on the need for more effective value assessment methodologies for high-priced potential cures, stressing the importance of more robust and comprehensive re-assessment supported by long-term data collection, rather than primarily relying on external reference pricing. Each type of stakeholders exhibited a cautious approach to their specific uncertainties, suggesting that new funding strategies should accommodate these uncertainties with predefined guidelines and agreements prior to the initiation of managed entry agreements.

Public preferences in healthcare resource allocation: A discrete choice experiment in South Korea.

OBJECTIVES: This study aimed to explore the public view on priority-setting criteria for healthcare resource allocation. Specifically, it investigates how the value of a quality-adjusted life year (QALY) varies depending on patient characteristics. METHODS: A discrete choice experiment was conducted using an online sample of the general South Korean population. Respondents were presented with two competing treatment scenarios. The attributes of the scenarios were age at disease onset, life expectancy without treatment, life-years gain with treatment, health-related quality of life (HRQoL) without treatment, and HRQoL gains with treatment. Two hundred choice sets were generated and randomly allocated into 20 blocks. A conditional logit model was used to estimate the factors affecting the respondents' choices. RESULTS: A total of 3,482 respondents completed the survey. The larger the QALY gain, the more likely it was that the scenario would be chosen but with a diminishing marginal value. Respondents prioritized 40-year-old patients over 5-year-olds and 5-year-olds over 70-year-olds and prioritized baseline HRQoL of 40% and 60% over 20%. Patients at the end of life were not preferred to those with a longer life expectancy. CONCLUSION: Overall, respondents preferred health-maximizing options without explicit consideration for end-of-life patients or those with poor health. In addition, they revealed a kinked preference for patient age, prioritizing middle-aged patients over children and older people.

Protective effect of Lycium barbarum leaf extracts on atopic dermatitis: in vitro and in vivo studies.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of Lycium barbarum leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity. MATERIALS/METHODS: AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells. RESULTS: Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 µg/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells. CONCLUSIONS: These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant. Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.

A Measles Outbreak in a Local Children's Hospital in Korea, 2019.

A measles outbreak with 20 confirmed cases occurred at a local children's hospital in Daejeon from March 28 to April 21, 2019. The index patient was a 7-month-old girl with a recent history of travel to Vietnam. Contact tracing, active surveillance, and post-exposure prophylaxis were conducted by health authorities. Among the 20 patients, 11 (55%) were infants (0-11 months of age), three (15%) were aged 1-3 years, one (5%) was aged 4 years, and five (25%) were adults. Fifteen (75%) patients did not have a history of measles vaccination, and five (25%) had received only one vaccine dose. This study described the importance of prompt application of infection control measures in susceptible environments, including hospitals. Age-appropriate vaccination and providing information on infectious diseases to international travelers and multicultural families in Korea is vital.

A Comparative Analysis of Anticancer Drug Appraisals Including Managed Entry Agreements in South Korea and England.

OBJECTIVES: This study aimed to compare appraisal decisions about anticancer drugs between the health technology assessment (HTA) agencies in Korea and England, and investigate whether the decisions and supporting evidence are comparable. METHODS: This study identified 49 anticancer drugs listed by the Korean Ministry of Health and Welfare between January 2014 and December 2019. Of those, 46 anticancer drugs for 58 indications were included for analysis. Official appraisal documents from both countries for 58 drug-indication pairs were compared and assessed in terms of clinical and economic evidence. Evidence items and their groups for analysis were predefined. RESULTS: Three-quarters of cases were recommended with managed entry agreements (MEAs) in England and three-fifths in Korea. Finance-based MEA types were most common in both countries. Korean and English authorities made consistent decisions in 48 cases (83%) when classifying decisions as 'recommended' and 'not recommended', while the degree of agreement lowered to 16 cases (28%) when subdividing decisions according to MEA types. When the evidence base was identical, their decisions were more likely to be consistent. Regarding clinical evidence, while the majority of cases referred to the same pivotal studies, differences between the committees' recognized comparators and the appraisal date caused discrepancies in decisions. Economic evidence, including incremental cost-effectiveness ratio (ICER) estimates, was identical in only 12 cases (21%), which contributed to discrepancies. CONCLUSION: England relies on economic evaluation, with increasing use of data collection agreements, in contrast with Korea's new procedure exempting companies from providing economic evaluation. While there is possibility for international cooperation in the assessment of clinical evidence, transferability issues exist, particularly with regard to economic evidence.

Regulatory Effects of Lycium barbarum Extract and Isolated Scopoletin on Atopic Dermatitis-Like Skin Inflammation.

Lycium barbarum and scopoletin are widely used in oriental Eastern medicine and are often consumed as teas. In this study, proinflammatory cytokines expressed in human keratinocytes (HaCaT) were induced by skin diseases caused by 2,4-dinitrochlorobenzene (DNCB) and tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ). The inhibitory activity of L. barbarum EtOH extract (LBE) and scopoletin on proinflammatory cytokines and chemokines was investigated. In the DNCB-induced animal model, oral administration of LBE inhibited skin lesions and proinflammatory cytokines and chemokines and showed inhibitory effects in vitro. Additionally, as a result of examining the efficacy of scopoletin isolated from L. barbarum, scopoletin in HaCaT cells showed inhibitory effects on proinflammatory cytokines and chemokines. It shows promise in the treatment of chronic skin diseases.

Systematic Review and Quality Assessment of Health Economic Evaluation Studies (2007-2019) Conducted in South Korea.

BACKGROUND: South Korea formally adopted economic evaluation in December 2006 to aid drug reimbursement decision-making. While this policy change is applied only to pharmaceuticals, it has also sparked interest in economic evaluations for non-pharmaceutical interventions and programmes. OBJECTIVE: This study aimed to provide a snapshot of the current practice for published health economic evaluation studies and critically assess the quality of these studies. METHODS: An electronic search was performed on multiple databases (EMBASE, PubMed, NHS Economic Evaluation Database, Scopus, Korean Medical database, Korean studies Information Service System, and Research Information Sharing Service) to identify health economic evaluation studies published between January 2007 and December 2019. The inclusion criteria were peer-reviewed, original health economic evaluations (cost-utility, cost-effectiveness, cost-minimisation, and cost-benefit analyses) published in English or Korean. Two reviewers selected studies for inclusion and extracted data from the included studies. Key characteristics of these studies were descriptively summarised, and study quality was assessed using the Quality of Health Economic Studies (QHES) instrument on a 100-point scale. RESULTS: A total of 162 studies were included in this review (63 for drugs, 51 for non-pharmaceutical treatments/health technologies, and 48 for health programmes). These numbers confirm a significant increase in the number of publications since the policy introduction. However, the quality of these studies remained relatively low, with a mean QHES score of 57.9 (± 16.0). Study quality also varied substantially, with the QHES scores ranging from 15 to 87. The scores were notably lower in studies with non-pharmaceutical interventions and programmes, cost-effectiveness analyses or cost-benefit analyses, retrospective study-based or simple modelling-based analyses, and those locally published. In addition, a considerable proportion of these studies did not state or specify essential components of economic evaluation, such as perspectives (30.2%), time horizons (29.6%), discount rates (34.6%), and sensitivity analyses (24.7%). While the use of local data either fully or partially was relatively higher for unit costs (94.4%) and resource utilisation (90.1%), it was lower for utility weights (47.1%), treatment effects (63.0%), and baseline risks (70.4%). Transferability or generalisability issues were infrequently discussed when relying on foreign sources. In addition, the included studies were often not well structured, making it difficult to assess their quality. CONCLUSION: These findings suggest that there is still much room for improving the quality of health economic evaluation studies conducted in South Korea. Policymakers should critically evaluate available cost-effectiveness evidence, especially for non-pharmaceutical interventions and programmes, when using it for decision-making in South Korea.

How Sensitive is Sensitivity Analysis?: Evaluation of Pharmacoeconomic Submissions in Korea.

Purpose: We aimed to describe the types of uncertainties examined in the economic evaluations submitted for reimbursement in Korea and their impact on the incremental cost-effectiveness ratio (ICER). Method: Fifty dossiers were submitted by pharmaceutical companies to the economic subcommittee of the Pharmaceutical Benefit Coverage Advisory Committee (PBCAC) from January 2014 to December 2018. The types of uncertainties were categorized as structural and parametric, and the frequencies of the sensitivity analysis per variables were analyzed. The impact of uncertainties was measured by the percent variance of the ICER relative to that of the base case analysis. Results: Of the 50 submissions, varying discount rate (44 submissions), followed by time horizon (38 submissions) and model assumptions (29 submissions), were most frequently used to examine structural uncertainty, while utility (42 submissions), resource use (41 submissions), and relative effectiveness (26 submissions) were used to examine parametric uncertainty. A total of 1,236 scenarios (a scenario corresponds to a case where a single variable is varied by a single range) were presented in the one-way sensitivity analyses, where parametric and structural sensitivity analyses comprised 679 and 557 scenarios, respectively. Varying drug prices had the highest impact on ICER (median variance 19.9%), followed by discount rate (12.2%), model assumptions (11.9%), extrapolation (11.8%), and time horizon (10.0%). Conclusions: Variables related to long-term assumptions, such as model assumptions, time horizon, extrapolation, and discounting rate, were related to a high level of uncertainty. Caution should be exercised when using immature data.

Factors associated with the mental health status of isolated COVID-19 patients in Korea.

BACKGROUND: The COVID-19 pandemic has a substantial impact on the physical and mental health status of patients with COVID-19. This study's objective was to evaluate the factors associated with mental health in patients isolated with COVID-19. METHODS: It is a retrospective, cross-sectional study. One hundred and two patients discharged from COVID-19 hospitalization in Korea were analyzed. The primary outcome was the correlation between psychological problems such as anxiety, depression, and fear of stigma and physical symptoms such as respiratory symptoms, gastrointestinal symptoms, headache, and fever. Mental and physical symptoms were ascertained using closed and multiple-choice questions. The secondary outcome was the correlation between mental issues, demographic factors, and disease severity. Hypoxia and the need for oxygen therapy, a need for remdesivir antiviral treatment, and indications of pneumonia progression on chest x-ray were confirmed through a review of medical records and used to measure disease severity. RESULTS: Patients with COVID-19 indicated feelings of depression (48.1%), anxiety (49.1%), and fear of stigma (60.45%), and some continued to experience physical symptoms even after discharge. Logistic regression revealed that gastrointestinal symptoms positively correlated with depression (p < .05) and headache positively correlated with fear of stigma (p < .05), while the other factors were not statistically significant (p > .05). CONCLUSIONS: This study showed that psychological symptoms persisted even after discharge. Gastrointestinal symptoms and headache were influential factors in predicting depression and fear of stigma. Based on this, dedicated COVID-19 hospitals should provide mental health support and preventive management.

Korean Guidelines for Pharmacoeconomic Evaluations: Updates in the Third Version.

The first version of the pharmacoeconomic (PE) guidelines was published in South Korea in 2006. Despite its first revision in 2011, there were still ambiguities in its interpretation. Moreover, methodologies for estimating effectiveness and costs have also evolved since then. Under these circumstances, the Health Insurance Review and Assessment Service published the third version in January 2021. This article reviews the revision process and major changes made in the new edition of the PE guidelines. The revision was processed through reviews of the previous 50 PE submissions, international guidelines, academic literature, and surveys and advisory meetings to obtain stakeholders' opinions. The analysis perspective has changed from a limited societal perspective to a healthcare system perspective. In addition to the drug with the highest market share, drugs used in clinical trials can be selected as comparators under certain conditions. The discount rate decreased from 5% to 4.5%. Furthermore, the revised guidelines provide more detailed and specific instructions for items including non-inferiority margin, extrapolation, utility elicitation, and uncertainty. Treatment switch and co-dependent technology guidelines are newly included; the budget impact analysis guideline is deleted. Through this revision, transparency and consistency of decision-making is expected to improve.

Elevated Plasma Apurinic/Apyrimidinic Endonuclease 1/Redox Effector Factor-1 Levels in Refractory Kawasaki Disease.

Kawasaki disease (KD) refers to systemic vasculitis of medium-sized vessels accompanied by fever. The multifunctional protein apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) is a new biomarker for vascular inflammation. Here, we investigated the association between APE1/Ref-1 and KD. Three groups, including 32 patients with KD (KD group), 33 patients with fever (Fever group), and 19 healthy individuals (Healthy group), were prospectively analyzed. APE1/Ref-1 levels were measured, and the clinical characteristics of KD were evaluated. The mean age of all patients was 2.7 ± 1.8 years, but the Healthy group participants were older than the other participants. Fever duration was longer in the KD group than in the fever group. APE1/Ref-1 levels were significantly higher in the KD group (p = 0.004) than in the other two groups, but there was no difference between the healthy and fever groups. APE1/Ref-1 levels did not differ according to fever duration or coronary arterial lesion but were higher in refractory KD cases than in non-refractory cases. APE1/Ref-1 levels were significantly higher during the acute phase of KD. We propose that APE1/Ref-1 could be a beneficial biological marker for the diagnosis and prognosis of KD, especially in refractory KD.

How can we improve patients' access to new drugs under uncertainties? : South Korea's experience with risk sharing arrangements.

BACKGROUND: New drugs including cancer drugs and orphan drugs are becoming increasingly more expensive. Risk sharing arrangements (RSAs) could manage the risk based on both financial impact and the health outcome of new drugs if reimbursed. To improve patients' access to new drugs under uncertainties, many developed countries have adopted RSAs. In this study, we aimed to understand the effects of RSAs in South Korea on patients' access. METHODS: We reviewed current status of RSA drugs in South Korea. The number of appraisals and time gap between market approval and reimbursement per RSA drug were considered to quantify improvement of patients' access as they showed how rapidly decisions on reimbursement of RSA drugs were derived. Then, we applied a comparative analysis to determine whether the RSA drugs in South Korea were reimbursed in the UK, Italy, and Australia. Most data for this study were obtained from websites of the governmental department/agencies responsible for appraisal of drug reimbursement in each country. And literatures related to RSAs were investigated as well. RESULTS: The eligibility for Korean RSAs had two key components - drugs for cancer and rare diseases and not having other alternative treatments. As of the first half of 2019, there were 39 RSA drugs reimbursed in South Korea, the majority of which were financial-based schemes. Refund and expenditure cap were the representative types (89.7%). After introduction of RSAs, the time gap and number of appraisals were decreased. Based on the indications of RSA drugs, the level of drug coverage in South Korea was found lower than Italy, similar to the UK, and higher than Australia. CONCLUSIONS: RSAs in South Korea significantly enhanced patients' access to new drugs and led to the alleviation of patients' out-of-pocket expenses. The drug coverage of South Korea had a level comparable to that of other countries. This study provides implications for countries that have a dual mission of containing pharmaceutical expenditure and improving access to new drugs.

A Review of Utility Measurement Methods Used in Pharmacoeconomic Submissions to HIRA in South Korea: Methodological Consistency and Areas for Improvement.

Pharmacoeconomic (PE) guidelines, first published in 2006 and later updated in 2011, were developed to guide the preparation and submission of PE data to the Health Insurance Review and Assessment Service (HIRA) for drug reimbursement decision making in South Korea. This study, which was conducted as part of a project for revision of the PE guideline, reviewed utility values used in the PE submissions processed at HIRA during 2014-2018 to identify aspects of the current guidelines that may need to be revisited. A total of 50 PE submissions were processed at HIRA over the 5 years. Of these, 47 submissions that used quality-adjusted life-years as an outcome measure were included in this review. Data were extracted from full copies of the manufacturer's initial submissions and committee documents provided by HIRA. Of the 47 submissions, nearly half (n = 23, 48.9%) used published sources to obtain health state utility values, followed by direct methods using time trade-off (n = 7) or standard gamble (n = 2) and indirect methods with patient-level data using the EQ-5D-3L (n = 4) or the EQ-5D-5L (n = 2). Mapping, using the EQ-5D-3L as a target measure, was also adopted in six submissions, although it was somewhat unfavourably described in the guideline. Notably, 52.2% of the submissions with published sources took utility values from different sources for different health states defined in a single model. In addition, details of utility measurement methods or mapping functions taken from published sources were relatively poorly reported. Moreover, the preferences of the Korean general public, preferred by the guideline, were rarely reflected in the utility values used in submissions relying on published sources (95.7% for foreign values only/mixed) and mapping (66.7%). While most submissions with direct and indirect methods used domestic preference values, the former was occasionally criticised by assessment committees because of health state descriptions. This review highlights a considerable amount of inconsistency in the measurement of utility values used in the PE submissions during 2014-2018, indicating a strong need for methodological standardisation.

Public Preferences in Resource Allocation for Insurance Coverage of Dental Implant Service in South Korea: Citizens' Jury.

The Korean government sought to include dental implant services for the elderly in the benefits package of the national health insurance. In 2014, the Citizens' Jury was held to discuss the topic, during which thirty jurors, randomly selected from the 2665 applicants, participated in a day-long deliberation process after having an information session on the topic by a team of experts. There was a substantial shift in opinion during the deliberation session toward a more cost-conscious view. Most jurors supported limiting the coverage of dental implant to only one tooth per individual given the extent of the financial burden that will be imposed on the population. They opposed covering implant services for the front teeth, given that the implant of front teeth generally serves aesthetic purposes rather than restoring mastication function. The government's final decision in 2014 was to offer coverage up to two teeth, regardless of tooth location. This scheme based on the jury's recommendations in 2014 has been implemented without policy failure to date, which shows that the lay public can meaningfully contribute to a decision-making process regarding controversial agendas such as benefits packages for expensive health services.

First Case of Peroxisomal D-bifunctional Protein Deficiency with Novel HSD17B4 Mutations and Progressive Neuropathy in Korea.

Peroxisomal D-bifunctional protein (DBP), encoded by the HSD17B4 gene, catalyzes ß-oxidation of very long chain fatty acids (VLCFAs). The deficiency of this peroxisomal enzyme leads to the accumulation of VLCFAs, causing multisystemic manifestations including the brain, retina, adrenal gland, hearing, and skeletal system. Herein, we report the first Korean neonatal case of peroxisomal DBP deficiency and the clinical prognosis over 2 years. This patient showed craniofacial dysmorphism, club foot, and seizures with cyanosis one day after birth. Elevated VLCFAs levels were indicative of a peroxisomal disorder. Targeted exome sequencing was performed and two missense mutations p.Asp117Val and p.Phe279Ser in the HSD17B4 gene were identified. The patient had type III DBP deficiency; therefore, docosahexaenoic acid and non-soluble vitamins were administered. However, progressive nystagmus, optic nerve atrophy, and bilateral hearing defects were observed and follow-up brain imaging revealed leukodystrophy and brain atrophy. Multiple anti-epileptic drugs were required to control the seizures. Over two years, the patient achieved normal growth with home ventilation and tube feeding. Hereby, the subject's parents had support during the second pregnancy from the proven molecular information. Moreover, targeted exome sequencing is an effective diagnostic approach, considering genetic heterogeneity of Zellweger spectrum disorders.

Who should be given priority for public funding?

BACKGROUND: This study explored if Koreans consider the type of disease, rarity, and availability of alternative treatments as priority criteria in limited healthcare resource allocation. MATERIALS AND METHODS: A web-based survey was conducted with a representative sample of 3,482 Korean adults. Participants were divided into six cohorts, differing in terms of the disease being compared and the cost and benefits of the treatments. Each cohort was asked two questions: 1) How to allocate a fixed budget into each of the two groups (cancer vs non-cancer, rare vs common, no other treatments available vs several treatments available), all else being equal; 2) allocation choices when conditions of two groups differed. The McNemar test was used to assess changes in responses between the two questions. RESULTS: Under the control condition, the majority chose to treat an even number of patients with cancer and non-cancer diseases, and preferred to treat common diseases and those with no alternative treatments. However, when the treatment effects or costs of two comparison groups changed, choice shifted toward more effective or less costly treatment. CONCLUSIONS: While Koreans generally support the principle of health maximization, they also believe that priority should be given to diseases that previously did not have any treatments. However, no priority was given to cancer or rare diseases.

Anti-inflammatory effect of Lycium barbarum on polarized human intestinal epithelial cells.

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5-50 µg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.

Anti-photoaging effect of skin cream manufactured with ziyuglycoside I isolated from Sanguisorba officinalis on ultraviolet B-induced hairless mice.

In this study, skin cream containing ziyuglycoside I isolated from Sanguisorba officinalis was manufactured and examined the protective effects of the skin cream against UVB-induced hairless mice. UVB-induced hairless mice were topically treated with the skin cream once a day for 5 weeks. Application of the skin cream did not exhibit side effect on body growth showing normal body weight and food efficiency in the mice. The skin cream treatment also was inhibited mRNA expression of interleukin (IL)-1ß, matrix metalloproteinase (MMP)-2, MMP-9, and MMP-2 protein expression in the mice. Furthermore, the skin cream treatment inhibits epidermal wrinkle formation, wrinkle depth, wrinkle thickness, and collagen degradation in UVB-induced hairless mice. Therefore, the skin cream was able to play a role in the attenuation of photoaging caused by UVB irradiation via downregulation of mRNA expression of inflammatory cytokine IL-1ß, MMP-2, MMP-9, and suppression of MMP-2 proteins expression.

Role of Health Technology Assessment in Drug Policies: Korea.

South Korea is the first Asian country to mandate the submission of pharmacoeconomic data for reimbursement decision making. For a new drug to be listed, it must demonstrate its value in terms of comparative effectiveness and cost effectiveness. The Health Insurance Review and Assessment Service (HIRA) judges the submitted drug's value and decides whether its coverage is appropriate on the basis of the recommendation of the Pharmaceutical Benefit Coverage Assessment Committee. Once the drug has been accepted by HIRA, the National Health Insurance Service and the sponsoring company negotiate the price and expected sales volume. Even if HIRA acknowledges the value of the drug, it cannot be listed if the negotiation fails. In the off-patent market, generic and original branded drugs are treated equally in terms of pricing. Once generics enter the market, both drug prices should be lowered to 53.55% or less of the on-patent price. Since the current system was implemented, concerns have been raised about a decline in the accessibility of new drugs, especially for high-priced drugs used to treat serious diseases. In 2013, several measures had been introduced aimed at improving the accessibility of these drugs. A risk-sharing scheme and an increase in the maximum acceptable cost-effectiveness ratio were subsequently initiated. Although these schemes have been successful in improving access to high-priced drugs, they are often criticized for reducing transparency in pricing. Finding a balance between accessibility and efficiency is still a challenge in Korea.

Role of economic evidence in coverage decision-making in South Korea.

OBJECTIVES: The South Korean government required the submission of economic evidence when it implemented the Positive-List System in December 2006. This study investigates the key factors that influenced actual public insurance reimbursement decisions, including the role of economic evidence, after 10 years of decision practice under compulsory health technology assessment (HTA) for new drugs. METHOD: Logistic regression analysis was used to estimate the impact of the variables involved, including cost-effectiveness ratio as a key variable, on reimbursement decisions. The latter were defined as "yes" or "no" at a submitted price and indication. Only cases (n = 91) that present a cost-effectiveness ratio, and that have been reviewed based on this ratio from January 2007 to December 2016, were included in the analysis. RESULTS: Cases with higher cost-effectiveness ratios were less likely to be accepted. In addition, drugs that were used to treat severe diseases and drugs with no substitute were more likely to be recommended. The probability of acceptance declined along with the level of uncertainty in the submitted evidence. The acceptance rate for severe-disease drugs has increased since 2013, when the government introduced several policies that lowered the existing barriers to positive reimbursement. However, such an increase was not statistically significant. CONCLUSIONS: Cost-effectiveness is one of the most influential factors in drug-reimbursement decisions. However, inclusion of other explanatory variables, in addition to the cost-effectiveness ratio, predicted the results of decisions more accurately.